WHO Classification of Tumours * 5th Edition Female Genital Tumours Edited by the WHO Classification of Tumours Editorial Board Pee ened yeeContents List of abbreviations Foreword WHO classification of tumours ofthe female genital tract ‘Tumours ofthe ovary Tumaurs ofthe pertoneum Tumours of the fallopian tube ‘Tumaurs othe broad ligament and ator uterine ligaments ‘Tumours ofthe uterine corpus Gestational trophoblastic disease ‘Tumaurs of the urine cervic Tumours ofthe vagina Tumours ofthe vulva Neuroendocrine neoplasia Haematoiymphoid proliferations and neoplasia ‘Mesenchymal tumours of the lower genital tract Melanaoytic lesions "TNM staging of gynaecological tumours (Ovarian, fallopian tube, and primary peritoneal carcinoma ‘Tumours ofthe uterus ~ endometrium Uterine sarcomas Gestational trophoblastic neoplasms ‘Tumours othe cervix uter ‘Tumours ofthe vagina ‘Tumours ofthe vulva "TINM staging of tumours of soft tissues ‘General introduction 1 Tumours of the ovary Introduction Serous tumours ‘Benign serous tumours Serous cystadenoma, adenofibroma, and surface papiloma Borderie serous tumours Serous borderine tumour ‘Malignant serous tumours Low-grace serous carcinoma High-grade serous carcinoma Mucinous tumours Benign mucinous tumours ‘Mucinaus eystadenoma and adenofibroma Borderline mucinous tumours ‘Mucinous borderine tumour Malignant mucinous tumours ‘Mucinous carcinoma Endametroid tumours Benign endometriid tumours Endomettioid cystadenoma and acenotiioma Borderline endometrioia tumours Endometroid borderline tumour Malignant endometroid tumours Endometroid carcinoma Clear cel tumours ‘Benign clear cell tumours lear cel cystadenorna and adenofibroma Bordering clear cell tumours Clear cell borderine tumour 29 31 32 36 38 43 48 50 53 55 56 58 ee 63 Malignant clear cell tumours Clear cell carcinoma ‘Seromucinous tumours Benign seromucinous tumours Seromucinous cystadienoma and adenofibroma Bordrtine saromucinous tumours Seromucinous bordering tumour Malignant seromucinous turnours Soromucinous carcinoma Brenner tumours ‘Benign Brenner tunours Brenner tumour Borderie Brenner tumours Borderline Brenner tumour ‘Malignant Brenner tumours Malignant Brenner tumour Other carcinomas ‘Mesonephric-lke adenocarcinoma LUnaifferantated and dedifferentiated carcinomas Garcinesarcoma Mixed carcinoma Mesenchymal tumours Endometroiastremal sarcoma ‘Smooth muscle tumours (Ovarian myxoma Other ovarian mesenchymal tumours Mixed epitheial and mesenchymal tumours Mixed malignant epithalial and mesenchymal tumours ‘Acenasarcoma Sex cord-siromal tumours Pure sivomal tumours (Ovarian fibroma, Thecoma Luteinzed thecoma associated with sclerosing peiitoritis ‘Sclerosing stromal tumour Microcystic stromal tumour ‘Signet-ring stromal tumour Leydig cell tumour ‘Steroid coll tumour Ovarian fibrosarcoma Pure sex cord tumours ‘Adult granulosa cell tumour ‘Juvenile granuiosa cell tumour Seral cell tumour Sex cord tumour with annular tubules Mixed sex cord-stromal tumours Seriali-Leyaig cell tumour Sex cord-stiomal turiour NOS Gynanctoblastoma, Germ call tumours ‘Mature teratoma Immature teratoma Dysgerminoma Yolk sac tumour Embryonal carcinoma Non-gestational chariocarcinoma Mixed germ cell tumour Monodermal teratomas and somaticype tumours arising from a dermoid cyst Struma ovati Ovarian carcinoid 65 68 69 70 n 73 6 a Bt 85 87 89 90 a 13 116 n7 19 121 123 125 127 129 1 192 134Nouroectodermal-type tumours Monodermal cystic teratoma Somatic neoplasms arising tram teratomas Germ cell-sex cord-stromal tumours Gonadoblasioma Mixed germ cel-sex cord-stromal tumour, unclassified Miscellaneous tumours Fate cystadenoma, adenoma, and adenocarcinoma Wioitfian tumour Sold pseudopapilary tumour Small cel carcinoma of the ovary, hypercalcaemic type Wiis tumour Mesothelial tumours (se¢ Ch. 3) Tumour-like lesions Folicle cyst Corpus luteum cyst Large soltary lutoinized follicle cyst Hyperteactio uteinalis Pregnancy luteoma Stromal hyperplasia and hyperthecosis Fibromatosis and massive oedema Leydig cell hyperplasia Metastases Endometriosis and related conditions Endometriosis and derived tumours 8. Tumours ofthe peritoneum Iniroduction Mesothelial tumours “Adenomatoid tumour \Well-ditferentiated papillary mesothelial tumour Mesothelioma Epithelial tumours Epithelial tumours of Mulerian ype Serous borderline tumour Low-grade serous carcinoma High-grade serous carcinoma Mesenchymal tumours specific to pertoneum ‘Smoath muscle tumours Leiomyomatosis pertonealis dissorinata Miscellaneous primary tumours ‘Desmoid flbramatosis Caletying fibrous tumour Extragastointestinal stromal tumour Solitary fibrous tumour Endometroid stromal sarcoma Desmopiastic smal round coll tumour ‘Tumourke lesions Mesotholial hyperplasia Peritoneal inclusion cysts ‘Transitional cell metaplasia Endosalpingiosic Histiocytie nodule Ectopic decidua Splenosis (Other tumour-like lesions Metastases Carcinomas and sarcomas Pseudomyxama pertonel Gliomatosis ‘Tumours ofthe fallopian tube Introduction Epithelia' tumours Benign serous tumours Serous adenolibxoma and papiloma 136 137 138 140 “3 14a 45 147 149 181 183 154 155 156 158 160 161 162 163 168 170 175 176 ww 179 181 188 186 187 188 190 102 193 195 197 199 201 203 204 205, 208 207 an 24 215. 216 217 Borderline serous tumours ‘Serous borderline tumour Malignant epithelial tumours High-grade serous carcinoma Endomeirioid carcinoma Carcinosarcoma Tumour-ike lesions. Paratubal cysts Tubal hyperplasia Tubo-ovarian abscess Salpinitsisthmica nodosa Metaplastc papillary lesion Placental ste nodule Mucinous metaplasia Endosalpingiosss Mixed epithelial and mesenchymal tumours ‘Adenosarcoma Germ cell tumours Teratoma 5 Tumours of the broad ligament and other uterine ligaments Introduction Mesenchymal and mixed tumours Leiomyoma ‘Adenomyoma ‘Adenosarcoma Leiomyosarcoma (Other mesenchymal and mixed tumours Miscellaneous tunours Wolffian tumour Papilary cystadenoma Ependymoma ‘Tumour-lke lesions ‘Adrenocortical remnants 8 Tumours of the uterine corpus Introduction Endometrial epithelial tumours and precursors Precursor lesions Endometrial hyperplasia without atypia Endometrial atypical hyperplasia / endometrioid intraepithelial neoplasia Endometrial carcinomas Endomaticid carcinoma Serous carcinoma lear cell carcinoma Unditiorentiated and deciferentiatod carcinomas Mixed carcinoma ‘Other endometial carcinomas Carcinosarcoma Tumour-lke lesions Endometrial palyp Endometrial metaplasia Arias-Stella reaction Mesenchymal tumaurs ofthe uterus ‘Smooth muscle tumaurs Userine leiomyoma Intravenous leiomyomatosis ‘Smoath muscle tumour of uncertain malignant potential Matastasizing leiomyoma Uterine leiomyosarcoma Endometrial stromal and related tumours Endometrial somal nodule Low-grade endometrial stromal sarcoma High-grade endometrial stromal sarcoma Unditierantiated uterine sarcoma 218 219 221 202 223 224 205 226 227 208 229 230 230 231 233 23 295 236 237 238 238 239, 240 242 24a 246 248 250 252 256 258 260 262 264 266 268 269 an 272 2m 279 281 283 286 287 280 2927 8 Miscellaneous mesenchymal tumours Uterine tumour resembling ovarian sex core turnour Perivascular epithelioid cell tumour (PEComa) Inflammatory myotibroblastic tumour ‘Other mesenchymal tumours of the uterus Mixed epithelial and mesenchymal tumours ‘Adenomyorna Atypical polypoid adenomyoma Adenosarcoma Miscellaneous tumours ‘Central primitive neuroectodermal tumour / CNS. ‘embryonal tumour Gorm call tumours Gestational trophoblastic disease Introduction Tumnourlke lesions Non-neoplasic lesions Exaggerated placental site reaction Placental site nodule and plaque ‘Nonermal (non-molar) vous lesions Molar pregnancies Partial nydatiiform mote Complete hydatiiform mole Invasive and metastatic hydaticiorm moles, Gestational trophoblastic neoplasms. Epithelioia trophoblastic tumour Placental site trophoblastic tumour Gestational choriocarcinoma Mixed trophoblastic tumour Tumours of the uterine cervix Inreduction Squamous epithoial tumours ‘Mimics of squamous procursor lesions Squamous metaplasia Atrophy ‘Squamous cell tumours and procursars Condyloma acuminatum (see Ch, 10) Squamous intraepitholial lesions Squamous coli carcinoma, HPV-associated ‘Squamous cell carcinoma, HPV-indepencient Squamous cell carcinoma NOS Glandular turoure and precursors Benign glandular lesions, Endocervical polyp Mallorian papiloma Nabotrian cyst Tunnel clusters Microglandular hyperplasia Lobular endocervical glandular hyperplasia Diffuse laminar endocervical hyperplasia Mesonephric remnants and hyperplasia ‘Avias-Stalla reaction Endocervicosis Tuboendometrioid metaplasia Ectopic prostale tissue Adenocarcinomas ‘Adenocarcinoma in stu, HPV-associated ‘Adenacarcinoma, HPV-associated Adenocarcinoma in situ, HPV-independont Adenocarcinoma, HPV-independent, gastric type Adenocarcinoma, HPV.indepencent, clear call ya Adenocarcinoma, HPV.independent, mesonephric. ‘ype Other adenocarcinomas Other epithelial tumours Careinasarcoma 294 296 298 300 301 303 305 307 308 309 310 att 313 315 a7 319 322 323 325, 227 332 9335 338 a9 sat 342 347 350 351 352 383 354 355 356 357 358 359 360 361 362 363 364 372 ara 316 are 382 Adenosquamous and mucoepidermoid carcinomas ‘Adonoid basal carcinoma Carcinoma, unclassifiable Mixed epithelial and mesenchymal tumours ‘Adenomyoma ‘Adenosarcoma Gorm cell tumours 9 Tumours of the vagi Intreduction Epithalal tumours Benign squamous lesions Condyloma acuminatum (se@ Ch. 10) Squamous papiloma Atrophy Tubulosquamous polyp ‘Squamous cell tumours and precursors ‘Squamous intraepithelial lesions ‘Squamous cell carcinoma, HPV-associated Squamous cell carcinoma, HPV-independent ‘Squamous cell carcinoma NOS Benign glandular lesions Villous adenoma Malierian papiloma Vaginal adenosis Endocervicosie Cysts Glandular tumours ‘Adenocarcinoma, HPV-associated Endometrioid carcinoma Clear coll carcinoma Mucinous carcinoma, gastric type Mucinous carcinoma, intostinal typo Mesonephric adenocarcinoma Carcinosarcoma Other epithelial tumours Mixed tumour of the vagina ‘Adenocarcinoma of Skene gland origin ‘Adenosquamous carcinoma ‘Adannaid basal carcinoma ‘Mixed epithelial and mesencrymal tumours Adenosarcoma Miscellaneous tumours ‘Germ call tumours 10 Tumours of the vulva Introduction Epithelial tumours ‘nigh squamous lesions Seborthaeic keratosis Condyloma acuminatum ‘Squamous cell tumours and precursors ‘Squamous intraepithelial lesions, HPV-associatod \uivar intraepithelial neoplasia, HPV-independent ‘Squamous cell carcinoma, HPV-associated ‘Squamaus cell carcinoma, HPV-independent ‘Squamaus cell carcinoma NOS Basal call carcinoma Glandular tumours and cysts ‘Mammary-type glandular lesions Papllary hidradenoma Chondroid syringoma Fibroadenoma Phyllodes tumour Adenocarcinoma of mammary gland type Barthoiin gland lesions Barthalin gland cyst Hyperplasia, adenoma, and adenomyoma 383 384 386 387 388 389 301 392 393 304 395 206 398 400 401 402 403 04 405 406 407 408 409 410 an a2 413 aus 415 416 a6 ar 418 419 420 421 422 424 426 423 432 434 434 435 438 437 438 433 440 441Bartnolin gland carcinomas Other cysts Adenocarcinomas of otner types Paget disaase Carcinomas of sweat gland origin ‘Adenocarcinoma of intestinal type Germ call tumours 11 Neuroendocrine neopl Introduction Neuroendacrine tumour Neuroendocrine carcinoma ‘Small cell neuroendocrine carcinoma Large cell neureendocrine carcinoma Mixed neuroendocrine-non-neuraendocrine neoplasms Carcinoma admixed with neuroendocrine carcinoma 12 Haematolymphoid proliferations and neoplasia Introduction Reactive lymphoid hyperplasia Florid reactive lymphoid hyperplasia Lymphomas, Difuse large B-cell ymphoma Extranadal marginal zone lymphoma Follicular lymphoma Burkitt lymphoma Myeloid leukaemia, ‘Myeloid sarcoma 13 Mesenchymal tumours ofthe lower genital tract, Introduction Adipooytic tumours pom Lipoblastome-tke tumour ofthe vulva Liposarcoma Fibrobiastic and myofbroblastic tumours Postoperative spindle cell nodule Fibroepithelil somal polyp Prepubertal froma Superficial myofibroblastoma Myofioroblastoma Cellar angiofioroma Angiomyofibroblastoma Solitary fibrous tumour Dermatofibrosarcoma protuberans NIRK-rearranged spindle cell neoplasm (emerging) Vascular tumours Kaposi sarcoma ‘Angiosarcoma ‘Smaath muscle tumours Letomyoma ‘Smooth muscle tumour of uncertain malignant potential Leiomyosarcoma 442 444 445 407 448 439 481 452 453 455 457 459 461 462 465 497 469 ari 473 474 arr 478 480 481 483, 405, 488, 488 490 491 493 495, 497 498 500 502 504 508 508, 509 Skeletal muscle tumours ‘Rnabdomyorna Rhabdomyosarcoma Peripheral nerve sheath tumours Benign peripheral nerve sheath tumours Granular cell tumour ‘Tumours of uncertain differentiation ‘Superficial anglomyxoma Deep (aggressive) angiomyxoma Epitieioid sarcoma Alveolar soft part sarcoma Undifferentiated small round cell sarcomas Ewing sarcoma +14 Melanocytic lesions Naevi ‘Acquired melanocytic naevus Congenital melanocytic naevus Blue naevus Atypical melanocytic naevus of genital ype Dysolastic melanocytic naevus Melanoma Mucosal melanoma 16 Metastasis “Metastasis tothe lower female genital tract 16 Genetic tumour syndromes of the female genital tract BRCA1/2-associaled hereditary breast and ovarian cancer syndrome Lynch syndrome Cowden syndrome \U-Fraumeni syndrome Peutz-Jeghers syndrome ‘Ataxia-telangiectasia Carney complex DIGERt syndrome Ovarian dysgenesis Yon Hippel-Lindau syndrome Hereditary leiomyomatosis and renal cel carcinoma (ther genetic tumour syndromes Contributors: Declaration of intorosts IARC/WHO Committee for ICD-O Sources References: Subject index Previous volumes in the series sit B12 515 Sir 519 522 524 526 827 528 530 532 534 535 537 539 540) 543 544 546 548 550 552 554 555 556 558 560 561 563 564 570 srt 572 sr7 625 632List of abbreviations 30, three-dimensional AIDS ‘acquired immunodeficiency syndrome AR androgen receptor cAMP teyclc adenasine monophosphate a confidence interval IN ‘cervical intraepithelial neoplasia Ns. ‘central nervous system cr ‘computed tomography MMR mismatch repait-deficient DNA. deoxyribonucleic acid EBV Epstein-Barr virus ER. jstrogen receptor Fat female genital tract FIGO Intemational Federation of Gynecology and Obstetrics FISH fluorescence in situ hybridization FNA fine-needle aspiration ca germinal-centre B cel HEE haematoxylin and eosin HIV human immunodeficiency virus HP high-power fells) HEV human papilomavicus HRHPY high-risk human papillomavius IARC International Agency for Research on Cancer loot International Ciassifcation of Diseases, 11th revision IcD-0 International Ciassication of Diseases for Oncology ICD-0-3 International Classification of Diseases for Oncology, Sed edition 'g i> ko LaPV MRI mRNA MSL Mss. ratio NK coll NMDAR Nos: NSE PAS PASD POR PR RNA RT-PCR ‘SEER Program STR TOGA NM uice w VaIN vin Immunoglobulin intemal arom duplication kilobase(s) low-risk human papillomavirus ‘magnetic resonance maging ‘messenger ribonucleic acid ‘microsatelite instability microsatelite stably rhuclear-o-cytoplasmic ratio patural ker cel Nmetny!