Fundamentals of Surgical Pathology Shameem Shariff
Page numbers followed by f refer to figure and t refer to table.
Abscess 218, 263, 442
crypt 197
Acantholytic acanthoma 357
Acanthoma 364
epidermolytic 357
Acanthosis 19, 21
Acanthotic lesions, massive 168
Acellular structure 462
Achlorhydria 178
bacilli 354
stain 87
Acinar cell
carcinoma 150f, 244f
cystadenocarcinoma 239
Acini, malignant 79
Acquired immunodeficiency syndrome 112, 190, 193, 199, 281, 304
Acral keratosis 339
Acrodermatitis enteropathica 193
Actin 475
Actinobacillus 435
Actinomadura madurae 355
Actinomycetem comitans 435
Actinomycosis 21, 256
organisms 32
Adamantinoma 391
Adenoacanthoma 35
Adenocarcinoma 26, 27f, 27t, 28, 28t, 55, 79, 147, 175, 183, 267, 273t, 275, 275t, 461, 465
endometrioid type of 63
high-grade serous 40
in situ 24, 269
incidence of 270
invasive 270
mucinous 271
large duct 80, 81
low-grade serous 40
lung, conventional 469
microglandular 243
microinvasive 27
minimally invasive 270
morphologic variants of 27
peripheral 80
polymorphous low grade 151
types of 28
Adenofibroma 33
Adenoid cystic carcinoma 25, 144, 150, 153, 175, 368
Adenolymphoma 147
Adenoma 89, 268, 342
apocrine 460
double 345
follicular 339, 341
hepatocellular 231, 232
high grade 184
hyalinizing trabecular 342
low grade 184
malignum 27, 27f, 28, 28f, 28t
pleomorphic 145, 146, 146f, 147, 460
traditional serrated 203
Adenomatosis polyposis
familial 202
serrated 204
Adenomyoma 33
Adenomyosis 17, 32
Adenosarcoma 33, 40
Adenosis, microglandular 315
Adnexae 62
Alagille syndrome 226
Allred's quick score 326
Alpha 1 antitrypsin deficiency 225
Alport's syndrome 111
Alveolar damage, diffuse 266
Alveolar pattern 122f
Alveolar ridge
lower 156, 158
upper 156, 159
Alzheimer's disease 455, 456
Ameloblastoma 168
malignant 169
American Academy of Pediatrics 122
Amino acid 466
metabolism, disorders of 227
Amiodarone 266
Amnion nodosum 11
Amniotic fluid, formation of 11
Amoebic meningoencephalitis, primary 446
Ampulla 5
deposits 115
goiter 343
precursor protein gene 456
Amyloidosis 95, 101, 115
Anal canal, classification of tumors of 206
Androblastomas 50
Angioleiomyoma 411
Angiolipoma 398, 401
Angiomatosis 412
bacillary 412
Angiomyofibroblastoma 15, 21, 405
Angiomyolipoma 99, 120, 122, 411
epithelioid 120
aggressive 15, 21, 414
superficial 21, 414
Angiosarcoma 72, 120
Angiotensin-converting enzyme 264
Aniridia 423
Anitschkow cells 437
Ann Arbor staging system 307
anti-melanoma 469
antimitochondrial 223
mediated rejection
Banff classification 129
chronic active 128
Antigen 465
antibodies, antineutrophil cytoplasmic 106
carcinoembryonic 22, 26, 465
epithilial membrance 26
stimulation occurs 285
Anti-inflammatory drug, nonsteroidal 111, 181
Antiphospholipid syndrome 110, 228
Antral gastritis, diffuse 181
Antrum, polyps in 178
Appendix 188190
classification of tumors of 205
Arias-Stella reaction 31
Armanni-Ebstein anomaly 115
Arnold-Chiari malformation 14
Arrhenoblastomas 50
Arrhythmias 437
cardiac 446
Arteries 117
Arterioles 117
Arteriolosclerosis 110
hyaline 115
Arteriosclerosis 110
Aryepiglottic fold 166, 249, 252
Arytenoid cartilages and ventricles 249
Asbestos bodies 267
Asbestosis 267
Askin tumor 390, 470
Aspergillus 435
fumigatus 445
spores 445
anaplastic 452
diffuse 452
fibrillary 452
gemistocytic 452
Atherosclerosis 447
biliary 226
extrahepatic biliary 225
Atrial septal defect 14
Atrioventricular valves 433
Atrophic gastritis, multifocal 181
Atrophy 8
endometrial 36
Atropic glands 81
Attacks, recurrent 194
Atypia, greater degree of 44
Autosomal dominant 122, 123
adult polycystic kidney disease 122, 123
polycystic kidney disease 229
Autosomal recessive 122, 123
childhood polycystic kidney disease 124
disease 124
polycystic kidney disease 122
Bacillus Calmette-Guerin 77
Bacteria, pathogenicity 443
Bacterial overgrowth syndrome 190, 192
Balanitis 70
xerotica obliterans 72
Balanoposthitis 71
Balantidium coli 229
Balloon cell nevus 460
Banff classification 129
revised 129
Barrett's esophagus 173175
diagnosis of 174
Bartholin duct 142
Bartholin gland 18
cyst 18
Bartonella quintana 412
Basal cell
adenocarcinoma 148
adenoma 145, 147
carcinoma 357, 359, 461, 470, 470t
syndrome, nevoid 362
change 195
layer, irregular 167
proliferation 148
Basal keratinocyte necrosis 357, 360t
Basal lamina 462
epithelial 462
Basal low cuboidal cells 323f
Basaloid carcinoma 72, 469
Basaloid squamous cell carcinoma 23f, 25, 72, 168, 175
Basement membrane 114
destruction 357
Basophilia, cytoplasmic 191
Basophilic cytoplasm 291, 404
Battledore placenta 10
hyperplasia, monocytoid 304
lymphocytosis, monoclonal 287
lymphoma 284, 306
fiffuse large 89, 290
intravascular large 291
red pulp small 282
splenic 282
mature 282, 307
precursor 306
Beckwith Wiedcmann syndrome 384, 417, 423, 424
Behçet's colitis 199
Bezoars 178
Bicuspid aortic valve 435
Bile duct
adenoma 232
atresia, extrahepatic 224
carcinoma 233t, 469
disease, vanishing 224
interlobular 224
intrahepatic 232
major 216, 216f
Bile-plug syndrome 226
Biliary cirrhosis, primary 223
Billroth procedures 192
colonoscopic 194
cystoscopic 132, 137
endoscopic 176, 185
excision 310f
needle core 215, 329
small 8, 73
specimens, small 70
transbronchial 261
transplant 126
types of 125, 215, 441
Bizzare leiomyoma 38
Black nodular mass 133
Bladder resection specimens 138
Blastomyces dermatitidis 445
Bleeding diathesis, severe 100
Blood vessels 403f
mesenteric 187
Bloodless glomeruli 116
Blue cell neoplasia, small 420
Blue nevus 460
common 367
Bluish multiple cysts 312
Blunt duct adenosis 315
Bone 376
arrangement 377
biopsy 377
cells 376
compact 377
aneurysmal 390, 391, 393
unicameral 392
destruction, cortical 389
extremities 378
formation 392
histology 376
infarction 383
grossing of 377
synoptic reporting 394
marrow needle biopsy 377
matrix 376
and collagen, disorders of 381
mineralization of 381
necrotic 380
normal anatomy 376
remodeling 377
resorption, cycle of 377
tumors 380
classification of 383
malignant 389
TNM staging of 394
Borderline malignancy
Brenner tumor 40
serous tumor of 89
Borderline serous ovarian tumors 42
Borderline tuberculoid 353
Borrelia burgdorferi 438
Botryoid rhabdomyosarcoma 28
Bouin's fluid 1
Bowen's disease 19, 70, 71, 352, 357, 363
Bowenoid actinic keratosis 363
Bowenoid papulosis 19, 71
Bowman's capsule 103, 118
Bowman's layer 462
Bowman's membrane 462
Bowman's space 100
Brain 441
abscess 443
areas of 446f
biopsy 441
eating amoeba 446
normal anatomy 442
parasitic infections of 445
parenchyma 443
pathology 442
tissue 423
tumors 448
Breast 309
benign lesions 313
biopsies, minimally invasive 328
cancer, early 324
carcinoma 328
invasive 319
molecular subtypes of 327
technique in 328
excision biopsy 309
fibrocystic disease of 313
gross pearls 312
histopathology synoptic report 331
incisional biopsy 309
like subtypes 328
mastectomy 309
microscopy pearls 313
mucinous carcinoma of 321f
normal histology 313
parenchyma, infiltration of 314f
secretory carcinoma 321
specimens received 309
tru-cut biopsy 309
tumors, WHO classification of 319
wide local excision 309
Brenner tumor 18, 40, 41, 44, 50, 89
benign 40
malignant 40, 44
proliferating 44
British Society of Gastroenterology 174
British Testicular Tumor Panel and Registry 89
Brodie's abscess 388
Bronchiectasis 267
Bronchioalveolar tumor, intravascular sclerosing 272
Bronchiolar alveolar carcinoma 471t
Brown bowel syndrome 189
Brown tumor 382, 393
Broyles ligament 250
Brucella 435
Buccal gingival gutter 167
Buccal glands 142, 143
Buccal mucosa 158
Budd-Chiari syndrome 218, 227, 230
Bulbar polio 444
Bulbospinal polio 444
Bullous impetigo 356
Bullous pemphigoid 361
Burkitt's lymphoma 293, 294, 301
Buschke-Lowenstein tumor 72
Byler's disease 226
Byler's syndrome 226
Cafe-au-lait spots 417
Call-Exner bodies 48
Calponin 466
Calretinin 467
Calyceal diverticulum 123
Calymmatobacterium granulomatis 19
Campylobacter jejuni 199
Campylobacter pylori 181
Canada-Conkhite syndrome 201
Canalicular adenoma 146, 148
Canaliculitis 461
Cancer genome atlas 37
Cancer syndrome, inherited 417
Candida 435
pseudohyphae 119f
Candidiasis 173
Capsular invasion 341
Carbohydrate metabolism, disorders of 227
Carbon monoxide 446
Carcinofibroma 33
Carcinoid 41, 47, 206
atypical 28
tumors 182, 271
Carcinoma 1618, 20, 28, 31, 70, 72, 81, 89, 324
adenosquamous 25, 35, 55, 72, 81, 168, 175, 183, 243, 268, 272
anaplastic 243
apocrine 368
breast 312, 318, 469
ciliated 36
colon 188f, 197, 467
cuniculatum 72
cytokeratins positivity in 466f
embryonal 46, 89
embryonic antigen 27
endometrial 32, 34t, 35, 37, 473
endometrium 6
epithelial-myoepithelial 144, 151, 153
esophagus 175
ex pleomorphic adenoma 147
extraovarian papillary serous 42
fibrolamellar hepatocellular 230
follicular 341
hepatocellular 231233, 233t, 423
hyalinizing trabecular 342
in situ 27, 71, 202, 239
ductal 318t
infantile pancreatic 244
intraductal 79
intraepithelial 35
intramucosal 175, 202
invasive 67, 240, 333
micropapillary 321, 321f
lung 471t
lymphoepithelioma-like 168, 272
midline 168
prostate 472t
small cell 23, 29, 29t, 32, 36, 51, 81, 244, 258, 472
stomach 183
superficial 7
unclassified 268
undifferentiated 18, 32, 175
Carcinosarcoma 33, 40, 312
Cardiac arrest 446
Cardiobacterium homini 435
Cardiomyopathy 439
dilated 439
histiocytoid 439
hypertrophic 439
primary 439
unclassified 439
Cardiovascular system 433
normal anatomy 433
Carney complex 417
Caroli's disease 229
Castleman's disease 281, 292, 301, 304
Caterpillar cells 437
Cauliflower like
appearance 133
mass 16
Celiac disease 192t
Cell 179, 317
adenocarcinoma, mixed 32
adipocytic 401f
carcinoma, mixed small 271
endothelial 467
hyperplasia, reserve 20
inflammatory 191, 444
membrane protein 468
morphology 292, 317
neoplasms, histiocytic 283
of origin 287, 288
peripheral palisading of 23f
resemble mature lymphocytes 287f
surface glycoprotein 465
variant, ciliated 32
angiofibroma 21, 405
blue nevus 367, 460
components 465
crescents 110
inflammatory reactions 443
leiomyoma 38
schwannomas 373
variant 32
Cellularity, mixed 300
Central nervous system 116, 441, 445t
Centrilobular cholestasis 224
Centrocyte 286
blood flow, stagnant 446
hemispheres 453
hypoxia, causes of 446
Cerebrospinal fluid 443
adenocarcinoma 473
in situ 23
adenofibroma 24
adenomyoma 24
endocervical type of 27
angiosarcoma 24
biopsy histopathology report 54
cancer 56
carcinoma 24
epithelium 20
polyp 23
neoplasia 1, 23, 24, 55
leiomyoma 24
leukemia 24
lymphoma 24
squamous cell carcinoma in situ 23
tumor, WHO classification of 23
Wilms’ tumor 24
chronic herpetic 54
chronic papillary 54
nonspecific chronic 54
Cervix 1, 3, 4, 15, 20, 24, 27t, 32, 67
adenocarcinoma of 23
basal carcinoma of 23
cystic carcinoma of 23
adenosarcoma of 24
adenosquamous carcinoma of 23
alveolar soft part sarcoma of 24
carcinoma of 6, 7, 17, 23f, 25, 25t
carcinosarcoma of 24
clear cell adenocarcinoma of 23
dermoid cyst of 24
early invasive adenocarcinoma of 23
glassy cell carcinoma variant of 23
large cell neuroendocrine carcinoma of 23
leiomyosarcoma of 24
malignant peripheral nerve sheath tumor 24
mature cystic teratoma of 24
mesonephric adenocarcinoma of 23
mucinous adenocarcinoma of 23
Müllerian papilloma 23
myxoid tumor like appearance of 15
removal of 3, 8
serous adenocarcinoma of 23
small cell carcinoma of 23
squamotransitional carcinoma 23
intraepithelial neoplasia 23
papilloma 23
undifferentiated carcinoma of 23
well-defined cysts in 15
yolk sac tumor of 24
Chalazion 460
Chemotherapeutic agents 266
Cherubism 384
Chlamydia trachomatis 20, 31
Chlamydial infections 32
Chocolate cyst 18
Cholangiocarcinoma, intrahepatic 469
Cholangitis lenta 225
Cholecystitis, chronic 218
Cholestasis 224, 226
familial intrahepatic 226
intrahepatic 226
Cholestatic disease 224
Cholesterosis 218
Cholesteryl ester storage disease 227
Chondroblastoma 385, 393
lipoma 398, 401
syringoma 368, 369
Chondroma 385
Chondromyxoid fibroma 386, 393
Chondrosarcoma 39, 385387
conventional 386
extraskeletal myxoid 415
primary central 386
secondary 387
Chorangioma 11
Chordoid sarcoma 415
Chordoma 391
Chorioadenoma destruens 53
Chorioamnion 51
Choriocarcinoma 17, 33, 46, 53, 86, 89, 90, 475
development of 52
Chorionic villi 9
Choroid plexus
carcinoma 454
papilloma 454
tumors 448
Chromatin 47
Chromogranin 467
Chromophil 121
Chromophobe renal cell carcinoma 120
Churg-Strauss syndrome 264
Ciliary body lesions 463
Circummarginate placenta 11f
Circumvallate placenta 11f
Cirrhosis 105, 222
biliary 217
cardiac 217
classification of 222
micronodular 217
Cistern formation 52
Clear cell
acanthoma 357, 365
adenocarcinoma 32, 40, 89
carcinoma 18, 28, 29, 36, 44, 151, 474
change 31, 195
chondrosarcoma 387
cribriform hyperplasia 81
follicular neoplasm 342
metaplasia 31
oncocytoma 148
papillary renal cell carcinoma 120
renal cell carcinoma 120, 121
sarcoma 72, 120, 123, 416
squamous carcinoma 72
tumor 40, 272
Clitoral hypertrophy 50
Clitoris 18, 20
difficile 197, 199
sordellini 197
Coccidial infections 193
Coccidioides immitis 445
Coccyx 422
Codman's triangle 388
antibiotic-associated 197
collagenous 198
eosinophilic 198
indeterminate 196
ischemic 196
lymphocytic 198
Collagen vascular diseases 264, 439
Collecting duct
carcinoma 99, 120, 121
tumor of 89
Colon, tumor of 205
Colonic epithelium, cytokeratins positivity in 466f
Commissure tendon, anterior 250
Complete mole 52, 52t
Condyloma acuminatum 19, 21, 23, 26t, 72, 167, 352
Condylomata, anogenital 257
Cone biopsy 2
Congo red 434
Conjunctiva 462
Conjunctival papilloma 461
Conjunctivitis, inclusion 462
Connective tissue disorders 383
Cord 10
insertion of 10
Core biopsy 331
advantages of 329
limitations of 329
staining on 326
Cornea 462
Corneal endothelial cells 462
Corneal grafts 462
Corpus 1
luteal cyst, torsion in 18
luteum 17
cysts 39
Cortical nodule, small 99
Corticobasal degeneration 455
Corticomedullary junction 98, 98f
Cowden's polyp 182
Cowden's syndrome 201
Cranial nerve, tumor of 449
Craniopharyngioma 450
C-reactive protein 231
Crescent, formation of 103
Cribriform cystadenocarcinoma, low-grade 152
Cricoid cartilage 248
Cricopharyngeus muscle 171
Crohn's disease 167, 189, 195, 197t, 198, 199
heel length 14
rump 3
length 14
Cryptococcus 444
meningitis 297
neoformans 445
Cryptorchid testis 88
Cryptosporidium 190
Crystalloids, intraluminal 79
Cushing's syndrome 51, 245
Cutaneous myxoma 21
Cylindroma 368
Cyst 18, 19, 39, 98, 460
bilateral large 98
congenital 229
dermoid 89, 460
endometriotic 18
epidermal 460
epidermoid 89
follicular 18, 39
formation 423
gelatinous 445
glomerular 123
hemorrhagic 18
in cortex 17
in liver 218
in medulla 98
in wall 173
keratinous 143
lymphoepithelial 145
reniform mass of 98
simple 123, 229
with thick walls 99
with whitish thick laminated membrane 99
with yellow rim 18
Cystadenocarcinoma 149, 229
Cystadenofibroma 40
Cystadenoma 40, 146, 149
biliary 229
Cystectomy 133
Cystic cavities 47
Cystic conditions
benign 239
malignant 239
Cystic disease 124
acquired 120
renal 123
Cystic lesions, benign 460
Cystic teratoma
benign 18
mature 24, 47, 47f
Cysticercosis 445
Cystitis 86, 134
chronic tuberculous 134
common variants of 134
emphysematous 134
eosinophilic 134
interstitial 134
Cytogenetics 121
Cytokeratin 26, 408, 466
Cytomegalovirus 31, 173, 174
infection 444
Cytotrophoblasts 9
Dacryocystitis 461
Dandy-Walker malformation 14
Darier's disease 357, 360
Daughter cysts 228
De Quervain's thyroiditis 344
Dead bone 380
Decemet's membrane 462
Degenerative diseases 455t
Dementia, severe 456
Dendritic cell neoplasms 283
Denocarcinoma 81
Denys-Drash syndrome 423
Dermatitis herpetiformis 361
Dermatofibroma 371
Dermatofibrosarcoma protuberance 371, 372t, 406
pigmented 406
Dermatologic disorders 167
Dermatophytoses 354
Dermatoses 356
Descemet's membrane 462
Desmin 412, 468
Desmoplastic mesothelioma 467
Desmoplastic small round cell tumor 416
Diabetes mellitus 101, 220
Diabetic nephropathy 114
routine cases of 100
Diathermy loop excision 2
Diethylstilbestrol 36
Digestive systems 249
Digital fibromatosis 405f
Digital fibromyxoma 413
Digital papillary carcinoma 368
Distant metastases 84, 93, 131, 140, 278, 349, 374, 375, 419, 423, 432
Donovan bodies, demonstration of 19
Donovanosis 19
Dorsalis pedis vessel, dissection of 397
Down's syndrome 428, 456
Dubin-Johnson syndrome 217, 226
Duct papillomas 146, 149
Ductal adenocarcinoma 240, 242
Ductal carcinoma
in situ 316, 316f, 317, 317t
high grade 317t
low grade 317t
treatment of 317
variants of 317
variants of 243
Ductal hyperplasia, atypical 315317, 317t, 323, 329
Duodenal aspirates 193
Dysentery, bacillary 199
Dysgerminoma 18, 41, 45, 90, 474
Dysplasia 135, 175, 184
aplastic 123
argyrophilic cell 195
arteriohepatic 226
diffuse 123
diffuse cystic 99
exist, several distinct patterns of 123
fibro-osseous 392t
fibrous 389, 391, 392, 392t
glandular 23
severe 239
Dysplastic changes, severe 167
Dysplastic nevus
congenital 460
syndrome 367
Dysplastic nodules 231
acrospiroma 369, 460
cylindroma 369, 460
poromas 369
spiradenoma 370, 460
Echinococcosis 446
Echinococcus granulosus 228, 239
Echovirus 226
Ectocervical edge 55
Ectocervical mucosa 17
thickened 16
Ectocervix 1
Ectoderm 39
Ectopic origin, tumor of 268
Edema 197
inflammatory 443
Effusion lymphoma, primary 292
Egg basket appearance 300
Elastic tissue 316f
Elastofibroma 404
Elastosis, actinic 462
Electron microscopy 100, 102, 104, 108, 111, 117
Embryo 3
developmental changes of 14
Encephalitozoon intestinalis 194
Encephalomalacia 443
Enchondroma 383, 385
Enchondromatosis 384
Endobronchial lesion 263
Endocarditis 434
acute 435
infective 435, 438f
noninfective 436
subacute 435
Endocardium 437
adenocarcinoma, primary 27
elongated 16
length of 4
columnar cell neoplasia 24
epithelium 55
glandular hyperplasia, lobular 22
invasion 61
polyp 22, 23
sarcoma, undifferentiated 24
Endocervix 1
Endoderm 39
Endolymphatic stromal myosis 37
adenocarcinoma, primary 27
biopsy histopathology report 58
cancer histopathology report 60
hyperplasia 7, 3133
new WHO classification of 33, 34t
carcinoma 35
neoplasia 34
sarcoma, undifferentiated 32
stromal, mixed 33
Endometrioid 39
adenocarcinoma 23, 24, 27, 32, 35, 40
borderline tumor 40
tumor 40, 42, 44, 89
Endometriosis 22, 32
acute 31
chronic 31
Endometrium 3, 7, 27t, 29, 58, 59, 61, 469
carcinosarcoma of 17
hypersecretory 17
normal anatomy 3
secretory 17
thickened 17
Endomyocardial biopsy 434
complications 434
indications 434
techniques 434
Endosalpingiosis 42
Endothelial decompensation 462
Entamoeba histolytica 20, 229
Enterocytozoon bieneusi 194
Enteropathy, autoimmune 192
Enzyme histochemistry 232
Enzyme-linked immunosorbant assay 110
Eosinophils 191, 197
Ependymoma 453
Epidermis, atrophic 19
Epidermolysis bullosa
acquisita 361
simplex 357
cause of 86
nonspecific 86
Epithelial and
mesenchymal tumor, mixed 24, 33
stromal tumor, mixed 120
Epithelial cells 281
pleomorphic 275f, 322f
surface 191
Epithelial membrane antigen 90, 168, 408, 468
Epithelial proliferation 316f
Epithelial proliferative lesions 315
Epithelial tumors
malignant surface 72, 64, 146, 257
surface 40, 41, 474
Epithelioid appearance 305
Epithelioid cell 264, 301, 463
nevus 460
tumor, perivascular 33
Epithelioid variant 32, 411
Epithelium cells, columnar 323f
Epitheloid sarcoma 72
Erdheim-Chester disease 450
multiforme 357, 360
nodosum leprosum 354
toxicum neonatorum 358
Erythroleukoplakia 167
Erythroplasia 167
of Queyrat 71
Escherichia coli 118
Esophageal biopsy histopathology 208
Esophageal lumen 173
Esophageal resection 208
Esophageal tumors, WHO classification of 175
Esophagectomy specimens 171
Esophagitis, candidal 174
Esophagogastric junction 180f
Esophagus 171
endoscopic biopsy 171
lymphatic drainage of 171
normal anatomy 171
specimen handling 172
Esthesioneuroblastoma 255
Estrogen 475
receptor 27
European Grading System 317
Evan's tumor 409
Ewing sarcoma 120, 240, 384, 389, 415, 470, 472
Extracapillary proliferation 101
Extragonadal tumors, malignant 422
Eye 458, 458f
Eyelids 460
tumor of 460
Fabry disease 439
hemangioma 461
trichilemmomas 339
Fallopian tube 3, 5, 6, 17, 18, 32, 39, 63, 67
carcinoma 67
malignant tumor 18
tumor of 7
Familial intrahepatic cholestasis, progressive 226
Fatty liver disease, nonalcoholic 220
Faucial isthmus 161
Female genital tract 1, 474
lesions 473
normal anatomy 1
Femoral vessels, dissection of 397
Fenfluramine 439
Ferruginous bodies 267
Fetal surface 11
Fetus 3, 13
length of 15t
standard weights of 14
Fibrinoid necrosis 110
Fibroadenoma 314
juvenile 314
Fibroblastic tumor, malignant 408
Fibrocystic disease 314f
Fibrofolliculoma 369
Fibrohistiocytic tumors 384, 399, 409
benign 409
Fibroma 40, 50
congenital 408
irritation 166
non-ossifying 391
of long bones, ossifying 392t
Fibromatosis 404, 472
inclusion body 405
Fibropolcystic disorders 229
adult 408
infantile 408
inflammatory 407
cystic 225
endocardial 439
generalized 88
hepatoportal sclerosis, noncirrhotic portal 228
interstitial 110, 128
staging 220
hard gland 143
wall 218
Fibrous cortical defect 391
Fibrous histiocytoma
deep benign 410
malignant 416
Fibrous tissue, cellular masses of 392
Fibroxanthoma, atypical 371, 414
Fimbriae 5
Fine needle aspiration 328
biopsy 218
cytology 87, 328
First attack, acute stage of 194
Fixative-fatty liver 217
Flat lesion with
atypia 135
dysplasia 135
Flea bitten kidney 97
Follicles, cystic 39
differentiation, tumor with 370
hyperplasia, reactive 293, 293t
infundibulum, tumor of 369
keratosis, Inverted 460
lymphomas, grading of 292
neoplasms, variants of 342
Formalin fixation 441
Fouchet's stain for bile pigment 219
Foveolar hyperplasia 181
Fracture 383
Frank carcinomas 337
Friable mass, solid 144
Friedreich ataxia 439
Frontotemporal lobar degeneration 455, 457
Fuch's dystrophy 462
Fuhrman nuclear grading system 131
Fundic gland polyps 178, 201
Fundus 1
Fungal infections 264, 301, 354, 445
Galactosemia 217, 225
Gallbladder 215, 217, 218, 469
small 218
thickened wall of 218
Gallstones, nature of 219t
Ganglion cell 425f
Ganglioneuroblastoma 425, 426
Ganglioneuroma 426
Ganglionic dysfunction 177
Gangrene 187
Gangrenous intestine 187f
Gardner's syndrome 178, 387
Gastrectomy 192
specimen 176, 177
antral vascular ectasia 182
atrophy 181
carcinomas 183, 469
glands, mucus of 179
intraepithelial neoplasia 183
mucosal biopsies, endoscopic 179
stromal tumors 184
tumors, WHO classification of 183
autoimmune 180
chemical reaction 181
chronic 180, 181
eosinophilic 198
follicular 181
microscopic reporting of 182
Gastroenteritis 198
junction 171
reflux disease 173
autonomic nerve tumors 176
stromal tumor 183, 400, 472
tract 171, 206
Gaucher's disease 227, 383
Genes 324
Genetic disorders 226
abnormalities 423
rhabdomyoma 24
system, male 70
Germ cell 51, 88
aplasia 88
in situ 89, 91
noninvasive 89
tumors 18, 24, 33, 41, 45, 46, 88, 89, 120, 234, 422, 450, 474, 475
mixed 41, 89
nonseminomatous 89, 90
regressed 89
WHO classification of 89
Gerota's fascia 96
Gestational trophoblastic disease 33
Ghon's focus 263
Giant aneurysms 447
Giant cell 196, 390, 393
carcinoma 37
epulis 169, 393
fibroblastoma 371
fibroma 166
glioblastoma 453
granuloma, peripheral 169
hepatocellular 225
lesions 391, 393
multinucleate 19
osteoclast type of 409f
pleomorphic 243
reparative granuloma 393
response, multinucleated stromal 22
rich 391
tumors, osteoclastic 384
transformation 225
tumor 243, 390, 393, 409, 410
benign 390f
diffuse type 409
malignancy in 391
malignant 409
type of 313, 393f
Giant fibroadenoma 314
Giardiasis 193
Giemsa stain 19, 193, 219, 436
Gilbert syndrome 226
floor of 158
lymphatic drainage of 158
Glands 1
endometrial 32
enlarged 143
labial 142, 143
lacrimal 461
stratification of 27f
sublingual 142
Glandular epithelial cells 465
Glandular lesions
benign 23
non-neoplastic 22
Glandular neoplasm 76, 134
Glans penis 70
Glassy cell carcinoma 23, 25, 35
Gleason's grading 79, 80
Gleason's score 80
Gleason's system 79, 80
Glial fibrillary acidic protein 46, 452
Glial tumors 448
Glioblastoma 451, 452
variants of 453
Gliomas 448
Gliomatosis peritonei 422
Gliosarcoma 453
Glomerular diseases 101, 111
classification of 101
clinical patterns of 101
primary 101
Glomeruli 116, 127
Glomerulocystic disease, familial hypoplastic 123
acute postinfectious 101
anti-GBM 103
chronic 97
crescentic 101, 102
rapidly progressive 99, 102
diffuse 114
focal segmental 101, 112
Glomus tumor 72, 183
Glossopalatine glands 142, 143
Glucagonoma syndrome 245
Glutaraldehyde fixation 441
Gluten sensitivity enteropathy 191
Glycogen storage 439
Goblet cells 31
Goiter, dyshormonogenetic 343
Gomori's methenamine 32
silver stain 21, 219
Gonadal stromal elements 89
Gonadoblastoma 51, 89
Gonorrhea 87
Gorlin's syndrome 362
Graafian follicle 17
Graft-versus-host disease 199
Gram stain 436
Granular cell
layer 364f
schwannoma 373
tumor 72, 183, 413f
Granulation tissue 166
Granuloma 196, 197
annulare 355
eosinophilic 266
inguinale 19
noninfectious 355
Granulomatosis, allergic 264
Granulosa cell tumor 40, 48, 48f, 50, 89, 475
adult 48, 89
juvenile 48, 49, 89
Graves disease 344, 461
Growth factor system, platelet-derived 452
Growth pattern variants 32
Guillain-Barré syndrome 444
Gynandroblastoma 41, 51, 120
Hacek organisms 435
Haemophilus 435
aphrophilus 435
influenzae 443
parainfluenzae 435
Hailey-Hailey disease 359
follicles, tumor of 460
presence of 18
Hairy cell leukemia 282, 294
Hairy polyp 169
Hamman-rich syndrome 266
Hard palate 159
Hashimoto's thyroiditis 343, 344
Haversian canal system 377f
H-caldesmon 466
Headache 454
congenital 435
pre-existing structural 435
valves 433
Heck's disease 167
Helicobacter pylori 181
gastritis 184
infection 181
Hemangioma 72, 89, 120, 146
choroidal 463
epithelioid 391
Hemangiomapericytoma 407
Hematolymphoid neoplasms, classification of 282
Hematometra 32
Hematoxyphil bodies 107
