Wolffian Origin Research Articles

STK11 (LKB1) immunohistochemistry is a sensitive and specific marker for STK11 adnexal tumours.

STK11 adnexal tumour is a rare, recently described malignant neoplasm that is associated with Peutz-Jeghers syndrome. [Correction added on 3 October 2024, after first online publication: 'ST11' in preceding sentence has been corrected to 'STK11' in this version.] 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.

Exploring the histogenesis of STK11 adnexal tumour using electron microscopy

STK11 adnexal tumour is a recently described female genital tract tumour, usually identified in a paratubal location, often associated with Peutz-Jeghers syndrome (PJS) and with STK11 gene alterations identified in most of the cases. Morphologically, this tumour is composed of cells arranged in a variety of patterns, including cords, trabeculae, tubules and cystic and acinar structures. The cells are only moderately pleomorphic and mitotic activity is variable. As tumour cells express epithelial, sex cord stromal and mesothelial markers, STK11 adnexal tumour may be of sex cord stromal, epithelial or mesothelial origin; a Wolffian origin has also been suggested. We report the ultrastructural features of two STK11 adnexal tumours and compare their ultrastructural features with those of other sex cord stromal tumours, a granulosa cell tumour cell line, as well as the known ultrastructural features of epithelial, mesothelial and Wolffian cells. On ultrastructural examination, two STK11 adnexal tumours showed an admixture of elongated cells with regular elongated nuclei and polygonal cells with nuclei showing markedly irregular outlines and prominent nucleoli. Extracellular collagen fibres were identified. These are common ultrastructural features of sex cord stromal tumours, principally sex cord tumour with annular tubules; no ultrastructural features of epithelial, mesothelial or Wolffian cells were found. These findings in conjunction with the shared clinical and genetic association with PJS and shared molecular changes in STK11 gene suggest that STK11 adnexal tumour represents a poorly differentiated sex cord tumour.

Lésions de type mésonéphrique des organes génitaux féminins : un panorama depuis les tumeurs bénignes jusqu’aux aux entités malignes émergentes

Mesonephric lesions in the female genital tract are uncommon and heterogeneous. Those deriving from the upper tract differ from those developing in the lower tract, based on their morphology and immunohistochemical profile. Carcinomas of mullerian origine may display the morphology, the immunoprofile and even the molecular abnormalities of those deriving from mesonephric remnants and are designated mesonephric-like carcinomas. These are high-grade lesions despite their well-differentiated glandular morphology (wolf in sheep's clothing). New entities, such as STK11 adnexal tumors, have merged recently and should not be confused with adnexal tumors of wolffian origin (FATWO), which have a better prognostic and outcome. In this review, we provide an overview of these lesions and their mimickers, in order to help pathologists in the diagnostic approach of these complex and rare neoplasms.

Extrauterine Mesonephric-like Carcinoma: A Comprehensive Single Institution Study of 33 Cases.

Extrauterine mesonephric-like carcinoma (ExUMLC) shares histologic, immunohistochemical (IHC), and molecular (MOL) features with endometrial mesonephric-like carcinoma (EnMLC). Its rarity and histologic overlap with Mullerian carcinomas contribute to underrecognition of ExUMLC. Aggressive behavior of EnMLC is well-documented; behavior of ExUMLC is yet to be characterized. This study presents the clinicopathologic, IHC, and MOL features of 33 ExUMLC identified over a 20-year time period (2002-2022) and compares the behavior of this cohort to more common upper gynecologic Mullerian carcinomas (low-grade endometrioid, LGEC; clear cell, CCC; high-grade serous, HGSC) and EnMLC diagnosed over the same time period. ExUMLC patients ranged from 37 to 74 years old (median=59y); 13 presented with advanced stage (FIGO III/IV) disease. Most ExUMLC had the characteristic mixture of architectural patterns and cytologic features, as previously described. Two ExUMLC had sarcomatous differentiation, 1 with heterologous rhabdomyosarcoma. Twenty-one ExUMLC (63%) had associated endometriosis, and 7 (21%) arose in a borderline tumor. In 14 (42%) cases, ExUMLC was part of a mixed carcinoma representing >50% of the tumor in 12. Twenty-six cases (79%) were incorrectly classified as follows: LGEC or HGEC (12); adenocarcinoma, not otherwise specified (3); HGSC (3); LGSC (2); mixed carcinoma (1); carcinosarcoma, Mullerian type (2); seromucinous carcinoma (1); transitional pattern of HGSC (1); and female adnexal tumor of probable Wolffian origin (1). Three patients had occult synchronous endometrial LGEC. IHC facilitated diagnosis in all cases with an expression of GATA-3 and/or TTF-1 in conjunction with decreased hormone receptor expression in most tumors. MOL testing (n=20) identified a variety of mutations, most frequently: KRAS (15); TP53 (4); SPOP (4); and PIK3CA (4). ExUMLC and CCC were more likely to be associated with endometriosis ( P <0.0001). ExUMLC and HGSC had more recurrences compared with CCC and LGEC ( P <0.0001). Histologic subtype was associated with longer disease-free survival for LGEC and CCC versus HGSC and ExUMLC ( P <0.001). ExUMLC trended towards a similar poor overall survival as HGSC compared with LGEC and CCC, and EnMLC trended to shorter survival compared with ExUMLC. Neither finding reached significance. No differences were seen between EnMLC and ExUMLC with respect to presenting stage or recurrence. Staging, histotype, and endometriosis were associated with disease-free survival, but on multivariate analysis, only stage remained as an independent predictor of outcome. The tendency of ExUMLC to present at an advanced stage and have distant recurrence points to more aggressive behavior compared with LGEC with which it is most frequently confused, underscoring the importance of an accurate diagnosis.

