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Aims Methods and results Conclusions Recently, SOX17 has emerged as a promising biomarker for non‐mucinous Müllerian (ovarian and endometrial) carcinomas, demonstrating increased specificity in comparison to PAX8 while maintaining similar sensitivity. However, expression of SOX17 in mesonephric‐like adenocarcinoma (MLA), a carcinoma of the female genital tract with uncertain, but probably Müllerian histogenesis, remains unexplored. This study aims to address this gap.SOX17 immunohistochemistry was performed on whole tissue sections from 68 MLAs originating from the endometrium or ovary and seven cervical mesonephric carcinomas, as well as six mesonephric remnants/hyperplasias. Using a four‐tiered scoring system based on distribution and intensity of staining, 68% of MLA displayed a negative/low (< 10%) SOX17 expression pattern, which contrasts with the high expression observed in most Müllerian carcinomas. However, 22% of MLA demonstrated high SOX17 expression, similar to other endometrial and ovarian carcinomas. Similarly, five of seven (72%) mesonephric carcinomas of the cervix were SOX17‐negative, but two cases (28%) were positive. All mesonephric remnants/hyperplasias were SOX17 negative.The majority of MLA are negative or exhibit low SOX17 expression, in contrast to the diffuse and strong expression commonly seen in other types of Müllerian carcinoma. However, a subset of MLAs demonstrate high SOX17 expression. Therefore, absence of SOX17 staining is supportive for MLA when the differential includes another non‐mucinous Müllerian carcinoma. SOX17 may also be useful for differentiating mesonephric remnants/hyperplasias from Müllerian malignancies and benign Müllerian glandular lesions. [ABSTRACT FROM AUTHOR]

The article discusses the classification of struma ovarii, a type of ovarian teratoma that contains thyroid elements. The authors conducted a molecular analysis of cases of struma ovarii and found that molecular alterations were more common in cases with malignant behavior. They also identified specific gene mutations, such as BRAF and TERT promoter alterations, that were associated with malignancy. The study suggests that cases of struma ovarii resembling a follicular neoplasm should undergo molecular testing to predict the possibility of developing extraovarian spread. However, larger studies with long-term follow-up are needed to validate these findings. [Extracted from the article]

Associations between intraluminal tumor cell involvement in serially examined fallopian tubes and endometrial carcinoma characteristics and outcomes. Low-grade serous carcinoma (LGSC) is a fundamentally different and unrelated tumour type to HGSC and nearly always arises within the ovary (although, rarely, these arise as primary peritoneal neoplasms), often in a stepwise fashion from an epithelial inclusion cyst to a benign serous cystadenoma to a serous borderline tumour. 8 Wolsky RJ, Price MA, Zaloudek CJ, Rabban JT. Mucosal proliferations in completely examined fallopian tubes accompanying ovarian low-grade serous tumors: neoplastic precursor lesions or normal variants of benign mucosa?. [Extracted from the article]

Microcystic stromal tumour (MST) is a rare, usually benign, ovarian neoplasm characterized morphologically in its classic form by a distinctive triad of features comprising microcysts, solid cellular regions and fibrous stroma. Variant morphology also occurs, including the presence of nests, tubules, cords and signet ring cells. Immunohistochemically, this neoplasm is characterized by diffuse nuclear expression of β‐catenin, cyclin D1, Wilms' tumour 1 (WT1) and steroidogenic factor 1 (SF1), as well as diffuse staining with forkhead box ligand 2 (FoxL2) and CD10. Inhibin and calretinin are typically negative. At the genomic level, these neoplasms harbour mutually exclusive mutations in CTNNB1 or APC genes, with the former being significantly more common. This molecular characteristic raises possible links to other rare ovarian lesions, including solid pseudopapillary tumour, signet‐ring stromal tumour and Sertoli cell tumour. Rarely, MST is an extracolonic manifestation of familial adenomatous polyposis (FAP) and serves as a sentinel event that could trigger the identification of the syndrome. Herein, we review the published literature on ovarian MST and provide practical advice for pathologists reporting these rare neoplasms. [ABSTRACT FROM AUTHOR]

An updated World Health Organization (WHO) classification of female genital tumours was published in autumn 2020. We discuss the major new additions to and changes from the prior 2014 classification with a discussion of the reasons underlying these. A feature of the new classification is the greater emphasis on key molecular events with integration of morphological and molecular features. Most of the major changes from the prior classification pertain to uterine (corpus and cervix) and vulval tumours, but changes in all organs are covered. [ABSTRACT FROM AUTHOR]

This review covers the significant new developments in the pathological classification of gynecological tumors. Many of these were included in the updated World Health Organization Classification of Female Genital Tract Tumours, published in 2020. Topics include the compelling evidence that a large majority of extrauterine high-grade serous carcinomas arise from the fallopian tube; the Cancer Genome Atlas (TCGA) Classification of endometrial carcinomas; the discovery that most so-called synchronous endometrial and ovarian endometrioid carcinomas represent metastasis from the endometrium to the ovary; and the division of cervical, vaginal, and vulval carcinomas into clinically meaningful HPV-associated and HPV-independent types. Newly described tumor types are covered, including endometrial and ovarian mesonephric-like adenocarcinoma, uterine sarcoma types associated with specific molecular abnormalities, and gastric (gastrointestinal)-type adenocarcinomas of the endometrium and vagina. Important molecular events in ovarian sex cord-stromal tumors are also discussed. [ABSTRACT FROM AUTHOR]

In the last two decades or so, a spectrum of benign, premalignant and malignant cervical glandular lesions exhibiting gastric differentiation has been described, with gastric‐type adenocarcinoma representing the most common human papillomavirus (HPV)‐independent cervical adenocarcinoma. More recently, limited literature has reported a variety of gastric‐type glandular lesions at other sites within the female genital tract and, as in the cervix (the most common site for these lesions), a spectrum of benign, premalignant and malignant lesions has been proposed. We provide an update and review of the emerging spectrum of gastric‐type glandular lesions at female genital tract sites other than the cervix. In the endometrium, putative gastric‐type glandular lesions include mucinous metaplasia of gastric‐type, atypical mucinous proliferation of gastric‐type and gastric‐type adenocarcinoma. Similarly in the vagina, gastric‐type adenosis, atypical adenosis and adenocarcinoma have been described. There have also been occasional reports of gastric‐type lesions involving the ovary and fallopian tube. We provide guidance on how to recognise gastric‐type lesions morphologically and immunophenotypically and stress that sometimes these lesions occur at more than one site within the female genital tract (synchronous/multifocal gastric‐type lesions of the female genital tract), sometimes in association with Peutz–Jeghers syndrome. [ABSTRACT FROM AUTHOR]

