Search

Primary carcinomas of the vagina are uncommon and currently detailed recommendations for the reporting of resection specimens of these neoplasms are not widely available. The International Collaboration on Cancer Reporting (ICCR) is developing standardized, evidence-based reporting data sets for multiple cancer sites. We describe the development of a cancer data set by the ICCR expert panel for the reporting of primary vaginal carcinomas and present the core and noncore data elements with explanatory commentaries. This data set has incorporated the updates in the 2020 World Health Organization Classification of Female Genital Tumours, 5th edition. The data set addresses controversial issues such as tumor grading, margin assessment, and the role of ancillary studies. The adoption of this data set into clinical practice will help ensure standardized data collection across different countries, facilitate future research on vaginal carcinomas, and ultimately lead to improvements in patient care.

A cogent and comprehensive pathologic report is essential for optimal patient management, cancer staging, and prognostication. This article details the International Collaboration on Cancer Reporting (ICCR) process and the development of the vulval carcinoma reporting data set. It describes the "core" and "noncore" elements to be included in pathology reports for vulval carcinoma, inclusive of clinical, macroscopic, microscopic, and ancillary testing considerations. It provides definitions and commentary for the evidence and/or consensus-based deliberations for each element included in the data set. The commentary also discusses controversial issues, such as p16/human papillomavirus testing, tumor grading and measurements, as well as elements that show promise and warrant further evidence-based study. A summary and discussion of the updated vulval cancer staging system by the International Federation of Obstetricians and Gynaecologists (FIGO) in 2021 is also provided. We hope the widespread implementation of this data set will facilitate consistent and accurate reporting, data collection, comparison of epidemiological and pathologic parameters between different populations, facilitate research, and serve as a platform to improve patient outcomes.

Recent changes in the classification of cervical adenocarcinomas have re-categorized serous carcinoma as potentially nonexistent. However, clinical and pathological profiles of cervical adenocarcinomas with serous-like morphological features have not been systematically evaluated using the latest taxonomy and biomarkers. We studied 14 cases of primary cervical carcinomas with serous-like morphologies (papillary and micropapillary patterns). None of these cases exhibited evidence of serous carcinoma involving the upper tracts. Patient ages ranged between 34 and 86 years, most presented with abnormal uterine bleeding. Histologically, ten cases were classified as human papillomavirus (HPV)-associated carcinomas (eight usual-type endocervical adenocarcinomas and two adenosquamous carcinomas), of which six exhibited a papillary pattern and four had a micropapillary pattern. The four remaining cases were HPV-independent gastric-type adenocarcinomas, which displayed a papillary pattern in one case and a micropapillary pattern in three others. All ten HPV-associated carcinomas displayed block positive p16 and wild-type p53 by immunohistochemistry, with nine of them confirmed by HPV testing. Two of the four gastric-type adenocarcinomas had mutation-type p53, one of which also being p16 block positive. HER2 overexpression was demonstrated in 3/14 (21.4%) cases (2 HPV-associated and 1 HPV-independent). PD-L1 expression was identified in 4/10 (40%) cases, all HPV-associated. Targeted next-generation sequencing was performed in two cases with a micropapillary pattern, revealing a missense variant in ATM in an HPV-associated tumor and missense variants in TP53 and SMARCB1 in an HPV-independent tumor. The results demonstrated that primary endocervical adenocarcinomas can mimic the appearance of serous carcinoma, while not representing serous carcinoma. Serous-like papillary and micropapillary patterns may be present in both HPV-associated and HPV-independent cervical carcinomas, but none of the cases studied were unequivocally serous upon detailed analysis. Our findings support the exclusion of "cervical serous carcinoma" from existing classifications of cervical adenocarcinoma.

Current management of gynaecological neoplasms is underpinned by their molecular characteristics. For many neoplasms the underlying genetic abnormalities can be reliably detected using immunohistochemistry for protein expression as a surrogate. The three most widely utilized biomarkers in this regard in gynaecological neoplasms are p16, p53 and mismatch repair (MMR) proteins, and it is vital for all pathologists to be aware of the indications for their use, correct interpretation of expression patterns, awareness of technical and interpretive pitfalls as well as appropriate reporting terminology.