Mesonephric Adenocarcinoma and Mesonephric-like Adenocarcinoma of the Urinary Tract

Given the association of mesonephric adenocarcinoma (MA) of the uterine cervix with florid mesonephric hyperplasia, one would expect MAs to rarely arise in other anatomical locations that harbor mesonephric remnants. In contrast, mesonephric-like adenocarcinoma (MLA) is thought to arise from Müllerian origin without an association with mesonephric remnants. The current case series characterizes 4 cases of MA arising in the urinary bladder (1 woman and 3 men), 1 case of MA in the perirenal region (woman), and 1 case of MLA in the ureter (woman). All cases displayed morphologic features similar to MA of the uterine cervix and MLA of the ovary and endometrium, characterized by predominant tubular and focal glandular/ductal architecture. Mesonephric remnants in the bladder wall were closely associated with adjacent MA in cases 1 and 4. MLA in case 6 was associated with mesonephric-like proliferations and endometriosis. All cases (6/6) were diffusely positive for Pax8, and all displayed a luminal pattern of CD10 staining, except case 4 for which CD10 immunostain was not available for review. Gata3 was either focally positive (cases 1, 2, and 6), negative (case 3), or diffusely positive (case 5). TTF-1 was diffusely expressed in cases 1 and 3 and negative in cases 2, 5, and 6. Although a KRAS G12C somatic mutation was detected in case 6, hotspot mutations in KRAS, NRAS, and PIK3CA were not present in other tested cases. Our study demonstrates that MAs and MLAs of the urinary tract share similar histopathogenesis, morphology, and immunophenotype to their counterparts in the female genital tract. We propose that, in the urinary tract, MA might be classified as a distinctive tumor that arises from mesonephric remnants or presumed Wolffian origin if they are not related to Müllerian-type precursors. The tumor displaying similar morphology and immunoprofile to MA but associated with Müllerian-type precursors should be classified as MLA.

Female Adnexal Tumors of Probable Wolffian Origin (FATWO); Challenges and Diagnostic Clues on Intra-operative Frozen Section Diagnosis

Female adnexal tumors of probable Wolffian origin (FATWO) or Wolffian adnexal tumors (WAT) are rare neoplasms that arise from the remnants of the mesonephric duct. The tumor is usually benign but can histologically look similar to some other malignant tumors. FATWO is characterized by diffuse and tubular patterns. The intra-operative diagnosis of FATWO is challenging because of the tumor’s rarity and its morphologic overlap with these other entities, and FATWO should be considered in the differential diagnoses of sex-cord stromal tumors and ovarian carcinomas based on the exclusion of other neoplasms. The case was presented at College of American Pathologists (CAP) annual conference in Florida (September 2019), and the abstract was published in Archives as an online supplement only.