Objectives: The Lower Anogenital Squamous Terminology (LAST) recommendations classify human papillomavirus-associated squamous lesions into low- and high-grade squamous intraepithelial lesions (LSILs/HSILs). Our study aimed to assess interobserver agreement among 6 experienced pathologists in assigning 40 anal lesions previously diagnosed as anal intraepithelial neoplasia 2 (AIN 2) to either HSIL or non-HSIL categories.Methods: Agreement based on photomicrographs of H&E alone or H&E plus p16 immunohistochemistry was calculated using κ coefficients.Results: Agreement was fair based on H&E alone (κ = 0.42; 95% confidence interval [CI], 0.34-0.52). Adding p16 improved agreement to moderate (κ = 0.55; 95% CI, 0.54-0.62). On final diagnosis, 21 cases (53%) had unanimous diagnoses, and 19 (47%) were divided. When designating p16 results as positive or negative, agreement was excellent (κ = 0.92; 95% CI, 0.83-0.95). Among variables (staining location, extent, and intensity), staining of the basal/parabasal layers was a consistent feature in cases with consensus for positive results (20/20). Of the 67 H&E diagnoses with conflicting p16 results, participants modified 32 (48%), downgrading 23 HSILs and upgrading 9 non-HSILs.Conclusions: Although p16 increased interobserver agreement, disagreement remained considerable regarding intermediate lesions. p16 expression, particularly if negative, can reduce unwarranted HSIL diagnoses and unnecessary treatment. [ABSTRACT FROM AUTHOR]

Aims: Uterine plexiform tumourlets are traditionally regarded as microscopic epithelioid leiomyomas. They are typically solitary incidental findings, but may be multifocal (plexiform leiomyomatosis). We aim to report novel immunohistochemical and morphological findings, specifically the presence of spindled and epithelioid cell nodules, in these lesions. Methods and results: Three cases of plexiform leiomyomatosis and 16 solitary plexiform tumourlets were included. Two cases of plexiform leiomyomatosis and four solitary plexiform tumourlets demonstrated spindled and epithelioid cell nodules which, in one of the former cases, formed expansile masses up to 15 mm. The nodules demonstrated mild cytological atypia and occasional mitotic activity, and they were associated with a myxoid stroma and a lymphohistiocytic infiltrate which imparted a granulomatous appearance to the microscopic lesions. The plexiform tumourlets (solitary and multifocal) consistently expressed desmin, smooth muscle actin, ER and PR, and they commonly co‐expressed melanocytic and perivascular epithelioid cell (PEC) markers HMB45, MiTF and cathepsin K. The spindled and epithelioid cell nodules were generally negative for myoid markers and hormone receptors, but expressed p16, cyclin D1 and TFE3. All lesions tested were negative for cytokeratin, S100, melanA, inhibin, EMA, ALK and BCOR; fluorescence in‐situ hybridisation was negative for ALK, TFE3 and BCOR rearrangements in one of the larger spindled and epithelioid cell nodules. Conclusions: Plexiform tumourlets commonly co‐express myoid and melanocytic markers and may represent part of the spectrum of gynaecological PEC‐related lesions. Some cases are associated with spindled and epithelioid cell nodules that could potentially mimic other uterine myxoid neoplasms. [ABSTRACT FROM AUTHOR]

Aims: To report a series of benign ovarian seromucinous neoplasms, an uncommon and hitherto poorly described category of tumours included in the current 2014 World Health Organisation classification of tumours of the female reproductive organs. Methods and results: We report the clinicopathological features of a series of 22 benign ovarian seromucinous neoplasms (cystadenomas and adenofibromas or admixtures). The neoplasms occurred in patients aged 32–83 years (mean = 62, median = 65.5) and involved the left ovary (n = 14), the right ovary (n = 6) or both ovaries (n = 2). There was a common association with endometrioid elements (endometrioid differentiation within the cystadenoma/adenofibroma and/or endometriosis) and other endometriosis‐associated neoplasms. Conclusions: We speculate that some of these represent benign ovarian endometrioid neoplasms with foci of mucinous and/or serous differentiation, while others represent true mixed neoplasms. [ABSTRACT FROM AUTHOR]

The overlap between tumour typing and grading highlighting deficiencies in nomenclature Typing and grading are largely independent parameters although grading can only be performed once the tumour type is established, given that there are different grading systems for different neoplasms. Future classifications of tumours, such as those discussed above, should strive to make it clear that these represent fundamentally different tumour types rather than being different grades of the same neoplasm. [Extracted from the article]

Aims: Sertoli–Leydig cell tumours (SLCTs) are rare ovarian neoplasms that are commonly associated with somatic or germline DICER1 mutations, especially when of the moderately or poorly differentiated type. A large majority are unilateral, but bilateral neoplasms have been reported, sometimes in the context of germline DICER1 mutations (DICER1 syndrome). It is currently unknown whether these represent independent neoplasms or metastasis from one ovary to the other and we aimed to elucidate this. Methods and results: We report three cases of bilateral ovarian SLCT (all in patients with DICER1 syndrome) and review all reported cases of bilateral neoplasms. In the three cases (all moderately or poorly differentiated neoplasms), the time interval between the discovery of the tumours in each ovary ranged from 2.7 years to 6 years. In all cases, different DICER1 somatic hotspot mutations within the two tumours provided definitive proof that they represent independent neoplasms; this may be important clinically. Our literature review revealed that, when this information was available, all patients with bilateral SLCT had a germline DICER1 mutation. Conclusions: Bilateral ovarian SLCTs represent independent rather than metastatic neoplasms, and essentially always occur in the context of DICER1 syndrome. [ABSTRACT FROM AUTHOR]

Endometriosis is an extremely common condition and, in most cases, establishing a histological diagnosis is straightforward, although a variety of benign alterations may result in problems with interpretation. In this review, I discuss selected uncommon variants of endometriosis or benign alterations that may result in diagnostic problems. The topics covered include the contentious issue of so‐called atypical endometriosis, stromal endometriosis, polypoid endometriosis, and the association of endometriosis with florid mesothelial hyperplasia. The propensity of endometriosis to undergo neoplastic transformation (especially to endometrioid and clear cell carcinoma) is well known. Selected issues relating to the various neoplasms that can arise in endometriosis are discussed, with a particular concentration on unusual variants of endometrioid carcinoma that result in a disproportionately high number of issues in referral practice. The propensity of ovarian endometrioid carcinomas to show an unexpected ('aberrant') immunophenotype with positive staining with 'intestinal' markers and negative staining with Mullerian markers is also discussed. Uncommon tumour types that may arise in endometriosis, namely seromucinous neoplasms, mesonephric‐like carcinomas, and somatically derived yolk sac tumours, are also covered. [ABSTRACT FROM AUTHOR]

Aims: To expand the morphological spectrum of ovarian microcystic stromal tumour, a rare neoplasm considered to have a relatively constant morphology with microcysts, solid cellular regions and hyalinised fibrous stroma. Methods and results: We report four ovarian neoplasms in patients aged 45, 56, 61 and 71 years with the characteristic immunophenotype of microcystic stromal tumour (diffuse nuclear positivity with betacatenin, cyclin D1 and WT1; diffuse cytoplasmic positivity with CD10; negative inhibin, calretinin, oestrogen receptor and progesterone receptor). The tumours had variant morphology (diffuse, nested and corded arrangements in three cases, including one with spindle cell elements; nested, corded and tubular in the other). A CTNNB1 point mutation in exon 3 (c.98C>G,p.S33C; c.100G>A,p.G34R; c.97T>G, p.S33A) was present in the three cases with material available for testing. Conclusions: We feel that the cases we report are related to microcystic stromal tumour but with variant morphology; as such, the morphological spectrum of ovarian microcystic stromal tumour is broader than hitherto reported. [ABSTRACT FROM AUTHOR]

