Endometrial Carcinoma, Grossing and Processing Issues: Recommendations of the International Society of Gynecologic Pathologists.

Endometrial cancer is the most common gynecologic neoplasm in developed countries; however, updated universal guidelines are currently not available to handle specimens obtained during the surgical treatment of patients affected by this disease. This article presents recommendations on how to gross and submit sections for microscopic examination of hysterectomy specimens and other tissues removed during the surgical management of endometrial cancer such as salpingo-oophorectomy, omentectomy, and lymph node dissection-including sentinel lymph nodes. In addition, the intraoperative assessment of some of these specimens is addressed. These recommendations are based on a review of the literature, grossing manuals from various institutions, and a collaborative effort by a subgroup of the Endometrial Cancer Task Force of the International Society of Gynecological Pathologists. The aim of these recommendations is to standardize the processing of endometrial cancer specimens which is vital for adequate pathological reporting and will ultimately improve our understanding of this disease.

Pathologic Prognostic Factors in Endometrial Carcinoma (Other Than Tumor Type and Grade).

Although endometrial carcinoma (EC) is generally considered to have a good prognosis, over 20% of women with EC die of their disease, with a projected increase in both incidence and mortality over the next few decades. The aim of accurate prognostication is to ensure that patients receive optimal treatment and are neither overtreated nor undertreated, thereby improving patient outcomes overall. Patients with EC can be categorized into prognostic risk groups based on clinicopathologic findings. Other than tumor type and grade, groupings and recommended management algorithms may take into account age, body mass index, stage, and presence of lymphovascular space invasion. The molecular classification of EC that has emerged from the Cancer Genome Atlas (TCGA) study provides additional, potentially superior, prognostic information to traditional histologic typing and grading. This classifier does not, however, replace clinicopathologic risk assessment based on parameters other than histotype and grade. It is envisaged that molecular and clinicopathologic prognostic grouping systems will work better together than either alone. Thus, while tumor typing and grading may be superseded by a classification based on underlying genomic abnormalities, accurate assessment of other pathologic parameters will continue to be key to patient management. These include those factors related to staging, such as depth of myometrial invasion, cervical, vaginal, serosal surface, adnexal and parametrial invasion, and those independent of stage such as lymphovascular space invasion. Other prognostic parameters will also be discussed. These recommendations were developed from the International Society of Gynecological Pathologists Endometrial Carcinoma project.

Microscopic Heterotopic Extraovarian Sex Cord-Stromal Proliferations: Expanding the Histologic Spectrum.

Microscopic, heterotopic extraovarian sex cord-stromal proliferations have only recently been reported in the literature. We describe the largest series to date, of 30 cases of microscopic, incidentally detected, heterotopic extraovarian sex cord-stromal proliferation, in women aged 25-79 yr who had undergone surgery for a range of benign and malignant gynecologic conditions. In 14 patients the foci of proliferation comprised ovarian cortical stroma, in some cases with an ovarian fibroma-like appearance. Ten cases of adenofibroma and cystadenofibroma were also identified, including 1 Brenner adenofibroma; 2 cases comprised both ovarian cortical stroma and serous cystadenofibroma; 4 cases showed sex cord proliferation resembling microscopic adult granulosa cell tumors. Immunohistochemistry, where possible, confirmed the sex cord nature of the heterotopic proliferations. The foci of proliferation were <1-7 mm, and most were at the fimbrial end of the fallopian tube. These proliferations are likely to be encountered with increasing frequency as we sample the adnexa more extensively. Previous reports postulated that the proliferations probably represent embryonic rests caused by anomalous migration but we suggest that incorporation of exposed ovarian parenchymal tissue into the fimbrial stroma at the time of ovulation may be another possible cause.

Disease Distribution in Low-stage Tubo-ovarian High-grade Serous Carcinoma (HGSC): Implications for Assigning Primary Site and FIGO Stage.