-D-aspartate receptor rot otherwise specified neuron-spectfic enolase periodic acic-Schif pariodic acid-Schiff with diastase polymerase chain reaction progesterone receptor ribonucleic acic reverse transcriptase polymerase chain reaction Surveillance, Epidemiology, and End Results Program short tandem repeat The Cancer Genome Atlas tumour, node, metastasis Union for International Cancer Contral Ultraviolet ‘vaginal intracpithaial neoplasia volver intraepithelial neoplasia List of abbreviations xiForeword The WHO Classification of Tumours, published as a series of books (also known as the WHO Blue Books) and now as a website (https:(tumourclassification iarc.wha.it), is an essential tool for standardizing diagnostic practice worldwide. It also serves as a vehicle for the translation of cancer research into practice. The diagnostic criteria and standards that make up the classification are underpinned by evidence evaluated and debated by experts in the field. About 200 authors and editors participate in the production of each book, and they give their time freely to this task. | am very grateful for their help; itis a remarkable team effort. This fourth volume of the fifth edition of the WHO Blue Books has, lke the preceding three, been led by the WHO Classification of Tumours Editorial Board, which is composed of standing members nominated by pathalogy organizations and expert mem- bers selected on the basis of informed bibliometric analysis. The diagnostic process is increasingly multidisciplinary, and we are delighted that several radiology and clinical experts have joined us to address specific needs. ‘The most conspicuous change to the format of the books in the fith edition is that tumour types common to multiple systems are dealt with together ~ so there are separate chapters on neuroendocrine neoplasia, haematolymphoid proliferations and neoplasia, mesenchymal tumours, and melanocytic lesions, There is also a chapter on genetic tumour syndromes. Genetic disorders are of increasing importance to diagnosis in individual patients, and the study of these disorders has undoubtedly informed our under- standing of tumour biology and behaviour over the past decade, We have attempted to take @ more systematic approach to the multifaceted nature of tumour classification; each tumour type is described on the basis of its localization, clinical features, epidemiology, etiology, pathogenesis, histopathology, diagnostic molecular pathology, staging, and prognosis and prediction. We have also included information on macroscopic appearance and oytolagy, as well as essential and desirable diagnostic criteria. This standardized, modular approach makes it easier for the books to be accessible online, but it also enables us to call attention to areas in which there is litle information, and where serious gaps in our knowledge remain to be addressed, The organization of the WHO Blue Books content now follows the normal progression from benign to malignant ~ a break with the fourth edition, but ane we hope will be welcome, ‘The volumes are stil organized by anatomical site (digestive system, breast, soft tissue and bone, etc), and each tumour type is listed within a taxonomic classification that follows the format below, which helps to structure the books in a systematic manner: * Site: eg. ovary * Category; e.g. endometrioid tumours ‘+ Family (class); ¢.g. malignant endometrioid tumours * Type; e.g, endometrioid carcinoma * Subtype; eg. seromucinous carcinoma ‘The issue of whether a given tumour type represents a distinct entity rather than a sublype continues to exercise pathologists, and itis the topic of many publications in the literature. We continue to deal with this issue on a case-by-case basis, but we believe there are inherent rules that can be applied, For example, tumours in which multiple histological patterns contain shared truncal mutations are clearly of the same type, despite the differences in thelr appearance. Equally, genetic heterogeneity within the same tumour type may have implications for treatment. A small shift in terminology in the fifth edition is that the term “variant” in reference to a specific kind of tumour has been wholly superseded by “subtype" in an effort to more clearly differentiate this meaning from that of “variant” in reference to a genetic alteration. The WHO Blue Books are much appreciated by pathologists and of increasing importance to practitioners of other clinical dis- Ciplines involved in cancer management, as well as to researchers. The editorial board and | certainly hope that the series will Continue to meet the need for standards in diagnosis and to faciltate the translation of diagnostic research into practice worldwide. Itis particularly important that cancers continue to be classified and diagnosed according to the same standards internationally so that patients can benefit from multicentre clinical trials, as well as from the results of local trials conducted on different continents, Drlan A. Cree Head, WHO Classification of Tumours Group International Agency for Research on Cancer ‘August 2020 xi ForewordWHO classification of tumours of the ovary Serous tumours B4s1/0 Sercus cystadenoma NOS 84610 Serous surface papilloma 9014/0 —_Serous adenofibroma NOS 9014/0 __Serous cystadenofibroma NOS {8442/1 Seraus borderline tumour NOS 346012 __Seraus borderline lumour, micropapillary variant 8460/2 Seraus carcinoma, non-invasive, low grade 84603 Low-grade serous carcinoma 46113 High-grade serous carcinoma ‘Mucinous tumours {8470/0 Mucinous cystadenoma NOS 9015/0 Mucinous adenofibroma NOS '8472/1_Mucinous borderline tumour B480/3 Mucinous adenocarcinoma Endometrioid tumours 8380/0 Endometrioid cystadenoma NOS 8381/0 Endometrioid adenofibroma NOS 8380/1 Endometioid tumour, borderine 8380/3 Endometrioid adenocarcinoma NOS 474i ——‘Seromucinous carcinoma Clear coll tumours 8443/0 Clear cell cystadenoma 831310 Cleat cell oystadenofibroma 831311 Clear cell borderine tumour 8310/3 Clear cell adenocarcinoma NOS ‘Seromucinous tumours 47410 Seromucinous cystadenoma 9074/0 Seramucinaus adenotioroma 8474/1 Seramuscinous borderline turrour Brenner tumours 9000/0 Brenner tumour NOS 9000/1 Brenner tumour, borderine malignancy 9000/3 Brenner tumour, malignant Other carcinomas 8111/9" Mesonephric-ke adenocarcinoma 8020/3 Carcinoma, undifferentiated, NOS 8020/3 Dediforontiated carcinoma 8980/3 Carcinosarcoma NOS 8929/3 Mixed cell adenocarcinoma ‘Mesenchymal tumours 8931/3 Endometrioid somal sarcoma, low grade 8920/3 Endomerrioid stromal sarcoma, high grade 8890/0 _Leiomyoma NOS 8890/3 Leiomyosarcoma NOS 8897/1 Smooth muscle tunour of uncertain malignant potential 8640/0 Myxoma NOS Mixed epithelial and mesenchymal tumours 8939/3 Adenosarcoma Sox cord-stromal tumours Pure stromal tumours {8810/0 Fibroma NOS 8810/1 Cellular flororma 8600/0 Thecoma NOS 8601/0 Thecoma,luteinized {8602/0 _Sclerosing stromal tumour ‘8590/0 Microcystic somal tumour ‘8590/0. Signet‘ing stromal tumour 8650/0 Leycig cell tumour ofthe ovary NOS. 8670/0 Steroid cell tumour NOS 8670/3 Steroid call tumour, malignant 8810/3 Fiorosarcoma NOS Pure sex cord tumours 86203 Adult granulosa cell tumour of ovary 8622/1 Granulosa cell tumour, jwenle ‘8640/1 Sertolicell tumour NOS 8623/1 Sex cord tumour with annular tubules Mixed sex cord-stromal tumours 8631/1 Sertol-Leydig cell tumour NOS 8631/0 Sertol-Leyaig coll tumour, well differentiates 8631/1 Sertol-Leycig coll tumour, moderately differentiated 8631/2 _Sertali-Leyaig cell tumour, pooty lferentiated 8633/1 _Sertoli-Leyaig cell tumour, retform 8590/1 Sox cord tumour NOS 8632/1 Gynandroblastoma Germ cell tumours 9080/0 Teratoma, benign 9080/3 Immature teratoma NOS. 9060/3 _Dysgerminoma 9071/3 Yak sac tumour NOS 9070/3 Embryonal carcinoma NOS 9100/3 Choriocarcinoma NOS ‘9085/3 Mixed germ cell tumour ‘Monodermal teratomas and somatic-type tumours arising from a dermoid cyst 9020/0 Struma ovari NOS 9090/3 Struma overi, malignant 9091/1 Strumal carcinoid 2064/3 _Teratoma with malignant transfoimation 9080/0 Cystic teratoma NOS ‘9064/3 Teretoma with malignant transformation Germ call-sex cord-stromal tumours 9073/1 Gonadobiastoma Dissecting gonadoblastoma Undifferentiated gonadal tissue 8504/1 Mixed gecm coll-sex cord-stromal tumour NOS Miscellaneous tumours 911010 Adenoma of rete ovari 9110'3 Adenocarcinoma of rete vari 9110/1 Wolffian tumour ‘8452/1 Solid pseudopapillary tumour of ovary 8044/3 Smal cell carcinoma, hypercalcaemic type Smal cell carcinoma, large cel variant 8960/3 Wilms tumour WHO classification of tumours of the ovaryTumourlke lesions Folicle cyst Corpus luteum cyst Large solitary lusinizd folicle cyst Hyperreacto luteinais 8610/0 Pregnancy lutooma ‘Stromal hyperplasia and hyperthecosis Fibromatosis and massive oedema Leydig coll hyperplasia Metastases to the ovary “These morphology codes are from the international Classification of Diseases for Oncology, tied edition, second revision (ICD-0-3.2) [1149 ‘Behaviour is coded /0 for benign tumours; /1 for unspectied, borderline, or uncertain behaviour; /2 for carcinoma in situ and grade I intraepthalial neoplasia, 2 for malignant tumours, primary site; and /6 for malignant tumours, metastatic site, Behaviour code (6 is not ‘generally used by cancer registries, ‘This classification is modified from the previous WHO classification, taking ino account changes in our understanding of these lesicns. + Codes marked with an asterisk were approved by the |ARCNWHO Committee for ICD-O at ts meeting in June 2020.WHO classification of tumours of the peritoneum Mesothelial tumours 9054/0 Adenomatoid tumour NOS 9052/0 Wel-ditferertiated papillary mesothelioma, benign 9050/3 Mesothelioma, malignant 90523 Epithelioid mesothelioma, malignant 9051/3 Sarcomatoid mesothelioma, 9053/3 Mesothelioma, biphasic, malignant Epithelial tumours (of Mllerian type) 8442/1 Sorous borderline tumour NOS 8460/3 Low-grade serous carcinoma 8451/3 High-grade serous carcinoma Mesenchymal tumours specific to peritoneum 8590/1 Leiomyomatoss, pettonealis disseminata '8822/1 Abdominal fbromatosis 8817/0 Calcifying fibrous tumour 3936/3 Gastroinestinal somal tumour 8815/1 Soltary fibrous tumour NOS Fat-forming (ipomatous) solitary flbrous tumour Giant cell-ich solitary fibrous tumour Dedifferentiated soltary fibrous tumour 8815/3 Solty fibrous tumour, malignant 8931/3 Endomerioid stromal sarcoma, low grade 8930/3 Endomeirioid stromal sarcoma, high grade 8806/3 Desmoplastic small round cell tumour Tumour-like lesions Mesothetal hyperplasia 9055/0 Peritoneal inclusion cysis, Transitional cell metaplasia Endosalpingiosis Histioeytc nodule Ectopic decidua Splenosis Motastases to the peritoneum Carcinomas and sarcomas 8480/6 Peeudomyxoma peritone: Gliomatosis These morphology codes are from the international Classification of Diseases for Oncology, third edtion, second revision (ICD-0-3.2) (1149), ‘Behaviour is coded /0 for benign tumours; /1 for unspecified, borderine, or uncertain behaviour, 2 fr carcinoma i sity and grade II intraepithelial neoplasia; /3 for malignant tumours, primary site; and /6 for malignant tumours, metastatic site. Behaviour code /6 is not ‘generally used by cancer registries. This classification is mociied from the previous WHO classification, taking into account changes in our understanding of these lesions. WHO classificatian af tumours af the neritanelimWHO classification of tumours of the fallopian tube Epithelial tumours ‘Mixed epithelial and mesenchymal tumours 9014/0 Seraus adenofibrama NOS 8993/3 Adenosarcoma ‘3442/1 Serous borderline tumour NOS High-grade serous carcinoma Germ cell tumours Endometicid adenocarcinoma NOS 9080/0 Mature teratoma NOS Garcinosarcoma NOS. 9080/3 Immature teratoma NOS Tumour-like lesions Paratubal cysts Tubal hyperplasia Tubo-ovarian abscess Salpngitsisthmica nodosa Metaplastic papillary lesion Placental ste nodule Mucinous metaplasia Endosalpingiosis ‘These morphology codes are from the International Classification of Diseases for Oncology, third eition, second revision {ICD.0-8.2) [1149] Behaviour is codes /0 for benign tumours; /1 for unepectied, borderline, or uncertain behaviour, /2for carcinoma in situ and grade Il intraepithelial neoplasia; (3 for malignant tumours, primary sito; and /6 Yor malignant tumours, metastatic site. Behaviour code (6 is not generally used by cancer registries. This classification ia modified fram the previous WHO classfication, taking info account changes in our understanding ofthese lesions. 