Hematuria 99
glomerular 99
Hemicolectomy 186f
Hemiglossectomy 157, 251
specimen, grossing of 157
Hemimandibulectomy 158, 159f
Hemochromatosis 217, 227, 439
Hemolytic disease 226
Hemolytic uremic syndrome 115, 116
Hemophagocytic syndrome 303
Hemorrhage 17, 18, 30, 423
cysts 17
endomyometrium 17
subarachnoid 447
Hemosiderin laden macrophages 39
Henoch-Schönlein purpura 104
carcinomas 465
fibrosis, congenital 229
neoplastic cords 232f
parenchymal tumors 215
resections 215, 216
vein outflow obstruction 227
acute 220
autoimmune 222
B surface antigen 221
C virus 301
chronic 221
Hepatoblastoma 232, 428
Hepatocellular carcinoma, primary 218t
Hepatorenal syndrome 100
Herpes gestationis 357, 360
Herpes simplex 19
encephalitis 443
infection 20
Herpes virus 301
Hibernoma 398, 401
Hidradenitis suppurativa 352
Hidradenocarcinoma 368
Hidradenoma 368
papilliferum 368
Hidrocystoma 368
Hilar mass 263
Hilar sinus 421
Hilus cells 51
Hirschsprung's disease 424
benign fibrous 72, 372t
fibrous 371
Histoplasma 435
capsulatum 445
Hobnail cell 28
change 31
metaplasia 31
Hodgkin's cells 300
Hodgkin's disease 299, 300
Hodgkin's lymphoma 146, 283, 299301, 302t, 303, 307, 468f
classical 283, 300
Homer-Wright rosettes 424
Honeycomb lung 265
Hormone 465
status 325
scoring systems for 326
syndromes, ectopic 245
Howship's lacunae 377
Human chorionic gonadotropin 13, 90
Human immunodeficiency virus 444
infection 105
Human leukocyte antigen 111, 281
Human papillomavirus 19, 71, 167
Hunner's cystitis 134
Huntingtons’ disease 455, 456
Hürthle cell
neoplasm 342
variant 340
Hyaline fibromatosis, juvenile 405
Hyaline thrombi 107
Hyaluronic acid 148
Hydatid cyst 99, 228
Hydatid disease 446
Hydatidiform mole 33, 52
Hydroa vacciniforme 299
Hydrocele 87
Hydrocystoma 460
Hydronephrosis 100
advanced 99
Hydropic abortus 52, 52t
Hydrosalpinx 18
Hyoid bone 249, 252
conjugated 226
hereditary 226
unconjugated 226
Hyperemia 197
Hypereosinophilic syndrome 198
Hyperestrinism 51
Hyperglycemia 220
Hyperkeratosis 16, 19, 167
epidermolytic 19
Hyperkeratosis, focal epithelial 167
Hyperlipidemia 401
Hyperparathyroidism 346, 382
familial idiopathic 346
secondary 347
tertiary 347
Hyperplasia 33, 34, 135
adenomatous 218
atypical adenomatous 269
atypical endometrial 33, 34, 34t
atypical lobular 318f
benign prostatic 77
crypt 191
diffuse 343
fibromuscular 182
flat 135
florid follicular 304
focal nodular 230, 232
inflammatory papillary 166
non-atypical 32
papillary 342
reactive 460
simple 33
atypical 7, 3234
Hyperplastic polyps 178, 200
microscopy of 200
Hypertension 220
malignant 100, 118
uncontrolled severe 100
Hypertriglyceridemia 220
cardiac 439
congenital 203
left ventricular 439
right ventricular 439
Hypocellular upper dermis 19
Hypochlorhydria 178
Hypogammaglobulinemia 193
Hypoglycemia 245
Hypopharyngeal wall lesions 164
Hypopharynx 161
Hypophosphatemia 382
Hypospermatogenesis 88
Hypotension, sudden 446
Hypoxia 446
Hysterectomy 3
radical 3
simple 3
total abdominal 3
Iliac nodes, common 56, 62
Immature teratoma 46
grading of 46
Immunofluorescence 102, 104, 108, 111, 117
microscopy 100
Immunoglobulin components 465
Immunohistochemistry 26, 175
In situ adenocarcinoma 27
In situ anaplasia 195
Infarction, hemorrhagic 144
Infection 173, 226, 301, 442
bacterial 352
modes of 118
sites of 442
Infectious disease 444
Infective endocarditis, ring abscesses in 436f
Inferior vena cava 421
Infertility 87
Inflammation 19, 197, 460
acute 442
interstitial 110
Inflammatory infiltrate, mild 167
Infundibulum 5
Inguinal lymph node 70
dissection 71
Insulinomas 245
International Federation of Gynecology and Obstetrics 35
staging for
carcinoma of cervix uteri 57
endometrial carcinoma 62
fallopian tube 68
ovarian malignancy 66
International Society of Gynecological Pathologist's Classification of Endometrial Epithelial Metaplasias 30
International Society of Nephrology 108t
International Society of Urologic Pathology 80
and World Health Organization 80
Interstitial fibrosis
diffuse 264
severe 265
Interstitial pneumonia 265
nonspecific 265, 266
Interstitium 127
Intestinal endoscopic biopsies, reporting of small 210
Intestinal mucosa, ulceration of large 190
Intestinal polypeptide, vasoactive 245
Intestine 472
large 185, 189
small 185, 189, 211
Intracystic papillary carcinoma 323
Intradermal nevus 460
Intraepidermal bullae 359t, 360t
Intraepithelial lesion, stratified mucin producing 24
Intraepithelial neoplasia 205
Intraluminal acid mucin 79
Intratubular germ cell 422
neoplasia 89
neoplasm 91
Intra-urothelial neoplasia
high-grade 135
low-grade 135
depth of 61
maximum depth of 55
Invasive lobular carcinoma, classic 320
Invasive mole 53
Invasive squamous cell carcinoma, early 23
Iris 463
Iron deficiency anemia 182
Ischemic colitis, types of 196
Islet cell tumors 244
Isospora belli 193
Isthmus 1, 5
Ivor-Lewis procedure 171
Jaw, osteosarcoma of 389
Jiroveci pneumonia 297
Johnson's score 88
Jones Methenamine silver stain 115
Junctional nevus 366, 460
Juxtaglomerular apparatus 100
Kaposi's sarcoma 72, 168, 183, 301
Karyorrhexis 106, 110
Keratin 475
Keratinizing 23
Keratoacanthoma 364, 460
multiple 365
Keratoconus 462
Keratosis 8, 19, 167
actinic 357, 363
Keratotic lesions 461
bilateral large 98
biopsy 125
clear cell sarcoma of 424
cystic disease of 122
cysts of 122
disease 123
sporadic glomerulocystic 123
dysplastic 14
grossing of 95
large 97
neoplasm 151
normal-sized contracted 98
polycystic disease of 100
rhabdoid tumor 424
small contracted 97, 98
tumors, classification of 423
WHO classification of tumors of 120t
Kikuchi's lymphadenitis 301
Kikuchi-Fujimoto disease 301
Kimmelsteil-Wilson nodules 115
Kimura's disease 303
Kingella species 435
Klinefelter's syndrome 88
Klippel-Trenaunay syndrome 412
Knodell's score 221
Koilocytosis 19, 21, 24
Kraurosis vulva 19
Krukenberg tumor 18, 50
Kupffer cell activation 225
Kuttner's tumor 143
majora 18, 20
minora 18, 20
Lamina propria 167, 181, 191
papillae of 174
Laminar endocervical glandular hyperplasia, diffuse 22
Langerhan's cell 303
histiocytosis 380, 385
Langhans giant cells 87, 264, 301
Large B-cell lymphoma 282, 291
Large cell
acanthoma 357
calcifying sertoli cell tumor 89
carcinoma 268, 271, 272
lymphoma 255
anaplastic 298
neuroendocrine carcinoma 23, 120, 272
variant 425
Laryngeal framework 249
Laryngeal surfaces 248
Laryngectomy specimen, total 253
Laryngoscopic biopsies 251
Larynx 248, 256
grossing of 251
infections 256
Legg-Perthes disease 383
Leiomyoblastoma 38
Leiomyoma 32, 38, 72, 120, 183, 398
epithelioid 38
hemorrhagic cellular 38
metastasizing 32, 33
mitotically active 38
schwannoma like 38
venign metastasizing 38
Leiomyomata 17
diffuse 32
hereditary 120
intravenous 32
Leiomyomatous submucosal polyp 17
Leiomyosarcoma 24, 32, 38, 39, 61, 120, 474
Lentigo simplex 357
Lepidic cell 440
Lepidic growth 269
Lepidic predominant invasive carcinoma 471t
Leprosy 352
lepromatous 353
reactions 354
Leptospirosis 226
extracellular 456
exudative 115
intraocular 462
malignant 177, 240
multiplicity of 218
non-neoplastic 86, 186, 381, 393
patchy distribution of 191
pathologic 312f
precursor 257, 319
premalignant 175, 183, 233
purulent 443
red velvety 167
size of 8
Leukemia 33, 282, 461, 472
acute lymphoblastic 467
antigen, acute lymphoblastic 284, 467
chronic lymphocytic 287
derivation 284
antigens 465
infiltration 110
Leukoplakia 19, 70, 167
homogenous 167
Lewy bodies 456
Leydig cell 48, 50, 51, 88, 89
hyperplasia 88
tumor 89
malignant 89
Lhermitte-Ducklos disease 448
Libman Sacks endocarditis 438f
Lichen planus 19, 356, 357
erythema multiforme 357
Lichen sclerosis 19
et atrophicus 19
Lichen scrofulosorum 352
Lichen simplex chronicus 19
Lichenoid keratosis 167
Li-Fraumeni syndrome 384, 448
Limb 402
lower 378
upper 378
Lingual glands 142
Lip 156
biopsies 156
bits 156, 157
drains, lower 156
excision 156
lymphatic drainage of 156
Lipid cell tumors 51, 475
Lipid metabolism, disorders of 227
Lipoadenoma 345, 398
Lipoid nephrosis 111
Lipoleiomyoma 38
variant 32
Lipoma 398, 401
like tumor 99
pleomorphic 398, 402
Lipomatosis 401
Lipoproteins 220
Liposarcoma 39, 402, 404
pleomorphic 402, 403, 403f
subtypes 402
Listeria monocytogenes 443
Liver 215, 217, 232
abscess, amebic 229
biopsy interpretation 218
microscopy 219
cysts of 228
disease, alcoholic 217, 219
hemosiderin lipofuscin, pigments in 228t
tumors 421
classification of 422t
Lobular carcinoma 151, 311, 320f
Lobular carcinoma in situ 317
Lobules, cancerization of 317
Loop electrosurgical excision procedure 2
Lucio reaction 354
Lugol's iodine 172
application of 172
Luminal ductal cells 146f
Luminal epithelium 324
Lung 261
adenocarcinoma of 471t
biopsy 276
carcinomas 470
cystic conditions of 267
disease, interstitial 265
parenchyma 263
primary adenocarcinoma of 270, 270t
resection for tumor 262
small cell carcinoma of 273t
classification of 267
TNM staging of 277
Lupus anticoagulant 110
Lupus nephritis 110
classification of 108t
clinically silent 100
diffuse 108
focal 108
modified WHO classification of 107
original WHO classification of 107
Lupus vulgaris 352
Lutein cells 51
Lyme disease 438
Lymph node 68, 172, 238, 254, 279, 303, 311, 391, 423
dissection 280
enlarged 281
largest 71
levels of 157f, 312f
normal anatomy 279
regional 84, 93, 140, 277, 280, 334, 349, 374, 375, 394, 419, 432
retroperitoneal 422
secondary in 304
single 279
spleen and thymus 281
Lymphadenitis, dermatopathic 303
Lymphadenoma 146
Lymphadenopathy 281
massive 303
Lymphangiectasia 190
intestinalis 193
Lymphangioma 72, 120, 240
Lymphatic circulation 250
Lymphedema 226
Lymphocyte 87, 191, 353, 437
depletion 300
intraepithelial 190, 191
rich 300, 305
Lymphocytic lymphoma, small 287
Lymphocytic thyroiditis, subacute 344
Lymphoepithelial lesion, benign 461
Lymphoepithelioma 23, 72
Lymphogranuloma venereum 19, 305
Lymphoid 24, 33
aggregates 197
cells 255
interstitial pneumonia 265, 266
tissue 161
mucosa-associated 289
tumors 135
Lymphoma 72, 175, 183, 205, 206, 240, 281, 282, 297, 301, 391, 449, 472
angioimmunoblastic 297
derivatives 285t
extranodal marginal zone 289
follicular 89, 292, 293t
lymphoblastic 296
lymphocytic 287f
lymphoplasmacytic 288
malignant 24, 33, 205, 320, 390, 461, 468
splenectomy for staging 281
Lymphoproliferative disorder 299
post-transplant 283
invasion 61
system 279
Macchiavello's stains 436
Macronodular cirrhosis 217
Macroscopy 63, 64, 67
Madura foot 354
Madurella grisea 354
Madurella mycetomatis 355
Maffucci syndrome 384, 385, 412
Malakoplakia 87, 134, 343
Male breast, tumor of 320
Malformation, arteriovenous 447
Mallory's hyaline 220
Malt lymphoma 268, 282
Mammary dysplasia 312
marginal 158
middle 158, 159f
partial 158
Mantle cell 285
lymphoma 288
development 289f
Masson's hemangioma 169
Masson's trichrome 434
Massons’ bodies 266
Mast cell neoplasm 307
Mastectomy 310f, 331
Mastitis 313
acute 314f
chronic 313
granulomatous 313
Maxillectomy 159
McCarty's H-scoring system, modified 326
McCune-Albright syndrome 384
Medullary carcinoma 99, 243, 320, 343
Medullary cystic disease 122
complex 122, 124
Medullary sponge kidney 123, 124
Medulloblastoma 449, 451, 454
Meibomian gland carcinomas 461
Meig's syndrome 50
Melanoacanthoma 357
Melanocytic lesions 72
Melanocytic nevi 366, 461
congenital 367
Melanocytic tumor 24, 134, 365, 449
Melanoma 20, 467
choroidal 463
malignant 17, 176, 365, 366, 416, 463
of soft parts, malignant 416
Melanosis, congenital oculodermal 461
Melanotic paraganglioma 33
Melanotic schwannoma 400
Melignant melanomas 463
Melkersson-Rosenthal syndrome 167
Membranoproliferative glomerulonephritis 101, 104
types of 105t
glomerulonephritis 101, 113
lupus nephritis 108
Menetrier's disease 178, 182
Meninges 441
Meningioma 449, 451, 454
Meningitis, bacterial 442
Meningomyelocele 14
Menstrual cycle, normal 29
Mental retardation 423
Merkel cell carcinoma 373, 472
Mesangial cells 100
Mesangial hypercellularity 101
Mesangial lupus nephritis, minimal 108
Mesangial matrix 127
Mesangial proliferative lupus nephritis 108
Mesangial sclerosis, diffuse 113, 114
Mesangiocapillary glomerulonephritis 104
Mesenchymal chondrosarcoma 387
Mesenchymal neoplasms 414
Mesenchymal tumor 24, 32, 33, 72, 76, 120, 134, 175, 183, 205, 206, 234, 240, 268, 449, 461
benign 234
malignant 33, 72, 234
Mesoblastic nephroma 123, 424
Mesoderm 39
Mesodermal tumors, malignant mixed 35
Mesonephric duct rests 22
Mesothelioma 274, 275f, 275t
conventional peritoneal 42
malignant 274
Metabolic disorders 226, 227
Metabolic liver diseases 227
Metanephric adenofibroma 120
Metanephric adenoma 120
Metanephric stromal tumor 120
Metanephric tumors 120
Metaphyseal fibrous defect 391, 393
Metaplasias 20, 30, 182
apocrine 314f, 324
ciliated 31
endometrial 30
eosinophil 31
intestinal 31, 182, 182t
transitional 20
Metaplastic cells, eosinophilic 42
Metastasis 394
sites of 53
Metastatic cancer 41
Metastatic carcinoma 29, 218, 218t
Metastatic colorectal
adenocarcinoma 270t
carcinoma 270, 471t
Metastatic disease 422, 431, 463
Metastatic neoplasms 455
Metastatic neuroblastoma 389
Metastatic nodule 423
Metastatic tumors 72, 77, 120, 320, 450
Methenamine silver stain 436
Methyl green pyronin 434
Methysergide 439
Meyenburg's complexes 229
Michaelis Gutmann bodies 87
Microcystic adenoma 241
Microcystic adnexal carcinoma 368
Microcystic serous adenoma 239
Microglandular hyperplasia 22, 28
Microglial nodules 444
Microgranulomas 196
Microinvasive carcinoma 20, 26, 55
Microsporidium 190
Mikulicz's disease 461
Mikulicz's syndrome 461
Miliary tuberculosis 264
Miliary white nodules 189
Minimal change disease 101, 111, 112
typical of 112
Mitoses 81
Mitotic activity 440
Mitral stenosis, setting of 437
Mitral valve surface 436f
Molar pregnancy 33
Mole, partial 52, 52t, 53
Molecular classification 451
Molluscum bodies 352
Molluscum contagiosum 352
Mongolian spot 367
Monodermal teratoma 43, 89
Mons pubis 18
Mouth, floor of 158
Mucha-Habermann disease 167
Mucin cells 31
adenocarcinoma 23, 32, 36, 40, 81, 152, 243
borderline tumor 40
carcinoma 368
pure 321
cystadenocarcinoma 89, 241
cystadenoma 89, 241
ovary 43f
cystic neoplasms 241
metaplasia 30, 31
tumors 18, 40, 43, 474
Mucocele, extravasation 166
Mucoepidermoid carcinoma 149, 175
Mucosa, hemorrhagic 133
Mucosal atrophy 197
Mucosal deep fissures 189
Mucosal prolapse syndrome 200
Mucous membrane 159
Mucus nodules 1
Mullerian ducts 41
Müllerian epithelium 20
Müllerian origin 43
Müllerian papilloma 23
Müllerian system 41
Müllerian tumor 465
malignant mixed 17, 24, 39, 40, 61, 474
mixed 28
Multicentric carcinoma 324
Multicystic dysplasia 123
Multicystic dysplastic kidney 123
Multicystic kidney 123
Multicystic renal dysplasia 99
Multifocal carcinoma 324
Multifocal cystic change 123
Multilayered epithelium 24
Multilocular cyst 122, 123
goiter 336
mass 406
Multiple malformation syndrome 123
Multiple myeloma 294
Multiple neoplasia syndrome 417
Multiple nodules 263
Multiple osteochondromas 384
Multiple papillae 133
Multiple papillomas 322
Multiple pouches 190
Multiple schwannomas 417
Multiple superficial erosions 178
Multiple system atrophy 455
Multipotential cells, carcinoma of 20
Mumps 87, 144
Muscle tumor, smooth 32, 33, 399, 410
Muscular dystrophy 439
Muscularis mucosa 174
Mycetoma 354
Mycobacteria, atypical 305
Mycobacterium avium 190, 193
Mycoplasma 31
fungoides 299
superficial 354
Mycotic infections 445t
Myelodysplastic syndrome 228
Myeloid sarcoma 89
Myeloma 391
asymptomatic 294
staging system 307
Myocarditis 438
drug-related 439
hypersensitivity 439
lymphocytic 438
signs of 438
symptoms of 438
Myocardium 434, 437, 438
carcinoma 148
cells 151, 317, 467
Myoepithelioma 144, 145, 148
Myoepithelium 324
sarcoma, low-grade 407
tumor 399, 404, 408
Myofibroma 411
Myofibromatosis 411
Myogenic tumors 384
Myogenin 412, 466
Myoglobin 412
Myointimoma 72
Myolipoma 401
Myometrial invasion 36, 53
Myometrium 17, 59, 62
Myositis ossificans 404
Myxofibrosarcoma 409
Myxoid 32
liposarcoma 403
variant 32
Myxoinflammatory fibroblastic
sarcoma 407
tumor, atypical 407
Myxoma 413
cardiac 439
cells 439
Nabothian cysts 55
Naegleria fowleri 446
Naegleriasis 446
NAME syndrome 417
Napkin ring stricture 190
angiofibroma 256
carcinomas 255
Nasopharynx 160
Nausea 454
Neck dissection
modified radical 254
standard radical 254
Necrobiosis lipoidica 355
Necrosis, severe 222
Needle biopsy 75, 85, 95
routine 125
Neisseria gonorrhoeae 31, 86
Neonatal cholestasis 225
Neonatal hepatitis 225, 226
syndrome 225
Neoplasia 97, 184
invasive 184
noninvasive 184
benign 257
papillary 323f
cystic 7, 133
follicular 341
hematopoietic 384
invasive 135
thecoma fibroma group of 49f
cells 150f, 244f
cysts 229
lesions 52, 188, 312, 393
polyps 202
Nephrectomy 95
partial 95, 96f
radical 96
simple 96
specimen 429
Nephritic syndrome 101
Nephritis, hereditary 111
Nephroblastoma 120, 423
cystic partially differentiated 120, 123
Nephrogenic rests 120
congenital mesoblastic 120
cystic 120, 122, 123
multilocular cystic 122
Nephronophthisis 124
juvenile 122
Nephrosclerosis 118
benign 97, 118
Nephrosis, congenital 123
Nephrotic syndrome 101
congenital 113
familial 123
idiopathic 99
Nephroureterectomy 96
Nerve sheath tumor 400, 412
malignant peripheral 24
Nerve tumors, peripheral 168
Nesidioblastosis 244
Neural tumors 371
Neurenteric cysts 173
Neuroblastic tumor 427f
stroma-poor 425
Neuroblastoma 423426, 472
grading of 426
peripheral 470
staging of 431
stroma-rich 425
Neurodegenerative diseases 455
Neuroectodermal tumor 33
Neuroendocarcinoma, small cell 271
carcinoma 28, 258, 467
small cell 120, 255
cell hyperplasia, diffuse idiopathic 271
cervical carcinomas 28
neoplasms 175, 183, 204, 205, 240
tumor 23, 120, 134, 206, 257, 268, 271
well-differentiated 89, 120
Neuroepithelioma, peripheral 470
Neurofibroma 72, 372, 400
Neurofibromatosis 384, 417
Neutrophils 30, 31
cells, type C 367
compound 366, 460
of Ito 367
of Ota 367, 460, 461
Niemann-Pick disease 225, 227
Night sweats 412
depressed 312
eczema 312
tumor of 320
NK cell lymphoma 256
Nodes, number of 71
Nodular appearance 133
Nodular cystic hyperplasia 32
Nodular diabetic glomerulosclerosis 114
Nodular fasciitis 404
Nodular hyperplasia 75, 343
diffuse 230
Nodular pleura 263
Nodular regenerative hyperplasia 218, 230
Nodular sclerosis 300
Nodular ulcerating growth 71
Nodule 230, 282
endometrial stromal 32
regenerative 231
Nonchoriocarcinomatous trophoblastic tumors 89
Nonepithelial tumors 65, 205
Non-Hodgkin's lymphoma 204, 288, 288f, 292, 307
Noninvasive papillary urothelial carcinoma, high-grade 136
Non-lipogenic sarcoma 404
Nonmeningothelial tumors 449
Nonpolyposis colon cancer, hereditary 204
Nonseminomatous tumors 46
Non-squamous solid pattern 31
Notochordal tumors 384
Nottingham prognostic index 325
pleomorphism 145, 325
proliferation antigens 465
pseudoinclusions 340
raisins 19
Nuclei 324
Nut carcinoma 168, 256, 272
Oat cell carcinoma 258
Obliterative endarteritis 87
Obstruction, extrahepatic 226
Occasional cysts 98
Odontogenic tumors 168
Olfactory neuroblastoma 255
Oligoastrocytoma 453
Oligodendroglial tumors 453
Oligodendroglioma 453
anaplastic 453
variants of 453
Oligohydramnios 11
Olive tumor 177
Ollier's disease 384, 385
Oncocytic carcinoma 148, 244
Oncocytoma 120, 121, 144, 145, 148
Oncofetal antigen 465
Oncoproteins 465
Opportunistic infections 444
Oral cavity 156, 169
Oral intra-epithelial neoplasia 167
Oral mucosal papillomatosis 339
Oral squamous cell carcinomas 168
Orbit 458
Orcein stain 219
Orchidectomy specimen 85
Orchitis 86
autoimmune 87
granulomatous 87
Orepuce 70
Oropharyngeal wall 161
Oropharynx 156, 160, 161, 169
Osteiod osteoma 387
Osteoblastoma 388
aggressive 388
diagnosis of 390
Osteoblasts 376
Osteochondroma 385
Osteochondromyxoma 385
Osteoclast 377
rich osteosarcoma 393
stimulating factor 377
Osteoclastoma, grading of 391
Osteocytes 376
Osteogenesis imperfecta 14, 381
Osteogenic sarcoma 388, 391
small cell 390
Osteogenic tumors 384
Osteoid tumors 387
Osteoma 387
Osteomalacia 381
Osteoporosis 382
Osteosarcoma 39, 120, 388, 389, 423
diagnosis of 390
juxtacortical 389
small-cell 472
Ovarian carcinomas 465
Ovarian disease 40
Ovarian fimbria 5
Ovarian follicle 39
Ovarian tumors 7, 422
bilateral 18
cystic 18
solid 18
WHO classification of 40
Ovary 3, 4, 6, 8, 17, 32, 39, 6365, 67, 68, 423
cyst of 17
malignant tumor 18
normal anatomy 4
solid carcinoma of 49
Overgrowth syndrome 417
Overlap disease 223
Owl's-eye 444
Oxyphil 31
cell variant 340
Oxyphilic adenoma 144, 345
Page's criteria 316
Paget's disease 20, 72, 312, 368, 382, 389
extramammary 369
polyostotic 389
Pain abdomen 197
Palate, soft 161, 162
Palatine glands 142
Palatine tonsils 161
Pancellular dysplasia 195
Pancreas 237, 238, 469
annular 239
cysts of 239
edematous 239
endocrine tumors of 244
exocrine tumors of 241
giant cells tumor 243
Pancreatic biopsies 237
Pancreatic endocrine tumors 245
Pancreatic intraepithelial neoplasia 239, 240t
Pancreatic pseudocysts 239
Pancreatic tumors, WHO classification of 240
Pancreaticoblastoma 244
Pancreatitis 239
Pancytokeratin positive 148
Paneth cell metaplasia 194
adenocarcinoma 243, 270
adenoma 99, 120
basaloid carcinoma 72
Papillary carcinoma 72, 324t, 339
hemithyroidectomy for 337f
invasive 323f
low-grade 136f
noninvasive 136
solid 323
thyroid 469
variants of 340
Papillary cystadenoma lymphomatosum 147
Papillary endothelial hyperplasia, intravascular 169
Papillary epithelial neoplasm 242
Papillary fronds 41
Papillary lesion 319, 322
single 133
Papillary mesothelial hyperplasia 42
Papillary neoplasm 135, 136f
Papillary proliferation 31
Papillary renal cell carcinoma 120, 131
Papillary serous carcinoma 27, 36
Papillary squamous cell carcinoma 72, 168, 257
Papillary syringadenoma 370, 460
Papillary tissue, confluent 133
Papillary urothelial
hyperplasia 136
neoplasm 136
Papilllary mesothelial hyperplasia 43
Papilloma 268, 323f
benign 324t
intraductal 149, 241, 323, 323f
solitary adult 257
Papillomatosis 21
Papulonecrotic tuberculid 352
Para-aortic nodes 57, 62
Paraganglioma 258
Paraglottic space 250
Parakeratosis 16, 19
glomerular 116
infantile 444
Paramyxoma virus 144
Paranasal sinuses 258
Paraspinal nerve, tumor of 449
adenoma 345, 347t
variants of 345
carcinoma 346, 347t
gland 336, 338, 344
hyperplasia 345
Parenchymal tuberculomas 443
Parkes-Weber syndrome 412
Parkinson's disease 455, 456
Parosteal osteosarcoma 389
Parotid glands 142
Parotid salivary gland 142
Peau d'orange appearance 312
Pediatric cystic nephroma 120
Pediatric neoplasms 420
Peliosis hepatis 228
exenteration 7
lipomatosis 401
lymph nodes 8
nodes 56, 62
peritoneum 32
Pelvis 97
Pelviureteric junction 97
familial benign 359
foliaceous 356, 358
vulgaris 360
Penectomy specimens 70
Penile carcinomas, TNM clinical staging for 74
Penile intraepithelial
neoplasia 72
Penis 70
plastic induration of 71
WHO classification of tumors of 72
Peptic ulcer 176, 180
chronic 179t
Pergolide mesylate 439
Periappendiceal mass 189
Pericardium 437
Pericytic tumors 399, 411
Perinephric abscess 100
Periodic acid silver methenamine 95
Periodic acid-Schiff 11, 20, 147, 280, 436
Periosteal chondroma 383, 385
Periosteal chondrosarcoma 387
Periosteal osteosarcoma 389
Periportal cholestasis 224
Peritoneal implants 42, 47
Peritoneal papillary serous carcinomas 42
Peritoneal reflection 213
Peritoneal surfaces 42
Perityphlitis, ligneous 189
Perivascular tumors 399
Perl's prussian blue stain 267, 434
Peutz-Jegher polyp 182, 201, 205
Peyronie's disease 71
Pharyngeal wall
lesions 164
posterior 162
Pharyngectomy specimens 165
Pharyngoepiglottic fold 161
Pharynx 160
grossing of 162
Phentermine 439
Pheochromocytoma 120, 439
Phimoses 71
Phosphaturic mesenchymal tumor 414
Phthisis bulbi 462
Phyllodes tumor 315
Piecemeal necrosis
mild 222
moderate 222
Pigment-Laden macrophages 440
Pilar sheath acanthoma 369
Pilocytic astrocytoma 448, 453
Pilomatrical carcinoma 368
Pilomatricoma 369, 370, 460
Pilomatrixoma 370f
Pineal gland, tumor of 448
Pinguecula 462
Pinpoint erosions 189
Pityriasis lichenoides acuta 167
Placenta 9, 51
examination of 10
extrachorialis 10
membranacea 10
normal anatomy 9
singleton type of 9
tissue 14
Placental site nodule 23, 33
Plaques, presence of 456
Plasma cell 87, 191, 286, 462
dyscrasias 257
granuloma 343, 407
occasional 437
type 304
Plasmablastic lymphoma 292
Plasmacytoid lymphocyte 286
Plasmacytoma 89, 294
Pleomorphic sarcoma, undifferentiated 416
Pleomorphism 440
Pleura 262
decorticated specimen of 262
tumor of 274
Plexiform fibromyxoma 183
Plexiform fibrous histiocytoma 410
Plexiform neurofibroma 412, 413f
Plump macrophages 437
Pneumoconiosis 266
acute interstitial 266
cryptogenic organizing 265
desquamative interstitial 265
interstitial 264
Polio 444
virus 444
Poliomyelitis 443, 444
Poliovirus infection 444t
Polycystic appearance 48
Polycystic kidney 14
disease 229
Polycystic liver disease 229
Polycystic multiple follicular cysts 39
Polycystic ovarian disease 17, 40
Polycythemia vera 228
Polyembryoma 46
Polygonal cells, eosinophilic 122f
Polykaryocyte 303
Polyp 33
adenomatous 202
benign endometrial 17
cystic fundic 182
endometrial 17, 32
stromal 17
fibrovascular 173
hamartomatous 182, 200, 201, 204, 205
juvenile 182, 201
serrated 203
Polypectomy specimens 185
Polypoid 188
adenomyoma 33
endometrial carcinoma 17
mass 17
large 178
slender and small 16
small to large 16
variant, atypical 33
intestinal 387
lymphomatous 204
syndrome 178
Polyvesicular vitelline pattern 45
Porocarcinoma 368
Poroma 368
Portal hypertension 228
Portal vein thrombosis 230
Postcricoid carcinomas 165
Posthitis 71
Post-Turp granulomas 78
Pouch of Douglas 8
Pre-Epiglottic space 250
Pregnancy, toxemia of 51
Pressure, intracranial 454
Progerioid syndrome 417
Proliferative fasciitis 404
Proliferative phase, mid 29
Proliferative verrucous keratosis 167
Prominent nucleoli 33
Prostate 75, 467
adenocarcinoma 470