Abstract Sentinel lymph node (SLN) biopsy has been increasingly used in the management of early-stages cervical cancer instead of systematic pelvic lymph node dissection (PLND). The aim of this article is to give a critical overview of key aspects related to this concept, such as a necessity for reliable detection of micrometastases (MIC) in SLN and the requirements for SLN pathologic ultrastaging, low accuracy of intraoperative detection of SLN involvement, and still a limited evidence of oncological safety of the replacement of PLND by SLN biopsy only in ≥IB1 tumours due to unknown risk of MIC in non-SLN pelvic lymph nodes in patients with negative SLN, and absence of any prospective evidence. Highlights • Detection of micrometastases increases sensitivity of SLN, so SLN ultrastaging should be performed if PLND is avoided. • Intraoperative SLN evaluation fails to detect 30–50% of metastases. • Micrometastases in SLN is associated with decreased survival equivalent to macrometastases. • The risk of micrometastases in pelvic LN in cases with negative SLN is not known. • There is no prospective evidence on safety of SLN only concept in cervical cancer. [ABSTRACT FROM AUTHOR]

Since the realisation that most "ovarian" high-grade serous carcinomas (HGSC) arise from precancers and early cancers in the fallopian tube fimbria, much work has been devoted during the past two decades to the spectrum of tubal I TP53 i mutant lesions. Since the introduction of the SEE-FIM protocol for examining fallopian tubes more than 10 years ago and the concomitant increase in prophylactic and opportunistic salpingectomies, fallopian tubes are routinely undergoing far more scrutiny by pathologists than previously. A candidate precursor to pelvic serous cancer (p53 signature) and its prevalence in ovaries and fallopian tubes from women with BRCA mutations. [Extracted from the article]

Mucinous ovarian carcinoma (MOC) is a rare type of ovarian cancer with a better prognosis compared to other types. However, some patients with stage I disease experience tumor recurrence and poor outcomes. Recent studies have shown that the growth pattern of MOC, either expansile or infiltrative invasion, is a better predictor of clinical behavior than tumor grading. A study published in Histopathology found that MOCs with infiltrative invasion were associated with a higher risk of death, independent of other factors. The study also confirmed that MOCs with expansile invasion have better outcomes. The study recommends including the pattern of invasion in histopathologic reporting and risk stratification for MOC patients. Additionally, the study found that stromal markers FAP and THBS2 were more commonly expressed in MOCs with infiltrative invasion, which was associated with worse disease-specific survival. The study suggests that evaluating growth pattern and stromal markers can aid in the classification and understanding of biological differences in MOC. The authors emphasize the need for standardized criteria and increased awareness among pathologists for evaluating growth pattern in MOC. Pathologic staging and p53 mutation-type staining were also found to be important prognostic factors in MOC. The authors envision a future where patient management is based on important tumor parameters like growth pattern and p53 status, which can be easily incorporated into routine practice and may lead to improved patient stratification and tailored approaches. [Extracted from the article]

Aims Uterine tumour resembling ovarian sex cord tumour ( UTROSCT) is an uncommon mesenchymal neoplasm of uncertain histogenesis. While it is considered a neoplasm of uncertain but low malignant potential, there is limited evidence for this as there are no large studies with follow-up. We aimed to determine the clinical behaviour of this uncommon neoplasm and investigate clinicopathological parameters which predict behaviour. Methods and results From a series of 34 cases of UTROSCT, mainly from consultation practice, we obtained follow-up information which was obtained by contacting referring pathologists and clinicians. The follow-up periods ranged from 6 to 135 months (mean 39 months). Eight of 34 patients (23.5%) developed extrauterine metastasis to a variety of sites, including pelvic and abdominal peritoneum, ovary, lymph nodes, bone, liver and lung, and three patients (8.8%) died of tumour. Those neoplasms which exhibited malignant behaviour occurred on average in older patients, and were larger and more likely to exhibit necrosis, lymphovascular invasion, cervical involvement, significant nuclear atypia and significant mitotic activity. However, only the presence of necrosis and significant mitotic activity was statistically significant. Conclusions While our figure of 23.5% of cases exhibiting malignant behaviour may reflect some bias related to consultation practice our results show that, not uncommonly, these neoplasms have an aggressive clinical course with extrauterine metastasis. Given the overlap in pathological parameters between clinically benign and malignant neoplasms, UTROSCTs are all best regarded as potentially malignant. [ABSTRACT FROM AUTHOR]

Given the significant potential for misdiagnosis, for example, there can be marked overlap in the morphology of different ovarian sex cord-stromal tumours (so-called morphological mimicry), this has resulted in a tendency for a particular molecular event to be sometimes erroneously attributed to a certain tumour type. Microcystic stromal tumor: A distinctive ovarian sex cord-stromal neoplasm characterized by FOXL2, SF-1, WT-1, cyclin D1, and -catenin nuclear expression and CTNNB1 mutations. Given the increasing availability of molecular testing (targeted gene testing or large gene panels) and the tendency for testing to be performed on rare and unusual neoplasms, recent years have witnessed the "emergence" of multiple tumour types associated with characteristic and sometimes relatively specific molecular events. [Extracted from the article]

Extra-uterine high-grade serous carcinoma ( HGSC) accounts for most of the morbidity and mortality associated with ovarian carcinoma, and is one of the leading causes of cancer death in women. Until recently our understanding of HGSC was very limited compared to other common cancers, and it has only been during the last 15 years that we have learned how to diagnose this ovarian carcinoma histotype accurately. Since then, however, there has been rapid progress, with identification of a precursor lesion in the fallopian tube, development of prevention strategies for both those with inherited susceptibility (hereditary breast and ovarian cancer syndrome) and without the syndrome, and elucidation of the molecular events important in oncogenesis. This molecular understanding has led to new treatment strategies for HGSC, with the promise of more to come in the near future. In this review we focus on these recent changes, including diagnostic criteria/differential diagnosis, primary site assignment, precursor lesions and the molecular pathology of HGSC. [ABSTRACT FROM AUTHOR]

Aims The histogenesis and cell lineage of small-cell carcinoma of the ovary of hypercalcaemic type ( SCCOHT) is unknown. We aim to provide evidence that this may be a primitive germ-cell neoplasm arising from a teratoma. Methods and results Following the identification of two cases of SCCOHT associated with germ-cell tumours (one dermoid cyst, one immature teratoma with a focus of yolk sac tumour), we undertook a literature review to look for any prior reports of SCCOHT in association with other neoplasms or elements. This revealed two cases associated with immature teratomas, one arising in an ovary where a cystectomy had been undertaken previously for a teratoma and another in association with a mucinous borderline tumour. Mucinous elements have also been reported in SCCOHT, this type of epithelium potentially being of teratomatous derivation. We stained whole tissue sections of nine cases of SCCOHT and a tissue microarray ( TMA) containing 34 different SCCOHT with germ-cell markers SALL4, OCT3/4, alpha fetoprotein ( AFP) and glypican 3. All except one of the whole tissue sections and approximately half the TMA cases were positive with SALL4, while all cases were OCT3/4-, AFP- and glypican 3-negative, except for focal glypican 3 staining in an occasional case. Conclusions Our findings provide additional evidence to that proposed by others that SCCOHT is a primitive germ-cell neoplasm arising from a teratoma. [ABSTRACT FROM AUTHOR]

