ESGO-ESMO-ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease.

The European Society of Gynaecological Oncology, the European Society for Medical Oncology (ESMO) and the European Society of Pathology held a consensus conference (CC) on ovarian cancer on 15-16 June 2022 in Valencia, Spain. The CC panel included 44 experts in the management of ovarian cancer and pathology, an ESMO scientific advisor and a methodologist. The aim was to discuss new or contentious topics and develop recommendations to improve and harmonise the management of patients with ovarian cancer. Eighteen questions were identified for discussion under four main topics: (i) pathology and molecular biology, (ii) early-stage disease and pelvic mass in pregnancy, (iii) advanced stage (including older/frail patients) and (iv) recurrent disease. The panel was divided into four working groups (WGs) to each address questions relating to one of the four topics outlined above, based on their expertise. Relevant scientific literature was reviewed in advance. Recommendations were developed by the WGs and then presented to the entire panel for further discussion and amendment before voting. This manuscript focuses on the recommendation statements that reached a consensus, their voting results and a summary of evidence supporting each recommendation.

ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease†.

The development of guidelines recommendations is one of the core activities of the European Society for Medical Oncology (ESMO) and European Society of Gynaecologial Oncology (ESGO), as part of the mission of both societies to improve the quality of care for patients with cancer across Europe. ESMO and ESGO jointly developed clinically relevant and evidence-based recommendations in several selected areas in order to improve the quality of care for women with ovarian cancer. The ESMO-ESGO consensus conference on ovarian cancer was held on 12-14 April 2018 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of ovarian cancer. Before the conference, the expert panel worked on five clinically relevant questions regarding ovarian cancer relating to each of the following four areas: pathology and molecular biology, early-stage and borderline tumours, advanced stage disease and recurrent disease. Relevant scientific literature, as identified using a systematic search, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. The recommendations presented here are thus based on the best available evidence and expert agreement. This article presents the recommendations of this ESMO-ESGO consensus conference, together with a summary of evidence supporting each recommendation.

ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease.

The development of guidelines is one of the core activities of the European Society for Medical Oncology (ESMO) and European Society of Gynaecologial Oncology (ESGO), as part of the mission of both societies to improve the quality of care for patients with cancer across Europe. ESMO and ESGO jointly developed clinically relevant and evidence-based recommendations in several selected areas in order to improve the quality of care for women with ovarian cancer. The ESMO-ESGO consensus conference on ovarian cancer was held on April 12-14, 2018 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of ovarian cancer. Before the conference, the expert panel worked on five clinically relevant questions regarding ovarian cancer relating to each of the following four areas: pathology and molecular biology, early-stage and borderline tumours, advanced stage disease and recurrent disease. Relevant scientific literature, as identified using a systematic search, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. The recommendations presented here are thus based on the best available evidence and expert agreement. This article presents the recommendations of this ESMO-ESGO consensus conference, together with a summary of evidence supporting each recommendation.

Defining the Cervical Transformation Zone and Squamocolumnar Junction: Can We Reach a Common Colposcopic and Histologic Definition?

Quality assurance and research in colposcopy and cervical pathology require standardized terminologies and reporting. However, clinical and histologic definitions of the cervical transformation zone (TZ) and squamocolumnar junction (SCJ) vary considerably. We aimed to identify areas of agreement and areas where work is required to standardize the definitions of the TZ and the SCJ. We conducted a survey among the board members of the European Federation of Colposcopy member societies and members of the International Society of Gynecological Pathologists. Overall, 22 expert colposcopists and 34 gynecologic pathologists responded. There was broad agreement that the TZ is the area where squamous metaplasia has occurred. There was consensus that the original SCJ can appear colposcopically indistinct in cases of maturation of the metaplastic squamous epithelium but can be identified histologically by the presence of the so-called last cervical gland. It was agreed that the border between the metaplastic squamous epithelium and the columnar epithelium on the surface of the cervix is called the new SCJ. Areas where work is required include the questions as to whether the cervical crypts lined by columnar epithelium in the field of squamous metaplasia are an integral part of the TZ or not and whether the individual microscopic borders between the metaplastic squamous epithelium of glandular crypts and the residual columnar epithelium of glandular crypts should be considered as part of the new SCJ or not. This paper is a step in an attempt to standardize colposcopic and histologic definitions among colposcopists and pathologists.