size of 78
specific antigen 75, 78
transurethral resection of 83
WHO classification of tumors of 76
Prostatectomy, radical 76
Prostatic adenocarcinoma, Gleason's microscopic grading 79
Prostatic basal cells 466
Prostatic carcinoma 78, 83
TNM staging for 84
Prostatic glands 79
Prostatic intraepithelial neoplasia 75, 78
high-grade 79
Prostatic needle biopsies 82
Prostatitis 86
acute bacterial 77
allergic granulomatous 78
chronic bacterial 77
granulomatous 77
Prosthetic heart valves 435
Prosthetic valve 435
Protein 376
accumulated and location 455t
C deficiency 228
myogenic regulatory 466
S deficiency 228
Proteinuria 99
non-nephrotic range 99
Proteus mirabilis 118
Protoplasmic astrocytoma 452
Protozoal-giardiasis 193
Psammoma bodies 36
Pseudallescheria boydii 354
Pseudocyst 239
pancreas 239
Pseudoepitheliomatous hyperplasia 368, 460
Pseudoglandular carcinoma 72
Pseudohyperplastic carcinoma 72
Pseudomembranous colitis 197
Pseudomonas 86
Pseudopapillary tumor, solid 242
Pseudotumor 143
inflammatory 407
Psoriasis 19, 356
Psuedomultiple papillomas 322
Pterygium 462
Pulmonary carcinomas 467
Pulmonary chondromas 185
Punch biopsy 1, 132, 162
Putative tumor 452
Pyelonephritis 100, 118
active 100
acute 97, 118
chronic 98, 118
Pyloric metaplasia 182
Pyloric stenosis, hypertrophic 177
Pyogenic granulomas 166
disseminated 412
Pyometra 32
Pyriform sinus 161
cancers 165
Pyrrolizidine alkaloid 228
Radial scar, center of 316f
Radical neck dissection, extended 254
Rat placenta, endodermal sinus of 46
Rectal tumors 213
Rectovaginal septum 32
Rectum 8
tumor of 205
Red blood cells 280
Red hyperemic mucosa 133
Reed Sternberg cell 299
Reflux esophagitis 174
Reidel's thyroiditis 344
Renal agenesis, bilateral 14
Renal allograft biopsy 128
interpretation 126
Renal artery aneurysm 100
Renal biopsy 95, 99, 100
Renal carcinomas, TNM staging of 131
Renal cell
carcinoma 99, 119, 120, 123, 467, 470
multilocular cystic 123
tumors 120, 121t
Renal cystic dysplasia 123
Renal disease 115
congenital 123
end-stage 119
Renal failure
acute 99
chronic 100
Renal hematopoietic neoplasms 120
Renal medulla, cystic disease of 124
Renal medullary carcinoma 120
Renal neoplasm 119, 424
multilocular cystic 120
Renal parenchyma 119f, 421
Renal Pathology Society 108t
Renal pelvis, cystic hamartoma of 123
Renal tumor
ossifying 120
resection, adult 130
Renomedullary interstitial cell tumor 120
Resorption lacunae 377
bronchiolitis 265
distress syndrome, acute 265
epithelium 254
system 248, 249
lower 261
upper 248
Restrictive cardiomyopathy 439
Retention cyst 460
Retention mucocele 166
Reticulin around individual cells 50
Reticulin stain 37, 50
Retinal capillary hemangioma 463
Retinal cavernous hemangioma 463
Retinal epithelium 203
Retinal tumors 463
Retinitis 444
Retinoblastoma 417, 423, 427, 463
gross 427
syndrome 384
Retromolar trigone 156, 158, 161
tumor of 163
Retroperitoneum 402
Retrovirus 444
Reye's syndrome 227
Rhabdoid tumor 120, 424
Rhabdomyoblasts 428, 429
Rhabdomyomas 168
Rhabdomyosarcoma 39, 120, 168, 411, 428, 466
alveolar 412, 428, 429
embryonal 411, 423, 428, 429
pleomorphic 412
round cell 472
Rheumatic endocarditis 436
Rheumatic heart disease 438f
Rheumatic vegetations 437
arthritis 356, 383
nodules 356
Rhodanine 219
Rickets 381
Riga-Fede disease 167
Rochalimaea henselae 412
Rokitansky's protuberance 18, 47
Rosai-Dorfman disease 89, 281, 303, 450
Rothmund-Thomson syndrome 384
Rotor syndrome 226
Round-cell tumors 472, 473t
Rubeanic acid 219
Salivary duct carcinoma 144
Salivary gland 124, 469
classification of tumors of 145
cysts of 145, 145f
major 142
minor 142145
neoplasm, malignant 149
normal anatomy 142
sublingual 142
tumors 257, 268
high grade 152
low grade 152
minor 144
types of 142, 142f
Salmonella typhimurium 199
Salpingo-oophorectomy, bilateral 3
Salpingo-oophoritis, chronic 18, 39
Sampling sinus 421
Sarcoidosis 264, 301, 355
Sarcoma 362
alveolar soft part 416
botryoides 15, 24
endometrial stromal 32, 61, 474
epitheliod 415, 472
high-grade undifferentiated 61
histiocytic 283
pleomorphic 384
unclassified 401, 416
undifferentiated 401, 416
Sarcomatoid carcinoma 29, 72, 243, 268, 272
Scalded skin syndrome, staphylococcal 356
Scanty lymphocytes 264
radial 315
U-shaped 97
Scarff-Bloom-Richardson grading system 325
Schaumann bodies 264, 355
Scheuer's staging 222
Scheurer system 222
Schiller-Duval bodies 45, 46
Schistosomiasis 446
Schmincke type 255
Schneiderian papillomas 254
Schneiderian respiratory membrane 254
Schwannoma 38, 72, 120, 372, 400
with cystic change 239
Sclerocystic ovaries multiple follicular cysts 39
Sclerosing adenosis 315
Sclerosing cholangitis, primary 223
Sclerosing epitheliod fibrosarcoma 409
Sclerosing lupus nephritis, advanced 108
amyotrophic lateral 455, 456
glomerular 110
Sclerotic cortex 17
Scrotal skin 70
Sebaceoma 369
adenoma 146, 149, 369
carcinoma 149, 369, 371
differentiation, tumor with 371
adenoma 460, 461
carcinoma 371
hyperplasia 460
lymphadenoma 149
Seborrheic keratosis 357, 365, 460
Secondary diseases 101
carcinoma 35
phase, mid 30
Segmental mandibulectomy 158
Selective neck dissection 254
Sellar region, tumor of 450
Semilunar valves 434
Seminal vesical glands 81
Seminoma 89, 90
classic 90
Sentinel lymph node 312
Septa, fibrous 230
adenocarcinoma 23, 32
borderline tumor 40
carcinomas 42
cystadenocarcinoma 89
cystadenoma 41f, 89, 241
microcystic adenoma 241
oligocystic adenoma 241
papillary cystadenoma 18
papilloma, surface 18
tumor 18, 40, 41
Serpigenous longitudinal deep ulcers 189
Sertoli cell 48, 50, 88, 89
only syndrome 88
tumor 89
malignant 89
Sertoli-Leydig cell 51
tumors 18, 41,50, 475
Serum antinuclear antibodies 265
Sessile serrated adenomas 203
Sex cord
stromal tumors 40, 48, 51, 89, 475
tumor 33, 41, 51
Sezary syndrome 299
Shigella organisms 199
Shikata orcein stain 219
Shrunken kidneys 100
Sialadenitis 144
acute 144
autoimmune 145
chronic 144
granulomatous 145
Sialadenoma papilleferum 149
Sialoblastoma 152
Sialometaplasia, necrotizing 145, 167
Sigmoidoscopy 197
Signet ring cell adenoma 81, 342
Silicosis 267
histiocytosis 303
hyperplasia 303
Sinusoidal ectasia 231
Sjögren's disease 265
Sjögren's syndrome 105, 145, 223, 461
Skeletal muscle tumors 400, 411
Skin 70, 350
common bullous lesions of 356
excision biopsy 350
grossing techniques 350
melanoma 373
microscopy pearls 352
mixed tumor of 369
nonmelanocytic tumors of 374
Peau d'orange appearance 312
punch biopsy 350
shave biopsy 350
Small cell carcinoma, extrapulmonary 28
Sneddon-Wilkinson disease 358
Soft tissue 396
giant cell tumor of 410
leiomyoma of 410
leiomyosarcoma of 411
masses 396
sarcomas, grading of 416
tumors 146, 258, 371, 387, 396
syndrome-associated 417t
TNM staging of 419
WHO classification of 399
Solar keratosis 363
Solitary bone cyst 392, 393
Solitary fibrous tumor 120, 276, 407, 467, 472
Solitary intraductal papilloma 322
Solitary kidney 100
Solitary neurofibroma 398
Solitary nodule in thyroid 344
Solitary polypoid lesion 133
Spermatic cord 86, 402
arrest 88
seminomas 90
tumor 89
Spermatogenesis 88
Spherical mass 189
Spinal polio 444
Spindle cell 175, 305, 398, 402
carcinoma 72, 120, 168
eosinophilic 410
nevus 460
pigmented 368
nodule, postoperative 24
Spinocerebellar ataxias 455
Spiradenocarcinoma 368
Spiradenoma 368
Spitz nevus 368, 460
Spleen 280, 282
normal anatomy 280
splenectomy 280
Spongiotic dermatosis 359
Spongy bone, cancellous 377
Squamotransitional carcinoma 23
Squamous cell 273t
carcinoma 20, 23, 24, 26t, 32, 36, 55, 71, 72, 81, 167, 168, 175, 258, 268, 269, 357, 362, 364, 469, 470, 470t, 471t
histological variants of 72
in lung 269f
invasive 352
microinvasive 23
mixed 72
section of 362f
variants of 168
dysplasia 268
islands of 23f
lesions, benign 23
neoplasm 134
papilloma 173, 460
Squamous epithelial cells 362f
Squamous epithelium 363f
nonkeratinized 174
stratified 47f
Squamous hyperplasia 19
Squamous intraepithelial
lesion 19, 24
high-grade 24
neoplasia 23
Squamous metaplasia 11, 20, 30, 31, 55
Squamous papilloma 19, 23, 24, 257
Squamous tumor 23
Staphylococcus aureus 144
Steatohepatitis 227
nonalcoholic 217, 220
primary nonalcoholic 220
Stein-Leventhal syndrome 17
Stellate abscesses 304
Stem cells, hematopoietic 467
Stereotactic core biopsy 330f
Sternocleidomastoid muscle 254
Steroid cell tumors 41
Stomach 176
biopsy histopathology 209
carcinoma resection histopathology 210
normal anatomy 176
polyposis syndrome 178
polyps of 182
Stone, types of 219
Strawberry gallbladder 218
faecalis 118
pneumoniae 442
Streptomyces somaliensis 355
Stroke 447
hypertensive 447
Stroma 32
endometrial 39
inflammation of 21
Stromal hyperplasia 40
Stromal hyperthecosis 40
Stromal mast cells 405
Stromal reactions, non-neoplastic 22
Stromal sarcoma 28
Stromal tumors 176
common 472
Stromatosis 22
Struma ovarii 41, 47
Strumal carcinoid 47
Subcorneal bullae 358t
Subcorneal pustular dermatosis 358
Subcutaneous 356
Subendothelial hyaline deposits 110
Subependymoma 454
Subepidermal bullae 357, 361t
Subepithelial tissue 461
gland 142, 143
lymph nodes 156
salivary gland 142
Submucosal glands 250
Subtotal hysterectomy 3
Subungual keratoacanthoma 365
Succinate dehydrogenase 467
Sun-burst appearance 388
Suprabasal bullae 357
Supraglottic laryngectomy specimen 252
Supraglottic larynx 248
Supranuclear palsy, progressive 455
Suprapubic prostatectomy 75
Surgery, types of 3, 143
Sweat gland tumors, benign 460, 461
Swollen pancreas 239
Symplastic leiomyoma 38
Symptomatic myeloma 294
Syncytial knots 9
Syncytiotrophoblastic cells 89
Syncytiotrophoblasts 9
Synovial sarcoma 120, 415, 472
Synovioma, benign 409
Syphilis 87
Syringocystadenoma papilleferum 149, 368
Syringofibroadenoma 368
Syringoma 368, 369, 460
Systemic lupus erythematosus 101, 106, 145
T cells 437
Tall cell variant 340
Tamoxifen related lesion 32
Tan tumor, solid 144
development and maturation 294
leukemia, adult 297
lymphoma 192, 294
enteropathy 298
extranodal 298
generic 297
hepatosplenic 299
lymphoepithelial 297
peripheral 297
mediated rejection 128
acute 128
chronic active 128
Telangiectasia 231
Tenal cysts tuberous sclerosis 123
Tendinous cords 433
Tendon sheath 409
giant cell tumor of 409
Tennis racket 303
Tent’ sign 370
Teratoma 41, 88, 89, 123
cystic 47
malignant 46
mature 86, 90
solid 48
mixed 89
Testicular biopsy 91
Testicular cancer 91, 93
Testis 70, 85, 422
germ cell neoplasia in situ of 91
miscellaneous tumors of 89
WHO classification of tumors of 89
Testosterone 475
Tetralogy of Fallot 14
Thecoma 18, 40, 49, 475
tumor of 89
Thoracotomy 171
right 171
moderate 100
severe 100
Thrombotic endocarditis, non-bacterial 438f
Thrombotic thrombocytopenic purpura 116
Thymectomy specimen 281
bits 281
Thymic carcinoma 306
Thymoma 305
classification of 305
clinical staging for 306
mixed 305
A 305
AB 305
C 305, 306
Thymus 281
needle biopsy 281
normal anatomy 281
Thyroglossal cysts 344
Thyroid 469
adenomas 339
biopsy 347
cancer 339
carcinomas 339
cartilage 250, 251, 252
follicles 290f
gland 336
maltoma of 290f
specimens, types of 336
tumors 339
TNM staging of 349
Thyroidectomy, total 336
Thyroiditis 223, 343, 344
subacute 344
components 465
core 219
biopsy 403f
handling 434
surrounding 324
Tongue 157
adenocarcinoma of 152
base of 161
biopsy of 157
geographic 167
hamartomas of 169
lymphatic drainage of 157
ulceration with eosinophilia 167
Tonsillectomy specimen 163
Touch preparations 442
Touton giant cells 410
goiter 344
myocarditis 439
Toxoplasmosis 226, 444
Trabecular adenoma 342f
Trabeculated myometrium 17
Transformation zone, large loop excision of 2
Transitional cell
carcinoma 32, 40, 44, 81, 135, 470, 472t
gross features of 137
tumors 40
Transthoracic trucut 261
Trichilemmal cyst 460
Trichilemmoma 370, 460, 461
Trichoblastoma 369
Trichodiscoma 369
Trichoepithelioma 370, 460
Trichofolliculoma 369, 460
Tricholemmal tumor, proliferating 368
Tricholemmoma 369
Tricuspid valve orifice 433
Tropheryma whipplei 193
lesions, non-neoplastic non-molar 33
neoplasms 33
tumor 89
placental site 17, 33, 53, 89
Tropical sprue 190, 192
Trypanosoma cruzi 438
Trypsinemia, hereditary 217
Tubal gestation, ectopic 18
Tubal metaplasia 20, 31
Tubal type ciliated columnar epithelium 41f
Tubectomy 5
Tuberculid 352
leprosy 352
Tuberculoma 264, 443
meningeal 443
Tuberculosis 87, 256, 263, 301, 352, 443
endometrial 32
fibrocaseous 264
hyperplastic 199
abscess formation 443
bronchopneumonia 264
epididymo-orchitis 87
granulomatous inflammation 77
meningitis 443, 443f
ulcer 199
Tuberous sclerosis 417
Tubes 8
Tubo-ovarian mass 18
Tubular adenomas 202
Tubular adenosis 315
Tubular androblastoma 50
Tubular atrophy 110, 128
Tubular carcinoma 368
breast 322
invasive 322f
Tubular diverticulum 189
Tubular necrosis, acute 99
Tubular papillary adenoma 368
Tubules 117, 126
annular 41, 51
Tubulocystic renal cell carcinoma 120
Tubulovillous adenomas 202
Tularemia 305
Tumor 17, 55, 70, 89, 99, 138, 139, 169, 209, 216
adenomatoid 33
adipocytic 399, 401
adnexal 461
anaplasia 423
appendageal 368
astrocytic 448, 451, 453
benign 72, 147, 368, 369, 413
epithelial 145
fibrohistiocytic 372
mesenchymal 33
bilateral 144
borderline 40, 42, 43
bulky polypoid 133
cardiac 439
cartilage 258, 384
cells, pleomorphic 72
chondrogenic 383
clinically indolent 362
cut surface of 7
cystic 18, 120, 143
sebaceous 369
trophoblastic 89
dermoid 203
diameter, maximum 213
differentiation 418
astrocytic 448
oligodendroglial 448
dimension 421
embryonal 448
sinus 41, 45
stromal 37, 467
ependymal 448, 453
epithelial 23, 32, 76, 175, 183, 205, 206, 232, 240, 267, 319, 384, 460, 474
myoepithelial 319
epitheliod trophoblastic 53, 89
extraprostatic 81
fibroblastic 399, 404
fibroepithelial 320, 362
fibrogenic 384
functional 245
gelatinous 440
glandular 23
gross description of 60
hematolymphoid 76, 89, 146, 258
hematopoietic 33
hemosiderotic fibrolipomatous 414
histiocytic 450
hyalinizing trabecular 339
induced osteomalacia 414
inflammatory myofibroblastic 407
intraocular 463
intraosseous 158
invades serosa 61
involvement 213
jaw resection for 158
juxtaglomerular cell 120
keratinocytic 357
lesions, non-neoplastic 256
like conditions 24
lipogenic 384
lymphohistiocytic 268
malignant 18, 368, 415
mixed 368
masses, white worm-like 17
medullary location of 99
metastasizing benign 147
miscellaneous 24, 51
mixed 368
osseous 378
painful 385
perforation, presence of 213
predisposition syndrome 417
primary 84, 93, 131, 140, 169, 277, 349, 374, 394, 419, 432
secondary 24, 146, 175, 183
solid 7, 18
circumscribed 144
stages, pathological 132
syndromes 384
inherited 373
thecoma fibroma group of 49
type 121
volume 81
Tumoral conditions 96, 97f
Tunnel clusters 22
Turcot's syndrome 203
Twin type placentas 12
Twinning, conjoined 14
decubitus 16
flask shaped 190
malignant 179t
region of 196
small superficial 15
transverse 189, 197
types of 196
Ulceration 8, 55
diffuse 190
Ulcerative colitis 194, 195, 197t, 199
chronic active 194
longstanding 194
Umbilical cord, swelling of 17f
Unilocular cyst 229
Urachial carcinoma 134
Ureter 97, 124
long segment of 97
Urethra 70, 137
atresia 14
opening 71
Urethritis 86
Urinary bladder 132, 134, 137, 470, 472t
location in 137
TNM classification of 140
Urinary system 95
Urinary tract, classification of tumors of 134
Urothelial neoplasm, noninvasive 134
Urothelial tract 135
Urothelial transitional cell neoplasms 135
Urothelial tumors 134
invasive 134
Uterine cavity 17
length of 4
Uterine segment, lower 1
Uterine smooth muscle tumors 472
Uterus 3, 17, 29, 67
corpus of 32
removal of 3, 8
WHO classification of tumors of 32
Uvula 162
Vacuolated cells 401f
Vacuum-assisted biopsy 331
Vagina 8, 32
Varioliform gastritis 181
Vascular disorders 446
Vascular immune deposits 110
Vascular tumors 384, 400, 412, 463
Vasculitis 101
Veno-occlusive disease 227, 228
Ventricular septal defect 14
Verhoeff's stain 316f, 434
Verner-Morrison syndrome 245
Verotoxin-producing escherichia coli 116
Verruca 363, 437
plana 357, 363
plantaris 357, 363
vulgaris 167, 257, 357, 363, 364f
Verruciform xanthoma 169
Verrucous carcinoma 20, 26t, 72, 168, 175, 257, 362, 469
Verrucous keratosis 167
Vessels 127
Vienna classification 175, 183
Villi, measurement of 3
Villoglandular papillary adenocarcinoma 28
Villoglandular variant 32, 35
Villonodular synovitis, pigmented 409
Villous adenomas 202
Villous blunting 191
Vimentin 474, 475
Viral encephalitis 444f
Viral endometritis 32
Viral esophagitis 174
Viral hepatitis 217
Viral infections 167, 352, 444f
acute 443
Virus 19
Visual disturbances 463
Vocal cord polyp with fibrin 257
Voice, deepening of 50
Vomiting 454
von Brunn's cell nests 134, 137
von Hansemann cells 87
von Hippel-Lindau disease 123
von Meyenburg's complexes 229
V-shaped scars 97
Vulva 8, 18, 32
myxoid lesions of 21t
Vulval intraepithelial neoplasia 19
Vulvar dystrophy, chronic 19
Vulvar ulcers 19
radical 8, 9
simple 8
types of 8
Wagner-Meissner’ corpuscles 372
WAGR syndrome 423
Waldenstrom's macroglobulinemia 288
Waldeyer's ring 288, 307
Wart virus infection 55
Warthin's tumor 143145, 147
silver impregnation technique 19
stain 19
Warty basaloid carcinoma 72
Warty carcinoma 72
Warty dyskeratoma 357, 364
Warty excrescences 71
Water clear variant 345
Watermelon stomach 182
Wedge biopsy 2, 85, 215
Wegener's granulomatosis 167, 264
Weigh placenta 9
Weight loss 412
Werner syndrome 384
Wharton's duct 142, 143
Whipple's disease 190, 191, 193
Whipple's procedure 237
Wilms’ tumor 99, 122, 123, 420, 423, 424, 429
study system 423
Wilson's disease 217, 227
Wireloops 107
Wolman's disease 227
World Health Organization 454
Xanthelasma 460, 461
Xanthoastrocytoma, pleomorphic 453
Xanthogranuloma, juvenile 72, 89
Xanthogranulomatous endometritis, diffuse endometrial 32
Xanthoma 178
Xanthomatous degeneration 455
Xerostomia 145
Yolk sac
elements 45, 90
tumor 18, 24, 41, 45, 89, 91, 422, 474
Zeil-Neelsen stain 264
Zellballen pattern 258
Zellweger's syndrome 226
Zinc deficiency 191
Zollinger-Ellison syndrome 182, 183, 245
Chapter Notes

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Female Genital TractChapter 1

Normal anatomy: The adult nulliparous uterus is a hollow, pear-shaped organ that weighs 40–80 g and measures 7–8 cm along its longest axis. It is divided into the cervix and the corpus (body). The portion of the corpus lying superior to a line connecting the insertion of the Fallopian tubes is the fundus. The portion of the corpus or body that connects with the cervix is called the isthmus or lower uterine segment.1
Cervix: Consists of ectocervix and endocervix.
A normal ectocervix is covered by a nonkeratinizing stratified squamous epithelium. Its height is influenced by endogenous hormone production and varies accordingly with age and hormonal stimulation.
During reproductive age the epithelium is high and well differentiated. It consists of a basal cell layer with elongated nuclei perpendicular to the basal membrane, of one to several layers of small parabasal cells, of a broad intermediate cell zone with abundant cytoplasmic glycogen, and a covering layer of narrow, superficial cells.
In childhood and in the postmenopausal period because hormonal stimulation is lacking, the squamous epithelium is low wherein it consists only of a few layers of small, poorly differentiated epithelial cells. The sparse cytoplasm is devoid of glycogen; stratification may be barely visible or even absent.
The normal endocervical mucosa consists of mucus-producing tubules and clefts (mucosal infoldings, usually called glands), loosely arranged in a fibrous stroma. A single layer of tall, columnar epithelial cells covers the mucosal surface and lines the intricate folds, clefts, and tubules. The small nuclei are basally placed during the early proliferative phase. The clear cytoplasm contains abundant mucus, especially in the late proliferative phase.1
The types of biopsies done on the cervix are: Punch, Wedge, Cone and Large loop excision biopsy.
Punch Biopsy
This is normally done when cervical intraepithelial neoplasia (CIN) is suspected. It is performed as a colposcopically directed biopsy.
Measure along the three dimensions.
The description should include color, presence or absence of ‘mucus nodules’ and cut surface appearance. Ideally the stroma should measure 3–5 mm in thickness.
Identify mucosal surface and mark the embedding surface straight away if the biopsy is 4 mm or less in thickness. Embed in such a way that the mucosal surface is at right angles to the cutting surface so that the mucosa would be on one aspect of the section (Fig. 1.1).
If more than 4 mm thick, bisect and again mark the embedding surface in such a way that the mucosa covers the tissue on one aspect (Fig. 1.2).
If Bouin's fluid is used as a fixative then the mucosa automatically curls up over the tissue thus enabling easy identification (Fig. 1.3).2
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Figure 1.1:
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Figure 1.2:
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Figure 1.3:
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Figure 1.4:
The entire tissue should be taken for section including scrapings and mucus if any.
Wedge Biopsy
It is performed when an invasive carcinoma is suspected and when facilities for colposcopy are not available.
  • Measure along three dimensions
  • Description should be as for punch biopsy
  • Identify mucosal surface and treat as above
  • All tissue should be taken for section including scrapings and mucus if any
  • While sectioning the slides should be marked serially as strip 1,2 and 3 for viewing.
Cone Biopsy
  • When a glandular lesion is suspected
  • Colposcope is not available and
  • In cases of a high transformation zone.
Formerly, a cone biopsy was performed using just a scalpel but now it is done using a laser or low voltage large loop diathermy: Loop electrosurgical excision procedure (LEEP) or large loop excision of the transformation zone (LLETZ) or diathermy loop excision (DLE): A wire loop is used through which an electrical current is passed at variable power settings. Various shapes and sizes of loop can be used depending on the size and orientation of the lesion. The transformation zone and lesion are excised to an adequate depth which in most cases is at least 8 mm, extending 4–5 mm beyond the lesion. A second pass with a more narrow loop can also be done to obtain an endocervical specimen for further histologic evaluation.
Complete cone or fragmented; color, presence of irregularities, erosions, polyps (size, shape, location), cysts, previous biopsy sites, etc.
Diameter and depth of the cone to be taken. Ink the surgical margin/surface.
Ideally the cone when taken should be marked by the clinician at the 12 o'clock position (center of anterior lip) to enable identification of the various quadrants.
Cut the anterior surface and open it and fix for 24 hours unless it is urgent when sectioning may be done immediately.
Take the length of the endocervical canal.
If the 12 o'clock position has been marked give bits representing each quadrant.
Take serial bits, maximum of 3 mm thickness (Fig. 1.4), in a clockwise direction, each in a separate block. The squamocolumnar junction should be present in every bit. Trim the periphery if necessary and embed separately for involvement of surgical margin. Mark the embedding surfaces serially.
Do not compromise on the number of blocks.3
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Figure 1.5: Courtesy: Haines and Taylor. Obstetrical and Gynecological Pathology, 5th edn; 2003
All tissue to be submitted if neoplasm is not seen grossly.
If tumor is seen grossly then one bit from each quadrant is adequate.
If the cone is not marked then serial sectioning and blocking is to be done without labeling the quadrants.
Bread slice in small loop excision.
The other method of cutting a cone is shown in Figure 1.5. Either way the entire cone is embedded.
Normal Anatomy
The endometrium is made up of glands and stroma. It is divided into a deeper basal layer and a superficial functional layer. The basal layer is the equivalent of the reserve cell layer of other epithelia and is responsible for the regeneration of the endometrium following menstruation. It is made up of weakly proliferative glands and spindled stroma. The functional layer is subdivided into stratum compactum (toward the surface) and the stratum spongiosum (close to the basalis). The stroma is mainly composed of endometrial stromal cells (whose appearance changes considerably during the menstrual cycle) and vessels (of which the spiral arterioles are the most distinctive).1
Preferably use a metal strainer or filter paper on funnel to collect the material weight to be taken.
Description: Curettage
Color and consistency; proportion of blood clot; whether the tissue is suggestive of products; decidual cast identified; shape of villi; presence or absence of gestational sac (under dissecting microscope if available).
Measurement of villi if distended.
  • Embryo: CH (crown heel), CR (crown rump) lengths, appearance—malformed, macerated.
  • Fetus: May sometimes be sent along with curettings. Look for the cord, if it is seen measure the length.
If curettage, all for section (1 g per cassette):
  • If products: Up to 2 g for processing (choose the representative bits).
  • If small vesicles are present all can be blocked—up to 3 blocks
  • Embryo: Block entirely or half.
  • Fetus: No bits need be taken unless specified. If cord is seen then take a bit (transverse section).
Types of Surgery
  • Simple hysterectomy: Removal of uterus and cervix.
    • Hysterectomy with bilateral salpingo-oophorectomy: Removal of uterus, cervix with both tubes and ovaries.
  • Subtotal hysterectomy: Sometimes cervix may not be removed.