The introduction of new sequencing technologies has resulted in the discovery of commonly mutated genes in uncommon cancers, including non-epithelial ovarian neoplasms and other rare gynaecological tumours, such as cervical embryonal rhabdomyosarcoma. In some of these neoplasms, mutations in certain genes are both frequent and specific enough for the genomic mutations and sometimes their associated protein loss or overexpression to be used as an aid to diagnosis. In this review, we contrast previous gene identification methods with newer ones, and discuss how the new sequencing technologies (collectively referred to as 'next-generation sequencing') have permitted the identification of specific molecular events that characterize several rare gynaecological neoplasms. We highlight the value of using sequencing to complement traditional pathological methods when diagnosing certain tumours, and provide practical advice to pathologists dealing with these neoplasms. We focus on adult granulosa cell tumours (somatic monoallelic mutations in FOXL2), Sertoli-Leydig cell tumours, gynaecological embryonal rhabdomyosarcomas (germline and somatic mutations in DICER1), and small-cell carcinoma of the ovary, hypercalcaemic type (biallelic mutations in SMARCA4). The new genetic findings provided by next-generation sequencing in these uncommon neoplasms have brought these disorders back into focus, and point the way towards new diagnostic, preventive and therapeutic avenues. [ABSTRACT FROM AUTHOR]

In the same series, other ovarian epithelial tumours also expressed CA19.9 (76% mucinous tumours, 40% endometrioid carcinomas, 57% clear cell carcinomas, 45% Brenner tumours).4 In our series, CA19.9 expression rates were higher (62% of cases) which may be secondary to increased sensitivity of current CA19.9 antibodies. Tubo-ovarian high-grade serous carcinomas commonly express CA19.9 Although our study relates to core biopsies, the finding of CA19.9 positivity in a significant proportion of tubo-ovarian HGSC should also be borne in mind when evaluating cytology specimens where the underlying tumour architecture is not readily apparent. [Extracted from the article]

Aims Stratified mucin-producing intraepithelial lesion ( SMILE) is an uncommon premalignant cervical lesion showing morphological overlap with cervical intraepithelial neoplasia ( CIN) and adenocarcinoma in situ ( AIS)/cervical glandular intraepithelial neoplasia. Given the limited literature on SMILE, we aimed to document its frequency and assess the associated pathology in a large series of cases. Methods and results Over a 6-year period, we documented all cases of SMILE and the associated findings. SMILE was diagnosed in 69 specimens from 60 patients (50 loop excisions and 19 punch biopsy specimens), constituting 0.6% of cervical specimens. Overall, SMILE coexisted with high-grade CIN in 93% of cases, AIS in 42%, and a carcinoma in 10%. When SMILE was diagnosed on a cervical punch biopsy, there was high-grade CIN in the follow-up loop in most cases. SMILE was consistently diffusely p16-positive and IMP3-negative. Conclusions Given the morphological overlap and significant association with high-grade CIN and AIS, we believe that SMILE is best regarded as a form of high-grade reserve cell dysplasia, probably arising from reserve or stem cells with the capacity for multidirectional differentiation. We recommend that management of SMILE should be as for AIS. [ABSTRACT FROM AUTHOR]

Aims To report a previously undescribed phenomenon of incidentally detected microscopic proliferations of sex cord cells, often mimicking adult granulosa cell tumour or sex cord tumour with annular tubules, in extraovarian locations. Methods and results The six cases were in patients aged 23-58 years. The proliferations were located in the fallopian tube in three cases, and in paraovarian connective tissues, the pelvic side wall, and appendiceal serosa (one case each). Microscopically, they were typically composed of well-demarcated nests of regular cells with round/ovoid vesicular nuclei, some containing grooves. Microfollicular and/or cribriform arrangements were present in three cases. In five cases, the sex cord lineage was confirmed by positive staining with inhibin and/or calretinin and other sex cord markers. FOXL2 mutation analysis was performed in one case, but was inconclusive. Bilateral oophorectomies and bilateral cystectomies were performed in three cases and one case respectively; there was no sex cord-stromal neoplasm in the removed ovaries. In the two cases in which the ovaries were not removed, imaging showed no suspicious features. Follow-up in four cases (11 months-6 years) has been uneventful. Conclusions The pathogenesis of these microscopic extraovarian sex cord proliferations is unknown, but they may represent non-neoplastic proliferations of embryonic remnants. [ABSTRACT FROM AUTHOR]

Aims To report a series of 10 cervical adenomyomas of endocervical type and the first case of a mesonephric adenomyoma. Methods and results The patients' ages ranged from 30 to 55 years. Most lesions were grossly polypoid; a minority were intramural or exophytic. In six of seven endocervical adenomyomas received in consultation, adenoma malignum was considered. A variety of benign lesions, including lobular endocervical glandular hyperplasia ( LEGH), adenofibroma, endocervicosis and tunnel clusters, were also considered. The endocervical adenomyomas consisted of bland mucinous glands, sometimes with focal epithelial metaplasia, within a prominent smooth muscle stroma. There was usually a focal lobular architecture and sometimes papillary infoldings. A characteristic feature was a rim of stroma surrounding glands, surrounded in turn by smooth muscle. Previously undescribed features were 'symplastic-like' smooth muscle, stromal adipose tissue, gland rupture with mucin extravasation, prominent adenofibroma-like areas and surface cervical intraepithelial neoplasia ( CIN). Diffuse oestrogen receptor ( ER) immunoreactivity was useful in excluding adenoma malignum and LEGH, which are hormone receptor-negative. The mesonephric adenomyoma consisted of a lobular arrangement of mesonephric glands [ ER/progesterone receptor ( PR)-negative; vimentin and luminal CD10 immunoreactivity] within a smooth muscle stroma. Conclusions Endocervical and mesonephric adenomyomas are rare lesions which are often misdiagnosed, possibly because of lack of familiarity among pathologists. [ABSTRACT FROM AUTHOR]

A minor component of smooth muscle may be present in the stroma of benign endometrial polyps and 2 distinctive endometrial polypoid lesions, atypical polypoid adenomyoma and adenomyoma, are characterized by stroma with a predominant smooth muscle component. In this report, we describe 2 unusual endometrial polyps in 43- and 60-year-old women in which the stromal component was predominantly composed of smooth muscle with an epithelioid appearance, a phenomenon which, as far as we are aware, has not been previously reported. [ABSTRACT FROM AUTHOR]