4 WHO claraification nf timers af the fallanian tine.il WHO classification of tumours of the broad ligament and other uterine ligaments Mesenchymal and mixed tumours Miscellaneous tumours 8890/0 Leiamyoma NOS. 9110/1 Wolfian tumour 8932/0 Adenomyoma NOS. 8450/0 Papilary cystadenoma NOS 8939/3 Adenosarcoma 9931/3 Ependyrmoma NOS 8890/3 Leiomyosarcoma NOS Tumourtke lesions ‘Adrenocortical remnants These morphology cades are from the International Classification af Diseases for Oncclogy, tha edtion, second revision (ICD-O-3.2) 11149} Benaviour is coded /0 for benign tumours; /1 for unspectieg, borderine, or uncertain behaviour 2 for carcinoma in stu and grade Il intraepithelial neoplasia; /3 for malignant tumours, primary site; and (6 for malignant tumours, metastatic site. Behaviour code /6 isnot ‘generally used by cancer regisris. ‘This classification is modified from the previous WHO classfcation, taking info account changes in our understancing of theso lesions,WHO classification of tumours of the uterine corpus Endometrial epithelial tumours and precursors Endometrial hyperplasia without atypia 8960/2 Atypical hyperplasia of the endometrium 8380/3 Endometroid adenocarcinoma NOS POLEultamutated endometroid carcinoma Mismaten repar-deicient endomerio’ carcinoma p53-mutant endometriaid carcinoma No specific molecular protle (NSMP) endometriid 8441/9 Serous carcinoma NOS 8310/3 Clear cell adenocarcinoma NOS 8020/3 Carcinoma, undiferentiated, NOS 8329/3 Mixed cell adenocarcinoma 9110/3 Mesonephric adenocarcinoma 8070/3 Squamous call carcinoma NOS 8144/3. Mucinous carcinoma, intestinal ype 11113" Mesonephrc-ike adenocarcinoma 8980/3. Carcinosarcoma NOS ‘Tumour-lke lesions Endometrial polyp Endometrial metaplasia Avias-Stella reaction Mesenchymal tunours specific to the uterus 8890/0 Leiomyoma NOS 8890/0 Lipoleiomyoma 8890/0 —_Leiomyoma, apoplectic 2890/0 Leiomyoma, hycropic 8890/0 Dissecting leiomyorna 8892/9 Collar leiomyoma 2896/0 _-Mysoid leiomyoma 8801/0 Epithelioid leiomyoma 8893/0 Symplastic liomyoma 8890/1 —_Leiomyomatosis NOS 8890/1 Intravenous le’orworatosis, 8897/1. Smooth muscle tumour of uncertain malignant potential 8891/1" Epithelioid smooth muscle tumour of uncertain ‘malignant potential 8896/1" Myxoid smooth muscle tumour of uncertain ‘malignant potential Spindle smooth muscle tumour of uncertain ‘malignant potential 8898/1 Metastasizing leiomyoma 8690/3 Leiomyosarcoma NOS ‘Spindle leiomyosarcoma 8891/3 Epithelioid leiomyosarcoma 88969 __Myxcid leiomyosarcoma. 8930/0 Endometrial somal nodule 8931/3 Endometrial stromal sarcoma, low grade 8930/3 Endometrial stromal sarcoma, high grade 8805/3 Undifferentiated sarcoma 8590/1 Uterine tumour resemiling ovarian sex cord tumour 871410 Perivascular epithelioid tumour, benign 8714/2 Perivascular epithelioid tumour, malignant 2825/1 Inflammatory myofibroblastic turnour Epithelioid myofibroblastic sarcoma ‘Mixed epithelial and mesenchymal tumours, 8932/0 Adenomyoma NOS 8932/0 Atypical polypoid adenomyoma 5939/3 Adenosarcoma Miscellaneous tumours 9473/3 Primitive neuroectodermal tumour NOS 9064/3 Germ cell tumour NOS. 9071/3 Yok sac tumour NOS 2080/0 Mature teratoma NOS 9060/3 Immature teratoma NOS ‘These morphology codes are from the Intemational Classification of Diseases for Oncology, third edition, second revision ((CD-0-3.2) {1149 Behaviour s coded 10 for benign tumcurs; /1 for unspecte, Dorderine, or uncerlain behaviour 2 for carcinoma in situ and grade Ih intraepithelial neoplasia: /3 for malignant tumouts, primary ste; and (6 for malignant tumours, metastatic site. Behaviour code /6 isnot igenorally used by cancer registries ‘This classification is mocifi from the previous WHO classification, taking into account changes in our understanding ofthese lesions, * Codes marked with an asterisk were approved by the |ARCWHO Committee for ICD-O at its meeting in June 2020.WHO classification of gestational trophoblastic disease ‘Tumour-lke lesions Gestational trophoblastic neoplasms Exaggerated placental sto reaction 9105/3 Trophoblastie tumour, epithelcid Placental site nodule and plaque 9104/1 Placental ste trophoblastic tumour 8100/3 Choriocarcinoma NOS ‘Abnormal (non-molas) vilous lestons 9101/3 Choriacarcinoma combines with other germ cell elemenis Molar prognancios 9103/0 Partial hydaticiform mole 9100/0 Complete hydatciorm mole 8100/1 Invasive hydatidform mele ‘These morphology codes are from the International Classification af Diseases foc Oncology, thid edition, secend revision (ICD-O'3.2) 1149} ‘Behaviour is coded /0 for benign tumours; /1 for unspeciied, borderine, or uncertain behaviour /2 fr carcinoma in stu and grade Il intraepithelial neoplasia; /3 for malignant tumours, primary site; and (6 for malignant tumours, metastatic site. Behaviour code /6 is not generally used by cancer registries. This classification is modified from the previous WHO classification, taking into account changes in our understanding of these lesions.WHO classification of tumours of the uterine cervix ‘Squamous epithelial tumours 8140/3 Adenocarcinoma NOS Squamous metaplasia '8483/3" Adenocarcinoma, HPV-associatod Atrophy 8482/3 Adenocarcinoma, HPV-independent, gastic type CCondyloma acuminatun 8310/3 Adenocarcinoma, HPV-independent, clear cel type 8077/0 Low-grade squamous intraepithelial lesion 911013 Adenocarcinema, HPV-independent, mesonephric B077I0. Cervical ntraepithetia neoplasia, grado 1 ‘ype 807712 High-grade squamous intraepithelial lesion ‘84g4/3* Adenocarcinoma, HPV-independent, NOS 8077/2 Cervical intaepithelial neoplasia, grade 2 8380/3 Endometioid adenocarcinoma NOS 8077/2 Cervical intraepithelial neoplasia, grade 3 8980/3 Carcinosarcoma NOS 80853 Sqvamous cel carcinoma, HPV-associated {8560/3 Adenesquamous carcinoma 2088/3 Squamous cell carcinoma, HPV-independent '8430/3_ Mucoepidermoid carcinoma BO7OI3 Squamous cell carcinoma NOS 8096/3 Adenoid basal carcinoma 80203 Carcinoma, undiferentiated, NOS Glandular tumours and precursors Endocervical polyp Mixed epithelial and mesenchymal tumours Mallerian papilloma 8932/0 Adenomyoma NOS Nabothian cyst Mesonephric:type adenomyorna Tunnel clusters Encocervical-type adenomyama ‘Microgiandilar hyperplasia 9933/2 Adenosarcoma Lobular endocervical glandular hyperplasia Diffuse laminar endocervical hyperplasia Germ cell tumours Mesonephric remnants and hyperplasia 90643 Germ cell tumour NOS ‘vias: Stella reaction 9080/0 Mature teratoma NOS. Endocervicosis 9084/0 Dermoid cyst NOS Tuboondometioid metaplasia 9071/3 Endadermal sinus tumour Ectopic prostate tissue 90713 Yolk sac tumour NOS. 8140/2. Adenocarcinoms in sity NOS 8100/3 Choriocarcinoma NOS 8483/2" Adenocarcinoma in situ, HPV-associated 8484/2" Adenocereinoma in stu, HPV-independent These morphology codes ate fom the International Classification of Diseases for Oncology third extion, sacand revision (ICD-O-8 2) {1449} Fae rare cosed 1 for benign tumouts;/1 for unspecified, borderline, or uncertain behaviour, /2 for carcinoma in sty and grade aera lal neoplasia’ /3 for malignant tumours, primary site; and /6 for malignant tumours, metastatic site. Behaviour code / not generally used by cancer registries ‘This classifcaton is modified from the previous WHO classification, taking into account changes in aur understanding ofthese lesions. = Codes marked with an asterisk were approved by the |ARCWWHO Committee for ICD-O at its meeting in June 2020,WHO classification of tumours of the vagina Epithelial tumours 8052/0 S600 807710 80710 aor7i2 80772 807772 8085/3 8086/3 8070/3, 8261/0 8263/0 81403 8483/3" ‘Condyloma acuminatum ‘Squamous cell papilloma NOS Vestibular micropapilomatosis, Solitary vaginal papilloma Atrophy “Tubulosquamous polyo Low-grade squamous intraepithelial lesion ‘Vaginal inteepithelial neoplasia, grade 1 High-grade squamous intraepithelial lesion ‘Vaginal intepithelial neoplasia, grade 2 Vaginal intiepithelial neoplasia, grade 3 ‘Squamous cell carcinoma, HPV-associated Squamous cell carcinoma, HPV-independent ‘Squamous cell carcinoma NOS Villous adenoma NOS TTubulovilous adenoma NOS Malierian papilloma. Vaginal adenosis, Endocervicosis Cysts Adenocarcinoma NOS ‘Adenocarcinoma, HPV-associated 8380/3 Endometrioid adenccarcinoma NOS 2310/3 Clear cell adenocarcinoma NOS. ‘8482/3 Mucinous carcinoma, gastric type {8480/3 Mucinous adenocarcinoma 9110/3 Mesonephric adenocarcinoma 8980/3 Carcinosarcoma NOS {8940/0 Mixed tumour NOS 8140/3 Carcinoma of Skene, Cowper, and Litré glands 8560/3 Adenosquamous carcinoma ‘8098/3 Adenoid basal carcinoma ‘Mixed epithelial and mesenchymal tumours 8933/3 Adenosarcoma ‘Miscellaneous tumours 9064/3 Germ cell tumour NOS 9071/3 Yolk sac tumour, pre-pubertal type 2080/0 Mature teratoma NOS. 2084/0 Dermoid cyst NOS ‘These morphology codes are from the International Classification of Diseases for Oncology, third edtion, sacond revision (ICD-0-3.2) |1 149} ‘Behaviour is coded [0 for benign tumours: /1 for unspestied, borderine, or uncertain behaviour 2 for carcinomain stu and grade Il intraepithelial neoplasia: /3 for malignant tumours, primary ste; and (6 for malignant tumours, metastatic ste. Behaviour code /6 isnot ‘generally used by cancer registries. This classification ie mocified from the previous WHO classification, taking nto account changes in out understanding ofthese lesions * Codes marked with an asterisk were approved by the [ARGMWHO Committee for ICD-O at is meeting in June 2020, WHO classification of tumours of the vagina 9WHO classifica’ Epithelial tumours 8077/0 8077/0 3077/2 0772 8077/2 8071/2 508513 2086/3 07018 3090/3 8405/0 90/0 2010/0 0201 2020/0 2020/1 9020/3 8500/3 These morphology codes are ‘Behaviour is coded /0 for benign tumours intraepithelial neoplasia; /3 for malignant tumours, prime ‘Seborrnoeic keratosis Conayloma acuminatum Low-grade squamous intraepithelial lesion ‘Vulvar intraepithelial neoplasia, grado 1 High-grade squamous intraepsthelil lesion ‘VuNar intraepithelial neoplasia, grade 2 ‘Vulvar intraepithelial neoplasia, grade 3 itierentiated vulvar intraepithelial neoplasia (VIN) Differentiated exophytic vulvar intraepithelial lesion ‘Vulvar acanthosis with aered differentiation ‘Squamous cell carciname, HPY-associated ‘Squamous cell carcinoma, HPVsndependent ‘Squamous cell carcinoma NOS ‘Basal cell carcinoma NOS Papilary higradenoma CChondroid syringoma NOS Fibroadenama NOS Phyllades tumour NOS Pryllodes tumour, benign Phyilades tumour, borderine Phyjlades tumout, malignant ‘Adenocarcinoma of anogenital mammary-ike glands ‘generally used by cancer registies. ‘This classification is mocitied from the previous WHO classification, ion of tumours of the vulva Barthotin gland lesions BBarthaln gland cyst ‘8140/0 Adenoma NOS '8932/0 Adenomyoma NOS BO7OIS Squamous cell carcinoma NOS 820013 Adenoid cystic carcinoma 8020/3 Carcinoma, poorly differentiated, NOS ‘8560/3 Adenosquamous carcinoma 8240/3 Neuraendocrine tumour NOS {8982/3 Myoepithelal carcinoma 3562/3 Epithelal-myoopitheiial carcinoma 8085/3 Squamous cal carcinoma, HPV-positive 3542/3 Paget cisease, extramammary ‘8400/3 Sweat gland adenocarcinoma 8401/3 Apocrine adenocarcinoma 8419/3 Ecorine adenocarcinoma 8409/3 Porocarcinoma NOS 820013 _ Adenoid cystic carcinoma 8144/3 Adenocarcinoma, intestinal type Germ cell tumours ‘9064/3 Germ cell tumour NOS 9071/3 Yolk sac tumour NOS. ‘rom the irteretional Classification of Diseases for Oncology, third ealtion, second revision (100-0-8.2) 1148} Tein ah pected, borderline, or uncertain behaviour [2 for carcinomain stu and grad I ray aite, and [6 for malignant tumours, metastatic site. Behaviour code /6 is not taking into account changes in our understanding ofthese lesions.WHO classification of neuroendoc! e neoplasia in the female genital tract s240'3 9240/3 24913 s0aH/3 8013/3 8045/3 B073/3 Neuroendocrine tumour NOS ‘Neuroendocrine tumour, grade 1 Neuroendocrine tumour, grade 2 ‘Small cell neuroendootine carcinoma Large cell neuroendocrine carcinoma Combined small cell neuroendocrine carcinoma Combined large cell neuroendocrine carcinoma ‘These morphology codes are from the International Classtcaton of Diseases for Oncology, third eation, sacond revision (ICD-O-3.2) [1149]. [Behaviour is coded [0 for benign tumours. /1 for unspeciieg, borderine, or uncertain behaviour; (2 for carcinoma in situ and grade I intraepithelial neoplasia; /3 for malignant tumours, primary site; and /6 for malignant tumours, metastatic site. Behaviour code /6 is not ‘generally used by cancer registtes. This classtication is modified from the previous WHO classification, taking into account changes in our understanding ofthese lesions. WHT rlawdirediro 7? ereimersiensien rareiania 9 the vein roviiel tetWHO classi cation of haematolymphoid