DICER1 hotspot mutations in non-epithelial gonadal tumours.

BACKGROUND: Non-epithelial gonadal tumours largely comprise sex cord-stromal tumours (SCSTs) and germ cell tumours (GCTs). Specific somatic mutations in DICER1, a microRNA maturation pathway gene, have been identified in these tumours. We conducted a study that aimed to confirm, refine and extend the previous observations. METHODS: We used Sanger sequencing to sequence the RNase IIIa and IIIb domains of DICER1 in 154 gonadal tumours from 135 females and 19 males, as well as 43 extra-gonadal GCTs from 26 females and 17 males. RESULTS: We identified heterozygous non-synonymous mutations in the RNase IIIb domain of DICER1 in 14/197 non-epithelial tumours (7.1%). Mutations were found in 9/28 SCSTs (32%), 5/118 gonadal GCTs (4.2%), 0/43 extra-gonadal GCTs and 0/8 miscellaneous tumours. The 14 mutations affected only five residues: E1705, D1709, E1788, D1810 and E1813. In all five patients where matched and constitutional DNA was available, the mutations were only somatic. There were no mutations found in the RNase IIIa domain. CONCLUSION: More than half (8/15) of Sertoli-Leydig cell tumours (SLCTs) harbour DICER1 mutations in the RNase IIIb domain, while mutations are rarely found in GCTs. Genetic alterations in SLCTs may aid in classification and provide new approaches to therapy.

Bone marrow micrometastases in esophageal carcinoma: a 10-year follow-up study.

Detection of bone marrow micrometastases (BMMs) in patients with esophageal carcinoma may indicate a metastatic phenotype. We assessed if the presence of BMMs had adverse prognostic significance in a 10-year follow-up study. Patients undergoing surgery for esophageal cancer were prospectively recruited between February 1999 and August 2000. Bone marrow aspirates were obtained from the iliac crest of patients under general anesthesia at the time of surgery. Immunocytochemical analysis using anticytokeratin antibodies CAM 5.2 and AE1/AE3 was undertaken to determine the presence of BMMs. Union International Contre le Cancer staging was recorded for all patients. Patient follow-up was completed over a 10-year period through analysis of the Northern Ireland Cancer Registry. Forty-two patients (male = 35) were included, with a mean age of 67.2 years (range 39-83). BMMs were detected in 19 patients (45.2%). International Contre le Cancer tumor staging was stage I = 6, stage II = 10, stage III = 24, and stage IV = 2. BMMs were associated with lymphovascular invasion (P= 0.02) and advanced T stage (P= 0.02). Overall, 10-year survival was 21.4% (n= 9), with a median follow-up of 877.5 days (interquartile range 391.5-2546.3). There was no statistically significant difference between the survival of patients with or without BMMs (1451.4 vs. 1431.6 days, P= 0.99). Univariate analysis demonstrated a trend toward decreased survival for patients with positive lymph nodes (P= 0.07), an increased T stage (P= 0.06), and lymphovascular invasion (P= 0.07). Multivariate analysis demonstrated that none of the variables were significant predictors of mortality. Although the presence of BMMs correlates with recognized adverse tumor characteristics in patients with esophageal cancer, micrometastases detected in the bone marrow at time of surgery does not influence long-term survival.

Enterobious vermicularis (pinworm) infestation of the vulva: report of 2 cases of a pseudoneoplastic lesion mimicking squamous carcinoma.