Aims Myogenin (myf4) is a nuclear transcription factor that is considered to be a sensitive and highly specific marker for skeletal muscle differentiation. Following the identification of focal strong nuclear staining with myogenin in two fibroepithelial polyps of the lower female genital tract (the index cases), we stained a series of vulvovaginal spindle cell lesions with this marker in order to investigate how widespread myogenin staining is in these lesions. Methods and results Fibroepithelial polyps ( n = 13), other vulvovaginal mesenchymal lesions ( n = 21) and vulval or vaginal spindle cell squamous carcinomas ( n = 4) were stained for myogenin. Apart from the index cases, all of the other cases were negative, except for one vaginal spindle cell squamous carcinoma, which showed focal weak nuclear immunoreactivity. Ten of 12 embryonal rhabdomyosarcomas of the lower female genital tract were myogenin-positive, as was a single vaginal rhabdomyoma. Conclusions Our study illustrates that focal myogenin immunoreactivity occurs uncommonly in fibroepithelial polyps of the lower female genital tract. This may result in diagnostic confusion and misdiagnosis as a skeletal muscle neoplasm, especially the sarcoma botryoides variant of embryonal rhabdomyosarcoma. [ABSTRACT FROM AUTHOR]

Invasion is a defining feature of malignancy, but the mechanisms of invasion in many common cancers, including gynaecological malignancies, remain unclear. However, it has been proposed that malignant cells may usurp a normal embryological process, epithelial-mesenchymal transition ( EMT), as a means of acquiring migratory capacity. The synergistic role of the tumour microenvironment in EMT induction has also been explored and helps to explain the spatially restricted distribution of EMT at the deep tumour margin (invasive front). Furthermore, tumour cells undergoing EMT may acquire cancer stem cell characteristics, and this may be relevant to the entire metastatic process and to tumour recurrence and treatment failure. Nevertheless, doubts persist regarding the role of EMT in malignant progression in vivo, partly because few studies have correlated molecular and histological alterations in clinical pathology specimens. In the current review we summarize the evidence for EMT in the common gynaecological epithelial malignancies, and discuss the morphological and immunohistochemical changes occurring at the invasive tumour front that may represent EMT-like processes. The possibility that carcinosarcomas represent a variant type of EMT with 'fixed' mesenchymal differentiation is also considered. Diagnostic histopathologists are ideally placed to critically evaluate the role of EMT in gynaecological and other types of malignancy. [ABSTRACT FROM AUTHOR]

McCluggage W G (2012) Histopathology New developments in endocervical glandular lesions There is evidence that the prevalence of premalignant and malignant endocervical glandular lesions is increasing in real as well as in apparent terms. In this review, new developments and selected controversial aspects of endocervical glandular lesions are covered, concentrating mainly on premalignant and malignant lesions. The terminology of premalignant endocervical glandular lesions is discussed with a comparison of the World Health Organization classification and the cervical glandular intraepithelial neoplasia (CGIN) system, which is in widespread use in the United Kingdom. Primary cervical adenocarcinomas comprise a heterogeneous group of different morphological types, and while it is known that the majority of these are associated with high-risk human papillomavirus (HPV), it has become clear in recent years that most of the more uncommon morphological types are unassociated with HPV, although they may sometimes be p16-positive. A spectrum of benign, premalignant and malignant cervical glandular lesions exhibiting gastric differentiation is now recognized; these include type A tunnel clusters, typical and atypical lobular endocervical glandular hyperplasia, adenoma malignum and gastric-type adenocarcinoma. The latter is a recently described variant of primary cervical adenocarcinoma which has a different morphological appearance to the usual endocervical type and which is probably associated with different patterns of spread and a worse prognosis. There is accumulating evidence that 'early invasive' cervical adenocarcinomas have an excellent prognosis and are suitable for conservative management. Immunohistochemical markers of value in the distinction between a primary cervical and endometrial adenocarcinoma are discussed. While it is well known that a panel of markers comprising oestrogen receptor (ER), vimentin, p16 and monoclonal carcinoembryonic antigen (CEA) is useful, several major pitfalls are pointed out and this panel of markers is predominantly of value in 'low-grade' adenocarcinomas. A related group of lesions, including cervical ectopic prostatic tissue and vaginal tubulosquamous polyp, are probably derived from para-urethral Skene's glands and may be positive with prostatic markers. Recent developments in cervical neuroendocrine neoplasms are discussed, as these are associated not uncommonly with a premalignant or malignant endocervical glandular lesion. [ABSTRACT FROM AUTHOR]

Aims DOG1 is a recently described marker of gastrointestinal stromal tumour (GIST) which is considered to be extremely sensitive and, among mesenchymal neoplasms, quite specific for this tumour type. Following the identification of DOG1 immunoreactivity in a uterine leiomyosarcoma, we wished to ascertain how prevalent DOG1 immunoreactivity was in this tumour type. Methods We stained a series of uterine leiomyosarcomas (n=26) with DOG1 and with CD117 (c-kit), another marker of GIST. Staining with both markers was classified as negative, focal (<50% tumour cells positive) or diffuse (≤50% tumour cells positive). Results DOG1 immunoreactivity was present in seven of 26 (27%) leiomyosarcomas. Staining was focal in five cases and diffuse in two. CD117 was positive in three of 26 (11.5%) cases, two focal and one diffuse. Two cases were positive with DOG1 and CD117. One of five uterine leiomyomas was focally positive with DOG1, and one extrauterine pelvic leiomyoma was diffusely positive with this marker. Conclusions Since GISTs have rarely been described as primary uterine neoplasms, the presence of DOG1 immunoreactivity in a uterine leiomyosarcoma may result in diagnostic confusion, and a panel of markers is necessary for diagnosis. Uterine leiomyosarcomas should be added to the list of mesenchymal neoplasms which may be DOG1 positive. [ABSTRACT FROM AUTHOR]

Endometriosis is a common condition in women of reproductive age and has a known propensity to involve abdominal wall scars. The authors report 2 cases of endometriosis presenting as mass lesions involving the abdominal wall at the site of insertion of ventriculoperitoneal and lumboperitoneal shunts. In both cases, there was clinical evidence of shunt compromise. Endometriosis involving the site of shunt insertion is an extremely rare phenomenon with, as far as the authors are aware, only a single previously reported case. However, it should be considered in the differential diagnosis when a mass develops at a shunt site in a woman of reproductive age. [ABSTRACT FROM PUBLISHER]