Female genital melanomas are rare. At diagnosis, most affected patients have advanced disease. Surgery remains the primary treatment, and adjuvant therapy is largely ineffective. Recently, immune checkpoints and the mitogen-activated protein kinase pathway have been explored as treatment targets. However, evaluation of these biomarkers in genital melanomas is limited. We evaluated the clinicopathological features of 20 vulvar, 32 vaginal, and three cervical melanomas and assessed programmed cell death ligand 1 (PD-L1) expression, CD8 tumor-infiltrating lymphocyte density, mismatch repair proteins, VE1 immunohistochemistry, and KIT and BRAF mutations. The median age of the patients was 66 years, and median tumor sizes were 25, 30, and 20 mm for vulvar, vaginal, and cervical tumors, respectively. Mean mitotic figures were 18, 19, and 30 per mm2. Thirty-seven patients (67%) had operable tumors. After a median follow-up of 15 months, only nine patients (16%) were alive. Eight of the nine survivors did not have lymph node metastasis. Using 5% as the threshold, PD-L1 expression was observed in 55%, 50%, and 33% of vulvar, vaginal, and cervical tumors, respectively, when the Roche SP263 antibody was used and 20%, 53%, and 0%, respectively, when the Dako 28-8 antibody was used. The median CD8 tumor-infiltrating lymphocyte density was significantly higher in vulvar/vaginal than cervical melanomas and correlated with PD-L1 expression. No cases exhibited loss of mismatch repair proteins. Five cases harbored KIT mutations, three of which were hotspots. BRAF V600E mutation was not detected. Univariable analysis showed that tumor size greater than or equal to 33 mm, mitotic figures of greater than or equal to 10 per mm2, lymph node metastasis, and low CD8+ tumor-infiltrating lymphocyte density were adverse prognostic factors. Thus, patients with genital melanomas have a poor prognosis, and evaluation of multiple biomarkers is necessary to identify patients who may benefit from immunotherapy or targeted therapy.

With the recent elucidation of gastric-type lesions in the female genital tract (especially in the cervix), occasional cases of endometrial adenocarcinoma displaying gastric (gastrointestinal) differentiation have been reported, but they are currently not recognized as a distinct pathologic entity. We report 9 cases of endometrial mucinous lesions which exhibit gastric (gastrointestinal)-type features by morphology and immunohistochemistry, including 4 adenocarcinomas and 5 benign mucinous lesions, in patients aged 32 to 85. The adenocarcinomas showed gastric-type morphology in all 4 cases and goblet cells in 1, with a component of benign gastric-type mucinous glands in 1 case. Immunohistochemically, the adenocarcinomas were positive for CK7 (4/4), CEA (4/4), MUC6 (3/3), PAX8 (3/4), CK20 (2/4), CDX2 (2/4), and estrogen receptor (1/4). They were negative for Napsin A (0/3), with mutation-type p53 staining in 2/4 cases, block-type p16 positivity in 1/4, and scattered chromogranin-positive cells in 1/2. Targeted next-generation sequencing revealed nonsense mutation in RB1 gene for the case with block-positive p16. Follow-up was available in all adenocarcinoma cases and indicated aggressive behavior; 2 patients were dead of disease at follow-up of 7 months to 3 years, 1 was alive with progression at 9 months, and 1 was alive without disease at 7 months. The benign mucinous lesions (including the benign component in 1 adenocarcinoma) exhibited gastric-type morphologic features in 5/6 cases, goblet cells in 5/6, and Paneth-like neuroendocrine cells in 1/6. These benign mucinous lesions were associated with an endometrial polyp in 5/6 cases. Cytologic atypia was present in 2/6 cases and a lobular architecture resembling cervical lobular endocervical glandular hyperplasia in 4/6. Immunohistochemically, the benign mucinous lesions were positive for CK7 (5/5), CDX2 (5/6), estrogen receptor (4/5), MUC6 (4/5), CK20 (3/5), PAX8 (3/5), and CEA (2/4), with scattered chromogranin-positive cells in 4/4 cases; in all cases tested Napsin A was negative, p53 was wild-type and p16 was negative. We propose the term "endometrial gastric (gastrointestinal)-type adenocarcinoma" for this distinctive group of rare aggressive endometrial carcinomas. We believe that benign or atypical gastric (gastrointestinal)-type mucinous lesions are putative precursors for these adenocarcinomas, comparable to recognized premalignant gastric-type lesions in the cervix and the vagina. Future recognition and reporting of these gastric-type endometrial mucinous lesions will help delineate their pathogenesis and clinical significance.