Female Adnexal Tumor of Wolffian Origin (FATWO): A Rare Ovarian Tumor

FATWOs are rare tumors arising from the remnants of the mesonephric duct with a low malignant potential. Here we report a case of 55 year old post menopausal female with abdominopelvic mass. The diagnosis of FATWO becomes challenging because of the rarity and heterogeneity of its histologic appearances. Therefore, a careful histopathological and immunohistochemical evaluation should always be performed. Keywords: Adnexal mass, Wolffian origin, benign.

The complex and often confusing history, histology and histogenesis of mesonephric, STK11 adnexal tumour and mesonephric-like neoplasms of the upper female genital tract (including broad ligament).

Mesonephric lesions in the female genital tract are uncommon, with those arising from the upper tract being much less frequent than those developing in the lower tract (mesonephric hyperplasia and carcinoma). The most common upper tract lesions include rete cyst/cystadenoma and female adnexal tumour of Wolffian origin (FATWO). The integration of morphological, immunohistochemical and molecular studies on FATWOs has enabled recognition of a novel entity, the STK11 adnexal tumour, which is often associated with Peutz-Jeghers syndrome (~50%) and frequently has a salivary gland morphology but an unknown origin. Similarly, 'mesonephric-like' adenocarcinoma, an entity with striking similarities to mesonephric carcinoma but currently favoured to be of Müllerian derivation based on its association with other Müllerian tumours and molecular findings, has also been recently described, and may histologically mimic both FATWOs and STK11 adnexal tumours. In this review, we provide a historical overview of upper female genital tract mesonephric proliferations and discuss mesonephric lesions, STK11 adnexal tumour, mesonephric-like adenocarcinoma, and mimickers, the most common being endometrioid carcinoma.

Female Adnexal Tumor of Wolffian Origin Presenting as Paratubal / Broad Ligament Masses: A Case Report

Introduction: A female adnexal tumor of probable Wolffian origin (FATWO) is a rare type of gynecological tumor that is difficult to diagnose based on laboratory and radiologic studies. Although FATWO is considered a benign tumor, recurrence and metastasis have been reported. Currently, there is no best surgical and surveillance approach for FATWO. We presented two Wolffian tumors as paratubal / broad ligament masses. Case Presentation: This is a report of a 32-year-old woman with vaginal discharge and incidentally pelvic mass diagnosis who underwent conservative surgery with a frozen section based on the Wolffian duct tumor. Immunohistochemically, the results confirmed FATWO. The patient was free of recurrence 20 months after conservative surgery. Conclusions: Although FATWO has benign behavior, some types of this tumor have malignant features, and there is no clear recommendation regarding optimal treatment and surveillance of FATWO. Therefore, based on the literature, pathologists are recommended to utilize a wide array of immunohistochemical stainings to offer appropriate diagnosis and optimal surgery to patients. Moreover, patients should be followed up for a long-term period until we have enough knowledge in the field.

Female Adnexal Tumor of Probable Wolffian Origin

Female adnexal tumor of probable Wolffian origin (FATWO) often is a diagnostic challenge given its rarity, histologic heterogeneity, and lack of specific immunoprofile. To further understand the clinicopathologic and immunohistochemical features of this rare entity. We studied the clinical, morphologic, and immunohistochemical features of a cohort of 11 FATWO cases from our institute. Patients' age ranged from 25 to 76 years (mean, 55 years). Tumor size ranged from 0.5 to 18 cm (mean, 2.7 cm). Histopathologically, most tumors presented with low-grade cytologic features with low mitotic activity and lack of necrosis. Three main growth patterns were appreciated: solid, tubular, and sievelike patterns. Higher-grade nuclear atypia, increased mitotic activity, and focal necrosis were seen in 2 cases. These 2 cases were clinically considered malignant FATWO mainly because of their extra-adnexal involvement. Immunohistochemical studies found that tumor cells were positive for CD10 (11 of 11, 100%), AE1/3 (8 of 8, 100%), CAM 5.2 (4 of 5, 80%), and cytokeratin 7 (CK7; 7 of 10, 70%), and focally positive for calretinin (4 of 10, 40%), inhibin (4 of 10, 40%), epithelial membrane antigen (EMA; 3 of 9, 33%), and steroidogenic factor-1 (SF-1; 2 of 8, 25%). Lack of immunoreactivity to PAX8 and GATA3 in almost all cases indicates that FATWO is different from the tumors derived from the Müllerian or mesonephric origins. All patients with available follow-up had favorable prognosis. The broad spectrum of clinical presentation, various morphologic features, and overlapping immunophenotype suggest that FATWO is a diagnosis of exclusion until it is further defined at the molecular and immunohistochemical levels.