The latest FIGO and TNM (eighth edition) staging systems for ovarian, tubal, and peritoneal neoplasms require primary site assignment as tubal/ovarian/peritoneal, but provide no guidance or criteria. Fewer than 10% of extrauterine high-grade serous carcinoma (HGSC) cases present at low stage (stage I/II). Low-stage cases offer a unique opportunity to understand the pattern of disease early in its evolution prior to wide dissemination and provide valuable evidence for guiding specimen handling and tumor staging. This study aimed to examine disease distribution in low-stage tubo-ovarian HGSC. Anonymized pathology reports of 152 stage I/II extrauterine HGSCs from 6 teaching hospitals were analyzed: group 1 (n=67) comprised cases with complete tubal examination by Sectioning and Extensively Examining the FIMbriated end of the tube (SEE-FIM) and group 2 (n=85) consisted of cases without documentation of both tubes being fully examined by the SEE-FIM or a SEE-FIM-like protocol. The stage, site/pattern of involvement, site/size of largest tumor focus and laterality of tubal and ovarian involvement were recorded. Tubal mucosal involvement was present in 95% of optimally examined cases and many factors influenced detection of tubal disease. Bilateral involvement, suggestive of metastasis, was significantly more frequent in the ovaries (35%) than the tubes (9%) (P<0.0001, Fisher exact test). No case showed a complete absence of tubal/ovarian involvement, questioning the biological existence of primary peritoneal HGSC. Disease distribution in low-stage cases supports a tubal origin for most HGSCs. Detailed tubal sampling upstages some apparent stage I cases through detection of microscopic tubal involvement.

Data Set for the Reporting of Carcinomas of the Cervix: Recommendations From the International Collaboration on Cancer Reporting (ICCR).

A comprehensive pathologic report is essential for optimal patient management, cancer staging and prognostication. In many countries, proforma reports are used but the content of these is variable. The International Collaboration on Cancer Reporting is an alliance formed by the Royal Colleges of Pathologists of Australasia and the United Kingdom, the College of American Pathologists, the Canadian Partnership Against Cancer and the European Society of Pathology, for the purpose of developing standardized, evidence-based reporting data sets for each cancer site. This will reduce the global burden of cancer data set development and reduplication of effort by different international institutions that commission, publish and maintain standardized cancer-reporting data sets. The resultant standardization of cancer-reporting benefits not only those countries directly involved in the collaboration but also others not in a position to develop their own data sets. We describe the development of an evidence-based cancer data set by the International Collaboration on Cancer Reporting expert panel for the reporting of primary cervical carcinomas and present the "required" and "recommended" elements to be included in the pathology report as well as an explanatory commentary. This data set encompasses the International Federation of Obstetricians and Gynaecologists and Union for International Cancer Control staging systems for cervical neoplasms and the updated World Health Organization classification of gynecologic tumors. The data set also addresses controversial issues such as tumor grading and measurement, including measurement of multifocal carcinomas. The widespread implementation of this data set will facilitate consistent and accurate data collection, comparison of epidemiological and pathologic parameters between different populations, facilitate research, and hopefully result in improved patient management.

Cervical cancer - does the morphological subtype affect survival rates?

A retrospective population-based observational study using cancer registration data of women diagnosed with invasive cervical cancer between 2006 and 2010, in England, was carried out to explore how different morphological subtypes affect survival rates. Age-standardised net survival rates by morphological subtype are presented alongside with excess mortality modelling accounting for the impact of demographic, diagnostic and tumour factors. The three main morphological subtypes (squamous cell carcinoma (SCC), adenocarcinoma and adenosquamous carcinoma) have similar one-year net survival rates of approximately 85%. After adjusting for other important determinants of survival, there were no differences at five-years amongst the three main morphological subtypes, with unadjusted survival rates of 55-65%. As expected, women presenting with neuroendocrine tumours had a much poorer outcome than other epithelial cervical malignancies, with 1-year survival of up to 55%, five-year survival of 34% and excess mortality rates compared to SCC varying between 1.9 and 5.9. Impact Statement What is already known on this subject: This is the first study on survival by cervical cancer morphological subtype using national cancer data. What the results of this study add: This study uses excess mortality modelling to investigate the effects of the morphological subtypes whilst adjusting the other factors that affect cervical cancer survival such as stage, age and grade. What the implications are of these findings for clinical practice and/or further research: It is known that cervical neuroendocrine tumours have a poor prognosis and this is confirmed by this study. Squamous cell carcinomas (SCC), adenocarcinomas (AC) and adenosquamous carcinomas (ASC) have the highest net survival and when accounting for other factors there are no differences amongst these morphological subtypes in terms of survival.