proliferations and neoplasia in the female genital tract 968013 969913 69013 9687/3 9930/3 Forid reactive lymphoid hyperplasia Diffuse large B-cell ymphoma NOS Exiranodal marginal zone lymphoma of mucose- ‘associated lympho tissue Folicular lymphoma NOS. Burkitt ymphoma NOS ‘Sporadic Burkit Iymphoma Endemic Burkit lymphoma Immunodeliciency-associated Burkitt lymphoma | Myeloid sarcoma | These morphology codes ae trom tho Iniemnaonal Cassticaton of Diseases for Oncology, third edtion, seeand revision (0-0-3) {1149} enc f7o for berign tumours; 1 for unspected, borderline, or uncertain behaviour, [2 for earcinom in stu and, grade 1 aan neoplasia [3 formalignant tumours, primary si; and f6 fr malignant tumours, metesiatic ste, Behaviour code 6 not generally used by cancer registries. ‘This classification is modified from the previous WHO classification, taking into account changes in our understanding cf these lesions.WHO classification of mesenchymal tumours of the lower genital tract ‘Adipocytic tumours ‘8850/0 Lipoma NOS 8861/0 Lipoblastoma-like tumour 8850/3 Liposarcomia NOS ‘8850/1 Atypical lipomatous tumour 8852/3 Myxcidliposarcoma 2651/3 Liposarcoma, wel differentiated, NOS 8858/3 Decifferentialed liposarcoma 8854/3 Pleomorphic liposarcoma Fibroblastic and myofibroblastic tumours Postoperative spindle cell nodule Fibroepithelial stromal polyp 2810/0 Fibroma NOS '2625(0 Myofibroblastoma 9160/0 Cellular angiofibroma 2826/0 Anglomyotibroblastoma 8515/1 Solitary fibrous tumour NOS 8815/3 Soltay fibrous tumour, malignant 2832/1 Dermatofibrosarcoma protuberans NOS 8633/1 Pigmentad dermatatiorosarcoma protuberans 8832/3 _Dermatafibrosarcoma protuberans, fibrosarcomatous NTAK-rearranged spinaie col neoplasm (emerging) Vascular tumours 9140/3 Kapos! sarcoma 9120/3 Angiosarcoma ‘Smooth muscle tumours ‘8690/0 Lecomyoma NOS BES1/0 Epithelioid leiomyoma 8896/0 __Mytoid leiomyoma 8697/1 Smoath muscle tumour of uncertain malignant potontial 8690/3 Leiomyosarcoma NOS 8881/9 Epithelioid letomyosarcoma 8696/3 Myxoid leiomyosarcoma ‘Skeletal muscle tumours 8905/0 Genital rhabdomyoma 8900/3 Rhabdomyosarcoma NOS 8910/3 Embryonal ehabdoryosarcoma NOS. 8920/3 Alveolar rhabdomyosarcoma 8901/3 Pleomarphic rhabdomyosarcoma NOS Peripheral nerve sheath tumours 9540/0 Neurfibroma NOS. ‘9560/0 Schwannoma NOS 9580/0 Granular cell tumour NOS 9580/3 Granular cell tumour, malignant ‘Tumours of uncertain differentiation 8841/0 Superficial angiomyxoma ‘8841/0 Aggressive angiomyxoma 8604/3 Epihelod sarcoma Classic epithelioid sarcoma Proximal o large cal epithelioid sarcoma 9581/3 Alveolar soft part sarcoma Undifferentiated small round cell sarcomas 9364/3 Ewing sarcoma “These morphology codes are from the International Classification of Diseases for Oncology, third edition, second revision (ICD-0-3.2) | 1149}. [Behaviour is coded [0 for benign tumours: /1 for unspectieg, borderine, or uncertain behaviour; [2 for carcinoma in situ and grade II invaepithelial neoplasia, /S for malignant tumours, primary site; and /6 for malignant tumours, metastatic site. Behaviour code /6 is not generaly used by cancer registies, This classfication is modified ftom the previous WHO classification, taking into account changes in our understanding of these lesions, sification of mesenchymal tumours of the lower aenital tract «13.WHO classification of melanocytic lesions in the female genital tract 7200 874010 875010 8760/0 876110 er6iit 8780/0 8730/0 ‘These morphology Behaviour is coded (0 for benign tum intraepithelial neoplasia, /S for malign Naevus NOS ‘Junotional naevus NOS intradermal naevus ‘Compound nasvus, Congenital malanocy'ic naevus NOS Giant pigmented naovus NOS Blue naaws NOS. Coliular blue naevus {generally used by cancer registries. This clas 7200 872710 87208 8745/3 87203 87463 ‘Atypical melanacytic naevus of genital type Dysplastic naevus ‘Malignant melanoma NOS ‘Desmoplastic melanoma Noduiar melanoma Mucosal lentiginous melanoma codes aro from the Intemational Classification of Diseases for Oncology, third edition, second revision (1CD-0-3.2) {114} sours 1 for unspectied, borderline, or uncertain behaviour, /2 for carcinoma i sit and grade Il rant tumours, primary site, and /6 for malignant tumours, metastatic site, Behaviour code /6 fs not sification is modified trom the previous WHO classfiation, taking info account changes in our understanding of these lesions.rr TNM staging of gynaecological tumours Gynaecological Tumours Introductory Notes The fllowing sites are included: = Vulva = Vagina = Cervix ues = Corpus uteri © Endometrium Uterine sarcomas. + Ovary, fallopian tube and primary peritoneal carcinoma + Gestational trophoblastic tumours Cervix uteri and corpus uteri were among the fist sites to be classiiec by the TNM system. Originally, carcinoma of the cervix uteri was staged following the rules suggested by the Radiological Sub-Commission of the Cancer Commission of the Health Organization of The League of Nations. These rules were then adopted, with minor modifications, by the newly formed Fadération internationale de Gynécologie ot ¢ Obstétrique (FIGO), Finally, UICC brought them into the TNM in arder to Correspond to the FIGO stages. FIGO, UICC, and AJCC work in clase collaboration in the revision process, The classification of tumours of ovary and fallopian tube has been revised inline with the recent FIGO update’ Each site is described under the folowing headings: + Rules for classification withthe procedures for assessing T.N, and M categories; additional methods may be used when they tenhance the acouracy of appraisal before treatment Anatomical subsites where appropriate Definition ofthe regional lymph nodes. TTNM clinical classification INM pathological ciasifcation * Stage Histopathological Grading ‘The definitions ofthe G categories apply to al carcinamas, These are: G-Histopathological Grading | GX Grade of cfereniaion cannot be assessed Gi Welldtierentated G2 Moderately aferenttea 63 Poorly difereniated or undiferertiatea Reference | 1 Prat J, FIGO Committee on Gynecologic Oncology. Staging Classification for cancer ofthe ovary, fallopian tube, and ppettoneum. Int J Gynecor Obstet 2014; 124: 1-5. ‘The information presented here hes been excerated tom the 2017 TNM ciaseicatian of malignant tumours, elgtth eden [295,2790}, © 2017 UICC. ‘A hop desk for specie questions about the TNM clagsieaton avaiable at ia fin uice orgitnn-nelp-deskTNM staging of ovarian, fallopian tube, and primary peritoneal carcinoma | Ovarian, Fallopian Tube, and Primary Peritoneal Carcinoma | (cD-0-3 ¢56; ICD-0-3 C57) ‘The definitions ofthe T,N, and M categories correspond to the | FO stages: Botn systems ae inctuded for comparson Denar | Tet ‘Surgical sl Rules for Classification Thee a ‘Tho classification applies to malignant ovarian neoplasms of both epithelial and somal orgin including those of borderline T168 Walgrat ca ences peronee! rralignancy or of low malignant potential’ corresponding 10 7 ‘common epithelial uours’ of the earlier terminology. [oop use wim pec exten low “The classification also appies 10 Carcinoma ofthe fallopian cA i aes er tac tubes and fo carcinomas ofthe pefioneum (Malleian origin). eet “There should be histological confirmation ofthe disease and 7 ‘xtnsion andor mols on ules ardor division of eases by histological type. 2a Tn come pa neon The following are the procedures for assessing T, N, and M ca ; canal Pies 7 Te Exlerion tier pele issues rckcing bow! wii tho gos | T catogories Clinical examination, imaging, surgical exploration Trot inchar sorta oerrartlacien (laparoscopyilaperotony) {bes er primary pottonealcarama wth Neategores Clinical examination, imaging, surgical exploration TaandlorNt IF Gybogealyerhielogealy corre soead | (aparescopylaparctor) ‘ihe potoneumcarsde epost Mcategories Cinical examination, maging surgical exploration rata the eortnaal lyn noes Alaparoseapyfaparoiony) ui evoperoneal yeh rede melas ony a Tim bymph pode metastasis not ore an | the ico stages a asec on upc! siaging. NM sages SOrmm ingeatet mension ho ‘based on cinical andlor pathological classification.) we vamp Diphroderreasass moretian fommin | areaiest mension | Wicrosoopie extapaverabove mepave | Regional Lymph Nodes aaanyn wing Diprioneal volvement wih or wiht | The egional mph nodes are he hypogast (otra) coon I ‘ropertoneal on node, cluding bowel | fige, extemal fac, lateral sacral, para-acric, and rtropertoneal invelverent | | nodes. Macroscopic parioneal mstastass | | boyond pee brim 2 om a iessin greatest ‘Ta0aryN 18 dimension, nung bowel invovement Tra incl ateemrn = Primary Tumour | ‘T-Primary Tumour Feronoa metastasis beyond pave Di oethan2emin grates mersinandl | 7 Tecan MC fics eens uno ena 7% Primary trou cannot be assessed Oo eccna 70 No evidence of pimary tumour Solemn eer erg | m 7 Taare tre ovaries (one Bath) Mi ty Datartmeastats(ecldes pertoneal | tr faopian tubes) asa) src ened one aro Tegan We wa TWA___ Poul eturon wih postive evoay |} we apaule tat no tumour on ovarian erie ‘arencyral metastas and metastasis © W\ GFlalopin ube aac re algna cls teva eeimandoinalegers(rekngingsra | ass orpertones washings. Iympn nodes and mph nodes aut he “arcu miedo bth ovaries or alopan ‘togomina cody) ' tubes, cape et, na uaa onavarian eee 18 GFatopen oe surface-nomalgrartcstsin Notes scieso:pationenlweshings "Liver capsule metasasis s Tstage Il. | mers > Tumour ited 10 oe bot orares or ® Liver parenchymal metastasis Mtfstage I. | fatpian tubes with any ofthe fokowing: “Tho Information presented hare has been excerpiod rom the 2017 THM classification of malignant tumours, eighth ection (295 2700}. © 2017 UICC. Chop desk for specie qesiens about he TNM Classtication is avllabe al ites Jw ic orgien-hop- caskN—Regional Lymph Nodes NX. Regional lymph nodes cannot be assessed NO No regional lymph node metastasis, Ni Regional lymph node metastasis Ni IAT” Retropertoneal iymph node metastasis only Nia IIATI_ Lymph node metastasis no more than 30 mm in greatest cimension Nib IAAI. Lymph node metastas's more than 10 mm in greatest dimension M_Distant Metastasis MO No aistant metastasis M1 Distant metastasis, Mia Plouraleftusion with positive cytology Mtb Parenchymal metastasis and metastasis to extra- ‘abdaminal organs (inlusing inguinal lymph nodes {and lymph neces outside the abdominal cavity) BTNM Pathological Classification ‘The pT and pN categories correspond to the T and N categories NO Histological examination of a pelvic lymphadenectomy ‘specimen will ordinarily include 10 or more iymph nodes. Ifthe lymph nodes are negative, bt the number ordinary ‘examined isnot met, classify as pNO, pM - Distant Metastasis" PNII_Distant motastasis microscopically confirmed Note *phlO and pMX are not valid categories, stage stage n No Mo Stage A Te No MO. Stage 8 a No Mo. Stage IC Te No Mo Stage 2 No Mo Stage tA Ta No NO Stage IS ra No Mo Stagellar ——TH2 Nt Mo Stage llaz —T3a NONI Mo. Stage 130 NON Mo Stage IC Tae NONI Mo Stage Any Any mi StagelVA AnyT ayn Mie Stage VE fang ny mi Reference 1 Tavassol FA, Devilee P (eds). WHO Classification of Tumours. Pathology and Genetics. Tumours ofthe Breast and Female Genital Organs. Lyon, France: IARC Press, 2003. ‘Ta information presented here has sen excerpted tom the 2017 TNM ciaesiicaon of malignant tumous, ghth ection [295,2790}.© 2017 UICC. Dr hslp desk for pectic questions apeutthe TNM oaesticaton avatabie al Mtosifww Uee orginm-nelp-desk TTNM etanina afavarian fallanian tiha and nrimary naritanaal carcinoma 17TNM staging of tumours of the uterus — endometrium Uterus — Endometrium (ICD-0-9 054.0, 1,8, 8, 9, C55) “The definitions ofthe T, N, and M categories correspond to the FIGO stages. Both sysiems are included for comparison. ules for Classification The classiication apples to endometrial carcinomas and carcinosarcomas (malignant mixed mesodermal tumours). There ‘should be histological vertcation with subdivision by histological type and grading ofthe carcinomas. The diagnosis should be based on examination of specimens taken by endometrial biopsy. “The folowing are the procedures for assessing T, N, and M categories: Teategories Physical examination and imaging including Urographiy anc cystoscopy Neategories Physical examination and imaging including Urography Mcategories Physical éxamination and imaging ‘The FIGO stages are based on surgical staging. (TNM stages | are based on cinical andjor pathoiogical classiticaton ) Anatomical Subsites 4. Isthmus uter (C54.0) 2. Fundus uteri (C543) 3, Endometrium (C54 1) Regional Lymph Nodes | The regional lymph nodes are the pelvic (hypogastric (obturator, internal iiac], carmmon and external lac, parametial, and sacral) ‘and the para-aortic nodes, TNM Clinical Classification Primary Tumour 1% Primary tumour cannot be assessed 70 No evidence of primary tumour 7 Tumour eontined othe corpus ter? Turour ited ta endometrium or invading | me (A ess than half of myometrium Tie 1p Temourinvades one hal or more of snyemotium te 11 Tumour invades cervical stroma, but does not extend beyond the ues @ i Loca ander regional prada pected he Tee Aone Ooctenensen or malas) Ta aera vehement | ee NIGH Metastasis ta pec lymh nodes etasasis to pare-satc lymph nodes wit or Nz G2 trout metastasis pewelmnph nodes 1 Ty Tumourinvadesbladdebowel micosa Notes ® Endocervical glandular involvement only should be considered as stage | ® Positive cytology has ta be reported separately without changing the stage. ‘The presence of bullous oedema is not sufficient evidence to classify as T4 NX. Ragional lymph nodes cannot be assessed NO No regional lymph node metastasis: Ni Regional lymph noce metastasis to pelvic ymph nodes N2_ Regional Iymph node metastasis to para-aortic lymph ‘odes with or without metastasis to pelvic lymph nodes N= Regional Lymph Nodes | M- Distant Metastasis MO No distant metastasis MI Distant metastasis (excluding metastasis to vagina, pelvic ‘efo8a, or adnexa, including metastasis o inguinal lymph ‘nodes, intra-abdominal lymph nodas other than para-aortic, cr pelvic nodes) BTNM Pathological Classification ‘The pi and pN categories correspond to the T and N categories, NO Histological examination of a pelvic lymphadenectomy specimen will idinariy include 10 or more lymph nodes, Ifthe lymph nodes are negative, but the number ordinarily ‘examined is not met, classify as pNO. “The information presented here has besn excerpte tom the 2077 TNM classiicaion of malignant tumours, eighth exten (299,2780}. © 2017 UICC. "Aa deck lor specie questions about he TNM cassiicaton i avalabe al ips wwwice.orgiinn-help-ceckpM - Distant Metastasis" PMI Distant metastasis microscopically confirmed Note pO and pMX are not valid categories, G Histopathological Grading For histopathotogical grading use Gt, G2, or G3. For details see Creasman etal. 2008" stage stage 0 Stage iA Stage 1 Stage I Stage A Stage Stage MC Siage INC SiagetIC2 Siage VA Stage NB 1s Ta m8 wR Tea 135 Tires mets mrs " any No No No No No No Nine Ni Ne Any anv ESSSSSS5555 Reference 1 Creasman WT, Odicino F, Maisoneuve P, Quinn MA, Beller U, Benedet JL, Heintz APM, Ngan HYS, Pecorell S. FIGO Annual Report on the results of treatment in gynaecological cancer. Yo. 26. Carcinoma of the corpus uteri. Int J Gynecol Obstet 2006; 95 (Suppl. 