Female Adnexal Tumour of Wolffian Origin: A Rare Case Report

Female Adnexal Tumour of Wolffian Origin (FATWO) is a rare tumour occurring in adnexal region, arising from the remnants of the mesonephric duct, in places like the broad ligament, fallopian tube, ovarian hilum, peritoneum. Here the authors have reported a case of FATWO in a 47-year-old woman occurring in the wall of fallopian tube and confirmed with immunohistochemistry. Most of these tumours behave in a benign fashion but certain histological features like hypercellularity, cellular pleomorphism and nuclear atypia cause significant confusion in histopathological diagnosis. Multiple differential diagnoses were considered. After careful histopathological examination and thorough investigation with multiple immunohistochemical stains, the diagnosis was ultimately established.

Female Adnexal Tumour of Wolffian Origin Masquerading as a Broad Ligament Fibroid: A Rare Case Report

Female adnexal tumour of Wolffian origin (FATWO), a rare neoplasm arising from the female adnexa, is typically benign in nature, although recurrences and metastasis have been reported infrequently. First identified and reported in the early 1970s, less than 100 cases have been reported thus far. We present a case of a 16-year-old girl with a left adnexal tumour of Wolffian origin who presented with excessive bleeding during mensuration. With no overt clinical signs, ultrasound revealed a left ovarian neoplasm which was confirmed by CT scan as a solid enhancing lesion in the left adnexa measuring 6.2 x 5 x 4.5 cm. A broad ligament mass was excised, and cytology of peritoneal fluid wash revealed no malignancy. Histomorphological examination and immunohistochemistry confirmed the diagnosis of FATWO. The postoperative course was uneventful; however, the patient was lost to follow-up. Due to the rarity of occurrence, asymptomatic presentation, its variable location, and its morphological diversity, the diagnosis of FATWO may present a challenge especially when the tumour arises in an ovarian location.

Whole-proteome analysis of mesonephric-derived cancers describes new potential biomarkers

Mesonephric carcinomas (MEs) and female adnexal tumors of probable Wolffian origin (FATWO) are derived from embryologic remnants of Wolffian/mesonephric ducts. Mesonephric-like carcinomas (MLCs) show identical morphology to ME of the cervixbut occur in the uterus and ovary without convincing mesonephric remnants. ME, MLC, and FATWO are challenging to diagnose due to their morphologic similarities to Müllerian/paramesonephric tumors, contributing to a lack of evidence-based and tumor-specific treatments. We performed whole-proteomic analysis on 9 ME/MLC and 56 endometrial carcinomas (ECs) to identify potential diagnostic biomarkers. Although there were no convincing differences between ME and MLC, 543 proteins showed increased expression in ME/MLC relative to EC. From these proteins, euchromatic histone lysine methyltransferase 2 (EHMT2), glutathione S-transferase Mu 3 (GSTM3), eukaryotic translation elongation factor 1 alpha 2 (EEF1A2), and glycogen synthase kinase 3 beta were identified as putative biomarkers. Immunohistochemistry was performed on these candidates and GATA3 in 14 ME/MLC, 8 FATWO, 155EC, and normal tissues. Of the candidates, only GATA3 and EHMT2 were highly expressed in mesonephric remnants and mesonephric-derived male tissues. GATA3 had the highest sensitivity and specificity for ME/MLC versus EC (93% and 99%)but was absent in FATWO. EHMT2 was 100% sensitive for ME/MLC & FATWObut was not specific (65%). Similarly, EEF1A2 was reasonably sensitive to ME/MLC (92%) and FATWO (88%)but was the least specific (38%). GSTM3 performed intermediately (sensitivity for ME/MLC and FATWO: 83% and 38%, respectively; specificity 67%). Although GATA3 remained the best diagnostic biomarker for ME/MLC, we have identified EHMT2, EEF1A2, and GSTM3 as proteins of interest in these cancers. FATWO's cell of origin is uncertain and remains an area for future research.