Enterobious Vermicularis (pinworm) infestation outside the gastrointestinal tract is rare. We report 2 patients with vulval involvement, one of whom presented with a clinically suspicious, rapidly growing mass. The histology of both lesions showed similar features of epidermal proliferation in the form of hyperkeratosis, acanthosis, and papillomatosis; this pseudoepitheliomatous hyperplasia raised the possibility of a well-differentiated squamous carcinoma. There was associated inflammation in both cases, including large numbers of eosinophils in 1 case. On the surface or within the keratin layer, structures with the morphology of enterobious vermicularis eggs were identified. In reporting this unusual pseudoneoplastic phenomenon, we stress the necessity for the pathologist to consider and look for parasites in proliferative squamous lesions of the vulva, especially when there is an associated inflammatory infiltrate rich in eosinophils.

Recent developments in vulvovaginal pathology.

This review discusses recent developments in vulvovaginal pathology. A variety of morphologically bland mesenchymal lesions occur at this site with considerable histological and immunohistochemical overlap. Aggressive angiomyxoma exhibits HMGA2 immunoreactivity in approximately 50% of cases, and this nuclear transcription factor is emerging as a useful and relatively specific marker for aggressive angiomyxoma, although occasional vulvovaginal smooth muscle neoplasms are positive. HMGA2 is useful in the diagnosis of aggressive angiomyxoma and its distinction from mimics, in the evaluation of resection margins and in the assessment of the presence or absence of residual disease in re-excisions. Aggressive angiomyxoma is almost invariably positive with oestrogen and progesterone receptors, and there have been several reports of a dramatic reduction in size following gonadotropin releasing hormone agonist therapy. Recent series of the relatively newly described entities cellular angiofibroma and superficial myofibroblastoma of the lower female genital tract have expanded upon the morphological spectrum of these neoplasms. Recently described mesenchymal lesions at this site include massive oedema and prepubertal vulval fibroma. Gastrointestinal stromal tumours have been described as primary neoplasms in the vagina, and rectovaginal septum and extragastrointestinal stromal tumour should be added to the differential diagnosis of a vulvovaginal mesenchymal lesion. Many mesenchymal lesions in the vulvovaginal region exhibit immunoreactivity with both CD34 and desmin, a somewhat unusual immunophenotype in mesenchymal lesions at other sites. It is now established that there are two distinct types of vulval intraepithelial neoplasia (VIN), most commonly termed classic and differentiated VIN, the former associated with human papillomavirus (HPV) infection. There are two corresponding types of vulval squamous carcinoma with HPV-associated and non-HPV-associated variants, the latter often arising in a vulval dystrophy and associated with p53 mutation. However, in some cases there is clinicopathological overlap between HPV-associated and non-HPV-associated squamous carcinomas, and immunohistochemistry with p16 is more reliable than morphology in predicting the presence of HPV. There have been new developments regarding Paget's disease of the vulva with the identification of markers that are useful in diagnosis and evidence that the neoplastic cells represent a proliferation of adnexal stem cells residing in sebaceous units. The newly described entity vaginal tubulo-squamous polyp typically exhibits immunopositivity with prostatic markers, possibly indicating derivation from displaced periurethral Skene's glands.

Morules in endometrioid proliferations of the uterus and ovary consistently express the intestinal transcription factor CDX2.

AIMS: To undertake an immunohistochemical analysis of squamous elements in endometrioid proliferations of the uterus and ovary and to compare the immunophenotype of typical squamous elements and so-called squamous morules. METHODS AND RESULTS: Cases of uterine or ovarian endometrioid glandular lesions with squamous elements were stained with CDX2, beta-catenin, oestrogen receptor (ER), CD10, p63 and high-molecular-weight cytokeratin LP34. Thirteen cases had typical squamous elements and 18 cases morules. Morules typically exhibited diffuse nuclear CDX2 and beta-catenin immunoreactivity and were positive for CD10 and LP34. They were usually ER- and p63-. In contrast, typical squamous elements were usually positive for ER, CD10, p63 and LP34. They were usually CDX2- or focally positive and exhibited no nuclear immunoreactivity for beta-catenin. Ten endometrioid carcinomas not exhibiting squamous differentiation were immunoreactive for CDX2; one was focally positive. Electron microscopy in two ovarian endometrioid adenocarcinomas with extensive morular differentiation showed that the morules exhibited epithelial features, but no overt evidence of squamous differentiation. CONCLUSIONS: Typical squamous elements and morules have an overlapping but differing immunophenotype. Morules exhibit no firm immunohistochemical or ultrastructural evidence of squamous differentiation, although immature squamous differentiation cannot be excluded. Nuclear beta-catenin positivity is in keeping with the observation that endometrioid glandular lesions with morules are often associated with beta-catenin gene mutation. The explanation for diffuse nuclear positivity with the intestinal transcription factor CDX2 in morules is not clear, but may be a result of overexpression of nuclear beta-catenin. We suggest that the term morular metaplasia is used instead of squamous morules.