  • Total abdominal hysterectomy (radical hysterectomy): Removal of uterus, cervix with both tubes and ovaries, upper one third vagina and pelvic lymph nodes.
In these cases while describing the specimen grossly, the nature of the surgery if known may be stated as–total, radical hysterectomy, etc. It is simpler however to describe the specimen as that consisting of the uterus, cervix, both tubes and ovaries, etc.
Take the weight of the uterus with adnexae if present. Normally uteri are sent opened along the anterior wall by the operating surgeon.
After weighing, section it longitudinally from the anterior through posterior surfaces. Even if the specimen is unopened section in a similar way by identifying the surfaces. The peritoneal reflection on the posterior aspect is lower. The cut should pass through the uterine cavity, the endocervical canal and squamocolumnar junction. Such sectioning helps preserve one-half for mounting (Fig. 1.6).4
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Figure 1.6:
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Figure 1.7:
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Figure 1.8:
  • Length of uterine cavity
  • Length of endocervical canal
  • Average myometrial thickness. If asymmetric then the range of myometrial thickness should be given.
Distortion of the endometrial cavity if any polyps and cysts of endometrium—measurement and description Fibroids—number and location—submucosal, intramural and subserosal, size—of smallest and largest, any change in the fibroid—hyalinization, red degeneration, calcification, cystic change and necrosis, etc. Serosal adhesions, if any.
Examine the squamocolumnar junction for any erosion, nabothian cysts, polyps, etc. If the latter are present describe these with regard to size, appearance, surface ulceration, etc.
Further sectioning of the uterus is done with the cuts going parallel to the central one. Cuts are made in both the halves. Any additional findings on this sectioning are recorded.
Alternatively the uterus can be cut coronally in parallel sections as shown in Figure 1.7.
Bits (Fig. 1.8)
  • A: One bit cervix anterior lip
  • B: One bit cervix posterior lip
    • Both bits to include squamocolumnar junction and any abnormal area.
  • C and D: Endomyometrium, 2 bits from opposite walls Additional bits to get full thickness if necessary.
  • E, F and G: Leiomyomata—one bit from the largest to include the center of the lesion. A maximum of 2–3 leiomyomata may be bitted routinely even if more are present.
Extra bits if polyps are observed; if these are small then include them with the bits of endomyometrium as shown in Figure 1.8.
Normal Anatomy
The ovaries are organs located in the pelvis lying lateral to the uterus close to the lateral pelvic wall, behind the broad 5ligament and anterior to the rectum. They are connected to the broad ligament by the mesovarium, a double fold of peritoneum, to the body of uterus by the ovarian ligament, and to the lateral pelvic wall by the infundibulopelvic ligament. During the reproductive period, their average size is 4 × 2 × 1 cm, and their average weight is 5–8 g; after menopause, they shrink to half their original size or less.1
  • Measurement (in three dimension) and weight (especially if sent alone)
  • External surface—smooth or irregular, adhesions, rupture, etc.
  • Cut surface—comment on: Capsule—thickened or normal, adhesions, hemorrhage, rupture, etc.; cortex and medulla, cysts—location and number, corpus luteum, appearance, calcification.
  • Section along the maximum diameter of the ovary.
Bits (Fig. 1.9)
  • H: One bit routinely to include cortex and medulla and adjacent cyst wall in case of a single cyst measuring < 2.5 cm in size. This bit may be combined with that of the Fallopian tube of the same side.
  • J: Cyst wall 3 bits inclusive of solid areas (in presence of larger cysts > 2.5 cm in size).
Fallopian Tube
Normal Anatomy
The Fallopian tube is a tubular hollow structure measuring 11–12 cm in length. It is divided into four segments: intramural (inside the uterine wall), isthmus (2–3 cm, thick-walled), ampulla (a thin-walled expanded area), and infundibulum (a trumpet-shaped ending that opens into the peritoneal cavity through the ostium and is fringed by the fimbriae). One of the latter structures, known as the ovarian fimbria, attaches the tube to the ovary.
Microscopically, the epithelium is composed of three distinct cell types: secretory, ciliated, and intercalated.1
  • Length and greatest dimension (without opening it).
  • Description: External surface, tubectomy scar if any, fibrin, hemorrhage, presence of rupture, placental tissue, blood clot, embryo, etc.
  • Section tube perpendicular to the length, multiple parallel cuts to detect any pathology; cuts should pass the proximal, middle and fimbrial portions.
  • Description: Lumen-patent, dilated, if dilated measure maximum diameter. Masses—size and appearance, invasion into wall, etc. Cysts—location, whether paraovarian, fimbrial, etc. size and appearance.
  • In case of ectopic gestation—open along the length of the tube.
Bits (Fig. 1.10)
  • H: One bit routinely from the ampulla is adequate and this may be combined with the bit from the ovary of the same side in routine hysterectomy specimens.
  • Tubectomy: Two bits one proximal and one distal to the tubectomy scar. In these cases the block must be separate from that of the ovary.
  • Ectopic: Two or more bits if necessary.
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Figure 1.9:
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Figure 1.10:
Description with regard to polypoid or ulcerative growth, size, involvement of entire or part of cervix (specify which portion), infiltration into isthmus, myometrium, etc. and surrounding structures.
  • A and B: Two bits cervix with tumor is routinely adequate.
  • C: Uninvolved cervix, opposite lip.
  • D, E, F: Isthmus, endometrium and myometrium, to be taken in continuity as shown in the diagram (F may be avoided if the tumor is very small).
  • G: Opposite endometrial wall.
  • H and J: Parametrium, right and left.
  • K, L, M and N: Vaginal cuff to be bitted entirely, marked as anterior, posterior, right and left lateral.
  • P and Q: Fallopian tubes and ovaries, as usual (not shown); except when involved, more bits may be taken from suspected areas.
Lymph nodes: Groups should be separately marked and sent by the clinician as external iliac–right and left:
  • Internal iliac: Right and left
  • Obturator: Right and left
  • Common iliac: Right and left
  • Others: Specify.
All lymph nodes in each group are to be grossed. The size of the smallest and largest is to be noted, number of lymph nodes in each group and number showing gross involvement. Bisect the node and give only one-half if the node is more than 5 mm; give the entire node if it is 5 mm or less. Mark the half that is not given with eosin in the specimen for future reference in order not to duplicate grossing of any node.
  • Description: Size and appearance of the tumor—solid, cystic, papillary, color, ulceration, necrosis, etc.
  • Involvement of the myometrium by tumor—<50% or >50%.
  • Involvement of the cervix, isthmus, parametrium, etc.
Bits (Fig. 1.12)
  • A, B: Cervix as routine, more bits if involved
  • C, D, E and F–tumor: Four bits to include neoplasm and in continuity, the whole thickness of the endomyometrium from mucosa to serosa.
It is important to comment on the maximum thickness of the myometrial involvement as invasion of less than half the myometrial thickness categorizes the tumor as stage I B and invasion up to half and greater than half categorizes the lesion into stage I C.
Ideally width of the myometrium should be measured along with the width of tumor invasion.
  • G–one bit: Uninvolved endometrium, opposite wall.
  • H and J: One bit each from right and left parametrium.
  • Fallopian tubes and ovaries: As routine unless involved when more bits may be taken.
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Figures 1.11A and B:
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Figure 1.12:
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Figure 1.13:
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Figure 1.14:
Lymph nodes: As for carcinoma cervix.
No obvious tumor in endometrium: Superficial carcinoma, endometrial hyperplasia, atypical hyperplasia, etc.
Preferably sample the entire endometrium or at least 6 blocks—three each from the anterior and posterior walls. Sections at any one level should include a continuity of the endometrium with myometrium and serosa. Lymph nodes as above.
  • Description: Capsule—intact or broken through.
  • Surface: Nodular or smooth, consistency firm or cystic.
  • Section across the greatest dimension. Subsequent sections should pass parallel to this at 0.5 to 1 cm in thickness.
  • Cut surface of the tumor: Solid or cystic, papillary or otherwise, cysts—uni or multiloculated, nature of contents, hemorrhage, necrosis, calcification, invasion of the capsule, etc. Comment on the normal ovarian tissue if present.
Solid Tumors (Fig. 1.14)
About 3 to 4 bits if the tumor is more than 5 cm, if more than 5 cm, one block per one cm of the tumor taken across its greatest dimension, particularly if the appearance is variegated.
Cystic Neoplasms
The cystic neoplasms are grossed as shown in the Figure 1.14.
  • Description: Note any swelling, distension of tube or nodularity on the outer surface and describe.
  • Make multiple sections perpendicular to the long axis.
  • Describe the cut section with regard to tumor nodules, papillary processes, hemorrhage, necrosis, etc.
Bits (Fig. 1.15)
  • A, B, C: Three or more to include tumor with adjacent wall.
  • D and E: Areas from proximal and fimbrial ends that may be uninvolved by tumor.
Sometimes a pelvic exenteration may be done in advanced carcinomas of the female genital tract particularly of the cervix. Such an exenteration may be an anterior pelvic exenteration—removal of uterus, cervix, both tubes and ovaries, vagina, pelvic lymph nodes, urinary bladder, and a portion of ureters and urethra.8
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Figure 1.15:
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Figure 1.16:
Posterior exenteration—removal of uterus, cervix, both tubes and ovaries, vagina, rectum and pouch of Douglas with pelvic lymph nodes.
In such extensive surgeries, the uterus, cervix and appendages are grossed as described before. Representative bits should be taken from the adjacent structures to confirm involvement by tumor. Surgical margins of rectum, bladder, ureters and urethra may also be taken as also pelvirectal lymph nodes.
Specimens Received
  • Small biopsies for non-tumoral conditions
  • Simple vulvectomy
  • Radical vulvectomy.
Biopsies for Non-tumoral Conditions
Measure the specimen in three dimensions:
  1. Describe any lesion if present
  2. If < 4 mm block entirely
  3. If > 4 mm, section it, describe the cut surface and block all tissue.
Vulvectomy Specimen
Mention the type of vulvectomy—simple or radical. Measure the size of the specimen in three dimensions. The first measurement is given horizontally along the maximum dimension and should include the inguinal region if present.
Measure the size of the lesion. Describe the lesion grossly—location, type of growth, surface ulceration, etc.
Appearance of the non-neoplastic surface—atrophy, keratosis, ulceration, etc.
In radical vulvectomy specimens, separate lymph nodes into groups and fix overnight in separate jars.
After removal of the lymph nodes from the specimen, pin it on a cork board using pins at regular intervals along the entire external borders and fix overnight.
Ideally two photographs may be taken and in one of them, the sites of sections taken should be marked.
For smaller tumors <2 cm in size, section radially, the cuts extending centrifugally, one next to the other, from the neoplasm to the closest skin surgical margin. For larger tumors, section vertically at 1 cm thickness.
Lymph nodes–(superficial/deep inguinal nodes): Size of the largest and number showing gross involvement.
Simple Vulvectomy
Bits (Fig. 1.16)
For tumors <2 cm:
  • A, B: Two bits tumor
  • C: One bit closest surgical margin
  • D: One bit labia majora and labia minora right side
  • E: One bit labia majora and labia minora left side
For tumors >2 cm, more bits may be taken.9
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Figure 1.17:
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Figure 1.18:
Radical Vulvectomy
Bits (Fig. 1.17)
  • A, B, C: Tumor 3 sections including edge with normal skin and deepest area of invasion.
  • D, E: Non-neoplastic skin from labia majora and minora (right and left).
  • F: One or two bits closest soft tissue surgical margins.
  • G, H, J, K: Lymph nodes (divided into groups).
Normal anatomy: The normal term placenta measures 15–20 cm in diameter and 1.5–3 cm in thickness, and weighs 450–600 g. The main components are the umbilical cord, amnion and chorion which are the membranes, villous parenchyma, and maternal decidual tissue.
The chorionic villi are covered by syncytiotrophoblasts and cytotrophoblasts. The syncytiotrophoblast is composed of multinucleated giant cells with abundant acidophilic cytoplasm. The cytotrophoblast, which is the progenitor of the syncytiotrophoblast, is made up of mononuclear cells with clear cytoplasm and a well-defined cell membrane. In the term placenta, the cytotrophoblast is inconspicuous and the syncytiotrophoblast is clumped in the form of ‘syncytial knots’.1
Conditions for which the placental examination may be performed are:
  • Any maternal complication or disease during pregnancy such as diabetes, toxemia and infection
  • Any complication of labor or delivery
  • Any abnormality of the infant including stillbirth, abortion or abnormality of the placenta itself.
Diagrammatic representation of the uterus of a pregnant woman showing normal placenta in situ (Fig. 1.18).
Singleton Type of Placenta2,3
Examine the placenta as soon as possible in the fresh state after delivery. Handle with care avoiding any laceration. Samples for smearing and microbial culture may be taken. Also take a small sample each for viral studies, immunofluorescence or for special fixation for electron microscopy. For chromosomal studies, chorionic villi are more appropriate (as fetal and umbilical cord tend to autolyze rapidly after intrauterine death). Gross photographs should be taken for record.
Weigh the placenta—ideally this should be done after trimming of the membranes, cutting the cord and removal of any extraneous material such as blood clot, etc.
Note the amount of blood clot in the container or separate pieces of membranes, cord or placenta and record the findings.10
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Figure 1.19:
Fixation: 10% neutral buffered formalin is ideal as a fixative. Formalin fixed tissue can be used for light microscopy and for immunopathologic techniques. The placenta should be allowed to lie flat in an adequate sized, round bottomed container with at least 3–4 times its own volume of fixative. Ideal time for fixation is 48–72 hours.
Examination of the placenta should be done in the following order: Examination of the membranes, cord, fetal surface and maternal surface.
  • Measure the distance from the placental margin to the nearest point of rupture, in cases of placenta previa this is zero. Examine for completeness, meconium staining, color and transparency, insertion into placental margin, edema, necrosis and retromembranous hemorrhage, etc.
  • Strips of membrane about 4–5 mm wide are cut starting from the site of rupture up to the placental margin (inclusive of it). These bits can be kept aside for blocking which may be done by:
    • Orienting the cut edge on the embedding surface, or
    • Making a Swiss roll with the ruptured site as the starting point and the placental margin as the end point, the amniotic surface being the inner aspect of the role (Fig. 1.19).
  • Trim the rest of the membranes from the placental margins.
At this stage, some of the abnormal types of placenta may be described:
Placenta membranacea: A rare condition in which most of the fetal membranes are covered by placental tissue thereby reducing the area of free membranes. This results in an extremely thin placenta with a large surface area of functional villous tissue. Complications of this are placenta accreta and placenta previa with accompanying premature separation.
Placenta extrachorialis (Figs.1.20A and B): In this type of placenta, the chorionic plate from which the villi arise is smaller than the basal plate, the transition from villous to non-villous chorion taking place not at the placental margin but at some distance within the circumference of the fetal surface of the placenta. There are two types: circummarginate in which the membranes lift directly from the chorionic plate and circumvallate in which the membranes fold back on the villi. The shortened chorionic plate thus results in a smaller than normal cavity limiting fetal growth. Also denuded placental tissue not covered by chorion results in marginal and retroplacental hematomas and frequently in antepartum bleeding. Chorioamnionitis may also ensue. These complications are associated more with the circumvallate type of extrachorial placenta.
  • Measure the length of the cord. Those over 70 cm in length and under 30 cm are considered to be abnormal.
  • The shortest distance between the cord insertion and placental margin is to be measured thereby showing a central, paracentral or eccentric (1–2 cm from the margin, e.g. Battledore placenta) insertion.
  • Insertion of the cord (membranous or non-membranous): A velamentous insertion is one in which the cord is implanted on the membranes away from the margin of the placenta. The vessels divide and course within the membranes before reaching the chorionic plate. In a velamentous insertion, look whether the vessels are intact or ruptured. Trauma may result in bleeding due to unprotected umbilical vessels running through the membranes.11
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    Figures 1.20A and B: (A) Circummarginate placenta; (B) Circumvallate placenta
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    Figure 1.21:
  • Examine the color and look for true knots, torsion, stricture, hematomas and thrombosis.
  • Make transverse sections of the cord at two or more points and assess the number of umbilical vessels. (normally the umbilical cord shows 2 arteries and one vein). Occasionally, one artery may be absent.
  • Remove the cord from the placenta by sectioning at 3 cm proximal to the insertion and take a 3 mm thick bit at its midpoint for blocking.
Fetal Surface
Examine this for color, meconium staining, appearance of fetal vessels, bleeding around these vessels or beneath the membranes, thrombosis of fetal vessels, subchorionic fibrin cysts (size and number), chorangioma (an increase in the number of vascular channels per villus), and presence of nodules on the amnion (amnion nodosum). Microscopically, these nodules are composed of deposits of amorphous cellular debris (vernix) which may be periodic acid Schiff (PAS) positive and contain fragments of hair. The nodules should be distinguished from squamous metaplasia of the amnion—this shows stratified squamous epithelium with keratohyaline granules. Squamous metaplasia is of no clinical significance whereas amnion nodosum reflects oligohydramnios of any cause. Frequently associated with oligohydramnios are congenital abnormalities of the fetal genitourinary system (as fetal urine takes part in the formation of amniotic fluid).
Maternal Surface
  • Examine the maternal surface for completeness, normal fissures, laceration (and its extent), retroplacental hemorrhage (size and distance from margin), gross hematoma and pale oval zones (areas of infarction—a fresh placental infarct is moderately firm and dark red; as it ages, it becomes progressively harder and its color changes to brown, yellow and white. An old infarct therefore appears as an amorphous, hard and white plaque).
  • Measure the maximum diameter and now the placenta may be weighed without the cord and membranes. Make a note of its shape.
  • Place the placenta maternal surface upwards on a flat surface and make parallel sections with a large sharp knife at an interval of 1 cm firmly holding the placenta onto the table with the left hand. The fetal surface will not cut through and will hold the slices together [bread loafing the specimen (Fig. 1.21)].12
  • Examine all the cut surfaces for presence of infarcts (location, size, fibrin deposition, pallor, consistency, calcification, consistency and age), cysts and tumor.
  • Describe any other lesion, location (central, lateral or marginal and depth (basal, intermediate, sub-chorionic).
  • Representative tissue blocks can be selected from appropriate marginal and central areas to include normal and abnormal tissue. One section should include the chorionic plate in an area with minimal subchorionic tissue.
Bits (Figs. 1.22 to 1.24)
  • A and B: Membranes, three or more bits in 2 blocks or Swiss rolls including placental margins (Fig. 1.22).
  • C: One bit cord, more if necessary (Fig. 1.23).
  • D, E, F: Placenta, to include normal and abnormal areas (Fig. 1.24).
Twin Type Placentas (Fig. 1.25)
  • If the placentas are separate (non-fused) then examine each placenta as a singleton.
  • If the placentas are fused
    • Note whether the two cords are labelled Twin A and Twin B, if not label them arbitrarily and make a statement to that effect.
    • Determine the presence and type of dividing membranes and state it:
      • If absent, monochorionic—monoamniotic
      • If present, check whether the dividing membrane is thick and opaque and is difficult to separate by stripping.
      • Also note presence of vascular anastomosis between the membranes, whether numerous or not.
        (if the dividing membrane is thick and opaque, difficult to separate by stripping and the vascular anastomosis few, then the placenta is dichorionic diamniotic. If the dividing membrane is thin and transparent and can be separated easily by stripping, and if the vascular anastomosis are numerous then the placenta is monochorionic diamniotic in type). The point of attachment of the membranes to the fetal surface is smooth in the case of monochorionic diamniotic placenta.2
  • Remove a rectangle 3 mm width of the dividing membrane and make a Swiss roll and embed it.
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    Figure 1.22:
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    Figure 1.23:
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    Figure 1.24:
  • Record the kind and number of vascular anastomosis in monochorionic diamniotic placenta; artery to artery, vein to vein and artery to vein (A-V) shunts if possible. The veins are larger and deeper than the arteries. For this 30–50 mL of saline solution containing a dye may be injected into the artery of one twin along the plane of fusion of the placenta and noting whether the fluid emerges from the vein of the other twin. The placenta must be intact to perform this test.13
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    Figure 1.25:
  • Divide the fused twin placenta along the vascular equator rather than through the base of the dividing membranes.
  • Examine each half as a singleton placenta.
Twin A
  • A and B: Membranes three or more bits in 2 blocks or Swiss rolls including placental margins.
  • C: One bit cord (more if necessary).
  • D, E, F: Placenta, to include normal and abnormal areas.
Twin B
Same as above.
Elective termination of pregnancy is often preferred in cases where fetal or chromosomal abnormalities would result in non-survival of the fetus. At times a medical termination of pregnancy may also be done for maternal causes. Though biochemical screening tests such as human chorionic gonadotropin (hCG) and α-fetoprotein on the maternal serum, ultra- sonography, chromosomal karyotyping and chorionic villi sampling can detect fetal abnormalities, these procedures sometimes may not yield conclusive results particularly in the first trimester of pregnancy. Therefore, there is a need to do a histopathological examination.4
Types of Specimens2
  • Material from dilatation and evacuation (D and C) procedures: This often results in fetal parts and placenta getting fragmented and admixed, rendering gross diagnosis and tissue sampling for histopathology difficult.
  • Abortion contents: The fetal and placental parts after D and C usually come in bits and pieces. They should be placed without any fixative in two or more sterile containers labeled with the mother's name and medical record number.
    If cytogenetic or biochemical testing is to be performed:
    • Remove fetal and placental parts from the containers and place them on a sterile field.
    • Using sterile instruments obtain tissues from at least two separate bits (i.e. fetal parts like lung, cartilage, skin, chest wall, etc. These tissues grow well in cell cultures) from these two separate containers. Approximately, 0.1–0.5 g of each sample is taken.
    • These specimens should be washed in 50–100 mL of sterile saline and placed in pre-thawed cell culture media [like Rosewell Park Memorial Institute (RPMI) media] and left at room temperature for transport to the cytogenetic laboratory for chromosomal studies.14
    • A separate sample may be taken for biochemical studies in the appropriate media. Biochemical studies may be performed on blood samples for estimation of bilirubin levels in cases of erythroblastosis fetalis and α-fetoprotein levels in neural tube defects.
  • After the above samples have been taken then the specimen may be put in fixative.
  • Sort placental fragments from fetal parts. Weigh placental fragments. Assemble segments of umbilical cord and note the length, diameter and number of vessels.
  • Sort fetal parts into body regions using skeletal fragments as a guide. Weigh the fetal parts and take any external measurements from recognizable body parts. For example, crown rump, crown heel lengths, hand and foot lengths, etc. Compare with standard tables of fetal measurements for the estimation of gestational age.
  • Examine the head. Note the morphologic appearance of the cranium and that of any residual brain tissue. Identify the vertebral column and spinal cord to determine the presence of any neural tube defect. Intracranial abnormalities such as Arnold-Chiari malformation, Dandy-Walker malformation, etc. can also be determined.
  • Examine skeletal fragments if present, orient these and take a radiograph to detect any skeletal abnormality.
  • Examine the viscera: If intact then examine their relationship to each other before separating them. Weigh them. Start with the most recognizable organs. Examine the gross appearance and take representative bits of both recognizable as well as from non-recognizable tissue (Note: do not put more than one unknown into a tissue cassette).
  • If all or part of the heart and lungs are recognizable, leave them together and perform as much of a gross dissection of the heart and attached vessels as possible; along the line of blood flow.
  • Examine gastric contents for meconium stain, blood or otherwise.
  • If one or both kidneys are identified intact in the retroperitoneum, note their size and position and trace the ureters to the bladder if possible. Section any tissue formed at the sites suspected for kidney.
  • Carefully examine the fetal fragments for presence of external and internal genitalia. Place into tissue cassettes any material in the pelvis to determine the histologic appearance for presence of gonads.
  • Placenta tissue: See section on placenta.
  • For small embryos: Submit whole or one half depending on the size.
  • Large fetuses: Submit representative portions from lung, stomach, kidneys, liver, spleen and genitalia.
  • For placenta: See section on placenta.
Some of the diagnoses that can be made by submitting tissue for histopathologic examination are:
  • Osteogenesis imperfecta
  • Polycystic kidney/dysplastic kidney
  • Bilateral renal agenesis/urethral atresia
  • Conjoined twinning
  • Tetralogy of Fallot
  • Atrial/ventricular septal defect
  • Meningomyelocele.
Gross on Fetus and Embryo4
Standard Weights of a Fetus
Standard Fetal Measurements
Diagrammatic representation of the measurement of embryos (Figs. 1.26A to C).
  • A: Crown heel length
  • B: Crown rump length
  • C: Greatest length.
Developmental Changes of an Embryo (Table 1.2)
Schematic drawing of the dorsal aspect of an 18-day presomite embryo. The embryo has a pear-shaped appearance and shows at its caudal end the primitive streak and node of Henson (Fig. 1.27).
Table 1.1   Weight of fetus in relation to age (gm)
Lunar month
Scammon and Calkins
Drawing of a cephalocaudal section of an 18-day embryo (Fig. 1.28) showing the notochordal process extending from the primitive pit to the prochordal plate and fused with the endoderm. The notochordal-endoderm plate gradually disappears and the remaining part of the notochord is then intercalated in the endodermal germ layer.
The left side of a 25-somites embryo approximately 28 days old (Fig. 1.29). The first 3 pharyngeal arches and the optic and the otic placodes are clearly visible.
A 5-week human embryo seen from the left. Crown rump length is approximately 7 mm. Note the paddle shaped limb buds. The otic and optic vesicles are seen (Fig. 1.30).
A 6-week human embryo seen from the left. Crown rump length is approximately 133 mm. The upper limb buds show a flattened terminal portion with four radial grooves. Note the formation of the eye and external auditory meatus flanked on each side by 3 hillocks derived from the mandibular and hyoid arches (Fig. 1.31).
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Figures 1.26A to C:
A 7-week human embryo seen from the left. Crown rump length is approximately 18 mm. The upper extremities are more advanced in development than the lower ones (Fig. 1.32).
An 8-week human embryo seen from the left. Crown rump length is approximately 30 mm. Note the size of the head in comparison with the remaining parts of the body. The eyelids are not present and the eyes are wide open (Figs. 1.33 and 1.34).
Table 1.2   Length of fetus in relation to age (cm)
Lunar month
Grown rump length
Crown heel length
Scammon and Calkins
Scammon and Calkins
  • Well-defined cysts in the cervix: Nabothian cysts; may be multiple and seen sometimes in a row along the ectocervix, T-Z zone and extending parallel to the endocervical canal. Cysts are filled with mucus.
Myxoid tumor like appearance of the cervix:
  • Extensive myxoid change and stromal reaction in the cervix
  • Aggressive angiomyxoma
  • Angiomyofibroblastoma
  • Sarcoma botryoides in case of children and infants.
Small superficial ulcer: Erosion or benign ulcer (both associated with changes of chronic cervicitis micro-scopically).
  • Well-defined cysts in the cervix: Nabothian cysts; may be multiple and seen sometimes in a row along the ectocervix, T-Z zone and extending parallel to the endocervical canal. Cysts are filled with mucus.
Myxoid tumor like appearance of the cervix:
  • Extensive myxoid change and stromal reaction in the cervix
  • Aggressive angiomyxoma
  • Angiomyofibroblastoma
  • Sarcoma botryoides in case of children and infants.
Small superficial ulcer: Erosion or benign ulcer (both associated with changes of chronic cervicitis micro-scopically).16
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Figure 1.27:
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Figure 1.28:
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Figure 1.29:
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Figure 1.30:
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Figure 1.31:
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Figure 1.32:
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Figure 1.33:
Slender and small polypoid mass: Benign endocervical polyp. This will have a smooth gray white cut surface and is generally pedunculated.
Small to large polypoid mass:
  • If the mass is globular with a whorled appearance on cut surface, then it is a leiomyomatous polyp.
  • Carcinoma polypoid type, this is firm, gray white, and friable, sometimes with surface ulceration.
Cauliflower like mass with a gray white cut surface: Carcinoma—generally will extend into the cervical stroma and upwards into isthmus of uterus.
Elongated endocervical canal with thickened ectocervical mucosa: Uterine prolapse. The mucosa is thickened due to parakeratosis and hyperkeratosis as a result of prolapse. Small ulcers “decubitus ulcers” may be present on the ectocervix.17
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Figure 1.34: The above figures to show the size of the head in relation to the rest of the body at various stages of development. Note the swelling of the umbillcal cord at its attachment to the abdominal wall. This is caused by herniation of the intestinal loops into the extra-celomic cavity in the umbilical cord
Irregular small to large ulcer with a firm base, poorly defined margins which are everted: Carcinoma cervix ulcerating type.
Tumor with some brown black pigment: Hemorrhage in carcinoma; malignant melanoma (rare in cervix, but can occur).
Polyp extending from the uterine cavity:
  • Endometrial polyp—benign
  • Leiomyomatous submucosal polyp from the uterus; it is round and globular with a whorled appearance on cut surface.
Thickened endometrium: More than the average endometrial thickness of 0.5–1 mm:
  • Secretory/hypersecretory endometrium
  • Superficial spreading endometrial carcinoma.
Membrane like white covering of the endometrial cavity (similar to ectocervical mucosa): Ichthyosis uteri (rare condition where entire endometrium undergoes squamous metaplasia—presence of squamous cell carcinoma to be ruled out by taking several bits).
Polypoid mass protruding into endometrial cavity:
  • Benign endometrial polyp
  • Endometrial stromal polyp
  • Leiomyomatous polyp if it has a whorled cut surface
  • Polypoid endometrial carcinoma (firm gray white cut surface).
Trabeculated myometrium of varying thickness with intervening hemorrhage cysts: Adenomyosis.
Small well-circumscribed masses of varying sizes in myometrium, c/s solid, whorled: Leiomyomata: these can be single or multiple and be located either in the intramural (confined to myometrium), submucosal or subserosal region. They sometimes show cystic change, hyalinization or myxoid change.
“Red degeneration” is seen in a leiomyoma due to infarction and in pregnancy. It generally has a reddish brown appearance of the whorled tissue. Presently the term appears outdated and now apoplectic/hemorrhagic leiomyoma may be replacing it.
White worm-like tumor masses: Extending into and occupying the myometrium merging in places with the endometrium: endolymphatic stromal myosis/low grade endometrial sarcoma.
Markedly enlarged uterus with tumor showing variegated appearance and deep infiltration into myometrium: Malignant mixed Mullerian tumor (carcinosarcoma of endometrium).
Translucent grape-like structures: Few mm to 1 to 2 cm across, filling and distending the uterine cavity—hydatidiform mole. In a complete mole there is extensive villous formation, in a partial mole some of the villi only show this change.
Tumor with extensive hemorrhage occupying the uterine cavity and extending into myometrium: choriocarcinoma.
Circumscribed nodule (as compared to choriocarcinoma) with less extensive hemorrhage endomyometrium: Placental site trophoblastic tumor.
Cyst of the ovary: Diameter should be >2.5 cm in size to justify the term “cyst in the ovary”, else it may be just a cystic change in either a Graafian follicle or corpus luteum
Single cyst in ovary: Solitary follicular cyst (5–10 cm in diameter) develops due to distension of a developing atretic follicle.