The Significance of Ultrasound Findings in Female Adnexal Tumor of Probable Wolffian Origin (FATWO): Case Review Series

Background: Kariminejad and Scully reported 9 cases that were difficult to identify outside the ovary Tumors, located in the broad ligament, fallopian tube mesentery, and ovary, named female adnexal tumors of probable Wolffian origin. Aim: To investigate ultrasound images with female adnexal tumors of probable Wolffian origin (FATWOs). Case Report: We reported ultrasound images in three women with female adnexal tumors of probable Wolffian origin (FATWOs) with detailed discussion. Ultrasonography showed a predominantly-solid mass with clear-cut boundary with neighboring normal ovary at the left mesosalpinx (broad ligament) in both cases. Doppler examination presented moderate color content in both tumors. Conclusion: Ultrasound images may provide a clue for preoperative diagnosis of FATWOs.

Paravaginal female adnexal tumor of probable Wolffian origin mimicking vaginal spindle cell epithelioma on biopsy

Female adnexal tumor of probable wolffian origin (FATWO) is a tumor of low malignant potential that arises predominantly in the broad ligament, mesosalpinx, and ovarian hilus. The rarity of FATWO increases its susceptibility to misdiagnosis as other tumors, especially when it occurs at an unusual site. We report a 29-year-old woman with a 7.2 cm left paravaginal FATWO that invaded into the vaginal lumen. The initial biopsy demonstrated features suggestive of vaginal spindle cell epithelioma, but with increased Ki67 proliferation index. Pathologists should be aware that the common sieve-like architecture of FATWO may not be apparent on small biopsies, which by sampling error may demonstrate predominantly the less common spindle cell architecture. Awareness of FATWO in the differential diagnosis of paravaginal tumors may help to avoid misinterpretation as vaginal spindle cell epithelioma, a previously unappreciated pitfall in the diagnosis of FATWO.

C-KIT Analysis and Targeted Molecular Sequencing of Mesonephric Carcinomas of the Female Genital Tract.

Mesonephric carcinoma is a rare malignancy, thought to derive from Wolffian remnants. To date, no targeted molecular therapeutic options have been identified. On the basis of limited case reports, c-KIT immunohistochemical expression has been reported in female adnexal tumors of Wolffian origin, and targeted therapy with Imatinib has been attempted with mixed success. Currently, it is unclear whether c-KIT immunohistochemical expression is seen in mesonephric carcinoma, a tumor that is thought to be related to female adnexal tumors of Wolffian origin, and how this correlates with KIT mutational status. In this study, we assessed the immunohistochemical expression of c-KIT and KIT mutational status, in a series of 13 mesonephric neoplasms (5 cervical [including 2 cervical carcinosarcomas], 3 uterine corpora, 4 ovarian, and 1 vaginal/pelvic). The intensity of staining and proportion of cells showing cytoplasmic/membranous staining for c-KIT were recorded. KIT was sequenced using a next-generation sequencing panel that targeted 120 hotspots and 17 exons in 33 known actionable cancer genes. This panel included KIT exons 9, 11, and 13, and 6 hotspots (T670, D816, D820, N822, Y823, A829). Although c-KIT immunohistochemical expression was observed in the majority of mesonephric carcinomas (10/12 cases; 83%), no KIT mutations were detected. This cautions pathologists against the use of c-KIT immunohistochemistry as a surrogate marker for KIT-activating mutations in this setting. Consistent with previous studies, the majority of mesonephric neoplasms (10/13; 77%) harbored KRAS mutations. Additional mutations were found in CTNNB1 (2/13, 15%), TP53 (2/13, 15%), and PIK3CA (1/13, 8%).

Targeted Genomic Profiling of Female Adnexal Tumors of Probable Wolffian Origin (FATWO)

