Tumor Of Probable Wolffian Origin Research Articles

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.

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 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.

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.

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.

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.

Female Adnexal Tumor of Probable Wolffian Origin: A Review.

Female adnexal tumor of probable Wolffian origin (FATWO) is an extremely rare gynecologic neoplasm of low malignant potential. Fewer than 90 cases of this entity have been described in the English-language literature. It is presumed to be derived from mesonephric (Wolffian) duct remnants in the upper female genital tract. We provide a literature review to increase awareness of this extremely uncommon entity. To review the clinical and pathologic findings of FATWO and to discuss common entities in the differential diagnosis. The study involved PubMed (National Center for Biotechnology Information, Bethesda, Maryland) searches, including multiple review articles, case reports, retrospective studies, selected book chapters, and University of Mississippi Medical Center cases. FATWO can affect patients from a wide age range and present with a nonspecific clinical presentation. It typically presents as solid tumors with occasional nodular, lobulated, or cystic appearances. FATWO can show a variety of histologic patterns which may result in diagnostic difficulties for pathologists. There is no single specific immunohistochemical stain for FATWO, and the pathogenesis and molecular alterations are not yet well understood. Although it is generally considered a benign entity, recurrent and metastatic cases have been reported. There are no current recommendations regarding the optimal clinical management of FATWO.

Female Adnexal Tumour of Probable Wolffian Origin (FATWO): Review of the Literature.

FATWO (female adnexal tumour of probable Wolffian origin) denotes a rare tumour of the female adnexa which has been described in nearly 80 cases worldwide and which presumably originates in the remains of the Wolffian ducts. In 10 to 20 percent of patients, a metastasis or recurrence was seen subsequently and for this reason, a malignant potential is attributed to the FATWO. Because of the small number of cases, there is no clear therapeutic recommendation. The method of choice currently is surgical treatment with hysterectomy and adnexectomy. The benefit of radio- and chemotherapies is not clear and a small number of treatment attempts with imatinib have been made in cases of CD117 positivity or treatment attempts on an endocrine basis. This work provides an overview of the literature on epidemiology, imaging and histopathological diagnostic features as well as therapeutic options of this same tumour form.

A case of female adnexal tumor of probable Wolffian origin treated with fertility-sparing surgery thereafter, the patient attained spontaneous pregnancy

A case of female adnexal tumor of probable Wolffian origin treated with fertility-sparing surgery thereafter, the patient attained spontaneous pregnancy

Female Adnexal Tumors of Probable Wolffian Origin (FATWO): A Case Series With Next-Generation Sequencing Mutation Analysis.

Female adnexal tumors of probable Wolffian origin are rare gynecologic tumors with <90 cases reported in the current scientific literature. Their clinical features have been described extensively; less is known about the pathophysiological mechanisms and the molecular alterations underlying their development and growth. We performed a complete histopathologic examination and a systematic mutation analysis using a next-generation sequencing approach on 3 female adnexal tumors of probable Wolffian origin from the archives of our institution to detect possible genetic alterations and to explore their role in the development of these rare tumors. The 3 cases contained missense mutations in different genes belonging to distinct molecular pathways: CTNNB1 and MET mutations for the first case, PIK3CA for the second one, and BRAF and CDKN2A for the third one. Two variants with an unknown functional effect on the protein were found in KDR and TP53 genes. In conclusion, genetic heterogeneity was found in our series. No constant involvement of the most common pathways involved in tumorigenesis was found; nevertheless, further studies are necessary to confirm the results of this pilot study.

Recurrent female adnexal tumor of probable Wolffian origin treated with debulking surgery, imatinib and paclitaxel/carboplatin combination chemotherapy: A case report.