Embryonal rhabdomyosarcoma of the cervix with focal pleomorphic areas.

An embryonal rhabdomyosarcoma (sarcoma botryoides) of the cervix occurring in a 30-year-old woman is described. In addition to typical areas of the embryonal rhabdomyosarcoma, including cartilaginous elements, the neoplasm was characterised by the presence of foci composed of highly pleomorphic cells. The significance of this finding is uncertain. These foci may represent areas of dedifferentiation in an embryonal rhabdomyosarcoma.

Uterine tumour resembling ovarian sex cord tumour is an immunohistochemically polyphenotypic neoplasm which exhibits coexpression of epithelial, myoid and sex cord markers.

AIMS: To describe the clinicopathological and immunohistochemical findings in four cases of uterine tumour resembling ovarian sex cord tumour (UTROSCT). METHODS: Four UTROSCTs were stained with a wide range of antibodies, including epithelial (AE1/3, epithelial membrane antigen), myoid (desmin, alpha smooth muscle actin, h-caldesmon), sex cord (alpha inhibin, calretinin, melan A, CD99) and neuroendocrine (chromogranin, CD56) markers as well as hormone receptors (oestrogen receptor, progesterone receptor, androgen receptor), vimentin, CD10, WT1 and HMB45. RESULTS: The tumours ranged from 0.8 to 19.5 cm. Three were relatively well circumscribed intramural myometrial lesions; the other was a pedunculated mass attached to the uterine serosa. The tumours were variably composed of solid, corded, trabecular, nested, glandular and retiform arrangements of tumour cells. In three cases, cells with eccentric nuclei and abundant eosinophilic cytoplasm, resulting in a rhabdoid appearance, were a prominent feature. Three cases were diffusely positive with AE1/3 and all with epithelial membrane antigen. Positivity with myoid markers was common with 3, 4 and 1 case respectively staining with desmin, alpha smooth muscle actin and h-caldesmon; 2, 4, 1 and 2 cases respectively were positive with alpha inhibin, calretinin, melan A and CD99. All were chromogranin negative and exhibited diffuse strong staining with CD56. All were diffusely positive with oestrogen receptor, progesterone receptor, vimentin and WT1. Three cases were androgen receptor positive and all were CD10 and HMB45 negative. CONCLUSIONS: UTROSCT exhibits a polyphenotypic immunophenotype with coexpression of markers of epithelial, myoid and sex cord lineage as well as hormone receptors.

Endometrial hyperplasia involving endometrial polyps: report of a series and discussion of the significance in an endometrial biopsy specimen.