Female adnexal tumor of probable Wolffian origin (FATWO) is a rare gynecologic neoplasm of low-malignant potential presumed to be derived from mesonephric remnants in the upper female genital tract. Similarly, mesonephric remnants in the lower female genital tract are thought to be the origin for mesonephric carcinoma. Although the molecular alterations in mesonephric carcinoma have been recently reported, the pathogenesis of and molecular alterations in FATWO are not well understood. The aims of this study were to examine the molecular alterations in FATWO and to establish whether these neoplasms are molecularly similar to mesonephric carcinoma. Eight FATWOs underwent massively parallel sequencing to detect single nucleotide variations, copy number variations, and structural variants by surveying exonic DNA sequences of 300 cancer genes and 113 introns across 35 genes. Good quality DNA was isolated from 7 of 8 cases. Novel KMT2D variants (1 frameshift, 3 missense) were identified in 4 of 7 cases (57%), but were variants of uncertain biologic significance. STK11 mutations (both frameshift) were identified in 2 of 7 cases (29%); one of these was in a patient with a known history of Peutz-Jeghers syndrome. A mutation in the chromatin remodeling gene ARID1B was identified in 1 of 7 cases (14%). No cases harbored KRAS, NRAS, TP53, PIK3CA, PTEN, or DICER1 mutations. There were relatively low numbers of copy number variations, and no recurrent copy number variations were identified. One case demonstrated moderate copy gain of CCND1. No structural variants were identified. In summary, FATWO is characterized molecularly by the absence of KRAS/NRAS mutations (characteristic of mesonephric carcinoma), absence of DICER1 mutations (characteristic of Sertoli-Leydig cell tumor) and frequent KMT2D mutations of unknown biologic significance. FATWOs exhibit a limited number of molecular aberrations that are significantly different from those reported in tumors in the differential diagnosis, and our results question the relationship of mesonephric carcinoma with FATWO. Disease-defining molecular alterations for FATWO have yet to be discovered.

Malignant female adnexal tumor of Wolffian origin (FATWO)

Malignant female adnexal tumor of Wolffian origin (FATWO)

Female adnexal tumors of probable Wolffian origin: morphological, immunohistochemical, and molecular analysis of 15 cases.

Female adnexal tumors of probable Wolffian origin are rare and present a diagnostic challenge due to their morphological and immunohistochemical overlap with more common ovarian and broad ligament entities. We evaluated the morphological, immunohistochemical, and molecular features of 15 tumors of probable Wolffian origin. Patients ranged from 32 to 69 (mean 47) years and tumors from 1.8 to 30 (mean 10) cm. All except one arose in para-adnexal soft tissues. Follow-up was available for six patients, five of whom were alive and well, while the sixth, who had extra-adnexal disease at diagnosis, died from unrelated causes. The following patterns were noted: tubular (all tumors), solid 11/15 (73%), sieve-like 7/15 (47%), and reticular 1/15 (7%). A myxoid background was present in 3/15 (20%) of tumors and eosinophilic luminal secretions in 11/15 (73%). Most tumors (12/15, 80%) had low-grade nuclear atypia, while three showed foci with scattered high-grade atypia. Mitotic index ranged from 0 to 17 (mean 4) per ten high-power fields. Tumors were positive for pankeratin and negative for TTF-1. EMA, GATA3, and PAX8 were positive in 2/10 (20%; focal), 3/15 (20%; focal), and 1/15 (7%; focal) of tumors, respectively. CD10, SF-1, calretinin, inhibin, ER, PR, cytokeratin 7, and WT1 were variably expressed. Pathogenic mutations were rare and included STK11 (n = 3), APC (n = 1), and MBD4 (n = 1). Copy number variations were detected in the three tumors with STK11 mutations and a myxoid background. These data demonstrate that female adnexal tumors of probable Wolffian origin are morphologically and immunohistochemically diverse, but infrequently harbor pathogenic mutations. However, their lack of mutations in contrast to their mimickers may be a valuable tool in diagnostically difficult cases.

An unusual presentation of a granulosa cell tumor in broad ligament: morphological features and close differential

Background: Though Granulosa cell tumors (GCTs) are the most common ovarian sex cord stromal tumors, they are very rare in extra ovarian sites with a handful of cases reported in retroperitoneum, broad ligament, fallopian tube, mesentery and even in the adrenals. Female Adnexal Tumor of probable Wolffian Origin (FATWO), which is also a very rare tumor comes up as its closest differential because of a significant overlap of topographic, morphologic, and immunohistochemical (IHC) features. Case Summary: Present case is of a post-menopausal female who complained of abdominal swelling and post-menopausal bleeding. On CT, she was shown to have a broad ligament mass (fibroid) which was excised. On histopathological reporting the tumor showed mainly the lesser known morphological variants of GCT that lead to difficulty in reaching at the exact diagnosis and a differential of an extraovarian GCT [eGCT] vs. FATWO was given which on IHC finally turned out to be an eGCT. Conclusion: Broad ligament is the site of two very rare tumors of the female genital tract, i.e. eGCT and FATWO which are close mimickers of each other not only on topography, but also on morphology and immunohistochemistry. Hence distinguishing between these two entities may be quite challenging for a pathologist, but aid of certain features can be taken to arrive at the diagnosis many a times.