Dataset for reporting of thymic epithelial tumours: recommendations from the International Collaboration on Cancer Reporting (ICCR).

AIMS: The International Collaboration on Cancer Reporting (ICCR) is a not-for-profit organization formed by the Royal Colleges of Pathologists of Australasia and the United Kingdom, the College of American Pathologists, the Canadian Association of Pathologists-Association Canadienne des Pathologists in association with the Canadian Partnership Against Cancer, and the European Society of Pathology. Its goal is to produce standardized, internationally agreed, evidence-based datasets for use throughout the world. METHODS AND RESULTS: This article describes the development of a cancer dataset by the multidisciplinary ICCR expert panel for the reporting of thymic epithelial tumours. The dataset includes 'required' (mandatory) and 'recommended' (non-mandatory) elements, which are validated by a review of current evidence and supported by explanatory text. Seven required elements and 12 recommended elements were agreed by the international dataset authoring committee to represent the essential information for the reporting of thymic epithelial tumours. CONCLUSIONS: The use of an internationally agreed, structured pathology dataset for reporting thymic tumours provides all of the necessary information for optimal patient management, facilitates consistent and accurate data collection, and provides valuable data for research and international benchmarking. The dataset also provides a valuable resource for those countries and institutions that are not in a position to develop their own datasets.

Glomangiomyoma of the Vagina: A Report of 2 Cases and Literature Review.

We report 2 cases of vaginal glomangiomyoma in a 53-year-old who presented with a painful vaginal mass, and a 56-year-old who had postmenopausal bleeding and in whom an incidental vaginal mass was identified and resected at the time of hysterectomy. Histologic examination of the resected masses showed solid, circumscribed, benign, smooth muscle-predominant tumors with interspersed small islands of epithelioid glomus cells. The glomus cells were intimately related to small-caliber blood vessels and showed no cytologic atypia or mitotic activity. The tumor cells showed diffuse expression of smooth muscle actin, CD34, and focal expression of h-caldesmon, vimentin, and estrogen receptor. No immunolabeling for calponin B or desmin was found. To our knowledge, there are only isolated reports of vaginal glomus tumors, and these are the first reported case of vaginal glomangiomyoma in the literature.

Primary Mucinous Carcinoma of the Fallopian Tube: Case Report and Review of Literature.

Primary mucinous carcinoma of the fallopian tube is extremely rare. We report the detailed characterization of a mucinous carcinoma arising in the fimbrial end of the fallopian tube in a 74-yr-old woman. The patient presented with recurrent urinary tract infection and urinary tract obstruction secondary to a large right ovarian mass. She had an appendicectomy as an 11 yr old. Serum CA-125 was raised at 239 U/mL. Computed tomographic scans showed bilateral, cystic ovarian tumors but no other intra-abdominal abnormality. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omental biopsy. Microscopy showed mucinous carcinoma arising from the left tubal fimbriae, in association with mucinous metaplasia over the uninvolved fimbrial folds. There was no mucinous metaplasia in the contralateral fallopian tube, endometrial lining, cervix, or on the uterine serosal surface. A mucinous borderline tumor of gastrointestinal subtype was identified in the left ovary. The right ovary contained a benign mucinous cystadenoma of mixed gastrointestinal and endocervical-like/Müllerian subtype. The fallopian tube tumor expressed CK7, claudin 18, and MUC6, but not CK20, CDX2, CEA, pyloric gland mucin (recognized by HIK1083), ER, or vimentin. The immunolabelling pattern for p53 was wild-type, and p16 expression was nonblock. The metaplastic mucinous tubal epithelium also marked for CK7, CK20, CDX2, and CEA but had mutation-type p53 labelling (p53 null), a low Ki-67 index, and was immunopositive for HIK1083, MUC6, and claudin 18. This is the first detailed characterization of a primary mucinous fallopian tube carcinoma and the adjacent metaplastic mucinous epithelium, and confirms it to be of gastric type.