In view of the small number of recurrent and metastatic cases of female adnexal tumors of probable Wolffian origin (FATWO), there is a distinct lack of evidence to support recommendations regarding treatment. In the present study, a 37-year-old female was diagnosed with a left adnexal tumor and underwent a left salpingo-oophorectomy (SO). The tumor was found to arise from the left tubal fimbria and extend to the posterior leaf of the broad ligament. Pathological examination identified a number of solid, tubular and cystic architectures, with areas of hyalinization, hemorrhage and necrosis. Immunohistochemistry detected that the tumor cells were positive for cytokeratin (CK)7, vimentin, inhibin and calretinin, and negative for CK20, epithelial membrane antigen, and the estrogen and progesterone receptors. Thus, the patient was diagnosed with FATWO. Following 15 months, the patient developed recurrent tumors and subsequently underwent a total abdominal hysterectomy, a right SO and extirpation of the disseminated tumors, but with incomplete debulking. The tumor cells were immunoreactive for KIT. As there are a limited number of treatment options and few reported cases, limiting the therapy recommendations, imatinib mesylate was administered for 6 months and the tumors were temporarily stabilized for 4 months until the disease progressed. The patient underwent a further debulking surgery that did not achieve complete debulking and was subsequently administered a combination chemotherapy of paclitaxel and carboplatin. This regimen resulted in an almost complete response after 10 cycles. The tumors continued to decrease in size, and the tumors in the left side of the Douglas pouch and the right para-colic gutter were no longer detectable. To the best of our knowledge, the current study is the first to report carboplatin and paclitaxel combination therapy demonstrating a response of this degree to recurrent FATWO following the failure of imatinib treatment. However, surgical debulking remains the most effective treatment for FATWO when is it is possible. The precise role of chemotherapy, radiotherapy and molecular-targeting therapy in the treatment of recurrent or metastatic FATWO remains to be elucidated, and therefore, novel strategies to overcome this disease must be prioritized.

Value of PAX-8 and SF-1 Immunohistochemistry in the Distinction Between Female Adnexal Tumor of Probable Wolffian Origin and its Mimics.

Female adnexal tumors of probable wolffian origin (FATWOs) are rare. They can closely mimic endometrioid adenocarcinomas with a prominent spindle cell component and Sertoli cell tumors (SCTs). To further define their immunohistochemical profile and origin, we investigated the expression of PAX-8, PAX-2, and GATA binding protein 3 (GATA-3) (wolffian markers) and of steroidogenic factor-1 (SF-1) (sex-cord stromal marker) in FATWOs. We also studied the expression of PAX-8 and PAX-2 in endometrioid adenocarcinomas; of SF-1 in Sertoli-Leydig cell and SCTs; and of PAX-8, PAX-2, GATA-3, and SF-1 in rete ovarii-a proposed site of origin for FATWOs. A database search yielded 8 FATWOs, 18 ovarian/tubal/paraovarian endometrioid adenocarcinomas, and 8 ovarian Sertoli-Leydig cell and SCTs. Eleven cases with rete ovarii sections were included. Of the FATWOs studied, all were negative for PAX-8, PAX-2, GATA-3, and SF-1. Of the endometrioid adenocarcinomas studied, PAX-8 was positive in all and PAX-2 was positive in 57%. Of the Sertoli-Leydig cell and SCTs, all were positive for SF-1 except one. The rete ovarii were positive for PAX-8, weakly positive for SF-1, and negative for PAX-2 and GATA-3. Our study suggests that PAX-8 and SF-1 can be helpful in the distinction between FATWOs and endometrioid adenocarcinomas and SCTs, respectively. Our results do not support a Mullerian or sex-cord stromal or rete ovarii origin for FATWOs. It is curious, however, that FATWOs do not express wolffian markers-it is possibly related to their origin from a distinctive portion of the wolffian duct.

Targeted genomic profiling reveals recurrent KRAS mutations and gain of chromosome 1q in mesonephric carcinomas of the female genital tract

Mesonephric carcinoma is a rare form of gynecologic cancer derived from mesonephric remnants usually located in the lateral wall of the uterine cervix. An analogous tumor occurs in the adnexa, female adnexal tumor of probable Wolffian origin. The pathogenesis and molecular events in mesonephric carcinoma are not known. The aim of this study was to examine the molecular alterations in mesonephric carcinoma to identify driver mutations and therapeutically targetable mutations. This study consisted of 19 tumors from 17 patients: 18 mesonephric carcinomas (15 primary tumors and three metastatic tumors) and 1 female adnexal tumor of probable Wolffian origin. In two patients, both primary and metastatic tumors were available. Genomic DNA was isolated and targeted next-generation sequencing was performed to detect mutations, copy number variations, and structural variants by surveying full exonic regions of 300 cancer genes and 113 selected intronic regions across 35 genes. Fluorescence in situ hybridization (FISH) for 1p and 1q was performed in two cases. Eighty-one percent (13/16) of mesonephric carcinomas had either a KRAS (n=12) or NRAS (n=1) mutation. Mutations in chromatin remodeling genes (ARID1A, ARID1B, or SMARCA4) were present in 62% of mesonephric carcinomas. All mesonephric carcinomas lacked mutations in PIK3CA and PTEN. The most common copy number alteration was 1q gain, found in 12 (75%) mesonephric carcinomas; this was confirmed by FISH in two cases. Mesonephric carcinoma is characterized by molecular alterations that differ from those of more common variants of cervical and endometrial adenocarcinoma, which harbor KRAS/NRAS mutations in 7% and 25% of cases, respectively. KRAS/NRAS mutations are common in mesonephric carcinoma and are often accompanied by gain of 1q and mutations in chromatin remodeling genes. Targeting inhibitors of the RAS/MAPK pathway may be useful in the treatment of mesonephric carcinoma.