OBJECTIVES: Endometrial polyps are a common cause of abnormal uterine bleeding. Rarely, a hyperplasia, either complex or atypical in type, is identified within a polyp in a biopsy or polypectomy specimen. Currently, it is not known whether the hyperplasia is likely to be confined to the polyp or also involve nonpolypoid endometrium. We aim to assess the likelihood of hyperplasia being confined to an endometrial polyp. DESIGN: In this study, we identified 32 women from pathology archives in whom endometrial hyperplasia was present within a polyp. The number of endometrial polyps during the study period was 1031 and therefore 3.1% of all endometrial polyps diagnosed during the study period contained a hyperplasia. SETTING: A major teaching hospital in the UK. METHODS: The biopsies were retrieved from the pathology archives of Royal Group of Hospitals, Belfast, between 2000 and 2006. We traced any follow-up biopsy or hysterectomy specimens to evaluate the status of the surrounding endometrium. RESULTS: The hyperplasias were complex (n = 23) or atypical (n = 9) in type. In 14 of 27 (52%) women in whom nonpolypoid endometrium was available for histological evaluation, either on the original biopsy or in a follow-up specimen, hyperplasia involved the nonpolypoid endometrium, and in three other women, hyperplasia was present in a polyp in follow-up specimens. Women with atypical hyperplasia in a polyp were slightly more likely to have hyperplasia in the surrounding endometrium than those with complex hyperplasia. CONCLUSIONS: Our study illustrates that the risk of endometrial hyperplasia in a polyp concurrently involving nonpolypoid endometrium is significant. We suggest a strategy for the management of women with hyperplasia identified within an endometrial polyp in a biopsy or polypectomy specimen.

Squamous cell carcinoma arising in a dermoid cyst of the ovary: a case series.

OBJECTIVE: Malignant transformation in a dermoid cyst of the ovary is a rare complication, occurring in only 1-2% of cases, with squamous cell carcinoma being the most common type. Preoperative diagnosis is difficult because of the lack of specific symptoms and signs to suggest malignancy. Because of the small numbers of women involved, our knowledge of this rare tumour type is limited. This study aims to further characterise the population of women affected, the disease itself and the most appropriate management strategy. DESIGN: We identified 14 women with this diagnosis between 1989 and 2006. This is a descriptive study, looking at the patient characteristics, mode of presentation and the role of tumour markers and radiological imaging in diagnosis. We also examined the stage and pathological features of the tumour at presentation and the subsequent course of the disease. We have also described our experiences using surgery, chemotherapy and radiotherapy in the management of these women. RESULTS: We found that these tumours present at an age older than that of mature teratomas and that there are no reliable diagnostic tools or prognostic indicators. The behaviour of these tumours is unpredictable, and the role of chemotherapy and radiotherapy remains unclear. We suggest that repeated surgical resection of disease at the time of relapse could give a very durable response in selected women.

My approach to the interpretation of endometrial biopsies and curettings.

A major proportion of the workload in many histopathology laboratories is accounted for by endometrial biopsies, either curettage specimens or outpatient biopsy specimens. The increasing use of pipelle and other methods of biopsy not necessitating general anaesthesia has resulted in greater numbers of specimens with scant tissue, resulting in problems in assessing adequacy and in interpreting artefactual changes, some of which appear more common with outpatient biopsies. In this review, the criteria for adequacy and common artefacts in endometrial biopsies, as well as the interpretation of endometrial biopsies in general, are discussed, concentrating on areas that cause problems for pathologists. An adequate clinical history, including knowledge of the age, menstrual history and menopausal status, and information on the use of exogenous hormones and tamoxifen, is necessary for the pathologist to critically evaluate endometrial biopsies. Topics such as endometritis, endometrial polyps, changes that are induced by hormones and tamoxifen within the endometrium, endometrial metaplasias and hyperplasias, atypical polypoid adenomyoma, adenofibroma, adenosarcoma, histological types of endometrial carcinoma and grading of endometrial carcinomas are discussed with regard to endometrial biopsy specimens rather than hysterectomy specimens. The value of ancillary techniques, especially immunohistochemistry, is discussed where appropriate.