Frozen sections of uterine smooth muscle tumors are infrequently required, and related diagnostic difficulties are seldom discussed. We analyzed the clinicopathologic features of 112 frozen sections of uterine smooth muscle tumors and determined the accuracy, reasons for deferrals, and causes of interpretational errors. Most patients (median age, 45 y) presented with pelvic mass symptoms (53%). The main reasons for a frozen section examination were an abnormal gross appearance including loss of the usual whorled pattern of leiomyoma (36 cases, 32.1%), and intraoperative discovery of an abnormal growth pattern and extrauterine extension of a uterine tumor (28 cases, 25%). There were 9 leiomyosarcomas and 103 leiomyomas, including 18 benign histologic variants. An accurate diagnosis of malignancy was achieved in all leiomyosarcomas, with the exception of a myxoid leiomyosarcoma. In 99 cases (88%), the frozen section diagnosis concurred with the permanent section diagnosis (false positives, 0.9%; false negatives, 0%). Misinterpretation of stromal hyalinization as tumor cell necrosis in a leiomyoma with amianthoid-like fibers was a major discrepancy. Two minor discrepancies did not lead to a change in management. The diagnosis was deferred in 10 cases (8.9%) because of stromal alterations, unusual cellular morphology, uncertain type of necrosis, and abnormal growth patterns. Thus, although various stromal and cellular alterations can cause diagnostic uncertainty, leading to deferrals, frozen section diagnosis of uterine smooth muscle tumors has a high accuracy rate. While a definitive frozen section diagnosis of malignancy may be made when there is unequivocal atypia, indisputable mitotic figures, and tumor cell necrosis, it is important to remember that nonmyogenic mesenchymal tumors may also mimic uterine smooth muscle tumors. In a frozen section setting, it would be sufficient to issue a diagnosis of "malignant mesenchymal tumor." For tumors that do not meet the criteria for malignancy, issuing a frozen section diagnosis of "atypical mesenchymal tumor and defer the histologic subtyping to the permanent sections" is appropriate.

Simple Summary Uterine leiomyosarcoma is an aggressive tumor and the current staging system cannot differentiate the patients into different prognostic groups. This leads to difficulty in predicting the patients’ outcomes and planning for adjuvant therapy. We aimed to develop a prediction model that can predict the chance of survival by the third year. In this article, we had used different statistical tests to identify five readily available clinicopathologic parameters to build the prediction model. Internal validation was performed with satisfactory accuracy. Such a prediction model might help to predict survival outcome, and guide future research on the treatment modality. Abstract Background: The existing staging systems of uterine leiomyosarcoma (uLMS) cannot classify the patients into four non-overlapping prognostic groups. This study aimed to develop a prediction model to predict the three-year survival status of uLMS. Methods: In total, 201 patients with uLMS who had been treated between June 1993 and January 2014, were analyzed. Potential prognostic indicators were identified by univariate models followed by multivariate analyses. Prediction models were constructed by binomial regression with 3-year survival status as a binary outcome, and the final model was validated by internal cross-validation. Results: Nine potential parameters, including age, log tumor diameter, log mitotic count, cervical involvement, parametrial involvement, lymph node metastasis, distant metastasis, tumor circumscription and lymphovascular space invasion were identified. 110 patients had complete data to build the prediction models. Age, log tumor diameter, log mitotic count, distant metastasis, and circumscription were significantly correlated with the 3-year survival status. The final model with the lowest Akaike’s Information Criterion (117.56) was chosen and the cross validation estimated prediction accuracy was 0.745. Conclusion: We developed a prediction model for uLMS based on five readily available clinicopathologic parameters. This might provide a personalized prediction of the 3-year survival status and guide the use of adjuvant therapy, a cancer surveillance program, and future studies.