Review of Lung and Pleural Biopsies Received in a Gynecologic Pathology Department Over a 14-Yr Period.

Review of pulmonary biopsies received by Birmingham Women's Hospital to identify which gynecologic tumors most commonly metastasize to lung or pleura, and which may first present with pulmonary metastases. We reviewed all pulmonary biopsies over a 14-yr period. There were 25 lung and 9 pleural biopsies, from 33 patients. Twenty-one patients had known gynecologic tumors (1 vulval, 1 cervical, 9 endometrial, 4 uterine mesenchymal, and 6 ovarian). Eighteen of the 21 biopsies had been referred from other hospitals; in 4 cases review lead to an altered diagnosis. Three of the 21 biopsies had been sent directly to Birmingham Women's Hospital. The interval between primary diagnosis and pulmonary metastasis was known in 18/21 cases and ranged from 1 to 17 yr. Nine of 21 (43%) had metastatic endometrial carcinoma; the International Federation of Gynecology and Obstetrics (FIGO) stage was known in 7/8 cases: Stage I in 5, and II and IIIA in the remaining 2 cases. Of the further 12 patients with no history of gynecologic malignancy, 4 had pleural metastases from ovarian carcinoma, 3 had primary lung carcinoma, 3 had carcinoma of unknown primary, 1 had endometrial stromal sarcoma, and 1 with a suspected Müllerian tumor was lost to follow-up. Pulmonary metastasis can occur many years after a diagnosis of gynecologic neoplasia-usually endometrial carcinoma, even after initial presentation at low stage. It may also be the initial manifestation in some cases-particularly ovarian carcinoma with pleural involvement. Specialist review of lung and pleural biopsies is important to confirm the diagnosis and optimize patient management.

The Fallopian Tube Origin and Primary Site Assignment in Extrauterine High-grade Serous Carcinoma: Findings of a Survey of Pathologists and Clinicians.

Accumulating recent evidence suggests that the majority of extrauterine high-grade serous carcinomas (HGSCs) do not arise from the ovary as historically accepted but from the distal, fimbrial end of the fallopian tube from a precursor known as serous tubal intraepithelial carcinoma. There has been variable acceptance of this evidence among pathologists and clinicians dealing with "ovarian" cancer and this has resulted in wide variation in the assignment of primary site between different institutions when HGSC involves >1 anatomic site. This has obvious implications for cancer epidemiology, registration, and entry into clinical trials. We undertook a survey of members of several national and international gynecologic pathology and clinical cancer societies with a view to ascertaining the degree of acceptance of the fallopian tube origin of extrauterine HGSC and to explore various aspects regarding site assignment, pathologic sampling, diagnosis, FIGO staging, and reporting of these neoplasms. The results indicate wide acceptance among both pathologists and clinicians of the fallopian tube theory of origin of HGSC (86% pathologists, 92% clinicians), although there is significant variation regarding the perceived importance of assigning a primary site given the limited prognostic and therapeutic significance. Interestingly, clinicians feel it is more important to assign a primary site than pathologists (71% vs. 49%). The survey also indicates widespread acceptance of recently proposed criteria for site assignment in extrauterine HGSC.

The Chemotherapy Response Score (CRS): Interobserver Reproducibility in a Simple and Prognostically Relevant System for Reporting the Histologic Response to Neoadjuvant Chemotherapy in Tuboovarian High-grade Serous Carcinoma.