1): 105-143, ‘The infrmation presented here has been excarpted om the 2017 TNM classification of malignant umours, eighth eaten (298.2780). © 2017 UICC. “Atielp desk lor specie questions about he TNM classification fs vale t hipinma wie ori hep -cesk TNM staging of tumours of the uterus - endometrium 19TNM staging of uterine sarcomas Uterine Sarcomas (Leiomyosarcoma, Endometrial Stromal Sarcoma, Adenosarcoma) (ICD-O-9 C53, 54, 4.1, 54.2, 65) “The definitions of the T, N, and M categories correspond to the FIGO stages. Bath systems are included for comparison? ules for Classification The classlication apples to sarcomas except for carcinosarcoma, whichis classified as carcinoms of the fencometrium. There should be histological confirmation and ‘vision of cases by histological type “The following are the procedures for assessing T, N, and M categories: Teategories Physical examination and imaging Neategones Physical examination and imaging Meategories Physical examination andl imaging | the FIGO stages are based on surgical staging, (TNM stages ‘are based on clinical andor pathological classification) Anatomical Subsites 4. Cervix uter (C53) 2, Isthmus ute (C540) 3. Fundus uter (C543) Histological Types of Tumours Leiomyosarcoma 8890/3 Endometrial stromal sarcoma 8930/3 | Adenosarcoma 8933/3 Ragional Lymph Nodes: ‘The ragional lymph nades are the pelvic (hypogasttic [obturator internal lige}, Common and extemal iliac, parametral, and sacral) and the para-aortic nodes. | TM Clinical Casstcation Leiomyosarcoma, Endometrial Stromal Sarcoma T-Primary Tumour Tia_1A___Tumour Sem ess in greatest cimension Ti 1B Tumour mere than 5 om D 1 eratenen bees einen Tea__WA__Tumouriwales acnoxa Tab IG __ Tumour involves other pelvic issues T3b ft) ‘More than one site | = ‘Simuitaneous tumaurs ofthe uterine corpus and ovaryipevis| i association with ovarianipelvic endometriosis should be | Classified as independent primary tumours. Adenosarcoma T= Primary Tumour 7 Tumours othe wos : Tumour ised oto endonetion! m endocervin, . Turout mete tan aie Te B __monerim | Tee Tunourinvadea ore han ha oe | yar 7 Taro ends Bayo he tun win hops a Tapa _Twraurinoes har evi Tues | 7 Tumour votes abdorina aes | TWA Oveste Tae WB Mor ran an io | wi HG Metastasis oregon yp odes ™ TWA Tsu GGG Oem | ws NB Data metastasis Note Simutianeous tumours of the vsti corpus and ovaryipevis | in association with ovarian/pelvic endometriosis should be classified as independent primary tumours. | “The infomation presented here hes bean excerpts ftom the 2017 TNM eassiicaton of malignant tumours eighth edian (295,2780}. ©2017 UICC. SRG douk or specie quesions about he TNM classiicatcn fs avalable at tps wwnnice orgen-hep- deck,N—Regional Lymph Nodes NX. Regional lymph nodes cannot be assessed NO No regional iympn node metastasis, Ni Regional lymph node metastasis M~Distant Metastasis MO No distant metastasis: MI Distant metastasis (excluding adnaxa, pelvic ana abaominal issues) TNM Pathological Classification ‘The pT and pN categories correspond tothe T and N categories, pM - Distant Metastasis* MIT Distant metastasis microscopically confirmed Note pM and pMX are not valid categories, Stage - Uterine Sarcomas Stage 1 No Mo Stage A Ta NO Mo Stage 8 118 ND Mo. Siage iC Te ND MO. Stage R ND Mo Siage IIA Tea No Mo Siage Ii rp No Mo. Stage lia Ta No Mo Siage 118 130 No Mo Siagelnc = ThIar3 Nt Mo Stage IVA w Any Mo StageVa Any any Mt Nate * Stage IC does not apply for leiomyosarcoma and endometrial stromal sarcoma, References 1 Prat J FIGO staging or uterine sarcomas. Int Gynaecol Obstet 2009; 104: 177-178. 2 FIGO Committee on Gynecologic Oncology Report. FiGO Staging for uterine sarcomas. Int Gynaeco! Obstet 2009; 104: 179, The ntrmation presented hare hes been excerpted fom the 2017 THM cassiation of maignant tumours, eighth exton|205,2700), © 2017 UICC. "Anelp desk or specie questans about the TNM classticaion s avaiable a Migs ies orglnm helpdeskTNM staging of g Gestational Trophoblastic Neoplasms (WeD-0-3 658) ‘The folowing classification for gestational trophoblastic tumours eased on that of FIGO adopted in 1992 and updated in 2002" ‘Fae detintong of T and M categories correspond to the FIG Tages. Bo systems are included for comparison. In conast feather sites, an N (regional iymph nade) classification does. apply to these tumours. A prognostic scoring index, which is ceeaeeN actors other than the anatomic extent of the disease, easety io assign cases to high-risk and low-risk categories, and these catagories are used in stage gr0uping Rules for Classification The classification apples to choriacarcinoma (8100/3), Te sive nydatidform mole (9100/1), and placental site ophoblastic tumour (9104/1). Placental ste tumours should be weparted separately. Histological confirmation not sad il the human chorionic gonadotropin (BCG) level's eoxormally elevated. History of prior chemotherapy Yor this disease should be noted. Sra allowing are the procedures for assessing T and M categories: T categories: Cinical examination, maging and endoscopy, fand serumiurine phioG level Mcategories: Clinical examination, imaging, and assessment of serumiurine phCG level isk categories: Age. type of antecedent pregnancy, interval onthe from index pregnancy, pretreatment orununne piicG, diameter of largest tumour, site of metastasis, rumber of metastases, and previous faled chemotherapy are integrated to Provide a prognostic score that divides cases {ito low and high-isk categories, estational trophoblastic neoplasms ‘TM Clinical Classification ‘T— Primary Tumour 1K Primary tumaur cannot ve assessed 10 No evidence of primary tumour 7 i [Tumour confined to lee “Tumour eriendate aher genital srusttes: we " Yagina, ovary, oad ligament, faopian tube by metastasis or aect extension wa TL Metastasis 1 wnat) we WV Oer tant metastasis Notes MGhages | to IV are subdivided into A and B according to the prognostic score. Pattal metastasis (vagina, ovary, broad ligament, fallopian tube] is classified T2. Rey volvement of non-genital sructures, whether by deck ‘antiin or metastasis fs described using the M classification. TM Pathological Classification ‘The pT categories correspond to the T calogories pM Distant Metastasis" BMI Distant metastasis microscopically contmed Note "DMO and! pMX are not valid categories. Stage ‘sige! tT Mo stage 2 Mo. Stage It Any Ma stage Any mo. Reference Fegan HYS, Bender H, Benedet JL, Jones H, Montrucol GC. Pecorali §; FIGO Committee on Gynecologic Oncology. Gestational trophoblastic neoplasia Int J Gynecal Oostet 2002; 77: 285-287. : — ne njometon preerednare hes been excerptod mths 2017 TNA ciaslicaon omafgnan mous. On ses oe 2790), @ 2017 UICC, Tee ein dure TN lassicaon valle tipster org rep-askrT: TNM staging of tumours of the cervix uteri Cervix Uteri (icD-0-9. 653) ‘The definitions ofthe T and M categories correspond tothe FIGO. stages. Bath systems are included for comparison ules for Classification ‘The classification applies only o carcinomas. There should be | histological contimation ofthe cisease. ‘The loliowing are the procedures for assessing T, N, and M catagories: Teatagaries Clinical examination and imaging* Neategories _Ginical examination and imaging categories Cinical examination and imaging Note The use of diagnostic maging techniques to assess the size of the primary tumour is encouraged but is not mandatory. Other investigations, e.g, examination under anaesthesia, cystoscopy, sigmoidoscopy inavenous pyelograpiny, are optional and no longer mandatory, ‘The FIGO stages are based on clinical staging. For some Stage | subdivisions (IA-IB1) are mainly pathological including the nistological examination of the cervix (TNM stages are based ‘on clinical andlor pathological classification) Anatomical Subsites 1. Endocervx (C53 0) 2. Exocervix (C53.1) Regional Lymph Nodes The regional lymph nades are the paracarvical, parametil, hypogastric (intemal lac, obturator. common and external ac, presacral, lateral sacral nodes, and paré-aortic nodes." Note * Inthe 7th edition the para-aortic nodes were considered to be sistant metastatic bul fo be consistent with advice from FIGO the para-aortic nodes are now classified as regional NM Clinical Classification ‘T—Primary Tumour Primary tumour cannet be assessed 10 [Nb evidence of primary turour Te Carcinoma inst (preinvasive earenoma) Tumez confined he core Invasive carcinoma daagnosed only by ‘mtoscopy Siromalinvasion wih a maximal {depth of 8.0 mm measured fram the base tthe epthelum and horizontal spread of Zommor less" Tew Measured somal nvasion 3.0 mm orlessin Tat ‘Septhand 70mm or leas in hrzonal spread ‘Meseured tomal invasion more than ‘30mm ane not mare han 50 mm wih @ otiontal spread of 0 mm or ess Tz a2 7 ‘lineal visible lesion confined tothe conve me frmicroscopic sion greatar Pan Tal ‘citcaly vole lesion 4 0.0m oriess in ‘realest meson (nical visible lesion more than 4 Demin ‘reatet mension Tumour iwades beyond uenus ba not pele wal oro lower tro vagina Tet gt Tike Be n " T2a_IA___Tumour without parame ivasion Cincy visible lesion 40 emer lesan Lat greatost dimension eat Ch ly ws lesion mare han 4 Demin re82 a ine 2B __Tumour wth paramatial invasion Tlumaur valves lover td of vagina, crentonds to pevie wal or eau hydronephrosis or nor-functoning kidney m Téa A Tumaurinvalve lower hie of vagina Turnau erent pelo wall or causes 130 hyronephross or nar-functeringkisney 18 Turmourinvacas mucosa othe laser ar 2 rectum, or extends beyond ue pelvis" va Notes Extension to corpus uteri should be disregarded "The depin o invasion should be taken from the base of the epithelium, either surface or glandular. fom which itoriginates. The depth of invasion is defined as the measurement of the {tumour trom the epithelal-stromal junction ofthe adjacent most superficial papilae to the deepest paint of invasion All macroscopically visible lesions even with superficial invasion are TrbVIB, * Vascular space involvement, venous or lymphatic, does nat affect classification. Bullous o@dema is not sufficiont to classify a tumour as Ta ‘The information presented here has been excerpted tm the 2017 TNM claesifcaton of malignant tumours eighth econ [205,2700). © 2017 UICC. ‘tei desk lor specie quosions about the TNM classifeaton is avalable at ips: www ice orginm-nelp-desk TNM stunine oF umoure of the oarvis ule 23= __ Ne Regional Lymph Nodost Stage | Nx "Hagionalymph nodes cannot be assessed sige Te No Mo NO No regional iymph node metastasis, some, nH No wo Ni Regional iymeh node metastasis cs eee) No Mo Sage? Tee No No Nota Sage 1 No Mo *No FIGO equivalent oc eric i. na Sagelb2 Tite No Mo M-Distant Metastasis Sigel R No ey MO No distant metastasis Svea Tas, No ko Mi Distant metastasis (eludes inguinal lymph nodes anc Sagetal Tat No wo irrapertoneal disease) I excludes metastasis 0 vagina, geseine Re Ke i pee serosa, and acnexa eal % 8 Ky SagellA TB No vy Sageli® 130 Davi Mo [pINM Pathological Classification oo we *e ‘The pt and pN categories corespond tothe T and N categories age sy prance a “ SageVa | AnyT soy ue ro aeeece nee rosters Fee Cree maby pM - Distant Metastasis* BMt_ Distant metastasis microscopically confirmed Note. pM and phx are not valid categories “The information presented here hes been excerpted fom ne 2017 TNM classification of malignant tumour, eighth edtion 285,2790). © 2017 UICC. ra ols deck lor specie quosions about he TNM classiiealon Is avalable thitpswwr. ee orgtnm-hap-ceskTNM staging of tumours of the vagina Vagina (100-0-8.059) ‘The defintions ofthe T and M categories correspond