Simple Summary Vulvar squamous cell carcinoma (VSCC) is the most frequent malignant vulvar tumor, with a peak incidence in the 7–8th decades of life. However, VSCCs can also occur in young women. This unfortunate event is even rarer and more worrisome in pregnant women, being hard to manage for gynecologists, oncologists, and radiotherapists. Very few cases have been reported and we felt the need for an updated review on this topic. Thus, we performed a systematic literature review of VSCCs diagnosed during pregnancy, discussing the clinic-pathologic features, the implications in pregnancy outcomes, and the effects of such a diagnosis in the management of mothers and their babies. Abstract According to our systematic literature review (PRISMA guidelines), only 37 vulvar squamous cell carcinomas (VSCCs) were diagnosed during pregnancy (age range: 17–41 years). The tumor size range was 0.3–15 cm. The treatment was performed after (14/37, 38%), before (10/37, 27%), or before-and-after delivery (11/37, 30%). We found that 21/37 (57%) cases were stage I, 2 II (5%), 11 III (30%), and 3 IVB (8%). HPV-related features (condylomas/warts; HPV infection; high-grade squamous intraepithelial lesion) were reported in 11/37 (30%) cases. We also found that 9/37 (24%) patients had inflammatory conditions (lichen sclerosus/planus, psoriasis, chronic dermatitis). The time-to-recurrence/progression (12/37, 32%) ranged from 0 to 36 (mean 9) months. Eight women died of disease (22%) 2.5–48 months after diagnosis, 2 (5%) were alive with disease, and 23 (62%) were disease-free at the end of follow-up. Pregnant patients must be followed-up. Even if they are small, newly arising vulvar lesions should be biopsied, especially in women with risk factors (HPV, dermatosis, etc.). The treatment of VSCCs diagnosed in late third trimester might be delayed until postpartum. Elective cesarean section may prevent vulvar wound dehiscence. In the few reported cases, pregnancy/fetal outcomes seemed to not be affected by invasive treatments during pregnancy. However, clinicians must be careful; larger cohorts should define the best treatment. Definite guidelines are lacking, so a multidisciplinary approach and discussion with patients are mandatory.

Crosbie EJ, Ryan NAJ, Arends MJ, Bosse T, Burn J, Cornes JM, et al. The Manchester International Consensus Group recommendations for the management of gynecological cancers in Lynch syndrome. Genet Med. 2019;21:2390–400. Article Google Scholar Evrard C, Tachon G, Randrian V, Karayan-Tapon L, Tougeron D. Microsatellite instability: diagnosis, heterogeneity, discordance, and clinical impact in colorectal cancer. Cancers (Basel). 2019;11:1567. CAS Article Google Scholar Luchini C, Bibeau F, Ligtenberg MJL, Singh N, Nottegar A, Bosse T, et al. ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann Oncol. 2019;30:1232–43. CAS Article Google Scholar Cancer Genome Atlas Research Network, Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497:67–73. Article Google Scholar Talhouk A, McConechy MK, Leung S, Li-Chang HH, Kwon JS, Melnyk N, et al. A clinically applicable molecular-based classification for endometrial cancers. Br J Cancer. 2015;113:299–310. CAS Article Google Scholar Leon-Castillo A, de Boer SM, Powell ME, Mileshkin LR, Mackay HJ, Leary A, et al. Molecular classification of the PORTEC-3 trial for high-risk endometrial cancer: impact on prognosis and benefit from adjuvant therapy. J Clin Oncol. 2020. https://doi.org/10.1200/JCO.20.00549. Ryan N, Wall J, Crosbie EJ, Arends M, Bosse T, Arif S, et al. Lynch syndrome screening in gynaecological cancers: results of an international survey with recommendations for uniform reporting terminology for mismatch repair immunohistochemistry results. Histopathology. 2019;75:813–24. Article Google Scholar Mills AM, Longacre TA. Lynch syndrome screening in the gynecologic tract: current state of the art. Am J Surg Pathol. 2016;40:e35–44. Article Google Scholar Stelloo E, Jansen AML, Osse EM, Nout RA, Creutzberg CL, Ruano D, et al. Practical guidance for mismatch repair-deficiency testing in endometrial cancer. Ann Oncol. 2017;28:96–102. CAS Article Google Scholar Bartosch C, Clarke B, Bosse T. Gynaecological neoplasms in common familial syndromes (Lynch and HBOC). Pathology. 2018;50:222–37. Article Google Scholar Wong RW, Palicelli A, Hoang L, Singh N. Interpretation of p16, p53 and mismatch repair protein immunohistochemistry in gynaecological neoplasia. Diagnostic Histopathol. 2020;26:257–77. Article Google Scholar Singh N, Wong R, Tchrakian N, Allen S, Clarke B, Gilks CB. Interpretation and reporting terminology for mismatch repair protein immunohistochemistry in endometrial cancer. Br Assoc Gynaecol Pathol. 2020. https://www.thebagp.org/resources/. Download references Barts Health NHS Trust, London, UK Naveena Singh & Nairi Tchrakian Pamela Youde Nethersole Eastern Hospital, Hong Kong, Hong Kong Richard Wong University Hospital Network, Toronto, ON, Canada Shara-Gaye Allen & Blaise Clarke Vancouver General Hospital, Vancouver, BC, Canada C. Blake Gilks You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar You can also search for this author in PubMed Google Scholar Correspondence to Naveena Singh. The authors declare that they have no conflict of interest. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions Singh, N., Wong, R., Tchrakian, N. et al. Interpretation of mismatch repair protein expression using obsolete criteria results in discrepancies with microsatellite instability and mutational testing results. Comment on Hechtman et al. Mod Pathol 2020; 33:871–879. Mod Pathol (2020). https://doi.org/10.1038/s41379-020-00680-y Download citation Received: 03 July 2020 Revised: 01 September 2020 Accepted: 02 September 2020 Published: 26 September 2020 DOI: https://doi.org/10.1038/s41379-020-00680-y