Multiple small (0.5 cm or less) cysts in the cortex: Polycystic ovarian disease (PCOD) also known as Stein–Leventhal syndrome. Has a sclerotic cortex.18
Cyst with a yellow rim: Corpus luteum cyst usually < 6 cm in size.
Hemorrhagic cyst with a thin/thickened wall and brown contents:
  • Chocolate cyst/cysts or endometriotic cysts
  • Torsion in a follicular cyst
  • Torsion in corpus luteal cyst (last two, due to twisting of pedicle).
Cystic ovarian tumor:
  • Serous tumor (serous fluid or mildly viscous fluid)
  • Mucinous tumor (mucoid contents); may be multilocular
  • Yolk sac tumor (with necrosis and hemorrhage)
  • Benign cystic teratoma (presence of hair, pultaceous material/tooth/Rokitansky protuberance).
Solid ovarian tumor:
  • Fibroma-thecoma group
  • Granulosa theca cell tumors
  • Sertoli-Leydig cell tumors
  • Brenner tumor
  • Dysgerminoma
  • Clear cell carcinoma
  • Undifferentiated carcinoma.
Solid tumor with yellow/tan cut surface:
Cystic tumor with papillary/polypoid excrescences arising from the lining: Serous papillary cystadenoma/carcinoma.
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Figures 1.35A and B: (A) Excised right ovarian mass from a 55-year-old female; (B) Cut section shown is yellow and lobulated
Papillae and polypoid fronds cover the outer surface of the ovary: Surface serous papilloma.
Bilateral ovarian tumor:
  • Serous tumors
  • Mucinous tumors
  • Germ cell tumors including dysgerminomas
  • Krukenberg tumor.
Tubo-ovarian mass:
  • Chronic salpingo-oophoritis
  • Endometriotic cysts with secondary adhesions
  • Malignant tumor of either the Fallopian tube or ovary; one infiltrating the other.
Distended Fallopian tube:
  • Soft and cystic—hydrosalpinx
  • Hemorrhagic with rupture—ectopic tubal gestation
  • Firm to hard—carcinoma.
The mons pubis, clitoris, labia majora and minora constitute the vulva.
  • Cysts: The Bartholin gland is the major vestibular gland with a tubulo-alveolar structure, made up of acini composed of mucus secreting cells and a duct lined by transitional epithelium. A Bartholin gland cyst is a distension of the duct lined by transitional or stratified 19squamous epithelium, it is filled with mucin which is non-sulphated sialomucin.
    • Other cysts: These are the epidermoid cyst, cyst of the canal of Nuck, Gartner duct cyst, the latter being more common in the vagina.
  • Inflammations: Granuloma inguinale (Donovanosis) is a chronic inflammation caused by Calymmato-bacterium granulomatis, i.e. a Gram–ve, non-motile encapsulated bacillus. Presents in the vulvar region as a soft nodule which ulcerates. The diagnosis rests on the demonstration of Donovan bodies which are small encapsulated round to oval bodies in the cytoplasm of histiocytes, well identified by the Giemsa and Warthin Starry stain which gives them a “safety pin appearance”.
    • Lymphogranuloma venereum a veneral disease produced by Chlamydia group of organisms, serotypes L1, L2, L3. A small ulcer is seen at the site of contact which often goes unnoticed. Subsequently inguinal lymph nodes enlarge and give rise in their parenchyma, microscopically to stellate abscesses surrounded by pale epitheliod cells. Organisms are Gram-negative and stain black with Warthin- Starry silver impregnation technique. This later leads to fistula formation, strictures of the urethra, vagina and rectum. Diagnosis is confirmed by the Frie's test which is an intradermal skin test; complement fixation and/or by immunofluorescence.
    • Viruses: Herpes simplex causes vulvar ulcers-mononuclear and multinucleate giant cells show ground glass nuclei or eosinophilic intranuclear inclusions. Human papilloma viruses are among the most common vulvar infections and cause squamous proliferations of the skin and mucous membranes.
  • Leukoplakia: Refers to a white colored skin patch accompanied by pruritus. It is a clinical term. At times the lesions appear as red patches with excoriation and atrophy, called “Kraurosis vulva”. Histologically they prove to be either psoriasis, lichen planus, lichen simplex chronicus, lichen sclerosis, or squamous intra-epithelial lesion.
    • Lichen sclerosis et atrophicus (chronic vulvar dystrophy): Occurs at any age. Histology shows:
      • Atrophic epidermis
      • Hypocellular upper dermis which is edematous in the early stages and shows sclerosis later
      • Inflammation beneath this composed of lymphocytes. Rarely goes onto squamous cell carcinoma.
    • Keratosis (squamous hyperplasia): Acanthosis, prominent stratum granulosum, hyperkeratosis and a mild chronic inflammatory cell infiltrate, absence of atypia.
    • Mixed vulvar dystrophy is used when keratosis and lichen sclerosis et atrophicus co-exist.
  • Condyloma acuminatum: Venereal disease caused by human papillomavirus (HPV) type 6 and characterized by one or more soft elevated masses of variable size.
    • Microscopically: Papillary processes of well- differentiated squamous epithelium are seen with delicate, well-vascularized connective tissue stalks. Low power shows the epithelium to be undulating.
    • A flat condyloma is more common than a papillary one. Koilocytosis of the surface epithelium is seen in both, i.e. perinuclear vacuoles, minimal nuclear atypia and wrinkling of nuclear membranes “nuclear raisins”. Normal mitoses are seen in contrast to abnormal mitoses. The latter together with nuclear pleomorphism and nuclear enlargement are features of vulval intraepithelial neoplasia (VIN).
  • Squamous papilloma: Papillary lesion without the cytological features characteristic of HPV infection.
  • Epidermolytic hyperkeratosis: Related to Hailey-Hailey disease and shows similar histology with suprabasal clefts and dyskeratotic cells.
  • Bowenoid papulosis: Multiple often pigmented papules in or near the vulva of young patients. Clinically they resemble verrucae (HPV 16 associated), small condylomas or nevi.
    • Characterized microscopically by a degree of atypia approaching Bowen's disease. The intraepidermal portion of the hair follicle (acrotrichium) is spared. Acrosyringium is involved.
  • VIN (Bowen's disease): Elevated plaque-like lesion with a red velvety appearance, occurs in the labia majora but may extend down to the perineum and anus. Several cases are associated with HPV infection. The lesion may be single or multiple, scaly or eczymatoid
    • Microscopically: Hyperkeratosis, parakeratosis, acanthosis and a variable number of multinucleated dyskeratotic cells with abnormal mitoses involving the entire thickness of the epidermis. It corresponds to CIN III type of lesion in the cervix. Intraepidermal part of hair follicle is involved. This is classic type of VIN and due to HPV infection. A less common differentiated type of VIN is not caused by HPV infection.20
  • Carcinomas:
    • Squamous cell carcinoma: Constitutes 95% of malignant tumor of the vulva:
      • Frequently associated with malignant tumor elsewhere in the lower genital tract.
      • Two patterns are seen in the vulva:
        1. The common one occurs in the elderly and is not related to HPV. Microscopically characterized by a typical keratinizing squamous cell carcinoma and associated with keratosis.
        2. Younger women frequently HPV +ve, often with basaloid or warty histology and associated with VIN. Common on the labia majora and is generally well differentiated.
    • Microinvasive carcinoma: Depth of invasion in squamous cell carcinoma should be < 5 mm.
    • Verrucous carcinoma is distinguished from condyloma acuminatum by its larger size and the presence of club-shaped fingers of neoplastic epidermis invading the underlying stroma in a pushing fashion. Differentiation from a squamous cell carcinoma is by the absence of cytologic atypia and a pushing infiltrative margin of growth as compared to an irregular infiltrative margin in squamous cell carcinoma.
    • Melanomas: Rare cases of these occur in the vulvar, in the labia minora, clitoris or majora. They may be of the superficial spreading, nodular or acral lentiginous type.
    • Paget's disease: Carcinoma of multipotential cells located along the epidermal basal layer that differentiates along glandular (sweat gland) lines.
      • It presents as crusty, elevated, scaly erythematous lesions.
      • Microscopy: Large pale tumor cells that form solid nests, glandular spaces with a cleft between them and the upper keratinocytes of the epidermis. Cells contain acidic mucin.
      • Presence of melanin pigment does not rule out Paget's disease.
      • Immunohistochemistry (IHC): +ve for MUC 1, MUC 5AC, CK, EMA, CEA, B72.3, GCFD-15, and androgen receptors. ER and PR –ve.
      • CK 7+vity and CK20-vity rules out any extension from urothelial malignancy.
      • The incidence of underlying invasive carcinoma in vulvar Paget's disease ranges from 0% to 30% Table 1.3 gives detail on myxoid lesions of the vulva.
The Müllerian epithelium which lines most of the female genital system is well known for its capacity to differentiate into epithelium of ciliated, mucinous, endometriod, transitional and squamous types.
  • Squamous metaplasia: Occurs commonly in the reproductive age group due to chronic inflammation as a result of proliferation and metaplasia of reserve cells. The stages are:
    • Reserve cell hyperplasia
    • Immature squamous metaplasia wherein the epithelium shows multilayering with mucus cells in the upper reaches
    • Mature squamous metaplasia where the full thickness is replaced by cells showing intercellular bridges.
  • Transitional metaplasia: Seen in the exocervix of older women and often associated with atrophy. Resembles the transitional epithelium of urinary bladder and involves the entire thickness of the mucosa. Immunohistochemistry shows +ve CK 13, 17, and 18 as in normal urothelium.
  • Tubal metaplasia: Cervical epithelium contains three cell types as in normal Fallopian tubes—ciliated, secretary and intercalated cells. Deep-seated glands may be mistaken for carcinoma. Usually found following conization so represents an aberrant differentiation following injury.
  • Intestinal and oncocytic metaplasia occur but are extremely rare.
Inflammatory Conditions
  • Herpes simplex infection is quite common. Microscopy shows nuclear homogenization, subepithelial cleavage leading to bullae formation but rarely multinucleation.
  • Chlamydia trachomatis: Common venereal infection. Histology shows nonspecific chronic inflammation with lymphoid follicles. Organisms are not seen at histology but can be demonstrated by IHC.
  • Amebiasis occurring in the cervix produces a mass which can be mistaken for carcinoma. Diagnosis lies in the demonstration of Entamoeba histolytica on either the H and E stain or by special stains like the periodic acid-Schiff (PAS) and iron hematoxylin stains.21
    Table 1.3   Differences between the various myxoid lesions of the vulva
    Aggressive angiomyxoma (AA)
    Angiomyofibroblastoma (AMFB)
    Superficial angiomyxoma (SAM) (cutaneous myxoma)
    Cellular angiofibroma (CA)
    Age at presentation
    Reproductive years
    Reproductive years
    May extend to older age
    Reproductive years
    Mostly women
    Mostly women, has been reported in males
    Either sex
    Either sex
    Clinical presentation
    Simulates Bartholin gland cyst
    Polypoid submucosal
    Small dermal lobulated, sharply circumscribed
    Well circumscribed;
    Size and site
    Often >5 cm, around 10 cm; vulva, vagina, perineum
    <5 cm; commonly vulva,
    less common vagina
    Small can occur anywhere—dermal or subcutis
    1.5–2 cm; vulva, pelviperineal region may be larger
    circumscribed borders
    Sharply circumscribed/
    almost encapsulated
    Well circumscribed
    Cut surface
    Tan, pink, yellow
    Cellularity and cells
    Paucicellular bland stellate cells
    More cellular than AA; hyper and hypocellular areas; perivascular concentration of plump;
    stromal or epithelioid cells
    Stellate or spindle shaped fibroblasts in a vascular myxoid matrix. Epithelial component may be present as squamous keratinous cysts
    Cellular monotonous spindle cells, indistinct cytoplasm, wavy nuclei, wispy collagen, with small foci of mature fat
    Medium caliber, thick walled, pin wheel collagen
    Smaller than AA, perivascular concentration of plump cells
    Thin walled, inconspicuous
    Small to medium thick walled with mural hyalinization
    Other findings
    Extravasated RBCs
    Stromal neutrophils
    Carney complex
    Mitoses readily identified, no atypia
    Clinical course
    Local recurrence;
    never metastasis
    Does not recur
    Local recurrence
    Local recurrence is very infrequent
    ER and PR
    Mostly –ve, focal +
    + (focal)/–ve
    Mostly –ve, focal+
    + (variable)
    + (variable)
    + (variable)
    +ve in squamous elements
    (HMGA2: high mobility group AT-hook 2; MSA: muscle specific actin; SMA: smooth muscle actin)
  • Actinomycosis is seen in IUCD users: Organisms are seen as cotton wool colonies and stain +ve for silver stains (Gomori's methenamine silver stain).
  • Parasitic infections like Bilharziasis may be observed, diagnosed by demonstration of the ova.
  • Condyloma acuminatum: Grossly polypoid lesion characterized by undulating epithelium with papillomatosis, acanthosis, koilocytosis and variable inflammation of the stroma.
    • Presence of severe atypia should be reported as CIN II or CIN III. Mild atypia is part of the diagnostic feature of the lesion.
    • HPV 6 and 11 are the etiologic factors in 70–90% of the cases, occasionally HPV 16 may be 22encountered which is associated with high grade dysplasia. Other morphologic variants of HPV infection are more common and include “flat”, “spiked” and “inverted” condyloma and warty atypia. Histology: normal basal cells, expanded parabasal cell layer, orderly maturation and mitotic activity with no abnormal mitoses.
    • Koilocytotic atypia seen. Proliferative rate is higher than in metaplastic squamous epithelium.
Non-neoplastic Glandular Lesions
  • Endocervical polyp: Exaggerated versions of polypoid cervicitis, composed of a fibrovascular stalk and covering endocervical epithelium with squamous metaplasia. Stroma shows varying degrees of inflammation.
  • Tunnel clusters: Localized proliferations of endocervical glands with side channels growing out from them. Type A glands: smaller; noncystic tubules that resemble mucosal folds cut in various planes; may have florid glandular proliferation, and mild nuclear atypia, but are still lobular and have minimal mitotic activity. Type B glands: cystic or dilated tubules arranged in lobular units; often multifocal, up to 2 mm in diameter individually; lined by bland cells with no mitoses, no/minimal nuclear atypia. Cystic change (type B) may occur with inspissated secretions. In Type A lesions the lobular configuration is retained with absence of cystic change. The only significance of these clusters is that they should not be mistaken for malignancy (Figs. 1.36A and B).
  • Microglandular hyperplasia: Originally described in women on oral contraceptives and in pregnancy, can also be seen in the absence of these. Microscopy shows complex proliferations of small glands lined by flat cells with little or no atypia. Accompanying squamous metaplasia may simulate a carcinoma. The proliferation is negative for carcinoembryonic antigen (CEA) which differentiates it from an adenocarcinoma.
    • Diffuse laminar endocervical glandular hyperplasia: Is a non–neoplastic condition characterized by proliferation of medium sized, evenly spaced well differentiated glands within the inner third of the endocervical wall, sharply separated from the underlying stroma and often accompanied by stromal inflammation. Differential diag-nosis is adenoma malignum-Stromal infiltration, desmoplastic stromal response and cytologic atypia are absent in the glandular hyperplasia.
    • Lobular endocervical glandular hyperplasia: Distinct lobular proliferation of small to medium sized glands often centered around a larger central gland. Differential is again adenoma malignum and the same features as stated above differentiate the two.
    • Mesonephric duct rests: These can show atypical hyperplastic change. They are superficially located.
    • Endometriosis: Occur grossly as blue red nodules. Both glands and stroma should be present, if only stroma prevails, it is known as “stromatosis”
Non-neoplastic Stromal Reactions
  • Multinucleated stromal giant cell response: It may appear polypoid. An edematous cervical stroma shows reactive fibroblastic/myofibroblastic cells which may be mistaken for malignancy.
  • Decidual reaction: It occurs during pregnancy as multiple yellow elevations of cervical mucosa, soft and friable, bleeds easily on trauma.
    zoom view
    Figures 1.36A and B: (A) Type A tunnel clusters; (B) Type B tunnel clusters
    Microscopically decidual cells with abundant pale pink cytoplasm and bland nuclei. IHC: negative for keratin.
  • Placental site nodule: Well defined hyalinized lesion beneath the mucosa. Microscopy; intermediate trophoblastic cells show cytoplasmic vacuolation. Some nuclear atypia may be seen. DD is carcinoma and cartilage. Cells are reactive for keratin and human placental lactogen.
WHO Classification of Cervical Tumor8
Epithelial Tumor
  • Squamous tumor and precursors:
    • Squamous cell carcinoma, not otherwise specified
      • Keratinizing
      • Non-keratinizing
      • Verrucous
      • Warty
      • Papillary
      • Lymphoepithelioma-like
    • Squamotransitional carcinoma of cervix
    • Early invasive (microinvasive) squamous cell carcinoma
    • Squamous intraepithelial neoplasia of cervix
    • Cervical intraepithelial neoplasia (CIN 3)
    • Cervical squamous cell carcinoma in situ
    • Benign squamous cell lesions
      • Condyloma acuminatum
      • Squamous papilloma of cervix
      • Cervical fibroepithelial polyp
  • Glandular tumor and precursors
    • Adenocarcinoma of cervix
      • Mucinous adenocarcinoma of cervix
        • Endocervical
        • Intestinal
        • Signet-ring cell
        • Minimal deviation
        • Villoglandular
      • Endometrioid adenocarcinoma of cervix
      • Clear cell adenocarcinoma of cervix
      • Serous adenocarcinoma of cervix
      • Mesonephric adenocarcinoma of cervix
    • Early invasive adenocarcinoma of cervix
    • Cervical adenocarcinoma in situ
    • Glandular dysplasia
    • Benign glandular lesions
      • Müllerian papilloma of cervix
      • Endocervical polyp
  • Other epithelial tumors
    • Adenosquamous carcinoma of cervix
    • Glassy cell carcinoma variant of cervix
    • Adenoid cystic carcinoma of cervix
    • Adenoid basal carcinoma of cervix
    • Neuroendocrine tumor
      • Carcinoid-primary cervical
      • Atypical carcinoid-primary cervical
      • Small cell carcinoma of the cervix
      • Large cell neuroendocrine carcinoma of cervix
    • Undifferentiated carcinoma of cervix.
zoom view
Figures 1.37A and B: Basaloid squamous cell carcinoma with islands of squamous cells these showing characteristic peripheral palisading of cells. This is a rare differentiation in a carcinoma cervix. H & E x 100 and 400 respectively
Mesenchymal Tumors and Tumor-like Conditions
  • Leiomyosarcoma of cervix
  • Endometrioid stromal sarcoma, low grade
  • Undifferentiated endocervical sarcoma
  • Sarcoma botryoides
  • Alveolar soft part sarcoma of cervix
  • Cervical angiosarcoma
  • Malignant peripheral nerve sheath tumor of cervix
  • Cervical leiomyoma
  • Genital rhabdomyoma
  • Postoperative spindle cell nodule—cervix.
Mixed Epithelial and Mesenchymal Tumor
  • Carcinosarcoma of cervix (malignant Müllerian mixed tumor)
  • Adenosarcoma of cervix
  • Cervical Wilms’ tumor
  • Cervical adenofibroma
  • Cervical adenomyoma.
Melanocytic Tumor
  • Primary cervical malignant melanoma
  • Blue nevus of cervix.
Miscellaneous Tumors
  • Tumors of germ cell type
    • Yolk sac tumor of cervix
    • Dermoid cyst of cervix
    • Mature cystic teratoma of cervix.
Lymphoid and Hematopoietic
  • Malignant lymphoma—cervical lymphoma (specify type)
  • Cervical leukemia (specify type).
Secondary Tumor
Salient features of some neoplasia
Cervical intraepithelial neoplasia (CIN): Usually develops in the metaplastic squamous epithelium of the transformation zone of the cervix and thus lies on the ectocervix in the younger women and within the endocervical canal in the older patients.
  • Differentiation of CIN is rarely uniform throughout the affected area—it tends to be better differentiated towards the ectocervical region and lesser differentiated towards the endocervical region.
  • The progression to squamous cell carcinoma occurs in about 22% of cases with CIN 3 within 20 years of diagnosis.
  • CIN 1: Cytoplasmic maturation occurs in superficial 2/3rd of the epithelium. Loss of polarity, nuclear enlargement and hyperchromasia as well as mitotic activity are seen in the lower one-third.
  • CIN 2: The above-mentioned changes are seen in the lower 2/3rd and maturation seen in the upper third.
  • CIN 3: The changes are seen in the entire thickness of the metaplastic epithelium. Human papillomavirus types 16 and 18 are most commonly encountered in CIN 3 though they may also be associated with CIN 1 and 2.
SMILE: Stratified mucin producing intraepithelial lesion9
  • Premalignant lesion
  • Rare cervical intraepithelial lesion that is a variant of endocervical columnar cell neoplasia, consistent with neoplasm arising in reserve cells in transformation zone
  • Associated with squamous intraepithlial lesion (SIL) and invasive carcinoma
  • May be a marker of phenotype instability.
  • Microscopy
    • Multilayered epithelium resembling SIL with conspicuous cytoplasmic clearing or vacuoles in lesions otherwise resembling high-grade squamous intraepithedial lesion (HSIL) due to more extreme nuclear pleomorphism and hyperchromasia and higher proliferation index
    • Mucin present throughout the epithelium
    • Usually associated SIL or adenocarcinoma in situ (AIS)
    • Usually no squamous differentiation.
Squamous papilloma: Also called fibroepithelioma. It has a fibrovascular stalk covered by squamous epithelium but with no changes of koilocytosis.
Cervical carcinoma
Squamous cell carcinoma is the most common histologic subtype of cervical cancer.
  • All carcinomas of the cervix are broadly divided into squamous cell types and others. All the morphologic variants of squamous cell carcinomas (SCC) are outlined above (Table 1.4). Associated high risk types of HPV are primarily 16,18, also 31,33,35,39,45,51,52,56, 58,59,68,73, and 82.25
    Table 1.4   Common features of various carcinomas of the cervix
    Diagnosis: Various carcinomas of cervix
    Squamous cell carcinoma
    usual type (NOS)
    Infiltrating islands of cells with or without intercellular bridges. Keartin pearl formation may be seen depending on differentiation
    Adenosquamous carcinoma (ASC)
    • Arises from surface epithelium with surface dysplasia and/or carcinoma in situ (CIS)
    • Presence of squamous and glandular differentiation with intracellular and intraluminal mucin (mucicarmine and PAS positive, diastase resistant)
    • Absence of basaloid component with peripheral palisading or comedo-type necrosis
    • May be associated with SMILE
    • Absence of basement membrane material
    Basaloid squamous cell carcinoma (BSCC)
    • Arises from surface epithelium with surface dysplasia and/or CIS
    • Patterns: solid lobular, cribriform, cords, gland like, cystic
    • Tumor cells are basaloid with peripheral palisading
    • Intercellular deposition of basement membrane like material
    Adenoid cystic carcinoma (ACC)
    • Mucoserous gland origin; no surface connection
    • Nuclei: small, uniform, hyperchromatic, angulated, scant cytoplasm. Minimal mitotic activity, minimal pleomorphism
    • No squamous differentiation, ductal type foci are present
    SCC (large cell type non keratinizing type)
    • High grade, pleomorphic cells, atypical mitoses
    • No glandular differentiation
  • HSIL is an immediate precursor of cervical squamous cell carcinoma.
  • With the advent of widespread screening, many cervical carcinomas are detected at a subclinical stage, during evaluation of an abnormal Pap smear.
  • Gross: Polypoid or deeply infiltrative. Invasive cervical carcinoma may manifest as either fungating (exophytic) or infiltrative cancers.
  • On histologic examination, squamous cell carcinomas are composed of nests and tongues of malignant squamous epithelium, either keratinizing or nonkeratinizing, invading the underlying cervical stroma. Squamous cell carcinoma has to be differentiated from exophytic growths due to condyloma accuminata. Differences between Condyloma accuminata, squamous cell carcinoma and Verrucous form of squamous cell carcinoma have been given in Table 1.5.
  • Basaloid squamous cell carcinoma: Prominent peripheral palisading, squamous differentiation within islands, infiltrative growth, minimal stromal reaction and aggressive behavior.
  • Adenosquamous carcinomas are tumors composed of intermixed malignant glandular and malignant squamous epithelium, common during pregnancy.
  • Glassy cell carcinoma: Distinct type of poorly differentiated adenosquamous carcinoma, occurs in the younger age group and associated with pregnancy. Cytoplasm is moderate with a ground glass or finely granular appearance; PAS +ve cell wall; large nuclei with prominent nucleoli. Increased mitoses. Stroma shows eosinophils. Foci of squamous and glandular differentiated elements may be seen.
  • Minority show mucin in cytoplasm. Should be termed as squamous cell carcinoma with mucin secretion and not adenosquamous carcinoma.
  • Some squamous cell carcinomas show intense infiltration by eosinophils with or without accompyning blood eosinophilia, products of eosinotactic substances are produced by tumor cells.
  • Advanced cervical carcinoma extends by direct spread to involve contiguous tissues, including the paracervical tissues, urinary bladder, ureters, rectum, and vagina. Local and distant lymph nodes are also involved. Distant metastases may be found in the liver, lungs, bone marrow, and other structures.26
    Table 1.5   Differences between condyloma acuminatum, verrucous carcinoma and squamous cell carcinoma
    Condyloma acuminatum
    Verrucous carcinoma
    Squamous cell carcinoma
    Exophytic growth
    Variable size
    Exophytic growth
    Exophytic growth
    Variable inflammation in stroma
    Club-shaped proliferation
    into stroma
    Papillary pattern
    Diffuse infiltration
    Well differentiated
    Nuclear atypia marked
    Nil, exophytic growth
    +ve (subtype 6 and 11)
    +ve (16 and 18)
    Homogenous +ve
    Less uniform
    Local invasion
    Local and distant
  • Grading of squamous cell carcinomas is usually done on a 3-tier system-well, moderately and poorly differentiated. Formerly the classification and grading of Reagen and co-workers used: large cell keratinizing, large cell non-keratinizing and small cell carcinoma. This system originated on the basis that large cell keratinizing carcinomas are radio-resistant relative to non-keratinizing carcinomas. The small cell carcinoma had the worse prognosis. The main disadvantage of this system is that the small cell variant of this classification may be misinterpreted by the clinicians for the oat cell type of carcinoma which it is not, the latter having an even worse prognosis and a different line of therapy as compared to the squamous cell carcinoma.
  • Immunohistochemistry (IHC): All are +ve for keratins (wide range). Carcinoembryonic antigen +ve in 90% of cases. p63+ve, cathepsin B +ve (not as frequent as in adenocarcinoma), β hCG +ve. Estrogen receptor (ER) decreased expression as compared to the normal mucosa.
  • Spread: Sequential spread to paracervical, hypogastric, obturator, external iliac groups, etc. Distant spread to lungs and bone.
  • Microinvasive carcinoma: 4–7% of CIN are associated with superficially invasive, i.e. not more than 5 mm from the basement membrane carcinoma. Criteria for invasion include—desmoplastic response in the adjacent stroma, blurring of the epithelial-stromal interface, focal conspicuous maturation of the neoplastic epithelium with prominent nucleoli, scalloping of margins at the epithelial stromal interface and loss of polarity of nuclei and absence of palisading.
  • Adenocarcinomas: These constitute 5–15% of all carcinomas of the cervix. Adenocarcinomas are characterized by proliferation of glandular epithelium composed of malignant endocervical cells with large, hyperchromatic nuclei and relatively mucin-depleted cytoplasm, resulting in dark appearance of the glands, as compared with the normal endocervical epithelium (Fig. 1.38). There is an association between endocervical adenocarcinoma, ovarian mucinous adenocarcinoma and tubal adenocarcinoma.
Can be of the conventional type (endocervical type) (70% of cases), or special types as given below. The conventional type is composed of neoplastic glands of the endocervical mucinous type ranging from well to poorly differentiated. Simple complex glands, solid sheets or cords of cells are seen.
Histochemistry: Alcian blue and mucicarmine +ve in all conventional adenocarcinoma, similar to in situ carcinoma but different from the normal cervical mucus.
Immunohistochemistry (IHC): Cytokeratin (CK), carcinoembryonic antigen (CEA), epithilial membrance antigen (EMA) +ve; vimentin –ve. P16 (in K-4a) +ve (demonstrates link with HPV virus); HPV 16 and 18 +ve; ER, PR +ve in 1/4th cases; peptide hormones and amylase +ve.27
Prognosis: Overall prognosis is less favorable as compared to SCC. The endometriod variety behaves in a slightly better manner. CA 125 may be elevated and is a poor prognostic marker.
Differential diagnosis: From an endometrial adenocarcinoma extending into cervix is difficult. Some of the differentiating features are shown in Table 1.6.
In situ adenocarcinoma: It is now accepted as a well recognized entity. The features for diagnosis are:
  • Nuclear hyperchromasia and pleomorphism
  • ↑ mitoses
  • ↑ apoptotic bodies
  • +ve for CEA.
zoom view
Figure 1.38: Adenocarcinoma shows stratification of glands with infoldings and cribriform arrangement even in a well differentiated neoplasm in contrast to adenoma malignum. H & E x 400
Table 1.6   Differences between adenocarcinoma arising in the cervix and endometrium
Primary endocervical adenocarcinoma
Primary endometrial adenocarcinoma
Diffuse and abundant
In situ carcinoma
Will be seen in adjacent epithelium
Not seen
CD 10
+ve in 33% (luminal, limited)
+ve in 77% (cytoplasmic, membrane or both)
Strongly +ve
ER and PR
Weakly +ve or negative
Significantly +ve
++ 100 % of cases
+ less than 10%
(CEA: carcinoma embryonic antigen; ER: estrogen receptor)
Differential diagnosis: Tubal metaplasia and tubal endometrial hyperplasia
IHC: Carcinoma in situ is vimentin –ve, diffusely +ve for ink 4, B-cell lymphoma (Bcl-2) –ve, ↑index for molecular immunology borsted (MIB)–1.
Microinvasive adenocarcinoma: Focus of invasion not exceeding 5 mm.
Morphologic Variants of Adenocarcinoma
Endometrioid adenocarcinoma: Well differentiated tumor, can be associated with metachronous/synchronous endometrioid carcinoma of the ovary. DD: Primary from endometrium with endocervical spread.
Papillary serous carcinoma: Similar to endometrial and ovarian tumors.
Adenoma malignum: Minimum deviation adenocarci-noma constitutes 1–2% of all cervical carcinomas. This is so well differentiated structurally and cytologically that it could easily be missed if the deeply situated irregularly branching abnormal glands are not carefully examined. Called malignant due to presence of distorted glands and irregular outlines deeply positioned in the cervix and with stromal response as well as vascular and perineural invasion (Fig. 1.39). Mucin produced is of the neutral type. CEA +tivity differentiates it from benign lesions like microglandular hyperplasia, etc.