McCluggage W G, Connolly L E, McBride H A, Kalloger S & Gilks C B (2012) Histopathology 60, 547-553 HMGA2 is commonly expressed in uterine serous carcinomas and is a useful adjunct to diagnosis Aims: Serous carcinoma is the prototype of type 2 uterine carcinoma. In many cases, establishing a diagnosis is straightforward, but problems can arise in that papillary variants of endometrioid carcinoma may be mistaken for serous carcinoma, and glandular variants of serous carcinoma may be misdiagnosed as endometrioid carcinoma. Markers such as p53, oestrogen receptor and p16 may be of use in problematic cases, but there is overlap and these may not therefore be of value in an individual case. It has been shown recently that high-mobility group AT-hook 2 (HMGA2) is expressed by most ovarian serous carcinomas, and our aim was to ascertain whether it is also expressed in uterine serous carcinoma and of value in its distinction from endometrioid carcinoma. Methods and results: Whole tissue sections of uterine serous ( n = 33) and endometrioid ( n = 38) carcinoma were immunostained using HMGA2 antibody. As many of the diagnostic problems relate to the distinction between serous carcinoma and grade 3 endometrioid carcinoma, tissue microarrays (TMAs) containing uterine serous ( n = 71) and uterine grade 3 endometrioid ( n = 68) carcinomas were also stained. Staining was classified as negative (totally negative or occasional nuclei positive), 1+ (<10% of nuclei positive), 2+ (10-49% of nuclei positive), 3+ (50-74% of nuclei positive), or 4+ (≥75% of nuclei positive). On the whole tissue sections, positive staining was also classified as weak, moderate, or strong, and an immunohistochemical composite score, taking into account both extent and intensity of staining, was calculated. On whole tissue sections, there was a statistically significant difference between HMGA2 staining in serous and endometrioid carcinomas with regard to both extent and composite score, with higher expression in serous carcinomas ( P < 0.0001). Thirty of 33 (91%) serous carcinomas were positive, usually with diffuse (3+ or 4+) staining. All five cases of serous endometrial intraepithelial carcinoma (EIC) (the postulated precursor of uterine serous carcinoma) were positive, as were 14 of 38 (37%) endometrioid carcinomas, usually with 1+ or 2+ staining. There was a statistically significant difference in HMGA2 staining in the TMAs between the serous and grade 3 endometrioid carcinomas, with higher expression in the former ( P < 0.0001). Conclusions: Immunoreactivity for HMGA2 is diffusely positive in whole tissue sections in most uterine serous carcinomas and negative in most endometrioid carcinomas, although, as with other markers, there is overlap in individual cases. In conjunction with other markers, HMGA2 may be of value in problematic uterine carcinomas where the differential diagnosis includes serous and endometrioid carcinoma. As HMGA2 is expressed in serous EIC, this suggests that it may be implicated in the early development of uterine serous carcinoma. [ABSTRACT FROM AUTHOR]

Aims To describe an unusual and hitherto unreported pseudoneoplastic phenomenon that is characterised by the entrapment of benign squamous epithelium following cervical loop excision or punch biopsy and that may mimic invasive squamous carcinoma. Methods and Results The authors report six cases in patients aged 25-45 years in whom benign squamous epithelium is incorporated within the cervical stroma as a result of the healing process following prior loop excision (four cases) or punch biopsy (two cases). The entrapped nests of squamous epithelium typically have a hypereosinophilic appearance and are associated with a granulation tissue-like and inflammatory stromal response and sometimes with retraction artefact mimicking lymphovascular permeation. Conclusions The overall morphological appearances, especially in the context of a prior or current diagnosis of cervical intraepithelial neoplasia, may result in misdiagnosis as invasive squamous carcinoma. Pathologists should be aware of this pseudoneoplastic artefact so that an erroneous diagnosis of malignancy is not made. INSET: Take-home messages. [ABSTRACT FROM AUTHOR]

Background Uterine leiomyomas are extremely common in surgical pathology practice and in the vast majority there are no issues in diagnosis. Progestogens are widely prescribed drugs for a variety of indications, including abnormal uterine bleeding, and are often given to women with leiomyomas but the pathological features of leiomyomas treated with progestogens are poorly described. Methods We report the pathological features in eight cases of uterine leiomyomas in women who had been treated with oral progestogens or a progestogencontaining intrauterine device; all cases were received in consultation because the features raised concern for leiomyosarcoma, smooth muscle tumour of uncertain malignant potential or a benign leiomyoma with unusual features. Additionally, we reviewed a series of cases of uterine leiomyomas (n=99) in women who exhibited progestogenic effects in the endometrium. Results The morphological features in the consult cases, which were widespread and marked and which varied somewhat from case to case, included small and/or large areas of infarct-type necrosis (sometimes mimicking coagulative tumour cell necrosis) with surrounding increased cellularity, mitotic activity, nuclear pyknosis, cytoplasmic eosinophilia, epithelioid morphology, stromal oedema, haemorrhage, and myxoid change and infiltration by CD56 positive granulated lymphocytes. Sometimes the features resulted in an almost deciduoid appearance. Similar features were present to a minor degree in significant numbers of the additional series of cases. Conclusions Pathologists should be aware of these progestogen-associated features when reporting uterine leiomyomas whether or not the clinician has indicated that the woman is taking progestogens since otherwise a diagnosis of leiomyosarcoma or smooth muscle tumour of uncertain malignant potential may be rendered. Useful features in suggesting a benign leiomyoma, in addition to recognition of the morphological features described which, in combination, are characteristic of progestogens, are the lack of true nuclear atypia and the low mitotic activity away from the abnormal areas. [ABSTRACT FROM AUTHOR]

Aims: To describe a series of endometrial stromal sarcomas with large numbers of endometrioid-type glands. Methods and results: The eight tumours occurred in patients aged 42–74 years. In three cases, the neoplasm arose in the uterine corpus and in the others there was either an extrauterine origin or the origin could not be determined since multiple sites were involved. In four cases, glands were present throughout the neoplasm and in the others there were areas of typical endometrial stromal sarcoma without glands. In one case, glands were present only in the recurrent neoplasm. The malignant stromal component comprised, for the most part, typical endometrial stromal sarcoma. In two patients, repeated biopsy specimens from the vagina or cervix were initially diagnosed as endometriosis, and in some cases there was a significant delay in diagnosis. Apart from endometriosis, other diagnostic considerations, depending on the tumour location and exact morphology, included adenomyosis, adenosarcoma and carcinosarcoma. Conclusions: Endometrial stromal sarcoma with extensive endometrioid glandular differentiation is rare. The presence of glands often results in diagnostic difficulty with a significant risk of misdiagnosis or delay in diagnosis. It is likely that some cases reported in the literature as aggressive endometriosis represent this entity. [ABSTRACT FROM AUTHOR]

The authors comments on a study by Leuverink et al. which examines the value of mitotic indices and Ki-67 proliferation index in ovarian adult granulosa cell tumour (AGCT) prognosis. They examine the published literature in an attempt to ascertain whether there are any clinicopathological features that can predict aggressive AGCTs. They suggest that since there are no features that reliably predict malignant behaviour, all AGCTs should be considered low-grade malignant neoplasms with a potential for recurrence or metastasis.

We report 3 cases of a distinctive uterine leiomyoma containing numerous thick-walled vascular channels, which we term angioleiomyoma. The leiomyomas occurred in women aged 33, 44, and 49 and ranged from 1.5 to 6.0 cm. They were composed of bland, spindle-shaped cells with numerous evenly distributed, arteriole-like vessels with thick muscular walls throughout. The spindle cells often swirled around the vessels. In 1 case, fibrin was present within vessel walls. The spindle cells were positive with smooth- muscle markers and negative with HMB4S. We believe angioleiomyoma should be recognized as a distinct entity and included in the World Health Organization classification of tumors of the female genital tract as a benign leiomyoma variant, similar to cellular and atypical leiomyoma. Uterine angioleiomyoma has a close morphological resemblance to the similarly named skin tumor. We review uterine smooth-muscle and other mesenchymal neoplasms in which prominent vascular channels are a feature. [ABSTRACT FROM AUTHOR]