GATA3 Is a Sensitive and Specific Marker of Benign and Malignant Mesonephric Lesions in the Lower Female Genital Tract.

GATA3 is a transcription factor critical for embryogenesis, development, and cell differentiation. Recent studies have suggested that GATA3 is a sensitive and relatively specific biomarker for urothelial and breast carcinomas, with most Müllerian carcinomas being negative. We investigated GATA3 expression in mesonephric/Wolffian remnants and tumors in the female genital tract. A western blot was performed to assess specificity for the GATA3 antibody. GATA3 immunohistochemistry was performed on 59 formalin-fixed paraffin-embedded mesonephric samples, including 17 mesonephric remnants (MR; 11 cervical and 6 fallopian tube), 15 mesonephric hyperplasias, 21 mesonephric carcinomas, and 6 female adnexal tumors of probable Wolffian origin. Thirty conventional endocervical adenocarcinomas (ENDO-CA), 9 gastric-type cervical adenocarcinomas, and 165 endometrial adenocarcinomas (EM-CA) were also evaluated. GATA3 nuclear intensity and extent of staining was evaluated. The western blot revealed GATA3 expression in seminal vesicle and cell lines derived from breast and urothelial carcinomas, but not in other cell lines including ovarian, cervical, and endometrial cancers. All cervical MRs and mesonephric hyperplasias, 5/6 (83%) fallopian tube MRs, and 20/21 (95%) mesonephric carcinomas were GATA3 positive, although with great variability in both intensity (weak to strong) and extent (1+ to 3+) of staining. Only 1/6 (17%) female adnexal tumors of probable Wolffian origin showed weak multifocal staining. One of 30 (3%) usual-type ENDO-CAs and 3/165 EM-CAs exhibited weak-moderate GATA3 immunoreactivity; all gastric-type cervical adenocarcinomas were negative. GATA3 is a highly sensitive and specific marker for mesonephric lesions in the lower genital tract; however, its utility in the upper genital tract may be more limited. In addition, GATA3 can aid in distinguishing lower genital mesonephric lesions from usual-type and gastric-type ENDO-CAs and uterine EM-CAs.

An Unusual Case of Broad Ligament Malignant Tumor: Differential Diagnosis of Female Adnexal Tumor of Probable Wolffian Origin and Extraovarian Granulosa Cell Tumor

Female adnexal tumor of probable Wolffian origin (FATWO) and extraovarian granulosa cell tumor (GCT) are both exceptionally rare neoplasms with overlapping features and low-grade malignant potential. We report an unusual case of a stage IIIC malignant tumor of the broad ligament that rapidly progressed in a 29-year-old woman presenting with abdominal pain and fever. A computer tomography (CT) scan …

Female Adnexal Tumors of Probable Wolffian Origin with a Biphasic Histologic Growth Pattern and Positive for C-kit

Female Adnexal Tumor of Probable Wolffian Origin (FATWO) is believed to be derived from the mesonephric (Wolffian) remnants commonly located in the broad ligament. Here we report a case of FATWO with unique histologic growth pattern. The tumor has a solid growth pattern with both epithelioid and spindle cell components. Immunohistochemistry (IHC) showed tumor cells to be diffusely positive for Estrogen receptor (ER) and Progesterone receptor (PR). The epithelioid areas were positive for AE1/3, CK-7 and CAM 5.2. The spindle cell areas were positive for Vimentin and CD10. The tumor cells were negative for Inhibin, CK20, P53, CA125, CD99, Calretenin and CK5/6. Interestingly, the tumor cells are positive for C-kit, which provides additional evidence for possible therapy using tyrosine kinase inhibitors (TKI). However, the frequency of c-kit expression in this tumor and its relevance to therapeutic efficacy using TKI for the recurrent and metastatic tumor are unknown and merit further study.