  • Differential diagnosis
    • Endocervical type of cervical adenomyoma
    • Deeply located endocervical glands (in which stromal response and architectural disarray are absent, CEA is -ve.)28
    • Conventional adenocarcinoma cervix (has to be differentiated for prognosis and treatment purposes: see Table 1.7).
    Villoglandular papillary adenocarcinoma: Exophytic polypoid lesion with papillae lined by endocervical, endometrial or intestinal type epithelium with mild atypia. The superficial part looks like colorectal villous adenoma. Evidence of HPV infection observed. Prognosis is excellent.
    Clear cell carcinoma: (mesonephroid carcinoma of Mullerian origin). Exophytic tumor; glands are lined by large cells with abundant clear cytoplasm. Hobnail cells are common as also intraglandular papillary projections. Common in young patients, a smaller peak at 70 years of age. A relationship with DES exposure during prenatal period is known
    zoom view
    Figure 1.39: Section shows adenoma malignum with deeply situated branched glands with minimal atypia embedded in stroma. H & E x 100
    • Differential diagnosis: Microglandular hyperplasia
      • Aria stella reaction
    • IHC: CK, CAM 5.2, 34 βE12, CEA, CD15, vimentin bcl 2 and CA125 +ve. Variable +vity for ER. Negative for PR and CK 20.
    • Prognosis is relatively good.
Other types of adenocarcinomas: These are adenoid cystic, adenoid basal carcinoma and mesonephric adenocarcinoma.
Transitional cell carcinomas as occurring in the urinary bladder can also be seen in the cervix.
Extrapulmonary small cell carcinoma/atypical carcinoid and neuroendocrine carcinoma are the other carcinomas.
Neuroendocrine cervical carcinomas typically have an appearance similar to small-cell carcinoma of the lung; however, in contrast to the lung tumor, which is not related to HPV infection, cervical small-cell carcinomas are positive for high oncogenic risk HPVs. Morphologically these tumors have also to be differentiated from the small cell non-keratinizing variant of squamous cell carcinoma.(Table 1.8).
Table 1.7   Differences between adenocarcinoma and adenoma malingum
Adenoma malignum
Well differentiated
But admixed with less differentiated
Well differentiated throughout
Stromal response
HPV association
+ve (16, 18)
Ink 4 (HPV associated)
Alcian blue +ve (acid mucins)
Mucicarmine +ve
Neutral type
PAS +ve
Over expressed frequently
Lacks p53 expression
Association with
P-J syndrome
Table 1.8   Differences between small cell carcinoma and small cell variant of SCC
Small cell carcinoma
Small cell variant of SCC
Precursor lesion
CIN changes in adjacent epithelium is rare. Endocrine cell hyperplasia
CIN +ve
Cell of origin
Basal reserve cell
HPV assoc
Organoid arrangement in better differentiated tumors, else, insular, trabecular and rosettes
↑ mitoses, areas of necrosis ++
Diffuse sheets and large nests
Necrosis and mitoses
may be seen
May be combined with adenocarcinoma
Squamous cell carcinoma (amphicrine car)
+++; neuron-specific enolase (NSE) +ve, chromogranin, synaptophysin, 5HT, etc. +ve
Argyrophilia very rare; others -ve
Clinically aggressive
Less aggressive than small cell carcinoma
Other tumors: Botryoid rhabdomyosarcoma, mixed Mullerian tumor, stromal sarcoma. Difference between mixed mullerian tumor and carcinosarcoma is that in MMMT, the epithelial element is an adenocarcinoma whereas in a carcinosarcoma (sarcomatoid carcinoma), it is generally squamous with blending of two components.
Metastatic carcinomas: Common sites of metastasis are from the ovary, large bowel, stomach breast and kidney (clear cell carcinoma—RCC). Mesonephroid adenocarcinoma and RCC are both +ve for vimentin, but RCC is also +ve for CD10 and the former is not.
Stages of Normal Menstrual Cycle
Proliferative Phase
Early proliferative: (day 4 to 7)—surface epithelium thin; straight short glands; compact stroma with cells showing some mitotic activity and large nuclei (Fig. 1.40).
Mid proliferative phase: (day 8 to 10)—columnar surface epithelium; long curving glands; variable stromal edema; numerous mitoses in stromal cells (Fig. 1.41).
Late proliferative phase: (day 11 to 14)—undulant surface; tortuous glands showing active growth and pseudostratification; moderately dense stroma (Fig. 1.42).
zoom view
Figure 1.40:
zoom view
Figure 1.41:
zoom view
Figure 1.42:
zoom view
Figure 1.43:
zoom view
Figure 1.44:
zoom view
Figure 1.45:
Early secretory phase: Up to 48 hours after ovulation: no microscopic change seen 16th to 17th day: subnuclear vacuolation; with ↑ in size of vacuoles on day 17 “piano key appearance”; 18th to 19th day: ↓ in size of vacuoles; nuclei at base of cells; luminal secretion starts (Fig. 1.43).
Mid secretory phase: 20th day: peak of acidophilic intraluminal secretion (Fig. 1.44).
  • 21th day: Stromal edema begins
  • 22nd day: Stromal edema reaches peak; best time for implantation –“I am ready for you”.
Late secretory phase (Fig. 1.45):
  • 23rd to 24th day: Spiral arterioles become prominent and predecidual cells appear around spiral arterioles.
  • 25th day: Predecidual cells appear beneath surface epithelium
  • 26th day: Predecidual as solid sheets
  • 27th day: Neutrophils
  • 28th day: Necrosis and hemorrhage are prominent.
The normal endometrial epithelium as noted above is composed of cuboidal to columnar cells with faintly eosinophilic cytoplasm and oval to elongated nuclei. Ciliated cells are common especially in the proliferative phase; their presence should not be taken as indicative of tubal/ciliated metaplasia.
Endometrial metaplasias can be focal or diffuse. They are especially likely to occur in tamoxifen-associated endometrial polyps as well as in non-polypoid endometrium showing hyperplasias/carcinomas.
Often associated with exogenous hormone therapy, especially unopposed estrogen therapy. Other contributory factors are IUCD, chronic endometritis and pyometra.
The International Society of the Gynecological Pathologist's Classification of the endometrial epithelial metaplasias is as follows:
  • Squamous metaplasia
  • Mucinous metaplasia (including intestinal)31
  • Ciliary change
  • Hobnail cell change
  • Clear cell change
  • Eosinophilic cell change (including oncocytic)
  • Surface syncytial change
  • Papillary proliferation
  • Arias-Stella change.
Squamous metaplasia: Common in endometrial adenocarcinoma and endometrial hyperplasia
  • The squamous component in carcinoma may be benign, indeterminate or malignant. The WHO categorises adenocarcinoma with squamous differentiation as a variant of endometrioid adenocarcinoma and no longer accepts terms such as adenoacanthoma and adenosquamous carcinoma.
  • Morules (non-squamous solid pattern in carcinoma) differ from mature squamous metaplasia in that they lack intercellular bridges and keratinization. Morules and foci of mature squamous metaplasia co-exist.
  • Squamous metaplasia can also be seen in pyometra, chronic endometritis, cervical stenosis and IUCD.
Mucinous metaplasia: It is rare and endometrial cells are replaced by abundant mucin containing cytoplasm.
  • Normal endometrial cells contain luminal mucin and for metaplasia therefore abundant mucin should be seen.
  • Rarely intestinal metaplasia is seen in this mucinous epithelium (diagnosed by presence of goblet cells in addition to mucin cells).
  • DD is mucinous carcinoma which morphologically has bland cells; and microglandular hyperplasia. The latter occurs in young women.
Ciliated/tubal metaplasia: Diagnosis should be made only when one or more endometrial glands are lined predominantly by ciliated epithelium with a eosinophilic cytoplasm.
  • Occurs in endometrial hyperplasia.
Clear cell metaplasia: Seen as endometrial cells showing abundant clear cytoplasm, in pregnancy.
  • Importance lies in not misdiagnosing it as clear cell carcinoma. The architecture of the glands is maintained except perhaps when associated with complex hyperplasia. Clear cell carcinoma is also cytologically bland.
  • Features favoring clear cell metaplasia versus carcinoma are—focality of lesion, absence of a visible lesion on hysteroscopy, absence of stromal invasion and ER +vity. Most clear cell carcinomas are ER –ve.
Hobnail cell metaplasia: It is a reparative phenomenon and occurs after endometrial biopsy.
Oxyphil/eosinophil metaplasia: Epithelial cells with abundant eosinophil cytoplasm, seen in hyperplasia.
Arias-Stella reaction: Exaggerated secretory changes in the endometrium are accompanied by prominent nuclear changes like hyperchromasia and enlargement.
  • Normal and abnormal mitoses are present.
  • These changes are focal—may also occur in the cervix, endocervical polyps, adenomyosis and endometriosis.
  • They are seen in postabortal curettings in 20–70% of cases, persisting for weeks, also in normal and ectopic pregnancies and rarely following administration of exogenous hormones.
  • DD is clear cell type of adenocarcinoma.
Acute endometritis: It seen in abortions, postpartum states and instrumentation. Neutrophils at endometrial surface epithelium (> 5/hpf) should be observed to diagnose acute endometritis. (Neutrophils are normally present in the endometrium on days 26, 27, and 28).
Chronic endometritis: It shows infiltration of lymphocytes and plasma cells. Occurs as a sequelae to chronic cervicitis, pelvic inflammatory disease and IUCD. Lymphoid follicles with or without germinal centers are a normal occurrence in the functional layer of the endometrium and not considered as evidence of chronic endometritis. Therefore, identification of plasma cells is a must for diagnosis. Markers such as CD 38, CD 138/Syndecan-1 may be resorted to enhance presence of plasma cells.
Specific forms of endometritis are due to:
  • Chlamydia trachomatis and Neisseria gonorrhoeae
  • Mycoplasma
  • CMV
  • HSV
  • Mycobacterium tuberculosis.
Cytomegalovirus (CMV) generally occurs in immunocompromised patients and shows the characteristic large nuclear and cytoplasmic inclusions as seen elsewhere. Chlamydial infections and malakoplakia of the endometrium have been reported.
IUCD insertion: Results in focal or extensive chronic endometritis, necrosis and squamous metaplasia.32
  • May result in salpingitis and pelvic inflammatory disease (PID) with tubo-ovarian abscesses.
  • Actinomycosis organisms are implicated and identified as colonies of radiating filamentous structures staining +ve for Gomori's methenamine silver and periodic acid Schiff stains.
Pyometra: Accumulation of pus within the endometrial cavity due to obstruction and infection.
Hematometra: Accumulation of blood within the endometrial cavity as a result of occlusion at the cervical os. May result in a diffuse endometrial xanthogranulomatous endometritis or nodular cystic hyperplasia (focal response).
Endometrial tuberculosis: Presents as sterility. A granulomatous inflammation is seen with tubercles composed of epitheliod cells, accompanied with caseous necrosis.
Viral endometritis: (CMV and condyloma): CMV generally occurs in immunocompromised patients and shows the characteristic large nuclear and cytoplasmic inclusions as seen elsewhere.
Chlamydial infections and malakoplakia of the endometrium have been reported.
Adenomyosis and Endometriosis
Presence of islands of endometrial glands and stroma deep within the myometrium is called adenomyosis. Endometriosis is occurrence of similar tissue outside the corpus of the uterus—ovary, cervix, vagina, vulva, Fallopian tubes, rectovaginal septum, broad ligament, pelvic peritoneum, abdominal wall, small and large bowel, etc.
Microscopy: The endometrial glands and stroma should be present one low power (10x) field below the endomyometrial junction. Hemosiderin laden macrophages invariably accompany the adenomyosis of long duration and result from cyclical hemorrhages which accompanies endometrial tissue during menstruation. Two of the three components, i.e. endometrial glands, stroma, and hemosiderin laden macrophages should ideally be present to make the diagnosis.
Several theories have been put forward for the development of endometriosis—the most popular and widely accepted one is the metaplastic theory.
WHO Classification of the Tumors of the Uterus10
  • Epithelial tumor and related lesions
    • Endometrial carcinoma
    • Endometrioid adenocarcinoma
      • Variant with squamous differentiation
      • Villoglandular variant
      • Secretary variant
      • Ciliated cell variant
    • Mucinous adenocarcinoma
    • Serous adenocarcinoma
    • Clear cell adenocarcinoma
    • Mixed cell adenocarcinoma
    • Squamous cell carcinoma
    • Transitional cell carcinoma
    • Small cell carcinoma
    • Undifferentiated carcinoma
    • Others.
  • Endometrial hyperplasia
    • Non-atypical hyperplasia
      • Simple
      • Complex (adenomatous)
    • Atypical hyperplasia
      • Simple
      • Complex (adenomatous)
  • Endometrial polyp
  • Tamoxifen related lesion
  • Mesenchymal tumor
    • Endometrial stromal and related tumor
      • Endometrial stromal sarcoma, low grade
      • Endometrial stromal nodule
      • Undifferentiated endometrial sarcoma
    • Smooth muscle tumor
      • Leiomyosarcoma
        • Epithelioid variant
        • Myxoid variant
      • Smooth muscle tumor of uncertain malignant potential
      • Leiomyoma, not otherwise specified (NOS)
        • Histological variants
          • Mitotically active variant
          • Cellular variant
          • Hemorrhagic cellular variant
          • Epithelioid variant
          • Myxoid
          • Atypical variant
          • Lipoleiomyoma variant
        • Growth pattern variants
          • Diffuse leiomyomatosis
          • Dissecting leiomyoma
          • Intravenous leiomyomatosis
          • Metastasizing leiomyoma33
        • Miscellaneous mesenchymal tumors
          • Metastasizing leiomyoma
          • Mixed endometrial stromal and smooth muscle tumors
          • Perivascular epithelioid cell tumor
          • Adenomatoid tumor
          • Other malignant mesenchymal tumor
          • Other benign mesenchymal tumor
  • Mixed epithelial and mesenchymal tumor
    • Carcinosarcoma
    • Adenosarcoma
    • Carcinofibroma
    • Adenofibroma
    • Adenomyoma
      • Atypical polypoid variant
  • Gestational trophoblastic disease
    • Trophoblastic neoplasms
      • Choriocarcinoma
      • Placental site trophoblastic tumor
      • Epithelioid trophoblastic tumor
    • Molar pregnancies
      • Hydatidiform mole
        • Complete
        • Partial
        • Invasive
        • Metastatic
    • Non-neoplastic non-molar trophoblastic lesions
      • Placental site nodule and plaque
      • Exaggerated placental site reaction
  • Miscellaneous tumor
    • Sex cord like tumor
    • Neuroectodermal tumor
    • Melanotic paraganglioma
    • Tumors of germ cell type
    • Others
  • Lymphoid and hematopoietic tumor
    • Malignant lymphoma (specify)
    • Leukemia (specify).
Endometrial Hyperplasia
  • WHO Classification of endometrial hyperplasia11A has for several years been:
    • Hyperplasia (without atypia)
      • Simple
      • Complex
    • Atypical hyperplasia
      • Simple
      • Complex
The glands of simple hyperplasia are straight and non-branching, but variably dilated to produce an irregular pattern of lumens. Occasional luminal protrusions are acceptable. In contrast a complex architecture is present when the glands are arranged in close proximity or are individually characterized by prominent branching or infoldings.
Many non-atypical hyperplasias demonstrate altered differentiation patterns—papillary, eosinophilic and squamous.
Atypical endometrial hyperplasia: Most have a complex architecture.
  • Cytologic atypia is readily identified, stratification with loss of polarity
  • Nuclei are enlarged, rounded with irregular shapes
  • Coarsening of chromatin creating a vesicular appearance
  • Prominent nucleoli
  • Mitotic activity, variable amount.
  • The term EIN (endometrial intraepithelial neoplasia) (Table 1.9A) is presently considered synonymous with atypical endometrial hyperplasia11B (Emons G, et al. New WHO Classification. Geburtsh Frauenheilk. 2015;75:135-6).
    • In small distorted or poorly oriented samples atypical endometrial hyperplasia may be indistinguishable from a well-differentiated adenocarcinoma.
Grossly protrude into the endometrial cavity and exhibit secondary changes.
  • Lined by active pseudostratified epithelium exhibiting mitotic figures or in the postmenopausal female by flat inactive epithelium.
  • Glands and stroma are unresponsive to progesterone stimulation. Stroma is of fibroblast like cells containing abundant connective tissue with thick-walled blood vessels.
  • Some polypoid lesions exhibit simple or complex hyperplasia with papillary endometrial proliferations.
  • Rare functional polyps are seen.
  • Polyps occur with increasing frequency after exposure to tamoxifen.
  • Polypoid adenomyoma: Polyps with smooth muscle not connected with blood vessels.34
Table 1.9A   Former criteria for EIN which is now considered synonymous with atypical endometrial hyperplasia
EIN criteria
(All must be met in a single area of one tissue fragment)
Areas of glands >stroma, usually in a localized region
Cytology differs between architecturally crowded focus and background
Size >1 mm
Maximum linear dimension exceeds 1 mm
Exclude mimics
Benign conditions with overlapping criteria: Basalis, secretory, polyps, repair, etc.
Exclude cancer
Carcinoma with maze like glands, solid areas or significant cribriform pattern
TABLE 1.9B   New WHO classification of endometrial hyperplasia (Kurman et al. WHO press 2014)
New terminology
Genetic changes
Assoc with cancer
Progression to cancer
Hyperplasia without atypia
Hyperplasia without atypia
Low level of somatic mutations
Relative Risk (RR):
Atypical hyperplasia/endometrial intraepithelial neoplasia (EIN)
Microsatellite instability
PAX2 inactivation
Mutations – PTEN, KRAS, CTNNB1 (beta catenin)
RR: 14–45
Endometrial Intraepithelial Neoplasia11B (Atypical Endometrial Hyperplasia) (Table 1.9B)
Precursor lesion for endometrioid carcinoma (type I carcinoma) and was formerly considered separate from atypical hyperplasia. EIN should not be confused with an unrelated entity, serous intraepithelial carcinoma (serous EIC), which is an early stage of a different tumor type known as papillary serous adenocarcinoma which can occur as a primary in the uterus. EIN was characterized by
  • Clonal proliferation of architecturally and cytological altered premalignant endometrial glands
  • Prone to malignant transformation to endometrioid (type I) endometrial adenocarcinoma (Table 1.10)
  • Management follows guidelines established for atypical endometrial hyperplasia
  • Diagnostic tissue should be obtained 2–4 weeks after stopping exogenous hormones in patients on progestins.
The cells of an EIN/atypical endometrial hyperplasia are genetically different than normal and malignant tissues, and have a distinctive appearance under the light microscope. EIN cells are already neoplastic, demonstrating a monoclonal growth pattern and clonally distributed mutations. Progression of EIN to carcinoma, is accomplished through acquisition of additional mutations and accompanied by a change in behavior characterized by the ability to invade local tissues and metastasize to regional and distant sites.
Table 1.10   Characteristics of type I and type II endometrial carcinoma
Type I
Type II
55–65 years
65–75 years
Clinical setting
Unopposed estrogen
Thin physique
Clear cell
Mixed Müllerian tumor
Endometrial intraepithelial carcinoma
Molecular genetics
Spreads via lymphatics
Intraperitoneal and lymphatic spread
* MSI, microsatellite instability.
Endometrial Intraepithelial Carcinoma
  • Endometrial intraepithelial carcinoma (EIC) is the precursor lesion of serous carcinoma.
  • Characterized by epithelial cells that show marked nuclear abnormalities identical to that seen in serous carcinoma of the endometrium, yet lacking an invasive component.
  • EIC is commonly seen in endometrium adjacent to serous carcinoma and also is observed adjacent to malignant mixed mesodermal tumors (MMMTs).
  • Occasionally, EIC is seen without an invasive carcinoma present.
The changes often occur within a polyp.
Endometrial Carcinoma
Endometrial carcinoma is the most common invasive cancer of the female genital tract and accounts for 7% of all invasive cancer in women, excluding skin cancer. Two types of endometrial carcinoma are seen:
Type I
The most common one is due to excess of estrogenic stimulation and develops against a background of endometrial hyperplasia.
High-risk groups: These are those with obesity, diabetes, hypertensive and infertile patients, those on tamoxifen and those with functional ovarian tumors, etc.
Gross: Can develop in any part of the endometrial mucosa. Younger women show isthmic involvement.
  • On gross inspection, endometrial carcinoma can be either a localized polypoid tumor or a diffuse tumor involving the endometrial surface.
  • Spread generally occurs by direct myometrial invasion with eventual extension to the periuterine structures by direct continuity.
  • Spread into the broad ligaments may create a palpable mass.
  • Dissemination to the regional lymph nodes eventually occurs, and in the late stages, the tumor may metastasize to the lungs, liver, bones, and other organs.
Microscopy: 80% are of the conventional type of adenocarcinomas (endometrioid carcinoma/type I) with endometrial glands lined by tall columnar, stratified epithelium with mitoses, stratification and a back to back arrangement of the glands. Most are well differentiated, others have a solid component of malignant cells. Degree of nuclear pleomorphism is mild.
  • A grading system called the FIGO (International Federation of Gynecology and Obstetrics) is used for grading these conventional type of endometrial adenocarcinoma and its variants given below:
    • Gx: Grade cannot be assessed
    • G1: 5% or less non-squamous solid growth
    • G2: 6–50% of non-squamous solid growth
    • G3: > 50% of non-squamous solid growth.
  • Increase in grade by “1” based on marked nuclear atypia
  • IHC: ER and PR +ve; correlates with FIGO grade and stage.
    • CK 7, 8, 18, 19, +ve
    • Vimentin +ve in 65 to > 80% of cases
    • CEA: Focal +vity (in areas of squamous metaplasia);
    • CA 125, secretory component, Ulex europaeus +ve in 12% of cases.
    • CD 114: +ve in 50% of endometrial carcinoma and in 90% of normal proliferative endometrial glands.
      • Variants of endometrioid adenocarcinoma:
      • Villoglandular variant: One-fourth of endometrioid carcinomas have superficial papillary foci. These should not be diagnosed as the (aggressive) papillary serous carcinoma of the endometrium which is a variant of endometrial carcinoma.
    • Variant with squamous differentiation: Includes the old terms “adenoacanthoma” and “adenosquamous carcinoma”. The former is a well-differentiated endometriod carcinoma with benign appearing squamous elements derived from metaplasia of tumor glands. The latter is a mixed carcinoma with malignant appearing glandular and squamous elements (the latter component may be as high as 30% of the tumor). Patients have a worse prognosis than those with adenocarcinoma alone or adenoacanthoma as the adenocarcinoma element is poorly differentiated (not dependent on the squamous component).
    • Glassy cell carcinoma: It is a special type of adenosquamous carcinoma which occurs occasionally in the endometrium.
    • Secretory carcinoma: Neoplastic glands with subnuclear vacuolation (resembling 17th day endometrium) accompanied by late secretary pattern in the adjacent uninvolved endometrium. This pattern seen as a result of progesterone stimulation in the well-differentiated neoplastic glands.36
    • Ciliated carcinoma: Rare variant of endometrioid adenocarcinoma composed of ciliated cells. DD is ciliated cell metaplasia.
Type II
  • These generally occur in women a decade later than type I carcinoma, and in contrast to type I carcinoma they usually arise in the setting of endometrial atrophy.
  • Type II tumors are by definition poorly differentiated (grade 3) tumors and account for approximately 15% of cases of endometrial carcinoma.
  • The most common subtype is serous carcinoma, referred to as such because of morphologic and biologic overlap with ovarian serous carcinoma.
  • Generally, serous carcinomas arise in small atrophic uteri and are often large bulky tumors or deeply invasive into the myometrium.
  • The precursor lesion, endometrial intraepithelial carcinoma, consists of malignant cells identical to those of serous carcinoma but they remain contained to the gland surface without identifiable stromal invasion.
  • The invasive lesions may have a papillary growth pattern and therefore also called as papillary serous carcinoma or uterine papillary serous carcinoma.
  • Papillary serous carcinoma: These are highly aggressive form of endometrial adenocarcinoma closely resembling the ovarian papillary serous carcinoma. Pure serous carcinomas are rare (about 1.1% of all endometrial carcinomas in one study), generally occur in combination with endometrioid carcinoma. Papillary serous carcinoma can also occur with a similar serous papillary tumor of the ovary (grade 3 by definition).
  • Microscopy: Complex papillary pattern of growth, high degree of cytologic atypia with pleomorphism, hyperchromasia and macronuclei and giant nucleoli, numerous mitoses, extensive necrosis and psammoma bodies.
    • Myometrial invasion is invariably seen.
    • Differential diagnosis is endometrioid carcinoma with a villoglandular pattern of growth. Confusion is more because psammoma bodies can be seen in both, and both tumor can co-exist.
    • An important marker of differentiation is WT 1 which is always +ve in papillary serous tumor of the ovary but not in that of the endometrium
    • However, they can also have a predominantly glandular growth pattern that can be distinguished from endometrioid carcinoma by the marked cytologic atypia.
    • All of the non-endometrioid carcinomas are classified as grade 3 irrespective of histologic pattern.
    • Serous carcinoma, despite relatively superficial endometrial involvement, may be associated with extensive peritoneal disease, suggesting spread by routes (i.e. tubal or lymphatic transmission) other than direct invasion.
  • Mucinous adenocarcinoma: Abundant mucin secretion by the glands. The architectural distortion and cytologic atypia should differentiate it from mucinous metaplasia. Some cells containing mucin may also be seen in endometrioid adenocarcinoma which has also to be differentiated from this (technically this is endometrioid; so graded as 1 to 3; in the current classification listed separately).
  • Clear cell carcinoma: Large clear cells with distinct cellular margins with large amounts of glycogen, uniform nuclei and prominent nucleoli.
    • The papillary formations, hobnail appearance of cells are similar to its counterpart seen in the ovary, cervix and vagina. When seen in sheets the distinct cell margins are preserved. As in these areas it is of Mullerian origin rather than mesonephric (grade 3 by definition).
    • Not related to diethylstilbestrol (DES) exposure, as in the cervix.
  • Small cell carcinoma: Neuroendocrine carcinoma presents sometimes as a bulky polypoid ill-defined mass. May be associated with an adenocarcinoma or as a component of malignant mixed Müllerian tumor.
    • It has an aggressive behavior. Some tumor have cells that are intermediate or large in size as in tumor of the same name which occur in the lung, esophagus and other sites.
    • IHC: +positive for neuron-specific enolase (NSE), synaptophysin and chromogranin.
  • Squamous cell carcinoma (SCC): Pure form is extremely rare in the endometrium. An extension from cervical carcinoma has to be excluded. Occurs in the elderly patients with pyometra on a pre-existing squamous metaplasia.37
Giant cell carcinoma, endometrial carcinoma with trophoblastic differentiation, oxyphil cell carcinoma and a true mesonephric carcinoma are some of the other rare tumor seen in the endometrium.
The Cancer Genome Atlas (TCGA) Research Network published an integrated genomic characterization of endometrial carcinoma based on genomic data from array and sequencing based technologies. Four groups were outlined:
  • Copy number—high (frequently involving mutations of TP53); this group includes the vast majority of serous carcinomas and 25% of high grade endometrioid tumors
  • Copy number—low (frequently involving mutations of PTEN, PIK3CA, ARID1A and KRAS); this group is mostly composed of low grade endometrioid carcinomas
  • Microsatellite instability hypermutated (frequently involving alterations of mismatch repair protein genes)
  • Polymerase e (POLE) ultramutated; this group is mostly composed of endometrioid cancers; appear to have a better prognosis and favourable outcome than others.
Note: ER+/PR+/HER2- and ER-/PR-/HER2+ group of tumors exhibit exceptionally benign and aggressive behaviour, respectively.
Endometrial Stromal Tumors
  • Occur in middle-aged women and present with vaginal bleeding.
  • May present as polypoidal/masses/worm-like extensions into the myometrium.
  • Composed microscopically of stromal cells resembling normal endometrial stroma.
  • Reticulin stain: Reticulin fibers envelope individual cells as well as spiral arterioles. Blood vessels within the neoplasm are plenty and stand out prominently.
  • Foci of hyalinization and scattered cells with abundant eosinophilic cytoplasm may be observed.
  • A few glandular elements may be seen and endometrial granulocytes are prominent.
  • Stromal cells are +ve for vimentin and CD10 and –ve for h-caldesmon in contrast to smooth muscle tumor. They are also –ve for inhibin in contrast to granulosa cell tumor.
  • Tumors are divided into a benign category (endometrial stromal nodules with pushing margins or stromatosis with mildly infiltrative margins); and a malignant category (low grade) characterized by infiltration into myometrium with a tendency to permeate lymphatics (endolymphatic stromal myosis); increased mitoses and tendency for invasion into broad ligament, tubes and ovaries. Repeated recurrences and occasional metastasis have been reported.
    • Higher grade endometrial stromal sarcomas are defined by a high mitotic index, and have a high mortality rate. Evans subdivided this group into tumor which closely resembled endometrial stroma morphologically and those which were anaplastic or pleomorphic. These latter were called “undifferentiated” and are believed to be unrelated to low grade tumor and more closer to carcinosarcoma group of neoplasms.
  • Variants: Combined smooth muscle-stromal tumor: If an endometrial stromal sarcoma contains more then one third of the tumor to be of smooth muscle component. Behavior wise they behave as stromal tumor. The smooth muscle component shows a “star-burst” appearance of the collagen within it.
    • Differential diagnosis: Between a stromal sarcoma and leiomyosarcoma (Table 1.11).
Table 1.11   Differences between endometrial stromal sarcoma and leiomyoma
Endometrial stromal sarcoma
Gross: Multinodular and worm like
Localized to one area with irregular infiltrating margins
Spiral arterioles well brought out by reticulin stain
Large vesels: Absent
CD 10 +ve
Endometrial granulocytes +ve
h-caldesmon –ve
Desmin –ve
The most common tumor of the female genital tract, occurs in 20–25% of all women.
Gross: Characteristically multiple round well-circumscribed tumor varying in diameter from 5 mm to 20 cm or more.
  • On section have a white whorled appearance, and may show cystic change, hyaline change or focal necrosis. Myxoid change or hydropic degeneration may also be seen.
  • On occasion, a pedunculated leiomyoma may receive a portion of its blood supply from another vascular bed and become independent of the uterus—“parasitic leiomyoma”.
  • Microscopy: Complex interlacing fascicles of smooth muscles showing little or no mitotic activity. Mitoses is considered the most important feature in predicting malignant behavior.
  • Leiomyomas with 4 or less mitotes per 10 consecutive high-power fields (HPF) are considered benign.
  • Leiomyomas with 10 or more mitotes per 10 consecutive HPF are considered malignant.
  • Leiomyomas with 5–9 mitotes per 10 consecutive HPF are considered as STUMP, i.e. smooth muscle tumor of uncertain malignant potential.
  • Mitotic activity should be assessed in the most mitotically active part of the tumor and per se should not be taken as the sole criteria—coagulative necrosis and cytologic atypia are considered significant predictors of clinical aggression.