Background: Ewing's sarcoma and peripheral primitive neuroectodermal tumour (pPNET) are now regarded as two morphological ends of a spectrum of neoplasms, characterised by a t(11;22) or other related chromosomal translocation involving the EWS gene on chromosome 22 and referred to as Ewing family of tumours (EFTs). EFTs are extremely rare in the vulva and vagina, a review of the literature revealing only 13 previously reported possible cases, most of which have not had molecular confirmation. In this study, four new cases of EFTs involving the vulva (three cases) or vagina (one case) are reported. Results: The tumours occurred in women aged 19, 20, 30 and 40 years and ranged in size from 3 to 8 cm. Morphologically, all neoplasms had a lobulated architecture and were composed of solid aggregates of cells. In one case, occasional rosettes were formed. In all the tumours, there was diffuse membranous staining with CD99; nuclear positivity with FLI-1 was present in two cases. Three cases were focally positive with the broad-spectrum cytokeratin AE1/3, all were diffusely positive with vimentin and all were desmin negative. In two cases, a t(11;22) (q24;q12) (EWSR1-FLI-1) chromosomal translocation was demonstrated by reverse transcriptase-PCR (one case) and fluorescence in situ hybridisation (FISH) (one case), and in another case a rearrangement of the EWSR1 gene on chromosome 22 was demonstrated by FISH. In the other case, a variety of molecular studies did not reveal a translocation involving the EWS gene but this tumour, on the balance of probability, is still considered to represent a neoplasm in the EFTs. Follow-up in two cases revealed that one patient developed pulmonary metastasis and died and another is alive without disease at 12 months. Conclusions: This report expands the published literature regarding EFTs involving the vulva and vagina and stresses the importance of molecular techniques in firmly establishing the diagnosis, especially when these neoplasms arise at unusual sites. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions ST11 adnexal tumour is a rare, recently described malignant neoplasm that is associated with Peutz–Jeghers syndrome. It predominantly originates from the para‐adnexal soft tissues and often shows secondary involvement of the fallopian tube and ovary. STK11 adnexal tumours have a broad differential diagnosis due to their variable morphology and non‐specific immunoprofile, and diagnostic confirmation currently requires sequencing to identify an STK11 mutation. We investigate the diagnostic utility of STK11 (LKB1) immunohistochemistry (IHC) in a cohort of STK11 adnexal tumours and morphological mimics.IHC for STK11 was performed on 122 tumours, including 17 STK11 adnexal tumours and 105 morphological mimics (10 female adnexal tumours of Wolffian origin, 22 adult granulosa cell tumours, 10 juvenile granulosa cell tumours, four Sertoli–Leydig cell tumours, two Leydig cell tumours, one Sertoli cell tumour, one steroid cell tumour, four extra‐ovarian sex cord‐stromal tumours, 16 ovarian endometrioid carcinomas, eight tubo‐ovarian high‐grade serous carcinomas, five ovarian mesonephric‐like adenocarcinomas, 14 ovarian carcinosarcomas, five peritoneal malignant mesotheliomas, two pelvic plexiform leiomyomata and one ovarian solid pseudopapillary tumour). All STK11 adnexal tumours showed complete loss of cytoplasmic staining for STK11. All other tumour types showed retained cytoplasmic staining, except for one endometrioid carcinoma with mucinous differentiation which showed complete loss of STK11 expression and a high‐grade serous carcinoma with subclonal loss.STK11 is a highly sensitive and specific immunohistochemical marker for distinguishing STK11 adnexal tumour from its histological mimics, and can obviate the need for confirmatory molecular studies in the appropriate morphological context. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Novel staining pattern of p53 in Barrett's dysplasia - the absent pattern," by P. V. Kaye and colleagues in the 2010 issue.

The morphological spectrum of primary ovarian mucinous and seromucinous tumours is broad, and presents an array of diagnostic challenges, many unique to these tumour types. This reflects the heterogeneous nature of these lesions, their varied histogenesis and evolving classification systems over recent decades, with further modification to the seromucinous category incorporated in the recently published 5th edition of the World Health Organisation (WHO) Classification of female genital tumours. In this review we provide an update on the classification of these neoplasms and discuss their histogenesis and diverse morphology, focusing on areas which are diagnostically problematic. We also cover tumour grading, differential diagnosis, immunohistochemistry, the recent elucidation of the molecular underpinnings of ovarian mucinous neoplasia and discuss the gross and intra-operative handling of these tumours. A number of diagnostic issues remain unresolved, highlighting the importance of further research on this front, as well as a multidisciplinary approach in the care of patients with ovarian mucinous and seromucinous neoplasia. [ABSTRACT FROM AUTHOR]

The morphological spectrum of primary ovarian mucinous and seromucinous tumours is broad, and presents an array of diagnostic challenges, many unique to these tumour types. This reflects the heterogeneous nature of these lesions, their varied histogenesis and evolving classification systems over recent decades, with further modification to the seromucinous category incorporated in the recently published 5th edition of the World Health Organisation (WHO) Classification of female genital tumours. In this review we provide an update on the classification of these neoplasms and discuss their histogenesis and diverse morphology, focusing on areas which are diagnostically problematic. We also cover tumour grading, differential diagnosis, immunohistochemistry, the recent elucidation of the molecular underpinnings of ovarian mucinous neoplasia and discuss the gross and intra‐operative handling of these tumours. A number of diagnostic issues remain unresolved, highlighting the importance of further research on this front, as well as a multidisciplinary approach in the care of patients with ovarian mucinous and seromucinous neoplasia. [ABSTRACT FROM AUTHOR]

Lymphovascular space invasion (LVSI) is an important prognostic parameter in endometrial carcinoma (EC) and has gained increasing interest in recent years due to an expanding body of evidence of its independent prognostic value, especially when the presence of LVSI is quantified. A key strength of LVSI as a prognostic factor is that it can be detected on routine microscopic examination, without ancillary tests, and thus can be used in low‐resource settings. A weakness, however, is the lack of uniformly applied criteria for assessment and quantification of LVSI, resulting in interobserver variation in diagnosis. This is confounded by artefacts and other morphological features that may mimic LVSI (commonly referred to as pseudo‐LVSI). Despite these issues, multiple studies have shown that LVSI is strongly associated with lymph node (LN) metastasis and is an independent risk factor for LN recurrence and distant metastasis. Consequently, the presence of substantial/extensive LVSI has become an important consideration in formulating adjuvant treatment recommendations in patients with EC, and this has been incorporated in the recent International Federation of Gynecology and Obstetrics (FIGO) 2023 staging system. Herein, we review the current literature on LVSI in EC and discuss its role as a prognostic marker, the reproducibility of LVSI assessment and distinction between LVSI and its mimics. We provide illustrations of key diagnostic features and discuss the two‐tiered (none/focal versus substantial) system of LVSI classification. This work is intended to provide guidance to practising pathologists and unify the approach towards LVSI assessment in EC. [ABSTRACT FROM AUTHOR]