to the FIGO. stages, Both systems are included for comparison ules for Classification The classification applies to primary carcinomas only. Tumours present inthe vagina as secondary growths from either genital or extragenital sites ate excluded. A tumour that has extended ‘a the porto and reached the external 08 (orice of uterus) is classified as carcinoma ofthe cervix. A vaginal carcinoma occurring § years after successful treatment (complete response) of a carcinoma ofthe cervix ute is considered a primary vaginal carcinoma. A tumour involving the vulva is classified as carcinoma ofthe vulva. There should be histological confirmation ofthe disease. ‘The following are the procedures for assessing T. N, and M categories: categories Physical examination, endoscopy, and imaging | Neategones Physical examination and imaging ‘Meategories Physical examination and imaging ‘The FIGO stages are based on surgical staging. (TNM stages ate based on cinical andi pathological classiication ) | Regional Lymph Nodes | Upper two-thirs of vagina: the pelvic nodes including obturator, internal lac (hypogastric), external ilac, and palwe nodes, NOS, | Lower tid of vagina te ingnal ane femora nodes ‘TNM Clinical Classification Primary Tumour ™% Primary tumour carnat be assessed [No evidence af primary turnout Te Carcinoma st (preinvasive carcinoma) “Tunour conned 0 vagina “Turnout invades paravaginaltesuee | touscoount | Tour exons pai wal - Tumours nvceact iro Wo Dita ross Note * The presence of bullous oedema is not suflcient evidence to classiy a tumour as T4 N-Regional Lymph Nodes NX Regional lymph nodes cannot be assessed NO No regianal lymon nage metastasis, NI Regional lymph node metastasis M~ Distant Metastasis MO No distant metastasis Mi Distant metastasis, ‘TNM Pathological Classification The pT and ph categories correspond tothe T and N categories. [PND Histological examination of an inguinal lymphadenectomy specimen will ordinary include 6 or more lymph nodes. a pelvic lymphadenectomy specimen wil orcinanly include 40 or more lymph nodes. ifthe lymph nodes ara negative, ‘but the number ordinary examined 's not mel, classify 28 pNo, pM ~ Distant Metastasis" pM” Distant metastasis microscopically confirmed Note *pMO and pMX are not valid categories, ‘stage o Ta No Mo stage! n No Mo stage No Mo Stage I 13 No Mo. Tiara Nt Mo ‘stage WA 4 Any Mo. StageVB Any any Mi The information presented here has been excepted trom the 2017 TNM classification of malignant tumours eign edition 295,2790). 6 2017 UICC. ‘Ahelp desk or specie questions about the TNM classiiston avaiable at pana uice organ nelp-deskTNM staging of tumours of the vulva Vulva (100-0-3 681) ‘The definitions of the T, N, and M categories correspond tothe FIGO stages. ules for Classification ‘The classification applios only to primary carcinomas of the viva. There should be histological confirmation of he disease. ‘A carcinoma of the vulva that has extended tothe vagina Is classified as carcinama ofthe vulva ‘The following are the procedures for assessing T, N. and M categories: Teategories Physical examination, endoscopy, and imaging Neategones Physical examination and imaging Meategones Physical examination and imaging The FIGO stages are based on surgical staging, (TNM stages ‘are based on cinical andor pathological classification ) Regional Lymph Nodes: ‘The regional lymph nodes are the inguinotemoral (groin) nodes. ‘TNM Clinical Classification —Primary Tumour 1X Primary tumour cannot be assessed TO No evidence of primary tumour Tis Carcinoma in situ (preinvasive carcinoma), intraepithelial reoplasia grade il (VIN Ii) T1 Tumour confined to wulva or vulva and perineum Tia Tumour 2 cm or less in greatest cimension and with stromal invasion ne greater than 1.0 mm Tit Tumour greater than 2 om andlor with stromal invasion greater than 1 min" 12 Tumour invades any of the folowing structures: lower thre Urethra, lower third vagina, anus Ta" Tumour invades any ofthe following perineal structures: upper 2/3 urethra, upper 2/3 vagina, bladder mucosa, rectal mucosa, or fixed to pelvic bone Notes "The depth of invasion is defined as the measurement ofthe tumour from the epithetal-stromal junction ofthe adjacent most superficial dermal papilla io the deepest point of invasion, © T3is not used by FIGO, N-Regional Lymph Nodes NX Regional lymph nodes cannot be assessed [ES No regional lymph node metastasis, NI Regional lymph node metastasis wit the folowing features: Nia Oneortwo lymph node metastases each less than 5mm Nib One lymph node metastasis 5 mm or greater N2__ Regional iymoh node metastasis with tho following features: N2a_ Three or more lymph node metastases each less than 5 mn Nab Two or more lymph node motastases § mm or ‘greater Nac Lymph node metastasis with extracapsular spread N3_ Fixed or ulcerated regional lymph node metastasis, M- Distant Metastasis: MO No distant metastasis Mt Distant metastasis (including pelvic mph node metastasis) BTNM Pathological Classification The pT and pN categories correspond to the T and N categories, [BNO Histological examination of an inguinotemoral lymphadenectomy specimen will ordinary inckude 6 oF more lymph node. Ifthe lymph nodes are negative, but the number ordinarily examined is not met, classify a8 PNO. pM - Distant Metastasis" BMT” Distant metastasis microscopically confirmed Note *pMO and pMX are not valid catagories, Stage ‘tag 0 Ts No Mo Stage 1 No MO Stage IA Ta No Mo Stage IB re No Mo. Stage a No Mo Stage IIA mi Nia.ni Mo Stage IIE mre NeaN2b Mo Stage IC m2 Nae Mo Stage VA me Ns Mo B Any Mo stage vB AnyT any mi “The information presented here has been excerpted om the 201? TNM classification of malignant tumours, eighth ediion [26,2780 @ 2077 UICC. Amel desk for specie quesiens about he TNM claaieaton Is avalabe at ips ice xgtnm-nep-cosk,TNM staging of tumours of soft tissues Soft Tissues ((CD-0-9 038.1, 2, 8, C47-49) ules for Classification ‘There should be histological confirmation ofthe disease and division of cases by histological type and grade ‘The following are the procedures for assessing T, N, and M categories: Trealagories Physical examination and imaging Wecategoies Physical examination and imaging ‘Meategaries Physical examination and imaging Anatomical Sites 1. Connective, subcutaneous, anc other soft tissues (C49) peripheral nervas (C47) 2. Retropertoneum (C48,0) 3 Mediastinum: anterior (C38 1); posterior (C38.2); mediastinum, Nos (C383) Histological Types of Tumour Te following ristolagical types are not included: ‘+ Kaposi sarcoma, ‘+ Dermatofibrosarcoma (protuberans) ‘+ Fibromatosis (desmord tumour) ‘Sarcoma arising from the dura mater or brain ‘+ Angiosarcoma, an aggressive sarcoma, is excludes because its natural history is not consistent withthe ciasification, Note Cystosarcoma phyllodes is staged as a soft issue sarcoma of the superficial trunk. Regional Lymph Nodes ‘The regional lymph nodes are those appropriate tothe ste (ofthe primary tumour. Regional node involvement is rare an cases in which nada status isnot assessed either clinically or pathologically could be considered NO instead of NX or pNX TNM Clinical Classification T-Primary Turnour TX Primary tumour cannot be assessed TO Noevidence of primary tumour Extremity and Supericia Trk Tumour § cm or less in greatest dimension Simeon toe adhere hen ee ogee dimension 3. Tumour more than 10 em but ro more than 18 cm in greatest dimension T4 Tumour more than 15 cm in greatest dimension Retroperitoneum Tt Tumour 5 em or ess in greatest dimension 2 Tumour more than § cm but na more than 10 em in greatest imension 3. Tumour more than 10 em but ne more than 18 em in greatest dimension 4 Tumaurmore than 1$ em in groatast dimension Head and Neck Tt Tumour 2 em orless in greatest dimension 72 Tumaur more than 2 om but no more than 4 cm in greatest dimension 3. Tumour mare than 4 em in greatest dnension Téa Tumour invades the ortt, skull base or dura, central ‘compartment viscera, facial skeleton, andor pterygoid muscles 4b Tumour invades the brain parenchyma, encases the carotid artery, invades prevertebral muscie or involves the central nervous system by perineural spread Thoracic andl Abdominal Viscera Tt Tumour confined toa single organ “Tea. Tumour invades serosa or visceral peritaneum ‘72 Tumour with microscopic extension beyond the serosa 3. Tumour invades another organ or macroscopic extension ‘beyond the serosa ‘Multifocal tumour involving no more than two sites in one organ ‘Multifocal tumour involving more than two sites but not more than 5 sites ‘Tae Mulilocal tumour involving more than five sites Téa Tab N~ Regional Lymph Nodes NX Regional lymph nodes cannot be assessed NO No regional lymph node metastasis Ni Regional ymoh node metastasis M- Distant Metastasis MO No distant metastasis MI Distant metastasis, PTNM Pathological Classification ‘The pI’ and pN categories correspond to the T and N categotes, pM - Distant Metastasis* BMI Distant metastasis microscopically contiemed Note “pO and pM are not valid catagories ‘The intrmation presertea here as been excerpted fom the 2017 TWM classiicaton of maignan numous,elhth exon |285,279%), © 2017 UICC. "Ahelp desk or specie questans about the TNM classteaion avaliable a ribs: pwew lee rg -hok-desk "TN staaine of umeure ef seh tame 7Stage Extremity and Supericial Trunk and Rettopertoneum ‘StagelA TI Spel Terare No Stag t No Stage iA 12 No Sage li 7374 —NO ant Nt Sage AnT Any Note wo Mo Mo Mo Mo me G1Gx Low Grace GGX Low Grace G2GsHigh Grade G2GsHign Grade G2GsHign Grade Bay any *AJCC classifis Ni as stage IV for extromity and superficial trunk ‘Stage - Head and Neck and Thoracic and Abdominal Viscera, “There fs no stage for soft issue sarcoma ofthe nead and neck ‘and thoracic and abdominal viscera, ‘The ntrmation presentad hare has bash excerpted ftom the 2017 TNM ciassiiaton of maignant lumout, eighth edion [295,2790). © 2017 UICG. “Ahp desk or spect questions stout the TNM Classicaton Is avalaba a! Mos: fwww uc o%gfnm-help-desk oR TN ataninn af tumeure af anit tinanen,General introduction The classification of female genital tumours has evolved sig. nificantly over the past decade in light of new and often key molecular discoveries that have influenced the categorization of a number of these neoplasms. Distinctive molecular altera- tions are now known for many female genital tumours and have proved to be helptul for their correct categorization. Therefore, as in other organ systems, the morphological classification ‘continues to advance into an integrated morphological-molec- Ular classification that will have an impact on diagnosis and treatment, One of the best-known applications of molecular pethology pertains to endometrial carcinomas: surrogate immunohistochemical markers (except for POLE) are used to stratify these tumours into four subgroups with distinctive prognoses, as defined by The Cancer Genome Atias (TCGA] project. However, it is recommended that the molecular char- acterization of endometrial carcinoma should be restricted to high-grade tumours, because more than two thirds of endo- metrial carcinomas are low-stage and low-grade endometrioid carcinomas associated with an excellent prognosis and do not need molecular profiling, The classification of female genital tumours, as well as those of other organ systems, is intended for worldwide use, and there are many areas where, for various reasons, the application of immunohistachemistry or molecu- lar pathology is limited. Additionally, standard aspects of con- ventional pathology remain the bedrock of the interpretation and classification of female genital tract (FGT) neoplasms in routine practice, and to emphasize this point, the essential Giagnostic criteria for each entity in this volume are based on these characteristics. The organization of this fifth edition of the female genital tumours volume follows the general structure of other vol- umes in this series and differs from the prior eaition in several respects. To avoid repetition, new chapters have been created fo amalgamate entities that have similar morphological and molecular findings at different sites, including mesenchymal tumours of the lower FGT, metastases to the lower FGT, hae- matopoietic neoplasms, neuroendocrine neoplasms (NENS), ‘and associated hereditary syndromes. NENs of the FGT (with the exception of ovarian carcinoid tumours, due fo thelr spe- Gific characteristics and germ cell origin) are now classified following the terminology of their pulmonary and pancreatic Counterparts and a recently published consensus proposal initiated by the International Agency for Research an Cancer (IARC) and WHO {2292}, although studies are still needed with Tegard to optimal terminology in the FGT. Among the haemat- poietic neoplasms, emphasis is given to those entities more ‘commonly occurring within the FGT and specifically in each organ. Terminology is the common language used by patholo- gists and treating physicians for optimal patient care, and it should be consistently applied. Therefore, before making a change to terminology, itis important to consider the impact Lax SF Cheung AN Oliva E of that change. For this reason, the editorial board proferred to retain the existing, well-established terminology for several tumours. For example, in the ovary, the term “small cell car- cinoma of hypercalcaemic type" has been retained over the proposed thabdoid tumour