  • Cellular leiomyoma: Unusually hypercellular but otherwise unremarkable, behave like typical leiomyomas.
  • Hemorrhagic cellular leiomyoma: Apoplectic leiomyoma is a distinctive tumor that occurs in women taking oral contraceptives or who are pregnant or recently given birth. Histologically the tumor consist of circumscribed cellular proliferations of oval to spindle- shaped smooth muscle cells with central hemorrhage and edema. Cellularity is more marked around the area of hemorrhage.
  • Lipoleiomyomas: Tumors with an adipose tissue component.
  • Bizzare leiomyoma (symplastic leiomyoma): Tumors with bizarre shaped or multilobated and hyperchromatic nuclei, but absence of mitotic activity and necrosis. These changes are focal and may be associated with hormone administration—are of no clinical significance.
  • Epithelioid leiomyoma: Composed of cells which are round or polygonal (leiomyoblastoma); a second variant exists with “signet ring” type of cells with a clear or vacuolated cytoplasm. These tumor may recur but rarely metastasize. Features which correlate with aggressive behavior are—necrosis, infiltrative margins, diameter >60 mm and mitotic activity.
  • Schwannoma like leiomyoma: Histologically resemble schwannomas with palisading of nuclei and alternating Antoni A and B type patterns.
  • Mitotically active leiomyoma: Typical leiomyoma with increased mitoses (no abnormal forms) up to 15 mitoses/10 consecutive HPFS, no atypia seen.
  • Benign metastasizing leiomyoma: It is the name given to a uterine tumor with typical features of a leiomyoma without evidence of coagulative necrosis, increased mitotic activity and significant atypia accompanied by nodules in the lung, regional lymph nodes and other sites. The interval between hysterectomy for the tumor and appearance of nodules is about 15 years. Clinical course is indolent.
Present in up to 0.7% of hysterectomy specimens.
  • Grossly resemble leiomyomas but may show poor circumscription, hemorrhage and necrosis. The usual leiomyosarcoma is large (>5 cm) with interlacing fascicles of spindle shaped cells with blunt nuclear ends, easily recognized as malignant due to its pleomorphism and mitotic counts in the range of 15–30/10 HPF with areas of coagulative necrosis. At times these malignant features may not be frankly evident, then a leiomyosarcoma diagnosis is made on the following criteria:
    • > 10 mitoses/10 HPS; significant atypia, focal or diffuse in the presence of necrosis.
    • > 10 mitoses/10 HPS; significant atypia-diffuse, with or without necrosis,
    • Mitoses ≤ 10 mitoses/10 HPF; significant atypia either focal or diffuse; in the presence of necrosis.
A diagnosis of smooth muscle tumor of undetermined potential (STUMP) is made when:
  • Mitoses > 10 mitoses/10 HPF; significant atypia—focal; absence of necrosis
  • Mitoses ≤ 10 mitoses/10 HPF; significant atypia—diffuse39
  • Mitoses ≤ 10 mitoses/10 HPF; no atypia or only mild atypia in the presence of necrosis.
All mitotic counts should be done in consecutive fields in the most mitotically active portions of the neoplasm.
Malignant Mixed Müllerian Tumor
Seen in postmenopausal patients.
  • Presents with uterine bleeding and enlargement.
  • Gross: Mass usually located at the posterior wall near the fundus, they are more fleshy in appearance as compared to carcinomas.
  • Microscopy: Biphasic pattern with carcinoma co-existing with a malignant mesenchymal component. The former being of the glandular type (endometrioid) or clear cell type or serous papillary type. Squamous or undifferentiated type of carcinoma may also be seen. The latter may include endometrial stroma, smooth muscle (leiomyosarcoma), rhabdomyosarcoma, liposarcoma as well as chondrosarcoma or even osteosarcoma.
    • Both epithelial and stromal elements are derived from the same stem cell (metaplastic tumors).
    • Traditionally these were divided into homologous or heterologous type.
    • Based upon whether the sarcomatous element was intrinsic to the uterus (stromal or leiomyomatous) or extrinsic (rhabdo or chondro, etc.) respectively.
    • Prognosis is now considered to be the same for both, i.e. poor.
  • An ovarian follicle passes through primordial and mature stages. In the latter stage a follicle has a primary, secondary and tertiary stage, then becomes a graafian follicle, later undergoes atresia.
    • Single cysts can be follicular cysts or corpus luteum cysts.
      Size should be > 2.5 cm for it to be called a true cyst, else it is a cystic change in either a follicle or corpus luteum. Follicular cyst develops due to distension of an atretic follicle. It is lined by follicular cells. Does not exceed 10 cm in size. Corpus luteum cysts are single, <6 cm in diameter and are lined by theca lutein cells. Twisting of the pedicle can lead to torsion.
    • Solitary luteinized follicular cyst, a rare cyst, can measure up to 25 cm and is a rare finding in pregnancy and puerperium.
    • Multiple luteinized follicular cysts (theca-lutein cysts; hyperreactio luteinalis) seen in twin pregnancies, hydatidiform mole and choriocarcinoma.
    • Polycystic (sclerocystic ovaries) multiple follicular cysts or cystic follicles of varying sizes seen in Stein-Leventhal syndrome.
    • Endometriotic cyst, lined by columnar cells similar to the endometrial mucosal lining. The criteria to diagnose endometriosis of the ovary is to find two of the three following findings: (a) columnar glandular lining; (b) endometrial stroma; (c) hemosiderin laden macrophages. Many times the lining is shed off and the remains of these cysts are seen as hemorrhage with hemosiderin-laden macrophages.
    • Dermoid cyst lined with stratified squamous epithelium and is filled with sebum like pultaceous material. Microscopy shows derivatives from all layers—ectoderm, mesoderm and endoderm.
Chronic Salpingo-oophoritis
Nonspecific chronic salpingitis over a prolonged period of time results in adhesion formation between the Fallopian tube and ovary resulting in a tubo-ovarian mass. If this is accompanied by hydrosalpinx as a result of adhesions and obstruction, then the mass takes on a partly cystic appearance with the cut section showing multiloculations. Fibrous thickening of the walls occurs and finally results in bilateral tubo-ovarian masses, a not uncommon finding in surgical practice. The remnants of the ovarian stroma may show a few cystic follicles. The entire mass may be plastered onto the side of the uterus. Microscopy shows atrophy of the tubal plicae with dilatation of the lumen and chronic inflammatory cell infiltrate of the lamina propria of the tubal mucosa with ulceration depending on how severe the inflammation is. Adjacent oophoritis accompanies this.
The inflammation may be granulomatous in nature particularly if associated with tuberculosis of the endometrium.40
Stromal Hyperplasia
  • Abnormal proliferation of the ovarian stroma without the additional presence of lutein cells.
    • May be associated with steroid hormone production
    • Usually associated with androgenic manifestations as well as obesity, hypertension and disorders of glucose metabolism. Estrogenic changes when present may result from peripheral conversion of androstenedione to estrone.
    • Stromal hyperthecosis: Proliferation of ovarian stroma with lutein cells scattered singly and in small nests throughout.
  • Grossly: Ovaries are enlarged up to 7 cm in greatest dimension; replaced by solid white to yellow stroma, sometimes simulating bilateral solid tumor. A few follicular cysts may be seen at the periphery particularly in premenopausal women.
  • Microscopically: Stromal hyperplasia and presence of lutein cells which contain varying amounts of lipid in their cytoplasm and in premenopausal women the typical sclerosis of the outer cortex and follicular hyperthecosis characteristic of Polycystic Ovarian Disease, is observed.
    • Nodular hyperthecosis may also be seen which may be bilateral, associated with virilization, obesity hypertension and decreased glucose tolerance. May be associated with endometrial hyperplasia and carcinoma.
  • Polycystic ovarian disease: It is an important cause of an ovulatory infertility. A defect is seen in insulin metabolism; with peripheral insulin resistance in adipose tissue and skeletal muscle. This in turn leads to hyperinsulinemia, though ovaries remain sensitive to insulin. The insulin, insulin like growth factor-1 and luteinizing hormone cause thecal cell hyperplasia with increase in circulating levels of androgens, estrogens and arrest of follicular development.
    • Gross: Ovaries are enlarged, rounded with multiple small follicle cysts beneath their surface, occasionally they are of normal size. The superficial cortex is glistening and white giving the appearance of a true capsule. Cut surface shows multiple cysts of approximate equal size typically situated beneath the superficial cortex.
    • Microscopy: The central portion of the ovary consists of homogeneous stroma with rare or no evidence of corpora lutea/albicantia, follicular cysts or cystic follicles are lined by follicular cells, associated stromal hyperplasia and hyperthecosis may be seen.
Surface Epithelial-stromal Tumors
Serous Tumors
  • Benign (cystadenoma, cystadenofibroma)
  • Borderline tumors (serous borderline tumor)
  • Malignant (low and high grade serous adenocarcinoma).
Mucinous Tumors, Endocervical-like and Intestinal Type
  • Benign (cystadenoma, cystadenofibroma)
  • Borderline tumors (mucinous borderline tumor)
  • Malignant (mucinous adenocarcinoma).
Endometrioid Tumors
  • Benign (cystadenoma, cystadenofibroma)
  • Borderline tumors (endometrioid borderline tumor)
  • Malignant (endometrioid adenocarcinoma).
Clear Cell Tumors
  • Benign
  • Borderline tumors
  • Malignant (clear cell adenocarcinoma).
Transitional Cell Tumors
  • Benign Brenner tumor
  • Brenner tumor of borderline malignancy
  • Malignant Brenner tumor
  • Transitional cell carcinoma (non-Brenner type).
  • Adenosarcoma
  • Carcinosarcoma (malignant mixed Müllerian tumor).
Sex Cord-stromal Tumors
  • Granulosa tumors
  • Fibromas
  • Thecomas
  • Fibrothecomas41
  • Sertoli-Leydig cell tumors
  • Sex cord tumor with annular tubules
  • Gynandroblastoma
  • Steroid (lipid) cell tumors.
Germ Cell Tumors
  • Teratoma
    • Immature
    • Mature
    • Solid
    • Cystic (dermoid cyst).
  • Monodermal (e.g., struma ovarii, carcinoid)
  • Dysgerminoma
  • Yolk sac tumor (endodermal sinus tumor)
  • Mixed germ cell tumors.
Malignant, Not otherwise Specified
Metastatic cancer from nonovarian primary:
  • Colonic, appendiceal
  • Gastric
  • Breast
  • Pancreatobiliary.
Surface Epithelial Tumors
Müllerian ducts are the progenitor of the tubal, endometrial, and endocervical mucosa. The celomic epithelium is related to this embryologically, infact the entire pelvic and lower abdominal mesothelium and subjacent mesenchyme are referred to as the secondary Müllerian system.
The surface epithelium of the ovary in metaplasia/neoplasia undergoes a Müllerian differentiation and therefore result in any adult structure formed by the Mullerian ducts, i.e. tubal, endometrial and endocervical mucosa. Most surface epithelial neoplasms of the ovary arise from invaginated surface epithelial glands and cysts with subsequent differentiation towards any of the structures mentioned above. The cell type may be serous (tubal type epithelium), mucinous (endocervical epithelium), endometrioid (endometrium like) or transitional type (Brenner tumor). Therefore, epithelial/stromal tumors of the ovary and neoplasms of the endocervix, endometrium and Fallopian tube form a single histogenetic group.13
The pattern of growth may be cystic, solid, on the surface, or invasive. This is also related to whether the tumor is totally benign, of borderline malignant potential or malignant. The tumor are classified based on the epithelium, pattern of growth and behavior. Surface epithelial tumor are the most common type of ovarian tumor. Can be associated with breast carcinoma with mutations of BRCA1 and BRCA2 genes.
Serous Tumors
Incidence and salient clinical features:
  • Constitute 1/4th of all ovarian tumor.
  • Occur in the adults and 30–50% are bilateral.
Gross: Cystic masses, usually unilocular, containing clear sometimes viscous fluid.
  • Papillary formations are seen, most protrude into the cavity, occasionally occur on the outer surface
  • Malignant tumor are solid and invasive with necrosis and hemorrhage.
Microscopy: Cuboidal to columnar cells line the wall of the cysts as well as cover papillae in the better differentiated tumor. The epithelium is similar to the tubal epithelium (Fig. 1.46).
  • 30% of cases show presence of psammoma bodies
  • With prominent stroma and benign glandular elements a tumor is termed adenofibroma, with cystic change cystadenofibroma, with carcinomatous change cystadenocarcinoma.
  • Papillary fronds: Inside cavity-papillary serous cystadenoma, on the surface serous surface papillary tumor, with carcinomatous change serous surface papillary adenocarcinoma. The latter tumor is usually bilateral.
    zoom view
    Figure 1.46: Serous cystadenoma lined by tubal type ciliated columnar epithelium. H & E x400
  • Serous carcinomas: Serous adenocarcinomas, serous papillary adenocarcinomas, serous papillary cystadenocarcinomas, surface papillary adenocarcinomas—all show nuclear atypia, high mitotic activity, stratification and glandular complexity with branching papillary fronds and stromal invasion.
  • Borderline tumors: Branching papillae (hierarchical branching) focally covered by stratified epithelium with mild to moderate atypia with few mitoses have no stromal invasion. They are also called intermediate, indeterminate and tumor of low malignant potential.
  • Microinvasive: Serous tumors with individual cells or clusters of cells with abundant eosinophilic cytoplasm (eosinophilic metaplastic cells) or less commonly small confluent nests with a cribriform pattern seen in the subepithelium stroma to a depth of <3 mm. The prognosis is the same as noninvasive borderline tumor.
  • Micropapillary serous carcinoma: It shows a filigree pattern of highly complex micropapillae arising from large bulbous papillary structures. The micropapillae are covered by round to cuboidal cells with a high nucleo-cytoplasmic ratio. Prognosis is between borderline and frankly malignant.
IHC: CK 7+ve, CK 20-ve, CK 8, CK18, CK19, EMA, B72.3+ve; WT 1 diffuse +tivity; (negative in mucinous tumor and in serous papillary tumor of the endometrium; and +ve to a lesser extent in endometrioid tumor); CA125, SMO 47, MUC 5AC, BER-EP4 +ve. 50% of them are ER and PR +ve. They are also vimentin, S-100, β hCG, glycodelin, osteopontin, fibulin -1 and GLUT 1 +ve;, N-cadherin –ve; CEA -ve.
Differential diagnosis: Primary serous carcinomas of the ovary must be distinguished from secondary involvement by serous carcinoma of the endometrium. Prominent involvement of the ovarian lymphatics, surface ovarian involvement suggests that the tumor may be secondary in the ovary. Serous tumor of the endometrium are WT-1 negative as compared to primary serous tumor of the ovary which are WT-1 +ve.
Epithelial Papillary Processes on Peritoneal Surfaces
Could be either:
  • Peritoneal implants from borderline serous ovarian tumors
  • Extraovarian (peritoneal) papillary serous carcinomas
  • Conventional peritoneal mesotheliomas
  • Endosalpingiosis
  • Papillary mesothelial hyperplasia.
Peritoneal implants from borderline serous ovarian tumors: Occur in 15–59% of cases of borderline tumor. More often with an exophytic component of growth. Implants are of two types—(a) Invasive implants: Occur in 12% of cases. Associated with irregular infiltration and destruction of tissue. Resemble grade 1 serous carcinoma morphologically. Invasive implants may be associated with progressive disease. Psammoma bodies are less numerous as compared to the conventional papillary carcinoma and the atypia is mild to moderate. (b) Non- invasive implants are either epithelial or desmoplastic. In the former papillary proliferation of serous cells are present on the surface of the peritoneum with invaginations beneath the epithelial surface or between lobules of fat. Desmoplastic noninvasive implants show reactive stroma and are layered onto the peritoneal surface with granulation tissue, the cells being entrapped in scar tissue. Cells are irregularly arranged with abundant acidophilic cytoplasm.
Extraovarian (peritoneal) papillary serous carcinomas and conventional peritoneal mesotheliomas: Nodules with morphology similar to serous carcinoma but with no ovarian involvement. These are closer to ovarian serous tumor than to conventional peritoneal mesotheliomas. The issue is wrought with confusion because mesothelium in the abdomen has the added potential to differentiate along Müllerian lines; (in the thorax however the two, i.e. mesothelium and endodermal derived lung tissue are different). Primary peritoneal serous carcinomas (PPSC) and ovarian serous carcinomas are morphologically identical, management of both tumor is the same. However, serous carcinomas, i.e. ovarian and extra-ovarian are B72.3, EMA, Ber Ep4, and PLAP +ve whereas conventional peritoneal mesotheliomas are CK 5/6, calretinen and thrombomodulin +ve. WT 1 is +ve in both. Mesotheliomas are B72.3, BER-EP4 and EMA negative. Also a point to remember in the differential diagnosis is that primary ovarian tumor may be positive for ER and PR; whereas extra-ovarian are not.
Endosalpingiosis: Presence beneath the abdominal peritoneum of cuboidal to low columnar cells which are sometimes ciliated resembling Fallopian tube mucosa. 43Result from Mullerian differentiation/metaplasia of the celomic epithelium. May occur with borderline ovarian serous tumor or in their absence. Should be differentiated from them. Ovarian carcinomas express CEA, EMA and Ki-67 as compared to benign lesions.
Papilllary mesothelial hyperplasia: An innocuous proliferation of an irritated mesothelium in papillary morphology due to various causes.
Mucinous Tumors (Fig. 1.47)
  • Incidence and salient clinical features:
    • Less common than serous tumor.
    • 10–20% are bilateral.
    • Cases associated with Zollinger–Ellison syndrome have been described.
      (intestinal type of borderline tumor)
  • Gross: Larger than serous tumor, partially or completely cystic, often multiloculated.
    • Lumen is filled with mucus.
    • Microscopy: The epithelium in mucinous tumor of two types. Benign neoplasms are lined by endocervical epithelium lined by Müllerian origin: Most tumors of borderline malignancy and carcinomas show a gastrointestinal type of epithelium the histogenesis of which may be two fold—an overgrowth of gastrointestinal component from a teratogenous origin (monodermal teratoma) or metaplastic surface epithelium from Müllerian origin.
      zoom view
      Figure 1.47: Mucinous cystadenoma ovary with locules of cysts lined by columnar mucin secreting benign epithelium. H & E x 100
  • Three types—benign, borderline and malignant:
  • Benign: Cysts are lined by a single layer of tall columnar mucus secreting epithelium with basal nuclei (endocervical type epithelium).
  • Borderline tumor: Criteria for diagnosis: stratification with 2–3 cell thickness; are of two types:
    1. Intestinal type: Epithelium with a picket fence appearance—goblet cells, Paneth cells and endocervical cells. Mucin is of gastrointestinal and pancreaticobiliary type. The endocrine cells seen are argyrophilic and rarely argentaffinic. Gastrin secreting and ACTH secreting tumor are known to occur. Tumor are associated with carcinoid tumor of the ovary.
    2. Endocervical or Müllerian type: Characterized by tall non-ciliated cells with basally located nuclei and abundant intracellular mucin.
  • Associated with endometrial carcinoma and endometriosis.
    • Mixed types may be seen.
  • Malignant: Characterized by cellular atypia, increased layering of cells, greater complexity of glands and papillae, budding, bridging and appearance of solid foci. There is stromal invasion. According to Hart and Norris, if invasion is uncertain, the tumor is classed as borderline when the atypical epithelium is <4 cells thick (i.e. 2–3 cell in thickness) and as carcinoma if the epithelium is > 4 cell thick or greater.
  • If stroma is prominent the tumor is called mucinous adenofibroma (with benign epithelium) and cystadenofibroma with cystic change; cystadenofibrocarcinoma with malignant change.
  • IHC: Mucinous tumor are CK 7 +ve (strong +tivity), 50% of cases are focally +ve for CK20, WT-1 –ve and CEA +ve (particularly intestinal type). They are MUC 5 AC, DPC 4, and N-cadherin +ve. Keratin, EMA, and CA 125 +ve particularly in malignant tumor.
  • Colorectal carcinomas metastatic to the ovary are diffusely and strongly +ve for CK 20 and CK 7 –ve as well as CA125 -ve. Colorectal tumor are however also +ve for CEA.
  • Spread: Implants occur on the bowel, abdominal wall and urinary bladder. Extensive implants can occur in the abdomen with a giant cell response to the presence of mucus resulting in pseudomyxoma peritonei; although tumor arising from the appendix are the main etiologic cause for this.44
Endometrioid Tumors
Incidence and salient clinical features:
  • Origin: From pre-existing endometriosis or endometriotic metaplasia from Müllerian epithelium.
    • 10–25% of all primary ovarian carcinomas.
    • Co-exist with endometriosis in 10–20% of cases. May arise from endometriotic cysts.
    • Some are associated with endometrial hyperplasia and/or synchronous endometrial adenocarcinoma.
  • Gross: Solid or cystic, contents are hemorrhagic.
  • Microscopy: Resembles the ordinary/conventional endometriotic adenocarcinoma.
    • Most are well differentiated with or without papillary structures
    • 50% have foci of squamous metaplasia which may results in squamous cell carcinoma
    • Psammoma bodies are rare
    • 10% of tumor have non-neoplastic luteinized stromal cells
    • IHC: Endometroid carcinomas are vimentin +ve, CK 7 and 20 +ve, EMA +ve, CEA –ve, CA 19 +ve, human placental lactogen +ve and -ve for N-cadherins.
    • Three morphological forms exist—benign- endometriotic cysts may in essence be benign endometriotic tumors, atypical proliferating (equivalent to atypical endometrial hyperplasia) and borderline types (equivalent to well differentiated endometrial adenocarcinoma without invasion); and invasive types.
  • Prognosis: Twice as good as serous/mucinous carcinomas.
Clear Cell (Mesophroid) Carcinomas (CCC)
Incidence and salient clinical features:
  • 5% of all ovarian cancers, occur between 40 and 70 years of age.
  • Arise from remnants of Müllerian epithelium and not from mesonephric duct. Often mixed with endometrioid ovarian carcinoma.
  • Gross: Spongy often cystic appearance, may present as a unilocular cyst with a solid nodule protruding into it.
  • Microscopy: Tubular, cystic, papillary as well as solid sheet like pattern
    • Cores of papillae show hyalinization,
    • Stroma rich tumor are called clear cell adenocarcinofibroma, cystadenocarcinofibroma
    • Cells are large, some of the nuclei protrude into the lumen resulting in a hobnail configuration.
    • Cytoplasm is clear and contains glycogen, mucin and fat and shows PAS +ve diastase resistant hyaline globules which are negative for alpha-fetoprotein
      • IHC CK7, CK5/6, CAM 5.2, 34βE12, EMA, CEA, CD15, BerEp4, vimentin, bcl 2, p53 and CA 125 +ve. They are negative for CK20. The latter differentiates them from colorectal tumor which are CK 20+ve and CK 7-ve. Rare cases of metastatic clear cell carcinomas of the ovary are CD10+ve and clear cell steroid tumor of the ovary is alpha-inhibin positive.
      • Variable +vity for ER and PR, HER-2 new and alpha-fetoprotein (not in the hyaline globules).
    • Differential diagnosis: Dysgerminoma, Yolk sac tumor, metastasis from renal cell carcinoma.
Brenner Tumor and Transitional Cell Carcinoma
  • Incidence and salient clinical features:
    • 1–2% of all ovarian tumor. Seventy percent of cases occur in patients above 40 years of age. Associated with hyperestrenism; uterine bleeding from endometrial hyperplasia in postmenopausal women.
  • Gross: Unilateral firm white or yellowish white. Resemble fibromas and thecomas except for small cystic areas with yellowish brown fluid.
  • Microscopy: Solid and cystic nests of transitional epithelium surrounded by dense stroma fibroblastic in nature.
    • Nuclei of epithelial cells show longitudinal grooves similar to granulosa cell tumor.
    • Mucus cell metaplasia may be seen.
    • Proliferating Brenner tumor: Papillary hyperplasia with nuclear atypia; now considered to be borderline.
    • Borderline or low malignant potential Brenner: Greater degree of atypia but no stromal invasion.
    • Malignant Brenner tumor: With stromal invasion. May be associated with transitional cell carcinoma of the urinary bladder.
    • IHC: Brenner tumor are CK 7 and 20 +ve, EMA and CEA, CA125 +ve (malignant variants). They are also chromogranin and 5 HT +ve.
    • The occurrence of a primary transitional cell carcinoma of the ovary has also been postulated. This responds better to chemotherapy and is not associated histologically with features that characterize Brenner tumor, i.e. cysts lined with columnar to transitional epithelium.
Germ Cell Tumors
  • Constitute 20% of all ovarian tumor:
    • Most occur in children and young adults
    • 95% are benign cystic teratomas, the younger the patient the more the chances of malignancy
    • Combinations occur which are known as mixed grem cell tumor.
  • Incidence and salient clinical features:
    • Constitute <1% of all ovarian tumor and 5% of malignant ones
    • Most cases occur in patients <3 years of age
    • Bilateral in 15% of cases.
  • Gross: Solid ovarian tumor
    • Cut surface is solid and gray
  • Microscopy: Sheets and well-defined nests separated by fibrous strands infiltrated by lymphocytes (T-cells)
    • A pseudotubular/cord like arrangement may be seen at the periphery
    • Granulomatous foci are observed in the stroma
    • Individual cells are uniform, have large nuclei with one or more prominent elongated nucleoli and abundant clear to finely granular cytoplasm
    • Cytoplasm is rich in glycogen and the cell membrane is prominent
    • Differentiation towards other germ cell elements may be seen:
      • Scattered hCG +ve cells are noted due to syncytiotrophoblastic cells in 3% of dysgerminoma. These may have associated increased levels of serum hCG.
      • Early carcinomatous differentiation with increased mitoses of >30/HPF may also be observed, i.e. anaplastic dysgerminoma. This shows increased keratin +vity.
      • Yolk sac elements: Serum levels of alpha-fetoprotein with tissue reactivity for this marker.
      • This focal differentiation should be differentiated from mixed germ cell tumor (tumor with choriocarcinoma, embryonal carcinoma and yolk sac tumor) which is seen in 10% of dysgerminomas. Mixed germ cell tumor alter the prognosis significantly. The survival rates of pure dysgerminomas are 95%.
  • IHC: Dysgerminomas are Vimentin, Placental Alkaline Phosphatase (PLAP) +ve, CD 117 +ve, CK (erratically and focally) +ve; sometimes +ve for GFAP and desmin; trophoblastic beta hCG +/-ve.
Yolk Sac Tumors
  • Incidence and salient clinical features: Constitute 20% of all germ cell tumors.
    • Neoplasm of children and young adults. Rare above 40 years. Median age 19 years.
    • Serum alpha-fetoprotein levels are increased but hCG is normal.
  • Gross: Average diameter is 15 cm. Has a smooth external surface. C/S is variegated with yellow grey tissue, partially cystic with large areas of hemorrhage and necrosis.
  • Microscopy: The most common pattern is the reticular pattern with microcystic areas formed by a loose meshwork lined by flattened to cuboidal clear cells with glycogen.
    • Rounded or festooning pseudopapillary processes with central blood vessels covered by columnar epithelium are seen. These in turn lie in spaces lined by flattened cells: are called the Schiller-Duval bodies. Schiller-Duval bodies are seen in 75% of tumor.
    • Solid undifferentiated areas may be noted.
    • Intracytoplasmic and extracellular PAS +ve hyaline droplets are always present which stain for alpha-fetoprotein.
    • Polyvesicular vitelline pattern: Less common Vesicular patterns with central constrictions separated by dense spindle celled stroma dividing the vesicle into a small and large compartment. The large compartment is lined by flat cells and resembles the vestigial portion of the embryonic yolk sac; the smaller compartment is lined by tall epithelium that simulates the forerunner of the primitive gut and its derivatives in the embryo.
    • Other features of differentiation are hepatoid component, intestinal, parietal, yolk sac structures, and endometrial glands. The hepatoid component resembles hepatocellular carcinoma. Parietal differentiation is characterized by small extra cellular accumulations of basement membrane material typically within reticular areas. Intestinal differentiation shows the lining cells containing subnuclear vacuoles or resemble enteric epithelium with argyrophilia, goblet and rarely Paneth cells.46
    • When Schiller-Duval bodies are seen in good numbers then the tumor is termed as “endodermal sinus tumor”—proposed by Teilum who noted that these structures resembled “endodermal sinuses” of rat placenta.
  • IHC: Pan keratin +ve (differentiates it from seminoma), CK 7-ve (in contrast with endometriod and clear cell ovarian carcinomas), focal AFP +ve, focal alpha–1 antitrypsin +ve. WT –ve in contrast to serous ovarian carcinomas, and CD30 focally +ve (diffuse +tivity in embryonal carcinoma).
    • ER/PR negative (as compared to endometroid carcinomas).
  • DD: Clear cell carcinoma. Hyaline bodies are less common in clear cell carcinoma. Yolk sac tumors (YST) is EMA –ve whereas CCC is +ve.
Embryonal Carcinoma (Often Mixed with Nonseminomatous Tumors)
  • Tumor of the young, median age 15 years.
    • 47% of patients present in the prepubertal age and 43% present with precocious puberty.
    • Serum α-fetoprotein are often elevated, chorionic gonadotropins are invariably high resulting in a +ve pregnancy test.
  • Gross: Large tumor average diameter 17 cm, external surface smooth and glistening.
    • C/S predominantly solid and variegated. Extensive necrosis and hemorrahge.
  • Microscopy: Solid sheets and nests of large primitive cells occasionally forming papillae and abortive glandular structures, composed of or lined by large cells with amphophilic or vacuolated cytoplasm. Increased mitotic figures are observed.
    • Syncytiotrophoblast-like cells are frequently seen scattered among smaller cells, +ve for hCG.
    • Enteric glands, embryoid bodies may be seen.
    • Prognosis is better than for yolk sac tumor.
  • IHC: Embryonal carcinomas show diffuse +tivity for CD30 and β hCG in syncytiotrophoblastic cells.
  • It is a variant of germ cell tumor with numerous embryoid bodies mimicking normal embryos. In its classic form, the embryoid body consists of a central plate of a double layered epithelium, on either side of which are spaces or cavities. This plate is an arch or disc lined on one side by primitive tall columnar cells resembling embryonal carcinoma cells (cavity on this side resembles amniotic cavity) and on the other aspect of the disc lined by flattened cells in continuity with a cavity resembling the yolk sac.
    • Some teratomatous differentiation of endodermal type including hepatoid differentiation may be seen.
  • Most of these are metastasis from uterine tumor.
    • Rare ones are gestational due to ovarian pregnancy, or non-gestational as a component of germ cell tumor.
    • May be associated with mature cystic teratoma of the contralateral ovary.
  • Gross: May be solid or cystic.
  • Microcsopy: Typical admixture of syncytial and cytotrophoblastic elements in a necrotic and hemorrhagic background.
  • IHC: Choriocarcinoma is as a rule β hCG +ve, LK26+ve, CK 7+/–.
Immature (Malignant) Teratoma
  • Incidence and salient clinical features:
    • Occurs in children and adolescents
    • Less common in the ovary than mature cystic teratoma. More common in the testis.