Objective: Reproducible diagnoses of endometrial hyperplasia (EH) remains challenging and has potential implications for patient management. This systematic review aimed to identify pathologist-specific factors associated with interobserver variation in the diagnosis and reporting of EH. Methods: Three electronic databases, namely MEDLINE, Embase and Web of Science, were searched from 1st January 2000 to 25th March 2023, using relevant key words and subject headings. Eligible studies reported on pathologist-specific factors or working practices influencing interobserver variation in the diagnosis of EH, using either the World Health Organisation (WHO) 2014 or 2020 classification or the endometrioid intraepithelial neoplasia (EIN) classification system. Quality assessment was undertaken using the QUADAS-2 tool, and findings were narratively synthesised. Results: Eight studies were identified. Interobserver variation was shown to be significant even amongst specialist gynaecological pathologists in most studies. Few studies investigated pathologist-specific characteristics, but pathologists were shown to have different diagnostic styles, with some more likely to under-diagnose and others likely to over-diagnose EH. Some novel working practices were identified, such as grading the "degree" of nuclear atypia and the incorporation of objective methods of diagnosis such as semi-automated quantitative image analysis/deep learning models. Conclusions: This review highlighted the impact of pathologist-specific factors and working practices in the accurate diagnosis of EH, although few studies have been conducted. Further research is warranted in the development of more objective criteria that could improve reproducibility in EH diagnostic reporting, as well as determining the applicability of novel methods such as grading the degree of nuclear atypia in clinical settings. [ABSTRACT FROM AUTHOR]

Aims: Ovarian Wilms tumour (WT)/nephroblastoma is an extremely rare neoplasm that has been reported to occur in pure form or as a component of a teratomatous neoplasm. We hypothesized that teratoma‐associated and pure ovarian WT may represent different tumour types with diverging molecular backgrounds. To test this hypothesis, we comprehensively characterized a series of five tumours originally diagnosed as ovarian WT. Methods and Results: The five cases comprised three teratoma‐associated (two mature and one immature) and two pure WTs. Two of the teratoma‐associated WTs consisted of small nodular arrangements of "glandular"/epithelial structures, while the third consisted of both an epithelial and a diffuse spindle cell/blastemal component. The pure WTs consisted of "glandular" structures, which were positive for sex cord markers (including inhibin and SF1) together with a rhabdomyosarcomatous component. The two pure WTs harboured DICER1 pathogenic variants (PVs), while the three associated with teratomas were DICER1 wildtype. Panel‐based DNA sequencing of four of the cases did not identify PVs in the other genes investigated. Analysis of the HA19/IGF2 imprinting region showed retention of imprinting in the pure WTs but loss of heterozygosity with hypomethylation of the ICR1 region in two of three teratoma‐associated WTs. Furthermore, copy number variation and clustering‐based whole‐genome DNA methylation analyses identified divergent molecular profiles for pure and teratoma‐associated WTs. Conclusion: Based on the morphological features, immunophenotype, and molecular findings (DICER1 PVs, copy number, and DNA methylation profiles), we suggest that the two cases diagnosed as pure primary ovarian WT represent moderately to poorly differentiated Sertoli Leydig cell tumours (SLCTs), while the tumours arising in teratomas represent true WTs. It is possible that at least some prior cases reported as pure primary ovarian WT represent SLCTs. [ABSTRACT FROM AUTHOR]

Aims: NTRK‐rearranged sarcomas of the female genital tract mainly occur in the uterus (more commonly cervix than corpus) and are characterized by a "fibrosarcoma‐like" morphology and NTRK gene rearrangements. These neoplasms may exhibit histological overlap with other entities and can present diagnostic difficulties without molecular confirmation. Pan‐TRK immunohistochemistry was developed to identify tumours harbouring NTRK rearrangements. The aim of this study was to characterize pan‐TRK immunohistochemical expression in a large cohort of gynaecological mesenchymal neoplasms and investigate the utility of pan‐TRK immunohistochemistry to distinguish NTRK‐rearranged sarcoma from its mimics. Methods and results: A total of 473 gynaecological mesenchymal tumours (461 without known NTRK fusions and 12 NTRK‐rearranged sarcomas) were selected. Pan‐TRK immunohistochemistry (EPR17341, Abcam) was performed on whole tissue sections and tissue microarrays. Molecular interrogation of pan‐TRK positive tumours was performed by RNA sequencing or fluorescence in situ hybridization (FISH). Of the 12 NTRK‐rearranged sarcomas, 11 (92%) exhibited diffuse (≥70%) cytoplasmic pan‐TRK staining with moderate/marked intensity, while the other was negative. Eleven (2.4%) additional tumours also exhibited pan‐TRK immunohistochemical expression: three low‐grade endometrial stromal sarcomas, seven high‐grade endometrial stromal sarcomas, and an undifferentiated uterine sarcoma. Molecular confirmation of the absence of NTRK rearrangements was possible in nine of these tumours. Of these nine neoplasms, seven exhibited focal/multifocal (<70%) pan‐TRK cytoplasmic staining with weak/moderate intensity. Conclusion: Even though pan‐TRK immunohistochemical expression is not entirely sensitive or specific for NTRK‐rearranged sarcomas, these neoplasms tend to exhibit diffuse staining of moderate/strong intensity, unlike its mimics. Pan‐TRK should be performed in monomorphic uterine (corpus and cervix) spindle cell neoplasms that are negative for smooth muscle markers and hormone receptors and positive for CD34 and/ or S100. Ultimately, the diagnosis requires molecular confirmation. [ABSTRACT FROM AUTHOR]

Keywords: dissection; macroscopy; tissue sampling EN dissection macroscopy tissue sampling 930 933 4 06/04/20 20200601 NES 200601 Macroscopic examination and dissection of the specimen are the first steps in the histopathological assessment of any surgical specimen. Some poorly fixed tissues, such as testicular and ovarian germ cell tumours, may readily "liquefy", resulting in artefactual spread of tumour cells. The amount of tissue submitted in a cassette can be very variable, so it may be more appropriate to recommend submission of ' I x i square centimetres of tissue' rather than ' I x i number of blocks'. Very limited tissue sampling of TURP specimens would identify a tumour large enough to cause retention, and the more extensive sampling protocol designed to detect clinically occult cancer could be viewed as a form of cancer screening. [Extracted from the article]

Aims: Lymphovascular space invasion (LVSI) in endometrial cancer (EC) is an important prognostic variable impacting on a patient's individual recurrence risk and adjuvant treatment recommendations. Recent work has shown that grading the extent of LVSI further improves its prognostic strength in patients with stage I endometrioid EC. Despite this, there is little information on the reproducibility of LVSI assessment in EC. Therefore, we designed a study to evaluate interobserver agreement in discriminating true LVSI from LVSI mimics (Phase I) and reproducibility of grading extent of LVSI (Phase II). Methods and results: Scanned haematoxylin and eosin (H&E) slides of endometrioid EC (EEC) with a predefined possible LVSI focus were hosted on a website and assessed by a panel of six European gynaecological pathologists. In Phase I, 48 H&E slides were included for LVSI assessment and in Phase II, 42 H&E slides for LVSI grading. Each observer was instructed to apply the criteria for LVSI used in daily practice. The degree of agreement was measured using the two‐way absolute agreement average‐measures intraclass correlation coefficient (ICC). Reproducibility of LVSI assessment (ICC = 0.64, P < 0.001) and LVSI grading (ICC = 0.62, P < 0.001) in EEC was substantial among the observers. Conclusions: Given the good reproducibility of LVSI, this study further supports the important role of LVSI in decision algorithms for adjuvant treatment. [ABSTRACT FROM AUTHOR]