terminology, because although most of these tumours are associated with SMARCAS muta- tions, only a minority show overt rhabdoid morphology, and itis still controversial whether they are identical to rhabdoid tumours. On the other hand, some important revisions have been made since the fourth edition of the WHO classifica- tion. For example, serous borderline tumours with micropap- illary architecture are now included within the broad group of serous borderline tumours, and the term “non-invasive low-grade serous carcinoma’ is not recommended for them. Low-grade and high-grade serous ovarian carcinomas are considered distinct tumour types rather than a spectrum, because they have different origins, as well as different mor- phology and molecular and genetic signatures. Among the Uterine neoplasms, carcinosarcoma is now classified as an ‘endometrial carcinoma rather than a mixed tumour, on the basis of molecular and biological similarity to high-grade ‘endometrial carcinomas. Undifferentiated endometrial car- cinoma, including dedifferentiated carcinoma, is considered a distinct entity supported by molecular alterations involving the SWI/SNF pathway. Minor changes include the reclas- sification of different subtypes of endometrioid carcinoma (e.. with squamous differentiation) as simply patterns of endometrioid carcinoma, leading to a leaner classification. ‘Among the mesenchymal tumours, the category of smooth muscle tumours has been expanded with the new category of fumarate hydratase-deficient leiomyomas, and the cat- egory of high-grade endometrial stromal sarcoma has been expanded to include neoplasms with novel gene fusions (in particular involving the BCOR gene), whereas the undiffer- entiated uterine sarcoma entity has been redefined, In the category of mixed tumours of the uterus, the term “adenofi broma’ is no longer recommended. HPV has dramatically changed the approach to epithelial tumours of the lower FGT, and this shift is reflected herein ‘Adenocarcinomas of the uterine cervix are now divided into HPV-associated and HPV-independent adenocarcinomas, with implications for prognosis. More importantly, recent studies have put forward a reproducible histological surro- gate for HPV infection, allowing for such classification without HPV analysis. Squamous tumours of the lower FGT are also divided into HPV-associated and HPV-independent, because important differences in outcome oxist. Squamous precur- sor lesions throughout the lower FGT are primarily classified according to the binary Lower Anogenital Squamous Ter- minology (LAST) standardization project proposal, but the three-tiered intraepithelial neoplasia classification can siill be used. General introduction 28Most grading systems rely an mitotic activily and necrosis. ‘An important change in this edition of the WHO Classification of Tumours series is the conversion of mitotic count from the traditional denominator of 10 HPF to a defined area expressed in mme, This serves to standardize the true area over which mitoses are enumerated, because different microscopes have high-power fields of different sizes. This change will also be helptul for anyone reporting using digital systems. The approx imate number of fields per 1 mm? based on the field diameter and its corresponding area is presented in Table A. Finally, increased knowledge about hereditary tumour syn- cromes has enabled us to detect carriers at an early age through counselling and genetic testing, more commonly in Lynch Table A Approximate numberof fois per 1 mn based onthe fit ameter ad is 040 0126 8 oat ose 8 042 098 7 048 045 7 om ose 7 045 0159 6 046 0168 6 oar ours 6 048 0181 6 049 0188 5 050 0198 5 ost ozo 5 ose oar 5 053 022i 5 ose 0229 4 085 237 4 058 0286 4 osr 0255 4 08 028 4 059 o2r3 4 060 0283 4 ost 02 3 oe 0302 3 06 ost 3 ost ose 3 065 0332 3 068 03 3 oer 0382 a 068 0353 3 069 osm 3 30 General introduction syndrome but also for other rare syndromes. Lynch syndrome. patients may be the best-known example, because endometrial cancer is not infrequently their first presentation. Immunchisto. chemistry, which can be performed in most pathology settings, is key for triaging these patients for further studies. Another exam. ple is patients with Peutz—Jeghers syndrome, who typically have bilateral, smal, and multifocal sex cord tumours with annular tubules and may have cervical gastric-type mucinous adenocar. cinoma, typically associated with STK?" alterations, These exam. ples illustrate the increasingly important ole of pathologists in the ‘multigisciplinary assessment of hereditary diseases, The ICD-O topographical coding for the anatomical sites cov. ered in this volume is presented in Box A. Box A IC0-0 topographical coding lr the man anatomical tes coven this volume (617) (051 vlva i (051.0 Labium mus (51-1 Labi minus i 0512 Choris (51.8 Qvaaging lesion of viva i 51.9 VoWaNOS i (652 Vagina (52 Vagina NOS (058 Cervix ter (0580 Endocorix (053.1 Exocera (58.8 Oveagging lesion of cor ter (0539 Cen te i (54 Corpus utr i (54.0 Isthmus en (054.1 Endometium (542 Mjomeium (054.3 Fundus er (054.8 Overlapping lesion of cops or (549 Copus uteri (055 Uterus NOS (0558 Uterus NOS 56 Ovary (C569 01a (57 Other and unspecified female genital organs (57.0 Faloan tube (57.1 Broadligamere (0572 oud igament (657.3 Pararetium (57.4 Uterine adnexa 57.7 Othe pec pas of ele genial organs (0578 Qverapping leson of fra genta organs (57.9 Female genial rac NOS (058 Placenta (C589 PlaontaTumours of the ovary Edited by: Cheung AN, Ellenson LH. Giks CB, Kim K-R, Kong CS, Lax SF, Long McCluggage WG, Oliva E, Rabban JT, Soslow RA Sooner (reneres ined ere mere ene Cees Seen an Pema Curae eae eeemep ata Nees ote ee Wehner Rae Rotem eters (see eaeers recs Mesothelial tumours (see Chapter 3) eee Necro onenessTumours of the ovary: Introduction Estimated age-standardized incidence rates (World) in 2018, ovary, all ages seine) per 0000 $35 MM totale Fig. 1.01 Ovary cancer map Estimated age-standardzedinidence rates (ASR; Wor), pet 100000 person-years, of vain cancer in 2018 In 2018, ovarian cancer ranked as the eighth most common cancer diagnosis and cause of cancer death in women, with an eslimated 296 000 cases and 184 000 deaths worldwide {293}, The most common histological type is high-grade serous carcinoma (HGSC) [337]. There is geographical variation, with high incidence raies in North America, central-eastern Europe, and south-eastern Asia, and low rates in sub-Saharan Africa fand western Asia (293). In most countries where long historical data exist, a gradual deciine in the incidence of ovarian can- cer where rates were traditionally highest has been reported {37}. The observed deciine has been mainly attbuted to the widespread use of oral contraceptive pils that have long-lasting protective effects against ovarian cancer alter several years Of use {337,2753}. In addition, other reproductive factors such 2s higher parity (higher number of children) and breastfeeding have also been reporied as protective factors against ovarian cancer. In lsael, where women are reported to have some ofthe highest frequencies of germline BACAN2 mutation |337,2753), ‘which also increases ovarian cancer risk by 8-48% (2136), a Gooreasing trend has been noted. This finding indicates that high rates of riskreducing surgery can be added to the fac- tors mentioned above, Other factors, such as tobacco smoking and obesity, have been related to an increased risk of certain types of ovarian cancers {131}, with obesity being related to an ‘observed increase in ovarian cancer in younger cohorts in some 32 Tumours of the ovary McCluggage WG Lax SF Longacre TA Malpica A Sosiow RA, al et populations, Finally, there have been temporal changes linket to changes in the classification of borderline ovarian tumour {837}, which, since ICD-O-3 in 1990, are now grouped as non: malignant. This might have contributed to the decreasing rat in some countries, which by now should have stabilized, ‘The classification of ovarian neoplasms in this fith edition of the WHO classification of tumours is largely unchanged from the previous edition, One addition to the current classification ig mesonephric-like carcinoma |1737}. The category of mixed car cinoma has also been reintroduced in the current classification, although it is stressed that mixed carcinomas of the ovary are very uncommon and that most carcinomas that look mixed from ‘a morphological viewpoint in fact represent a single neoplastic type with areas morphologically mimicking another turnour type (984, 16071, The previous WHO classification fist divided ovarian serous carcinoma into low-grade and high-grade carcinomas, whict represent two completely different tumour types (with differen morphology, pathogenesis, molecular events, and progno sis) rather than low-grade and high-grade forms of the same neoplasm {2543), It is now well established that a significan majority of so-called ovarian HGSCs arise from the distal fim bral end of the fallopian tube from a precursor lesion know! ‘as serous tubal intraepithelial carcinoma, whereas almost a low-grade serous carcinornas (LGSCs) arise within the ovarov 19861952 evn 2062012 Jpn 4 oe eect eal ‘ere ie che chine ‘AustraiamNew Zealand “Zsa Kaa Contra & South Ameica casein sive suomi Eastem European Spe coun sant stem lor America Yea Eel Nom Ame iret ‘canadt sean Sept \Notthem Europe 4 ez sen seen act octane Southem Europe SE if coset cot Wiestem Europe Stand ont 0% 20% 40% 60% 80% 100% 0% 20% 40% 60% 80% 100% menses cre Fig 1.02 Ovarian cancer by histological pe. Distibuton of vaian cancer by hstotogical type selected countiestregion, 1988-1992 and 2008-2012, from benign and borderline serous tumours. Criteria for site assignment in extrauterine HGSC have been proposed (see Table 1.01, p. 34) {2550,1709,2549,2548, 2547], and the use of these criteria results in a high proportion of cases (~80%) being classified as tubal in origin, whereas primary peritoneal HGSCs are exceedingly rare. This diagnosis should be made only when there is no mucosal serous tubal intraepithelial carcinoma or HGSC within either tube — both of which should be macroscopi- cally visualized in their entirety and examined in total histologi- ally using the SEE-FIM (sectioning and extensively examining the fimbriated end) protocol - and no ovarian parenchymal Hasc. Seromucinous carcinoma was included in the previous clas- sification and was defined as a carcinoma composed predomi- nantly of serous and endocervical-type mucinous epithelium, often with foci containing clear cells and areas of endometrioid and squamous differentiation (2738). It has been removed from this classification because itis a poorly reproducible diagnosis and there is significant morphological averlap with other tumour ‘ypes, especially endometrioid carcinoma, Immunohistochemi- cal and molecular studies have also suggested that most of these tumours represent unusual morphological patterns of endometrioid carcinoma {2230}; therefore, seromucinous carci- noma is now considered a subtype of endometrioid carcinoma and is discussed in that section, Increasingly, immunohistochemistry (and molecular test- ing) is used to classify ovarian carcinomas, although mor- phology remains the mainstay in diagnosis. Previously there was poor interobserver agreement among pathologists in the classification of ovarian carcinomas, but the classification is now highly reproducible using madern diagnostic criteria sup- plemented (when necessary) by immunohistochemistry (1343, 1345}, Table 1.02 (p. 34) and Fig. 1.03 (p. 35) illustrate the immunophenotype of the most common primary ovarian carci- nomas; however, it should be remembered that aberrant stain- ing patterns are always liable to occur. There have also been advances in the panel of immunomarkers that can be used in the differential diagnosis of primitive germ cell tumours, and this is shown in Table 1.03 (p. 34), ‘The classification of ovarian sex cord-stromal tumours, germ cell tumours, miscellaneous turnours, and tumour-like lesions is largely unchanged from the previous WHO classification. The category of gynandroblastoma has now been reintroduced alter being removed trom the previous classification, One area of ovar- ian pathology in which significant recent advances have been made is the elucidation of the molecular events in ovarian sex cord-stromal tumours. These represent a heterogeneous group Of relatively uncommon neoplasms that in their classic forms are relatively easy to diagnose. However, there may be consider- able morphological overlap between the various tumour types, and immunohistochemistry, although useful in confirming a sex cord-stromal tumour, is of Ite value in cistinguishing between the types. Recent significant advances include the finding that adult granulosa cell tumours contain somatic FOXI.2 mutations. in > 90% of cases {2490}, and a significant proportion of mod- erately and poorly ifferentiated Sertoli-Leydig cell tumours contain DICER! mutations (somatic or germline) {604}. Ongoing studies are rapicly elucidating the molecular events in several Tumours of the ovary 33‘other tumour types within the sex cord-stromal category. For example, microcystic stromal tumour contains CTNNBT or less frequently APC mutations and may occasionally be an extra- colonic manifestation of familial adenomatous polyposis (1498, 1706,1162\. In problematic