    • Prognosis depends on the amount of immature component.
  • Gross: Solid, solid and cystic or chiefly cystic.
  • Microscopy: Composed of mixtures of embryonal and adult tissues derived from all three germ layers. Main component is neuroepithelial, but mesodermal elements are also common.
    • Some may have chiefly endodermal derivatives including esophagus, liver and intestinal structures.
    • Prognosis depends on the nature and amount of immature component. It is best when the immature element is neuroepithelial tissue. Glial fibrillary acidic protein (GFAP) differentiates between mature (+ve) and immature glial tissue.
  • Grading of immature teratoma: Norris and Taylor:
    • Grade I: Abundance of mature tissue intermixed with loose mesenchymal tissue, occasional mitoses, immature cartilage and tooth anlage.
    • Grade II: Fewer mature tissues, rare foci of neuro-epithelium with common mitoses; not exceeding 3 HPF (x40) fields in any one slide.47
    • Grade III: Few or no mature tissues, neuro-epithelial elements merging with a cellular stroma occupying 4 or more HPF (x40) fields.
    • Some authors have suggested combining of grade II and III into one high-grade category.
Mature Cystic Teratoma (Fig. 1.48)
  • Incidence and salient clinical features:
    • 20% of all ovarian neoplasms, most common ovarian tumor in childhood.
    • Gross: Multiloculated, the cystic contents is greasy composed of keratin, sebum and hair.
    • Teeth are often present. They are located in a well- defined nipple like structure covered with hair called the Rokitansky's protuberance. This solid structure shows a variety of tissues.
    • May contain imperfectly formed mandible or even a partial human body like structure, this is called “homunculus” and referred to as fetiform teratomas.
  • Microscopy: Ectodermal derivatives—100% of tumor; mesodermal structures 93%; endodermal derivatives 71%.
    • Cystic cavities lined by mature epidermis, skin appendages and neural tissues are extremely common, followed by cartilage, respiratory tissue and GI tract tissues. The gastric mucosa may develop peptic ulcer!
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      Figure 1.48: Mature cystic teratoma with cyst lining by stratified squamous epithelium with underlying adnexa, cartilage and adipose tissue. H & E x100
    • Thyroid tissue is seen in 10% of cases, melanin containing tissues, anterior pituitary, neuro-endodermal cells, prostate, pancreas and cavernous blood vessels.
    • Chromatin: Female nuclear sex chromatin pattern – 46xx pattern (parthenogenetic origin and arise from a single germ cell after 1st meiotic division).
    • Mature teratomas can co-exist with mucinous cystadenoma, Brenner tumor and fibro-thecoma.
    • Teratomas may rupture into the abdominal cavity provoking a foreign body giant cell response. Such an extensive reaction may look grossly like a carcinoma.
  • Peritoneal implants: Mature cystic teratomas may be accompanied by peritoneal implants, composed exclusively of mature glial tissue, a condition known as gliomatosis peritonei. Implants appear as miliary gray white nodules on the peritoneal surface/omentum and may be accompanied by fibrosis and chronic inflammation.
    • Peritoneal “melanosis” follows the rupture of a cystic teratoma.
    • Malignant change in cystic teratoma: Squamous cell carcinoma, carcinoid tumor, adenocarcinoma, malignant melanoma, Paget's disease, sarcoma of various types, primitive neuroectodermal tumors (PNET) and neuroblastoma can all occur but are rare.
    • Struma ovarii: Dominant growth of thyroid tissue in a teratoma sometimes to the exclusion of other components. Grossly—it is often cystic, Microscopically—thyroid tissue with all changes that can occur including goiter (leading to hyperthyroidism, thyroiditis and carcinoma) is seen.
    • Carcinoid: Occurs as part of a teratoma, or as a primary pure neoplasm arising de novo or as a metastatic neoplasm from elsewhere. Metastatic carcinoids may manifest as carcinoid syndrome and may be bilateral. In 16% of cases of carcinoid tumor the contralateral ovary is involved by a cystic teratoma or a mucinous neoplasm. Grossly—average size is 10 cm, external surface is smooth. C/S solid, firm, tan to yellow and homogeneous. Microscopy—similar to carcinoids elsewhere with either an insular pattern of growth, trabecular or mucinous (goblet cell carcinoid).
    • Strumal carcinoid: Combines features of carcinoid and struma ovarii.48
Mature Solid Teratoma
  • Predominantly solid gross appearance but multiple small cystic areas are also present. “Polycystic” appearance.
    • Adult tissues from all three germ layers are seen.
    • Young women predominantly in the second decade are affected.
    • Peritoneal implants may be seen.
Sex Cord Stromal Tumors
Constitute 5% of all ovarian neoplasms. Tumor differentiate towards sex cord specialized ovarian stroma, i.e. towards female type cells (granulosa and theca cells) and male type cells (Sertoli and Leydig cells). Combinations can occur with patterns produced during embryogenesis of ovary and testis. Hormonal activity accompanies these tumor.
Granulosa Cell Tumors
  • Incidence and salient clinical features:
    • Differentiate towards follicular granulosa cells. They are of 2 types: adult type and juvenile type.
  • Adult granulose cell tumor
    • Seen during the childbearing age but can occur later.
    • Three-fourth of cases show hyperestrinism; in children lead to isosexual precocious puberty and metrorrhagia in the adults. Some are hormonally inactive and others are androgenic.
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      Figure 1.49: Granulosa cell tumor (H&E x400) with nuclear grooves (mimicking coffee beans) and adjacent reticulin stain on the same which shows sparse reticulin surrounding sheets of cells as against a thecoma component where reticulin surrounds individual cells. Reticulin stain x 400
  • Gross: Encapsulated, smooth, lobulated outline.
    • C/S solid gray but may be yellow in luteinized tumors
    • Cysts filled with straw colored mucoid fluid may be present. Cystic change (either uniloculated or multiloculated) may be so prominent that a resemblence to cystadenoma may be observed (androgenic tumor).
  • Microscopy: Microfollicular with Call-Exner bodies; macrofollicular, trabecular, insular, watered silk, solid and diffuse sarcomatoid appearance are seen.
    • Theca cell component may be observed
    • Luteinization of granulosa and theca cells can occur particularly in pregnancy
    • Nuclei show folds/grooves resulting in coffee bean appearance (Fig. 1.49)
    • Bizzare nuclei and multinucleated giant cells are seen
    • IHC: Granulosa cell tumor are vimentin, inhibin, CD99, calretinin, S-100, SMA and desmoplakin +ve, follicle regulatory protein, and A 103 +ve. They are negative for CK7 and EMA. Express CK 8/18 in one third of cases; S-100 is also +ve.
Juvenile Granulosa Cell Tumor
  • Eighty percent of cases occur in the first 2 decades
    • A diffuse or macrofollicular pattern is more common; mucin +ve intrafollicular secretions; extensive luteinization; paucity of nuclear grooves; nuclear 49atypia and a high mitotic activity characterize the neoplasm.
    • Differential diagnosis: Solid carcinoma of the ovary; poorly differentiated carcinoid and transitional cell carcinoma. Nuclear features (absence of grooves) and diffuse keratin positivity in carcinomas differentiates it from granulosa cell tumor.
    • Prognosis: Juvenile granulosa cell tumors behave more aggressively.
Thecoma–Fibroma Group of Tumors (Figs. 1.50A to C)
  • Both are closely related and often mixed.
  • Thecomas: Incidence and salient clinical features: Occur after menopause in 65% of patients, usually unilateral. These tumor are generally estrogenic, luteinized thecomas are androgenic.
    • Gross: They are firm in consistency with a well- defined capsule. C/S is solid but a few cysts may be present. It has a yellow color as compared to fibromas.
    • Microscopically: Fascicles of spindle-shaped cells with centrally-placed nuclei and moderate amount of pale cytoplasm. Intervening collagen is seen with hyaline plaque formation
      • Oil red O theca cells show abundant intracytoplasmic neutral fat.
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        Figures 1.50A to C: Thecoma fibroma group of neoplasm with fibrous component (top left); with vacuolated cells containing fat; some eosinophilic differentiation indicating luteinized cells and reticulin stain with retic fibers surrounding individual cells. H & E x 400 and Reticulin stain x 400
      • Reticulin stain shows reticulin around individual cells as opposed to granulosa cell tumor where reticulin surrounds clusters of cells.
    • May be associated with stromal hyperplasia and transitions between the two are seen.
    • Some associated with steroid hormone secreting cells–lutein cells, i.e. luteinized thecoma.
    • Prognosis: Behave in a benign fashion.
    • IHC: Thecomas are vimentin and inhibin +ve.
  • Fibromas: Incidence and salient clinical features: Common ovarian tumor, usually unilateral and occur after puberty. Can be associated with ascites sometimes in combination with right sided pleural effusion–called as Meig's syndrome. This can be mistaken for malignancy (mechanism for the effusion is intrathoracic negative pressure with trans-diaphragmatic passage of fluid through peritoneal pores or lymphatics-other ovarian tumor can also give rise to this syndrome).
    • Gross: Solid, lobulated, firm and white with an average diameter of 6 cm. Sometimes myxoid change is seen. Gross appearances are similar to thecomas, Brenner tumors and Krukenberg tumor.
    • Microscopically: Closely packed spindle celled stroma arranged in a storiform pattern. Hyalinization and edema are noted.
    • If mitotic activity exceeds > 3/10 HPF then it is regarded as fibrosarcoma.
    • Prognosis: Benign; can recur.
    • Differential diagnosis: Sclerosing stromal tumors (benign ovarian neoplasm with many features of the fibro-thecoma group; occurs in younger age and differentiation towards smooth muscle is seen).
Sertoli-Leydig Cell Tumors (Older Names are Androblastomas, Arrhenoblastomas)
  • Threse are tumors composed of mixtures of cells which morphologically resemble male Sertoli and Leydig cells.
  • Incidence and salient clinical features: Uncommon tumor less than 0.1%. Seen in young patients. Bilateral in 2% of cases. Can occur in combination with mature cystic teratomas. 50% of cases show signs of androgen excess, i.e. defeminization (amenorrhea, breast atrophy, loss of subcutaneous tissue deposits) followed by masculinization (i.e. clitoral hypertrophy, deepening of voice, hirsutism). Symptoms regress after excision of tumor (Fig. 1.51).
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    Figure 1.51: Section shows a poorly differentiated Sertoli-Leydig cell tumor. Note the palisading/regimented appearance of the stroma which is unlike the stroma of a true sarcoma. H & E x400
  • Gross: Solid or cystic.
  • Microscopically: Variable:
    • Meyer's type I: Well-differentiated with Sertoli cell lined tubules and Leydig like cells.
    • Meyer's type II: Intermediate type: cords, sheets and aggregates of Sertoli like cells, separated by spindle celled stroma and recognizable Leydig cells.
    • Meyer's type III: Poorly differentiated: sarcomatoid, undifferentiated–masses of spindle-shaped cells.
    • Pure Sertoli cell tumor (tubular androblastoma, only Sertoli cell lined tubules), rich in lipid.
    • With heterologous elements (teratoid androblastomas) i.e. associated with tissues such as mucinous epithelium of gastrointestinal (GI) type, liver, skeletal muscle and cartilage.
    • Retiform: Typical Sertoli-Leydig cell tumor co-exist with formations resembling the rete of testis and ovary. The latter appear as cleft-like spaces lined by low cuboidal cells and blunt papillae with hyalinized and edematous cores.
  • Prognosis: Correlates with stage and degree of differentiation, well-differentiated tumors behave in a benign fashion and those with heterologous elements behave in a malignant fashion.
  • IHC: Sertoli-Leydig cell tumor express estrogen, testosterone, keratin and are negative for EMA and CEA. Stromal component is +ve for inhibin.51
Lipid Cell Tumors
  • Tumors composed of cells with morphologic features indicative of steroid hormone secretion. Characterized by abundant eosinophilic or vacuolated cytoplasm that is +ve for fat stains. Though such cells can be thecal (lutein cells), Leydig (Hilus cells) and adrenal cortical type cells (can be found in the hilus of the ovary and broad ligament); in several instances the exact origin cannot be pin pointed so the broad group “Steroid cell tumor” is preferred.
    • Salient clinical features: Androgenic hormones are produced by these tumor therefore virilizing features; Some with estrogenic and progesterone manifestations. Few meet the criteria for Cushing syndrome.
    • Gross: Unilateral and cut surface shows yellow or yellowish brown nodules separated by fibrous trabeculae.
    • Microscopically: Large rounded or polyhedral cells.
    • Prognosis: Incidence of clinical malignancy in 25% of cases.
    • IHC: Positive for vimentin in 3/4th of cases, 50% are +ve for keratin, actin is +ve in 1/3rd of cases; inhibin +ve, A103+ve, Mart-1 +ve.
Mixture in similar amounts of clearly identifiable granulosa, theca cells and Sertoli-Leydig cell elements. Rare, associated with androgenic, estrogenic or no hormonal effects.
Sex Cord Tumor with Annular Tubules
  • One-third of cases associated with Peutz-Jegher's (P-J) syndrome. Those with P-J syndrome are multifocal, bilateral, small and usually benign. Those without P-J syndrome are large, unilateral and clinically malignant in 22% of cases.
    • Hyperestrinism in 50% of cases.
    • Microscopy: Granulosa cell tumor with a pattern of growth reminiscent of Sertoli cells. The morphologic hallmark is the presence of simple and complex annular tubules containing eosinophilic hyaline bodies often calcified.
    • Differential diagnosis: Gonadoblastoma (has germ cell component).
It is a germ cell–sex cord stromal tumor.
Miscellaneous Tumors
Small cell carcinoma is a rare type of ovarian carcinoma: two types exist—pulmonary type and the small cell hypercalcemic type peculiar to the ovary. Small cell carcinoma–hypercalcemic type is EMA +ve and inhibin negative, pulmonary type is NSE and chromogranin +ve.
  • Inflammation: Of the placenta is called placentalitis or villitis. Inflammation of the fetal membranes is called chorioamnionitis and inflammation of the umbilical cord is called funiculitis.
    • Inflammation occurs as a result of:
      • Ascending infection through the birth canal—this is more common and due to bacteria; derived from a urinary tract infection, sexual intercourse, instrumentation, etc. The amniotic fluid is cloudy and the membranes (chorioamnion) show a polymorphonuclear infiltrate.
      • Hematogenous route is an uncommon bacterial infection of the placenta. Here the villi are affected more at histology as compared to the membranes. TORCH (toxoplasmosis and others); syphilis, tuberculosis and listeriosis should be ruled out as etiologic agents.
  • Toxemia of pregnancy: Results in placental ischemia due to defects in trophoblastic invasion of myometrial blood vessels and abnormal endothelialization.
    • Gross: Placental infarcts though a feature of normal full term placenta are larger and more numerous here.
    • Increased frequency of retroplacental hematomas
    • Microscopy: Increased villous ishemia; prominent syncytial knots; thickening of trophoblastic basement membranes and villous hypovascularity.
    • Fibrinoid necrosis of the entire vessel wall in small decidual arteries and intramural lipid deposition
    • Chronic villitis of unknown etiology—possibility due to fetomaternal immunological reaction.
  • Diabetes: Changes in the placenta and uteroplacental vessels are seen. There is extensive atherosclerosis and fibrinoid deposits in the decidua.52
Neoplastic Lesions
  • Hydatidiform mole: Patient presents in the 4th or 5th month of pregnancy with bleeding. In a complete mole, the uterus is disproportionately larger than the period of gestation. Rising levels of hCG are observed and toxemia of pregnancy (hypertension, edema and albuminemia) are frequently found.
    • Grossly: Bunch of grapes with nearly all villi showing swelling and hydropic change. An individual vesicle measures between 1 mm and 30 mm in diameter and the total weight is >200 g. In a hysterectomy specimen these swollen villi are seen to fill and distend the uterus. Characteristically there is no identifiable embryo, cord or amniotic membranes.
    • Microscopy: Vesicular swelling with trophoblastic hyperplasia.
      Table 1.12   Differences between hydropic abortus, complete and partial moles
      Hydropic abortus
      Complete mole
      Partial mole
      Most are Diploid (paternal
      Chromosomes only;
      Androgenic mole; ovum
      looses its chromosomes)
      (maternal and paternal),
      i.e. egg + one diploid sperm
      or 2 haploid sperms
      15–40% of spontaneous abortions
      1 in 2000 pregnancies
      15–35 % of all moles
      +ve; variable; blighted ovum
      Villous swelling not seen
      Nearly all villi are distended and vesicular
      Mixture of distended and normal villi
      Distended villi have irregular scalloped outlines
      Minimal trophoblastic hyperplasia and atypia
      At implantation site
      Marked trophoblastic hyperplasia and atypia at the site of implantation
      Proliferation focal and slight, atypia absent
      Occasional to few distended villi
      Numerous (nearly all)
      Distended + normal
      Polar proliferation of trophoblast
      Circumferential proliferation
      Nearly circumferential, less than in complete mole
      Vascularity of villi evident
      ↓ vascularity
      ↓ vascularity
      Cistern formation
      Cistern formation +ve
      Cistern formation +/-ve
      +ve in cytotrophoblast and
      Villous mesenchyme of normal pregnancy
      ↓ p57
      p57 expressed
      hCG in tissue
      Rarely progress to choriocarcinoma/invasive mole
      -2% lead to choriocarcinoma
      -10% develop into invasive moles
      • Cistern formation: Distended core of villus is traversed by widely separated strands of fibrillar material.
      • Blood vessels absent or scanty.
      • Trophoblastic hyperplasia is circumferential but haphazardly arranged around individual villi as opposed to polar proliferation seen in normal 1st trimester villi.
    • IHC: hCG widely distributed in molar syncytiotrophoblast regardless of gestational age.
    • Prognosis: The more pronounced the trophoblastic proliferation the higher the chance of development of choriocarcinoma (CC) (Table 1.12).53
  • Partial mole: 15–35% of all moles are of the partial type.
  • Gross: Associated with presence of an embryo though this is usually a blighted one.
    • Uterine size is nearly always small or appropriate for the gestational age.
    • Volume of placental tissue is normal and vesicular villi are mixed with normal appearing ones.
    • Microscopy: Shows cistern formation as well as stromal inclusion of trophoblast.
    • Villi have irregular scalloped outline and contain vessels with fetal nucleated red cells. Fibrosis of villous stroma is common.
    • Trophoblastic proliferation ++, though less as compared to a complete mole.
    • Cytoplastic vacuolation of syncytiotrophoblast is prominent.
  • Invasive mole: (Chorioadenoma destruens): Refers to a hydatidiform mole nearly always of the complete type but occasionally also of the partial type, in which the villi penetrate deeply into myometrium or its blood vessels.
    • Occurs in 16% of complete moles; due to the exaggerated capacity of the normal trophoblast for invasion.
    • This may be extensive and lead to persistent hemorrahge, but the serosa is intact.
    • Perforation occurs at times with destructive invasion, vascular invasion may result in trophoblastic nodules occurring elsewhere in the parametrial tissue.
    • Differential diagnosis: Presence of villi favor this as against a choriocarcinoma.
  • Rapidly malignant and extensively metastasizing neoplasm of trophoblastic cells derived from either a normal or abnormal pregnancy.
  • Clinical features: H/O discharge per vagina which is bloody, brown and foul smelling.
  • Titers of hCG are elevated to levels above those encountered in molar pregnancies. Sometimes highly necrotic tumor may be functionally inactive.
    • Occurs in the uterus or extrauterine sites (ectopic gestation)
    • Incidence: 1 in 20,000 to 30,000 pregnancies
    • 50% arise in hydatidiform mole, 25% in previous abortions, 22% in normal pregnancies, up to 3% in ectopic gestations, genital and extragenital teratomas.
    • Gross: Soft fleshy, yellow white tumor with a marked tendency to form large pale areas of ischemic necrosis, foci of cystic softening and extensive hemorrahge.
    • Microscopy: Tumor does not produce chorionic villi, in fact criteria for diagnosis is absence of villi except in very rare cases of gestational choriocarcinoma. Central cores of mononuclear cytotrophoblastic cells are surrounded by rims of multinucleated syncytiotrophoblastic cells. One element may be greatly in excess of the other. Cells resemble normal early placental trophoblast.
    • The nuclei of the cytotrophoblastic cells are large and vesicular with prominent nucleoli which may be multiple. Cytoplasm is generally clear but occasionally granular. The syncytial nuclei may also appear vesicular with prominent nucleoli but are smaller than cytotrophoblastic nuclei. The syncytial cytoplasm is deeply eosinophilic and frequently appears as a lacy network.
    • Trophoblastic cells show anaplasia with abnormal mitoses (confined to cytotrophoblast); it lacks a stromal vasculature. Myometrial invasion is seen by cells penetrating blood vessels, lymphatics and extention out onto the serosa of uterus and adjacent structures is also observed.
    • Hemorrhage, ischemic necrosis and secondary inflammation are noted.
    • IHC: hCG +ve; high Ki-67
    • Sites of metastasis: lungs (50%), vagina (30–40%) followed by brain, liver and kidney.
  • Epitheliod trophoblastic tumor: A form of CC predominantly composed of mononuclear cells. Tumor have a nodular appearance, expansive pattern of growth and composed of a mixture of mononuclear cells with eother eosinophilic or vacuolated to clear cytoplasm. Necrosis and hyaline fibrillar material surround groups of cells which survive around blood vessels. Behavior wise it is similar to placental site trophoblastic tumor (PSTT).
  • Placental site trophoblastic tumor:
    • Intermediate trophoblastic cells compose the placental site trophoblast and residual placental site (implantation site nodule) following pregnancy. This gives rise to the placental site trophoblastic tumor.54
    • PSTT is preceded by normal pregnancy in 50% of cases
    • By spontaneous abortion in 1/6th
    • By hydatidiform mole in 1/5th of cases.
    • β hCG levels are high. About 10% of cases result in disseminated metastasis and death.
    • These comprise <2% of gestational trophoblastic neoplasms and present as localized nodules projecting into the endometrial cavity or ill-defined mass in the myometrium. They are tan to yellow in color with foci of necrosis but not striking hemorrhage.
    • Usually are composed of neoplastic polygonal cells infiltrating the endomyometrium and recapitulates appearances at the normal placental bed. In contrast to the bilaminar pattern of choriocarcinoma, the infiltration is monotonous and resembles the intermediate trophoblast. Major point of differentiation from CC is preservation of intact venous sinuses or capillaries within the tumor masses. Intravascular proliferation too is less obvious. Mitoses is 1–10/10 HPF. It remains localized to the uterus for longer period of time.
    • Distinction from normal exaggerated placental site reaction is difficult.
    • IHC: Abundant hPL in diffuse pattern
      • hCG only focally; PLAL in only occasional cells
      • Ki 67 much higher than in placental site reaction but lower than in choriocarcinoma.
  • Prognosis: 30% mortality in FIGO III and IV at presentation.
Patient Data
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Useful Hints
  1. Margins need not be commented on in punch biopsies
  2. Microinvasive carcinoma: up to 5 mm in depth. Early stromal invasion: invades to a depth of 1 mm or less. Depth of 3 mm is taken by most authors as the upper limit for conservative management.
  3. Microinvasive adenocarcinoma is a possible but difficult diagnosis. Criteria include:
    1. Obvious invasion to 5 mm or less
    2. Usually complete obliteration of the normal endocervical crypts
    3. Extension beyond the normal glandular field
    4. A stromal response characteristic of invasive carcinoma.
  4. Microinvasive carcinoma can only be diagnosed on a cone or large loop excision biopsy specimen in which the lesion is seen in its entirety. N.B. If invasive foci are seen in three or more blocks of tissue, the third dimension of the lesion (which is not routinely measured) may exceed 7 mm (i.e. more than Stage IA2).
  5. The following detail should be recorded for all cases of invasive disease: tumor type, tumor grade, size of the lesion—maximum horizontal dimension, maximum depth of invasion, the presence or absence of lymphovascular invasion and adequacy of excision.
  6. * when all margins are free.
Gross Description
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Pelvic Nodes
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Common Illiac Nodes
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Para-aortic Nodes
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FIGO (International Federation of Gynecology and Obstetrics) Staging for carcinoma of the cervix uteri.
Cervical carcinoma confined to the uterus (extension to the corpus should be disregarded)
Invasive carcinoma, diagnosed only by microscopy with deepest invasion ≤5.0 mm and largest extension 7.0 mm.
Measured stromal invasion ≤ 3.0 mm and ≤ 7.0 mm
Measured stromal invasion of > 3.0 mm and not > 5.0 mm with an extension of > 7.0 mm
Clinically visible lesion limited to the cervix uteri or preclinical cancers greater than stage IA*
Clinically visible lesion ≤4.0 cm in greatest dimension
Clinically visible lesion >4.0 cn in greatest dimension
Cervical carcinoma invades beyond the uterus but not to the pelvic wall or to lower third of the vagina
Without parametrial invasion
Clinically visible lesion ≤4.0 cm in greatest dimension
Clinically visible lesion >4.0 cm in greatest dimension
With obvious parametrial invasion
The tumor extends to the pelvic wall and/or involves lower third of the vagina, and/or causes hydronephrosis or non-functioning kidney**
Tumor involves lower third of vagina, with no extension to the pelvic wall
Extension to the pelvic wall and/or hydronephrosis or non-functioning kidney
The carcinoma has extended beyond the true pelvis or has involved (biopsy proven) the mucosa of the bladder or rectum. A bullous edema, as such, does not permit a case to be allocated to stage IV
Spread of growth to adjacent organs
Spread to distant organs
* All macroscopically visible lesions–even with superficial invasion–are allotted to stage IB carcinomas. Invasion is limited to a measured stromal invasion with a maximal depth of 5.00 mm and a horizontal extension of not > 7.00 mm. Depth of invasion should not be > 5.00 mm taken from the base of the epithelium of the original tissue—superficial or glandular. The depth of invasion should always be reported in mm, even in those cases with “early (minimal) stromal invasion” (~ 1 mm).
The involvement of vascular/lymphatic spaces should not change the stage allotment.
** On rectal examination there is no cancer-free space between the tumor and the pelvic wall. All cases with hydronephrosis or non-functioning kidney are included, unless they are known to be due to another cause.
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Gross Description of Tumor
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Pelvic Nodes
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Common Iliac Nodes
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Para-aortic Nodes
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FIGO Staging for Endometrial Carcinoma
FIGO Stage (2009)
Tumor confined to the uterus, no or < half myometrial invasion
Tumor confined to the uterus, ≥ half myometrial invasion
Tumor involves the uterus and the cervical stroma
Tumor invades serosa or adnexa
Vaginal and/or parametrial involvement
Pelvic lymph node involvement
Para-aortic lymph node involvement, with or without pelvic node involvement
Tumor invasion bladder mucosa and/or bowel mucosa
Distant metastases including abdominal metastases and/or inguinal lymph nodes.
Histological Grading of Endometrioid Type of Adenocarcinoma
  • FIGO grade 1 (5% or less of non-squamous or non- morular solid growth pattern)
  • FIGO grade 2 (6% to 50% of non-squamous type or non-morular solid growth pattern)
  • FIGO grade 3 (> 50% of non-squamous or non-morular solid growth pattern).
Notes on Pathological Grading
  1. Notable nuclear atypia, inappropriate for the architectural grade raises the grade of a grade 1 or grade 2 tumor by 1.
  2. In clear cell adenocarcinoma; serous adenocarcinoma and squamous cell carcinomas nuclear grading takes precedence. The former 2 are considered high grade tumors.
  3. Adenocarcinomas with squamous differentiation are graded according to the nuclear grade of the glandular component, squamous element is ignored.
Rules Related to Staging
  1. Because corpus cancer is now staged surgically, procedures previously used for determination of stages are no longer applicable, such as findings from fractional D and C to differentiate between stage 1 and 2.
  2. Ideally width of the myometrium should be measured along with the width of tumor invasion.
  3. The staging system for uterine corpus carcinoma is used for uterine sarcomas.
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Microscopy: Ovaries
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Note: Borderline tumors should only be diagnosed after rigorous sampling has been done to exclude invasion. A distinction should be made between capsular breach due to surgical procedure and breach due to tumor invasion. Microinvasion in serous, mucinous tumor is < 5 mm from the basement; and in endometrioid tumor is < 5 mm in diameter.
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Note: Mixed tumor are reported if the minor component is > 10% of the tumor.
FIGO Staging for Ovarian malignancy:
Stage for ovary
Primary tumor cannot be assessed
No evidence of primary tumor
Tumor limited to the ovaries
Tumor limited to one ovary, capsule intact, no tumor on ovarian surface; no malignant cells in ascites or peritoneal washings
Tumor limited to both ovaries, capsule intact, no tumor on ovarian surface; no malignant cells in ascites or peritioneal washings67
Tumor limited to one or both ovaries with any of the following: Capsule ruptured, tumor on ovarian surface; malignant cells in ascites or peritoneal washings
Tumor involves one or both ovaries with pelvic extension
Extension and/or implants on uterus and/or tube(s); no malignant cells in ascites or peritoneal washings
Extension to other pelvic tissues; no malignant cells in ascites or peritoneal washings
Pelvic extension (2a or 2b) with malignant cells in ascites or peritoneal washings
Tumor involves one or both ovaries with microscopically confirmed peritoneal metastases outside the pelvis and/or regional lymph node metastasis
Microscopic peritoneal metastasis beyond pelvis
Macroscopic peritoneal metastasis beyond pelvis, 2 cm or less in greatest dimension
Peritoneal metastasis beyond pelvis more than 2 cm in greatest dimension and/or regional lymph node metastasis
Distant metastasis* (excludes peritioneal metastasis).
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FIGO stage for Fallopian tube:
Stage for Fallopian tube
Primary tumor cannot be assessed
No evidence of primary tumor
Tumor confined to Fallopian tube(s)
Tumor limited to one tube, without penetrating the serosal surface
Tumor limited to both tubes, without penetrating the serosal surface
Tumor limited to one or both tube(s) with extension onto or through the tubal serosa, or with malignant cells in ascites or peritoneal washings
Tumor involves one or both Fallopain tube(s) with pelvic extension
Extension and/or metastasis to uterus and/or ovaries
Extension to other pelvic structures
Pelvic extension (2a or 2b) with malignant cells in ascites or peritoneal washings
Tumor involves one or both Fallopian tube(s) with peritoneal implants outside the pelvis and/or positive regional nodes
Microscopic peritoneal metastasis beyond pelvis
Macroscopic peritoneal metastasis beyond pelvis, 2 cm or less in greatest dimension69
Peritoneal metastasis beyond pelvis more than 2 cm in greatest dimension and/or regional lymph node* metastasis
Distant metastasis** (excludes peritoneal metastasis)
* Regional lymph nodes are:
  • Hypogastric (obturator)
  • Common iliac
  • External iliac
  • Lateral sacral
  • Para-aortic
  • Inguinal nodes.
** Liver capsule metastasis is stage III; liver parenchymal metastasis is stage IV; pleural effusion must have positive cytology for stage IV.
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