A 3-tier histopathologic scoring system, the chemotherapy response score (CRS), was previously devised for reporting the histologic response to neoadjuvant chemotherapy in interval debulking surgery specimens of stage IIIc/IV tuboovarian high-grade serous carcinoma. This has been shown to predict the outcome and offer additional information to other methods of assessing the treatment response. In the present study, the reproducibility of this scoring system was assessed by determining the interobserver agreement among reporting pathologists. A total of 5 groups each comprising 3 pathologists with different levels of expertise were selected. The participants underwent an online tutorial on how to apply the CRS system. 40 cases (38 cases in 2 appraiser groups) were scored individually by each of the 15 pathologists. The interobserver reproducibility was calculated using Fleiss' κ, Kendall's coefficient of concordance, and the absolute agreement between (a) individual pathologists within 1 group, (b) with the majority score agreement between all groups, and (c) with all individual scores. The CRS system was found to be highly reproducible among all the pathologists' groups (κ=0.761). The agreement in identifying the group of patients with the best response to chemotherapy was exceptionally high (κ=0.926). We conclude that CRS has a high interobserver reproducibility, especially in identifying the subgroup of patients with the best chemotherapy response, justifying its inclusion in clinical trials and reporting practice.

Variations in Treatment of Cervical Cancer According to Tumor Morphology-Population-Based Cohort Analysis of English National Cancer Registration Data.

OBJECTIVE: This study aimed to investigate differences in the treatment of cervical cancer by tumor morphology after accounting for demographic, diagnostic, and tumor factors. METHODS: Retrospective population-based observational study using linked cancer registration and treatment data from administrative data sources of women diagnosed with cervical cancer (International Classification of Diseases, Tenth Edition C53, malignant behavior) during 2009 and 2010 in England. Descriptive analyses and multinomial regression modeling have been used to consider differences in treatment by morphological subtype. For each morphological subtype, number and percentage of cases are presented by demographic, diagnostic, and tumor factors and treatment modality. Relative risk ratios are provided for each treatment modality by morphological subtype and other specified factors. RESULTS: Forty-three percent of women were treated surgically; 36% by clinical oncology and only 8% by combination of surgery and clinical oncology. Compared with squamous cell carcinomas, both adenocarcinomas and adenosquamous carcinomas were more likely to be treated by trachelectomy, hysterectomy, radiotherapy with hysterectomy, or chemoradiotherapy with hysterectomy than by chemoradiotherapy without hysterectomy. These differences were explained mainly by a different stage distribution, but some difference remained after adjustment for other factors including stage. As clinically recommended, neuroendocrine tumors were not treated surgically. Further treatment differences were found by age, route to diagnosis, stage, and grade. Deprivation was not generally associated with treatment differences, with 1 exception that those from more deprived areas were less likely to be treated by trachelectomy. CONCLUSIONS: Important treatment differences according to tumor morphology remain after adjusting for relevant patient demographic, diagnostic, and tumor factors. In particular, the difference between the treatment of squamous cell carcinoma and adenocarcinoma is notable.

Factors Affecting Short-term Mortality in Women With Ovarian, Tubal, or Primary Peritoneal Cancer: Population-Based Cohort Analysis of English National Cancer Registration Data.

OBJECTIVE: International studies show lower survival rates in the United Kingdom than other countries with comparable health care systems. We report on factors associated with excess mortality in the first year after diagnosis of primary invasive epithelial ovarian, tubal, and primary peritoneal cancer. METHODS: Routinely collected national data were used for patients diagnosed in England in 2008 to 2010. A multivariate Poisson model was used to model excess mortality in 3 periods covering the first year after diagnosis, adjusting for various factors including age at diagnosis, route to diagnosis, tumor stage, tumor morphology, and treatment received. RESULTS: Of 14,827 women diagnosed as having ovarian cancer, 5296 (36%) died in the first year, with 1673 deaths in the first month after diagnosis. Age older than 70 years, diagnosis after an emergency presentation or by an unknown route, and unspecified or unclassified epithelial morphologies were strongly and independently associated with excess mortality in the first year after diagnosis. Of the 2100 (14%) women who fulfilled all 3 criteria, 1553 (74%) did not receive any treatment and 1774 (85%) died in the first year after diagnosis. In contrast, only 193 (4%) of the 4414 women without any of these characteristics did not receive any treatment, and only 427 (9%) died in the first year after diagnosis. CONCLUSIONS: Although our results are based on data from England, they are likely to have implications for cancer care pathways worldwide because most of the identified factors are not specific to the UK health care system. Our results suggest the need to increase symptom awareness, promote timely general practitioner referral, and optimize diagnostic and early treatment pathways within secondary care to increase access to treatment for women with advanced-stage invasive epithelial ovarian, tubal, and primary peritoneal cancer. This process should be pursued alongside continued efforts to develop primary prevention and screening strategies.