cases, demonstration of the appro- priate molecular abnormality assists in tumour classification, Similarly, small cell carcinoma of the ovary of hypercalcaemic type nas been shown to be characterized by deleterious germ- line or somatic mutations in a single gene, SMARCA¢ {2046, 2234.1192,2950}, which is part of the SWIISNF complex, ‘able 1.01 Crteri fr asiging primary se in exreueine hgh rade serous carnoma ‘STI present Folopnube Us HGSC patent Parr entire eng of ube nseparebierom bo ovarian Both falpian bes separate rom ovarian mass and, NoSTIC ormucneal HGSC in eter be" Fealeian tubes and vats ol avaiable for complete Racowint — uno Patologia facings consistent wih extraterne HSC Bath bes and beh vais uly examined ad No gross cr microscopic evdence of STIC or HSC in ‘tubes’ or avaries Peritoneal HSC. high-grade serus carcinoma; STI, sorus tubal intaeptheta carcinoma, "Grossi normal alopian tues have been examined using he SEE-FIM (secon. ing and extensively examining the tnbiated end) protocol to exclude microscopic disease. “Ths applies in smal biopsy samples ar HGSC deveoning aller revoussapingo ‘cophoretony wth incomplete ib! examination, andi may aly in postchemote gy sugeal specimens ‘table 1.03 Inmunoistacheical rfl of ovarian germ col tours Dysgeminore ‘ + + ‘ ‘lk sac tumour + ‘ me Embyonalcarinoma + ’ : 5 Chovocarcnoma es = mature teratoma oe : s = ynetovophetoste glartcels are preset tay re HOG poi. ns keene implicated in the pathogenesis of a growing number of other malignancies. Demonstration of this mutation and/or loss of immunabistachemical staining for SMARCA4 may, in the appro: priate morphological context, be crucial for the diagnosis ofthis highly aggressive neoplasm (525,480) in this edition of the WHO classification of tumours, the cat. egory of lymphoid and myeloid tumours is addressed in Chap- ter 12; Haematoymphoid proliferations and neoplasia, where these neoplasms are dealt with at all sites within the female gerrital tract ‘able 4.02 inmunchistochemial srng of major ovaanearcromehstoypes (13511946, 17511740 1950) a Losc 67-1008 © 96-10% os 8% ec fe Ade HSB I-BOH cece om IH TH we Eid sree OE ‘OCC, dea oa carcinoma EC, endometrod carcino: HGSO, hg rade sereus ‘arco; LGSC, low-grade serous carcinoma; MC, mucinous carcinome *Rbnomal 8 exgressen (associated wih TP53 mutton eters to overeression fang ela expression ivovng> 80% of tour cel uc, compete absence ‘of exgresenn in tumour cll auc wth retained intemal conte or uneguiccal tyeplamic exgression; his deren rom widype p59 expresso (rt asocaled wen TP53 ution * PAXS expression n mucinous carcinomas oten focal ard west.Fig 1.03 Typical immunoistacheical poll ofthe 5 principal isttypes of ovarian carcinoma. First raw: High-grade serous carcinomas HGSCs) express WT! dfueeyin anos al cases; however, occasional cases exhibit focal oc negative sianng This, combination wth mutaton type p88 staining, is highly sect for HGSC and can bo used ‘or confimatonofamarpholoical iagness. Muttion-1ype pSS xpression associated wth TPES matin) eersto overexpression tong nuclear expression woving > 80% ‘ltumou ol nui; corimany, complete absence of expresso in turaur celui with ese intral convo rarely, unequivocal ytoplasnic expression. Napsin A ‘exoression absentin HGSC,andciy amine of cases express PR, Second rows Low rade serous carcinomas (LGSCs) express WTT in viaty al cases n combination lh wittype p58 expression; the later characterize by variable elaring dbuton and intensity ntumeur col nucle. Napin Ais absent an PR is oxprssod ost cases Third row: Endometriod carnamas (ECs) are usualy WTt negate (neha 10-14% can express WT someinaifuse manner) and usual show wildype p53 exoression, [Ahough amino of €¢¢ exit mutation ype 95S staining, te combination of WT staring and mutaton-ype p53 staining occurs ony rarely. ECé donot express napsin A (wih are excepon), but PRs expressed ina large majnty of cases. Fourth row Clear cel carcinomas (COCs) almost never express WT, and they show wictype p53 Staningin tho vat majorty of cases, Napin Ais Hequont positive, although only focelin a subset, whch can lead oa false nogate result on smal biopsies. PR is usually absent ith row: Mucincuscarcnamas (MC ar tually always WTT-negalve: Many cases exhib mulation ype p58 staining, Napin A and PR are almost ways ngatve Tumours of the ovary 35Serous cystadenoma, adenofibroma, and surface papilloma of the ovary Definition Serous cystadenoma, adenolibroma, and surface papilloma are benign serous tumours composed of cells resembling fal- ‘opian tube epithelium, ICD-O coding ‘8441/0 Serous cystadenoma NOS ICD-11 coding 2F32.3 Serous ovarian cystadenoma 2F92.Y & XH5ZB5 Other specified benign neoplasm of ovary & Serous adenotibroma NOS 2F32.Y & XH38C4 Other specified benign neoplasm of ovary & Serous surface papilloma Related terminology None Subtypes) Serous surface papilloma; serous adenofibroma NOS; serous cystadenofibrama NOS Localization Ovary Clinical features Patients often present with symptoms related to an ovarian mass, or tumours may be found incidentally. Epidemiology Patients present over a wide age range. Longacre TA Davidson 8 Kong CS Malpica A Vang R Etiology Unknown Pathogenesis DNA copy-number changes may be seen in the stromal fibromatous cells and (rarely) in epithelial cells (1135,434) Macroscopic appearance Tumours vary widely in size, Cystadenomas exhibit smooth outer and inner surfaces; they may be septated and filed with watery fluid. Cysts < 1 om are designated as cortical inolusion cysts. Cystadenofioromas contain cysts. surrounded by a variable ‘amount of solid areas. Adenofibromas are typically solid and Punctuated with small cysts. Surface papillomas are exophytic Histopathology ‘The epithelial lining of these tumours consists of non-stratiied cuboidal or columnar cells (resembling tubal secretory or ciliated calls) in varying proportions, In some tumours, the epithelial lin- ing is flattened and nondescript, Serous cystadenamas are pre- dominantly cystic, Serous adenofibromas are composed of small Qlands and cysts in a prominent fibromatous stroma. Serous cystadenolibromas have cysts and broad and simple papillae embedded in prominent fioromatous stroma, Surface papillomas are characterized by small simple papillae. If < 10% of the total tumour volume (except for surface invalvement) shows epithe- lial proliferation within the cysts that would otherwise qualify as serous borderiine tumour, the tumour is designated as serous ‘oystadenoma with focal epithelial proliferation {1871,799,69. Cytology Not clinically relevant Fig. 1.04 A Ovarian serous oystadenobroma. The unours predominant cystic an the cst ning s mol smoeth, with some nodule areas, B Sercus cstederotiara, (Glands ined by bland utal-ype ethan, wth eccasioral ciate cel, are presentin a bromatous stoma. 36 Tumours of the ovaryDiagnostic molecular pathology Not relevant Essential and desirable diagnostic criteria Essenfal’ tumour with benign serous epithelium, with or without fibromatous stroma: for cystadenoma, the cysts should be > tom, Staging Not clinically relevant Prognosis and prediction Serous cystadenomas, adenofibromas, cystadenofibromas, ‘and surface papillomas are benign, but they may recur after incomplete excision. Tumours with focal intracystic epithelial proliferation are also considered to be benign, but data are lim- ited, Focal epithelia proliferation on the ovarian surtace, where itis exposed to the peritoneal cavity, may potentially be associ- aled with recurrent disease (69). epinelum pxject rom the ovarian sutace. ‘Tumours of the ovary 37i Vang Serous borderline tumour of the ovary ee ong CS Longacre TA Malpica A Definition ‘Serous borderline tumour (SBT) is a non-invasive, low-grade, proliferative serous epithelial neoplasm. ICD-O coding {8442/1 Serous borderline tumour NOS. 8460/2 Serous carcinoma, non-invasive, low grade loD-11 coding 2C73.4 Serous cystadenoma, borderline malignancy of ovary Related terminology Not recommended: non-invasive low-grade serous carcinoma: atypical proliferative serous tumour, serous tumour of low ‘malignant potential ‘Subtype(s) Serous borderline tumour, micropapillaryferiprform Localization Ovary Clinical features Patients present with symptoms attributable to an ovarian mass. Epidemiology Patients present over a wide age range, The median age is 50 years (1571,992} — ‘ i Etiology Fg..08 Serous borderne tumour A Papila ae architectural come, With hi Unknown artical branching. B Papas are ined by sailed epithelium wih dbtached sll ‘users of tumour ees Fig 1.07 Hicrnapilary serous borderine tou. A Meropapiry architectures prominent. B so-caled Maduse hed appearance, on 0 KmensaatieatesFig 1.08 Epiholatype non-invasive implants associated wit» ovaian serous bor eatin uu. A Complex papilary architects present within anopthlum ined ‘paca. B Peplae contin cos wih low grade nuclear features, Psammora bodes ‘ae preter. Pathogenesis Somatic mutations of KRAS or BRAF are most common in these tumours, although BRAF mutations are less frequent in advanced stage than in stage | tumours (2544,1060,105,1215, 1134,2981) iY as wi! Nh ww i: Fa 20 Desopse rinse ns see ih ot ss btn tynow A Loge snp gar wi sit opt satiatin a se wn Shin one stova 8 dose cls ron epson thin dovmapaste ona, Ths dg dn rubles nasa Macroscopic appearance Tumours are generally > § cm and may be intracystic (and lined by excrescences} andlor exophytic with surface involvement. Approximately one third are bilateral (more common in the rmicropapillaryleribriform subtype) (1571,2829}. Invasive glans associated wih ovarian srousborderine tumour Thee is dstcveiflvation of underkng issue. Smal papize and miropepiae are ark: Fig ly cronded and naphazarayaranged. The histological appearance is akin t that of nvasie low-grade serous carcinoma, 8 Smal paplae and mccpaplla ae present itn clear lacunar spaces and demonstrate lm- grade aypa, Psammoma bodes are aso spon. Tumours of the ovary 39Fige.11 Microinvasion in @ serous todeine tunau. Smal nests and incu frour cel wih abundant eosnopceytplsm noms) ae present win spaces do {aid of epithll inag in he stoma, This she mos commen pater of mirovasion Histopathology Typical SBT is characterized by hierarchical branching papillae vith variable amounts of stroma in the cores. The epithelium is stratified, wih tufting and cell detachment. There is an admix- ture of cell types and the nuclei are heterogeneous. Variable numbers of eosinophilic cells containing moderate amounts of cytoplasm are often seen as buddingyfree-floating clusters and single cells. If this intracystic epithelial proliferation accounts for < 10% of the tumour, the neoplasm should be classified as serous cystadenoma | adenofioroma with focal epithelial pro- Iferation {2474.69}, Some tumours have a prominent adencti- bromatous appearance. The micropapillary/cribriform subtype has elongated micro- papillae without stromal cores (at least 5 times longer than Fig. 1.13 Serous borderine tumou na peli mph node. Papiary proiteation of bland serous epthelum and psammoma bodies, athe le. Thee i alo endoslpa- {09 involving this nade, at the right. Fig.122 Mcrimasiv low-grade seas carcinoma. Crowded sal and medum zee apilaoin clea laconar spaces (<5 hm in greatest extent ae silat the morphol ‘ay ofan invasive low-grade serous carcinoma. wide) that directly emanate from large papillae (the so-called Medusa head appearance) andor small punched-out criori- form spaces. An area of pure micropapillary/cribriform growth measuring > 5 mm is required for the tumour to be classified 238 the micropapillaryferibriform subtype {1571,2823}. The cells have a high N-C ratio and the nuclei are small and uniform, with ‘small nucleoli. The nuclear features should not be high-grade, and mitoses are infrequent. Stromal microinvasion is defined as invasion < 5 mm in greatest dimension in any single focus. Patterns of microin- vYasion include small clusters of cells or individual cells with Abundant dense eosinophilic cytoplasm within stroma, 2s ‘well as small papillae within clear lacunar spaces cytologi- cally similar to the non-invasive component. No desmoplasia, should be present. These cells may sometimes be within lym phatic spaces (197,2396A). This pattern is diagnosed as SBT with microinvasion. However, it the morphology resembles low-grade serous carcinoma (LGSC) and invasion measures ‘< 5mm in greatest dimension in any single focus, the tumour Should be classified as microinvasive LGSC, and extensive ‘sampling should be performed to exclude larger foci of inva- sion {2473}, ‘The tern ‘implant’ is used in the context of extraovarian disease associated with SBT of the ovary. Implants of serous, borderline are, by definition, non-invasive; if there is invasion, a diagnosis of LGSC should be made [198A). Non-invasive implants that display hierarchically branching papillae ot dotached clusters of cells not associated with stroma are des- ignated as epithelial implants. Desmoplastic implants consist of single cells or olusters of cells embedded in reactive-appearing {granulation tissue-Ike or fascitis-ke) or desmoplastic stroma that predominates over the epithelial component and appears tacked on to the peritoneal surface. The epithelium frequently blends into the surrounding stroma. If a desmoplastic implant is present on the ovarian surlace or within the cyst of an ovarian ‘SBT, the term “autoimplant” is used,