Role of polymerase chain reaction and immunocytochemistry in the cytological assessment of lymphoid proliferations.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is used as a screening test to evaluate lymphadenopathy. The combined use of genetic analysis and flow cytometry for immunophenotyping has increased the accuracy of diagnosis and correct categorisation of lymphomas on cytological preparations. AIM: To show the utility of immunocytochemistry and polymerase chain reaction (PCR) in the evaluation of cytological preparations of lymph nodes. METHODS: Fine needle aspirates were obtained from 33 patients (initial presentation, n = 27; recurrence, n = 6). Routine examination was undertaken using immunocytochemistry and DNA PCR to detect clonality and specific translocations. The cytodiagnosis and subclassification of lymphoma was correlated with histological diagnosis in the available follow-up biopsies. RESULTS: 14 patients had a cytological diagnosis of non-Hodgkin's lymphoma (NHL), 4 had suspected NHL, 2 had atypical lymphoid proliferation and 13 had reactive hyperplasia. A World Health Organization (WHO) subtype was suggested in 8 patients. Incorporating the results of immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements enabled diagnosis of lymphoma in 17 patients, including 5 of the 6 patients suspected to have NHL or an atypical lymphoid proliferation. Identification of the translocations t (14;18) and t (2;5) helped WHO categorisation in 3 of the patients. The cytological findings were confirmed in 12 out of the 13 patients for whom histological follow-up was available. Seven of the 18 lymphoma patients were managed without a subsequent biopsy. We made one false-positive diagnosis of B-cell NHL on cytology. CONCLUSION: The use of immunocytochemistry and PCR is valuable in the definitive diagnosis and subtyping of malignant lymphomas on cytological preparations. The use of these techniques may avoid lymph node biopsies in some cases and allow definitive treatment based on aspirate findings alone.

Results of a questionnaire regarding criteria for adequacy of endometrial biopsies.

AIMS: Pathologists are faced with increasing numbers of endometrial biopsies containing scant tissue. Anecdotal evidence points to significant variation among pathologists regarding criteria used to assess adequacy, and no standard recommendations exist. An initial audit showing variation in endometrial biopsy adequacy reporting prompted this assessment of the criteria used by specialist gynaecological pathologists for the classification of adequacy. METHODS: A questionnaire regarding criteria used for endometrial biopsy assessment adequacy was sent to members of the British Association of Gynaecological Pathologists and the National Gynaecological Pathology External Quality Assessment Scheme (UK). One hundred and thirty questionnaires were distributed and 61 pathologists responded. RESULTS: The responses showed great variation in criteria used to classify endometrial biopsies as adequate. Most respondents felt it would be useful if criteria were proposed to aid this assessment. CONCLUSIONS: Wide variation exists among specialist gynaecological pathologists regarding what constitutes an adequate endometrial biopsy. The gynaecologist should interpret the biopsy report in the light of clinical, radiological, and hysteroscopic features. The presence of scanty tissue in postmenopausal women with a thin endometrium and no focal lesion is expected, and is not a reason for repeat biopsy. Pathologists should exercise caution before classifying endometrial biopsies as inadequate, because this may have medicolegal and management implications.

Serous adenocarcinoma of the sigmoid mesentery arising in cystic endosalpingiosis.

This case report describes a Mullerian serous adenocarcinoma arising within a multoloculated cyst lined by ciliated serous-type epithelium located in the sigmoid mesentery. Twenty years previously the patient underwent a hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. The ovaries contained bilateral serous cystadenofibromas, and multiple cysts lined by ciliated serous-type epithelium were present in the omentum. The resection specimen 20 years later contained a 14 cm multiloculated cyst located in the sigmoid mesentery. This was lined largely by benign ciliated serous-type epithelium but a focus of well differentiated serous adenocarcinoma projected into the lumen. Two further peritoneal cysts were present, both of which were lined by ciliated serous-type epithelium. There was a coincidental renal cell carcinoma. This is a unique case of multiple omental, peritoneal, and retroperitoneal cysts (classified as cystic endosalpingiosis), one of which developed a focus of serous adenocarcinoma. Although rarely serous adenocarcinomas, similar to those occurring within the ovary, arise in the retroperitoneum, this is the first reported occurrence in association with a pre-existing benign lesion.

Immunohistochemical study of testicular sex cord-stromal tumors, including staining with anti-inhibin antibody.