Data set for reporting of ovary, fallopian tube and primary peritoneal carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR).

A comprehensive pathological report is essential for optimal patient management, cancer staging and prognostication. In many countries, proforma reports are used but these vary in their content. The International Collaboration on Cancer Reporting (ICCR) is an alliance formed by the Royal College of Pathologists of Australasia, the Royal College of Pathologists of the United Kingdom, the College of American Pathologists, the Canadian Partnership Against Cancer and the European Society of Pathology, with the aim of developing an evidence-based reporting data set for each cancer site. This will reduce the global burden of cancer data set development and reduplication of effort by different international institutions that commission, publish and maintain standardised cancer reporting data sets. The resultant standardisation of cancer reporting will benefit not only those countries directly involved in the collaboration but also others not in a position to develop their own data sets. We describe the development of a cancer data set by the ICCR expert panel for the reporting of primary ovarian, fallopian tube and peritoneal carcinoma and present the 'required' and 'recommended' elements to be included in the report with an explanatory commentary. This data set encompasses the recent International Federation of Obstetricians and Gynaecologists staging system for these neoplasms and the updated World Health Organisation Classification of Tumours of the Female Reproductive Organs. The data set also addresses issues about site assignment of the primary tumour in high-grade serous carcinomas and proposes a scoring system for the assessment of tumour response to neoadjuvant chemotherapy. The widespread implementation of this data set will facilitate consistent and accurate data collection, comparison of epidemiological and pathological parameters between different populations, facilitate research and hopefully will result in improved patient management.

Growing Teratoma Syndrome: A Report of 2 Cases and Review of the Literature.

We report 2 cases of growing teratoma syndrome (GTS) in patients who had been treated with surgery and chemotherapy for immature ovarian teratoma. One of the patients presented with probable paraneoplastic encephalitis. Resection of "recurrences" in both patients showed deposits of mature teratoma and extensive gliomatosis peritonei. It is important for both pathologists and clinicians to be aware of this uncommon entity to avoid misdiagnosis of GTS as recurrence of immature teratoma and disease progression, and to avert unnecessary continuation of chemotherapy. GTS may occur several years after diagnosis of the primary tumor, and rarely develop in treated patients who have become pregnant. Surgical debulking is the optimal modality of treatment as GTS is not chemosensitive. If surgical debulking of GTS is incomplete, long-term follow-up with imaging is required to avoid complications such as bowel obstruction and the sequelae of pressure effects (such as vascular thrombosis, fistula formation, etc.) from bulky deposits of mature teratoma/GTS and gliomatosis peritonei.

Incidence and survival of gynecologic sarcomas in England.

OBJECTIVE: Gynecologic sarcomas account for approximately 3% to 4% of all gynecologic malignancies and are associated with poor outcomes compared with gynecologic carcinomas. The aim of this study is to report the incidence and survival rates of the main gynecologic sarcomas using national English cancer registration data. METHODS/MATERIALS: Records of gynecologic sarcomas diagnosed between 1985 and 2008 were extracted from the English National Cancer Data Repository. ICD-O3 morphology codes were used to assign tumor records to specific histologic subgroups. Incidence and 5-year relative survival rates were calculated. RESULTS: There were 5316 new cases of gynecologic sarcoma diagnosed in England between 1985 and 2008. Incidence rates increased significantly in the early 1990s, probably due to coding changes. Age-specific incidence rates were highest in women aged between 45 and 64 years. In the most recent period studied (2001-2008), incidence rates fluctuated between 8 and 9.6 per million. The most common anatomical site was the uterus (83% of all diagnoses), and the most common histologic diagnosis was leiomyosarcoma (52% of all diagnoses). Overall 5-year relative survival increased significantly between 1985-1989 and 2000-2004, from 34% to 48%. CONCLUSIONS: Gynecologic sarcoma incidence rates have varied little since 1993, whereas survival has improved significantly. These results are consistent with previously published small series and case studies, and provide a more complete picture of gynecologic sarcoma incidence and survival patterns in England.