Prognostication of malignant pleural effusion (MPE) guides treatment strategies but existing prognostication scores are yet to be validated in Asians. We aimed to evaluate the performance of these scores in an Asian population. A refined score was also proposed based on the impact of EGFR mutation on survival.Survival and clinical data of histocytologically-confirmed MPE patients from a Hong Kong hospital were analyzed with the LENT, modified-LENT, PROMISE and SELECT (converted from its original model) scores. A refinement of the LENT score for Asians was proposed by inclusion of EGFR status (EGFR-LENT), which was compared with the LENT score and validated in an independent patient cohort.All prognostication scores performed well on risk stratification by Kaplan-Meier curve (log rank p 0.0001) in 368 MPE patients except for LENT in low-risk group. C-statistics for LENT, modified-LENT, PROMISE and SELECT in predicting 3-month mortality were 0.77, 0.80, 0.80 and 0.82, respectively. The proposed LENT score refinement (EGFR-LENT) improved stratification among low-risk patients; with a higher C-statistic (0.83) in 3-month mortality prediction than LENT (0.77, p = 0.0121), PROMISE (0.80, p = 0.3713), and SELECT (0.82, p = 0.7908) scores. Validation of EGFR-LENT in an independent cohort (124 patients) confirmed good performance in predicting 3-month mortality (C-statistic 0.87, vs 0.79 in LENT, p = 0.0444).All existing scores had reasonable performance in prognosticating MPE, and LENT score refinement by inclusion of EGFR mutation status improved its performance among Asian MPE patients.

So-called gastric-type adenocarcinoma and related premalignant lesions have been characterized in the cervix, but similar lesions are not widely recognized in the vagina. We report a series of 11 vaginal glandular lesions exhibiting gastric differentiation, comprising 5 cases of adenocarcinoma and 6 of adenosis. All cases occurred in adults (aged 33 to 69) with no known history of diethylstilboestrol exposure. The vaginal adenocarcinomas exhibited morphologic features identical to gastric-type adenocarcinoma of the cervix, but 1 case additionally demonstrated basaloid and sarcomatoid components, which have not been previously reported in cervical gastric-type adenocarcinoma. Immunohistochemically, the adenocarcinomas were positive for MUC6 (4/5), PAX8 (3/5), CK7 (5/5), CK20 (1/5), CDX2 (5/5), CA19.9 (5/5), CEA (4/5), CA125 (5/5), and hepatocyte nuclear factor 1β (5/5). p16, estrogen receptor, and Napsin A were negative in all cases tested, whereas p53 exhibited mutation-type staining in 3/5 cases. In all 5 adenocarcinomas, a component of adenosis with benign or atypical nuclear features was identified; the adenosis displayed gastric morphology in 4 cases and tuboendometrial morphology in 1. The 6 cases of pure vaginal adenosis (without associated adenocarcinoma) all contained gastric-type mucinous glands together with tuboendometrial glands in 2 cases. There was focal intestinal differentiation with goblet cells in all 6 cases and neuroendocrine cells with eosinophilic granules in 3. Cytologic atypia was observed in 4/6 cases of pure vaginal adenosis. Immunohistochemically, the gastric-type adenosis (10 cases) was positive for MUC6 (10/10), estrogen receptor (5/10), PAX8 (8/10), CK7 (9/9), CK20 (2/9), CDX2 (5/9), CA19.9 (8/9), CEA (6/9), CA125 (6/9), hepatocyte nuclear factor 1β (10/10), and Napsin A (1/10). p53 exhibited wild-type immunoreactivity in all 10 cases, whereas p16 was negative in all cases tested. Scattered individual chromogranin-positive cells were present in all 5 cases of pure adenosis tested. Follow-up was available in 4 of the adenocarcinoma cases, with 3 patients dead of disease within 1 to 3 years and 1 patient alive with disease at 1 year. The morphologic and immunohistochemical findings in our study suggest a close relationship between vaginal gastric-type adenocarcinoma and adenosis exhibiting gastric differentiation. This probably represents a distinct pathway of vaginal gastric-type carcinogenesis analogous to that occurring in the cervix. We propose that gastric-type adenocarcinoma be recognized as a distinct histologic subtype of vaginal adenocarcinoma while vaginal adenosis of gastric-type represents a novel subtype of adenosis that requires further study to clarify its biological potential.