Inhibin is a peptide hormone produced by ovarian granulosa cells and testicular Sertoli cells. Ovarian granulosa cell and other sex cord-stromal tumors usually exhibit positive immunohistochemical staining with antiinhibin antibodies, and this may be valuable in differentiating these neoplasms from histologic mimics. In the present study, we investigated the immunohistochemical staining of testicular sex cord-stromal tumors using antiinhibin. Immunostaining with CAM5.2, vimentin, S-100 protein, desmin, epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), and placental alkaline phosphatase (PLAP) also was performed because few studies have investigated in detail the immunophenotype of testicular sex cord-stromal tumors. Fifteen of 16 Leydig cell tumors exhibited strong positive staining with antiinhibin. A proportion of Leydig cell tumors also stained positively with CAM5.2 (7 of 16), vimentin (14 of 16), S-100 protein (10 of 16), desmin (2 of 16) and epithelial membrane antigen (4 of 16). Four of six testicular sex cord-stromal tumors with varying degrees of Sertoli or granulosa cell differentiation were positive with antiinhibin, as were two of three sex cord-stromal tumors that were unclassified. Some of these tumors were positive with CAM 5.2, vimentin, S-100 protein, desmin, and epithelial membrane antigen. All tumors were negative with carcinoembryonic antigen and placental alkaline phosphatase. The immunohistochemical findings show that, analogous to their ovarian counterparts, most testicular sex cord-stromal tumors are immunoreactive with antiinhibin. Immunohistochemistry using this antibody as part of a panel may be valuable in confirming a diagnosis of testicular sex cord-stromal tumor and in differentiating these neoplasms from others that may mimic them.

Immunohistochemical staining of ovarian granulosa cell tumors with monoclonal antibody against inhibin.

Inhibin is a peptide hormone produced by ovarian granulosa cells and by granulosa cell tumors. Serum inhibin measurements have been used as a biochemical marker of the presence or progression of ovarian granulosa cell tumors and their metastases. In the current study, an antibody against the alpha-subunit of human inhibin was used to stain 16 cases of ovarian adult granulosa cell tumors, 15 cases of other ovarian sex cord-stromal tumors, and 51 cases of a range of ovarian and extraovarian neoplasms, many of which may mimic granulosa cell tumor. There was diffuse strong cytoplasmic staining of all cases of adult granulosa cell tumor. Diffuse positive staining also was observed in all Leydig cell tumors, and there was focal staining in a proportion of fibrothecomas. There was focal weak staining of one case of ovarian clear cell carcinoma but no staining of other ovarian and extraovarian neoplasms. Immunohistochemical staining with antibodies against inhibin is of value in the diagnosis of granulosa cell tumor and in the distinction of this neoplasm from others that may mimic it. The antibody also may be useful for the confirmation of late metastasis of granulosa cell tumor, especially when the previous history is not known.

Uterine serous carcinoma and endometrial intraepithelial carcinoma arising in endometrial polyps: report of 5 cases, including 2 associated with tamoxifen therapy.

Uterine serous carcinoma (USC) is the prototype of type II endometrial cancer. Endometrial intraepithelial carcinoma (EIC) is the precursor lesion of USC, Rarely, USC and EIC may arise within and be largely confined to otherwise benign endometrial polyps. This report describes 5 such cases. The patients ranged in age from 67 to 89 years, with a mean age of 75 years. In 2 of the cases there was a history of tamoxifen therapy. In 2 cases USC or EIC was confined to the endometrial polyp, and in 3 cases there was focal involvement of nonpolypoid endometrium. In 1 case there was a single small focus of extrauterine tumor within an ovarian vascular channel. In 2 cases the invasive tumor within the polyp also contained areas of endometrioid adenocarcinoma, and in 2 cases there was a component of clear cell carcinoma. In all cases USC and EIC were strongly reactive for p53 and showed a high proliferation index with MIB1. Two cases were negative with estrogen receptor, and 3 cases exhibited positive staining. The cases reported herein show that USC and EIC may rarely arise in benign endometrial polyps and that extrauterine involvement may be present without myometrial infiltration. Because 2 of the patients had been taking tamoxifen, this raises the possibility of an association between tamoxifen and the development of USC and EIC in the endometrial polyps that are characteristic of this medication.