Should All Cases of High-Grade Serous Ovarian, Tubal, and Primary Peritoneal Carcinomas Be Reclassified as Tubo-Ovarian Serous Carcinoma?

INTRODUCTION: The dualistic theory of ovarian carcinogenesis proposes that epithelial "ovarian" cancer is not one entity with several histological subtypes but a collection of different diseases arising from cells of different origin, some of which may not originate in the ovarian surface epithelium. METHODS: All cases referred to the Pan-Birmingham Gynaecological Cancer Centre with an ovarian, tubal, or primary peritoneal cancer between April 2006 and April 2012 were identified from the West Midlands Cancer Registry. Tumors were classified into type I (low-grade endometrioid, clear cell, mucinous, and low-grade serous) and type II (high-grade serous, high-grade endometrioid, carcinosarcoma, and undifferentiated) cancers. RESULTS: Ovarian (83.5%), tubal (4.3%), or primary peritoneal carcinoma (12.2%) were diagnosed in a total of 583 woman. The ovarian tumors were type I in 134 cases (27.5%), type II in 325 cases (66.7%), and contained elements of both type I and type II tumors in 28 cases (5.7%). Most tubal and primary peritoneal cases, however, were type II tumors: 24 (96.0%) and 64 (90.1%), respectively. Only 16 (5.8%) of the ovarian high-grade serous carcinomas were stage I at diagnosis, whereas 240 (86.6%) were stage III+. Overall survival varied between the subtypes when matched for stage. Stage III low-grade serous and high-grade serous carcinomas had a significantly better survival compared to clear cell and mucinous cases, P = 0.0134. There was no significant difference in overall survival between the high-grade serous ovarian, tubal, or peritoneal carcinomas when matched for stage (stage III, P = 0.3758; stage IV, P = 0.4820). CONCLUSIONS: Type II tumors are more common than type I and account for most tubal and peritoneal cancers. High-grade serous carcinomas, whether classified as ovarian/tubal/peritoneal, seem to behave as one disease entity with no significant difference in survival outcomes, therefore supporting the proposition of a separate classification of "tubo-ovarian serous carcinoma".

Problematic issues in the staging of endometrial, cervical and vulval carcinomas.

The International Federation of Gynecology and Obstetrics (FIGO) staging of tumours of the uterine corpus, cervix and vulva was revised in 2009. The greatest impact of the revised staging was on carcinomas of the uterine corpus. Uterine sarcomas are now staged separately. Changes to the staging system for vulvar carcinomas largely reflect the significance of lymph node status. Only minor amendments have been introduced for cervical carcinomas, which remain the only gynaecological tumours to be staged clinically. These revisions, based on recent evidence, require careful, more detailed assessment of several histological parameters at each anatomical site. The present review deals with the evidence and rationale underpinning the revisions, and includes practical guidance on tumour staging. This covers the assessment and measurement of myoinvasion and evaluation of cervical, parametrial, serosal and vaginal involvement in carcinomas of the uterine corpus; the identification and accurate measurement of stromal invasion in cervical and vulvar carcinomas; the assessment of unusual variants of carcinoma at each of these sites; and the assessment of lymph node involvement.

Three cases of an unusual pattern of invasion in malignant Brenner tumors.

Ovarian malignant Brenner tumors are rare neoplasms that are typically admixed with benign and borderline Brenner tumor elements. We report 3 cases of an unusual variant of malignant Brenner tumor where the infiltrative malignant component arose directly from a benign Brenner tumor rather than from borderline elements and did not exhibit a desmoplastic stromal response. Borderline elements were present in 1 case, but the invasive component did not arise from these. Our cases highlight that an absence of a borderline element should not dissuade the pathologist from diagnosing a malignant Brenner tumor.