We report 2 sex cord-stromal tumors with distinct components of fibroma and steroid cell tumor; one case was of ovarian and the other of extraovarian origin. In the ovarian tumor, there were discrete areas of fibroma and steroid cell tumor, not otherwise specified. The extraovarian case involved the pelvic soft tissues and comprised a cellular fibroma with subsequent recurrence 7 yr later as a steroid cell tumor, not otherwise specified. In both cases, aggregates of luteinized cells were present within the fibromatous component, raising the possibility that the steroid cell tumor arose from neoplastic transformation of these cells. While mixed ovarian sex cord-stromal tumors (gynandroblastomas) are well described, as far as we are aware there have been no prior reports of neoplasms containing a component of steroid cell tumor and fibroma.

Aims Accurate mitosis counting, which is important in the diagnosis of uterine smooth muscle tumours (USMTs), is often difficult and subjective. The mitosis-specific immunohistochemical marker phosphohistone-H3 (PHH3) has been shown to be diagnostically useful, but its expression, in relation to outcome, has not been thoroughly investigated. The aim of this study is to evaluate PHH3 as a diagnostic and prognostic marker in USMTs. Methods and results PHH3 expression was evaluated in 55 leiomyosarcomas (LMSs), 26 smooth muscle tumours of uncertain malignant potential (STUMPs), 18 leiomyomas with bizarre nuclei (LBN), and 12 leiomyomas (LMs). Scores were expressed as counts per 10 high-power fields (HPFs). Median follow-up durations of patients with LMS, STUMP, LBN and LM were, respectively, 39, 78, 65.5 and 49.5 months. Twenty-eight patients with LMSs (50.9%) died, and two (7.7%) patients with STUMPs experienced recurrence. The median PHH3 scores for LMSs were significantly higher than those for other categories of tumour. A score of ≥29/10 HPFs was also independently associated with a poor outcome. To test whether the PHH3 score could distinguish between benign USMTs with atypical histology and those that were clinically malignant, two biological groups were further delineated. Patients in group 1 (18 LBNs and 24 STUMPs) all had an uneventful outcome, whereas patients in group 2 (two recurrent STUMPs and 32 LMSs) all had a recurrence or tumour-related death. Median PHH3 scores for the two groups were, respectively, 2/10 HPFs and 27/10 HPFs. A PHH3 score of ≥7/10 HPFs was highly associated with malignancy. Conclusion PHH3 is useful in evaluation of the biological behaviour of USMTs, and may serve as a prognostic indicator for LMSs.

Women may be genetically susceptible to development of gynecological cancers. Major familial ovarian cancer syndromes include site-specific ovarian cancer, breast/ovarian cancer, and hereditary non-polyposis colon cancer (HNPCC). The former two syndromes are linked to BRCA1 and BRCA2 genes while DNA repair genes such as hMSH2 and hMLH1 are commonly involved in HNPCC. Carriers are also prone to endometrial carcinoma. BRCA mutation related ovarian tumours are more likely to be high grade serous whilst borderline tumours are conspicuously absent. Papillary serous carcinomas of the peritoneum and fallopian tube are also reported. In recent years, serous tubal intraepithelial carcinoma and transitional metaplasia, its mimick, are identified at the fimbria of prophylactic salpingo-oophorectomy specimens. Immunohistochemical studies for p53 and MIB1 may help in the diagnosis. Tubal pathology is also occasionally reported in Peutz-Jeghers syndrome. Such findings emphasize on the importance of careful pathological examination of the fallopian tube in genetically susceptible women.