SOX17 expression in mesonephric-like adenocarcinomas and mesonephric remnants/hyperplasia of the female genital tract: Expanding its utility as a Müllerian biomarker.

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

[A Case of Adenocarcinoma, HPV-independent, Mesonephric Type with Significant Response to Neoadjuvant Chemotherapy].

Adenocarcinoma, HPV-independent, mesonephric type (hereafter referred to as "mesonephric carcinoma") arising from the cervix is rare, its treatment has not been established, and its sensitivity to chemotherapy has not been fully investigated. Here we report on a 30-year-old female patient who presented at our hospital with a chief complaint of abnormal genital bleeding. We suspected cervical cancer. Based on examination, biopsy, and imaging, she was diagnosed with stage IIA2 adenocarcinoma of the cervix and was scheduled for surgery. Because she had a SARS-COV-2 infection, she was given two courses of paclitaxel-carboplatin (TC) therapy, based on the then-current surgical risk assessment after SARS-COV-2 infection, with a waiting period of at least 8 weeks. The patient was deemed to have a partial response and was treated with paclitaxel and carboplatin, after which she was deemed to have a partial response and underwent total hysterectomy. A diagnosis of stage IIA2 mesonephric carcinoma, ypT1b2N0M0, was made after histopathologic examination of an excised specimen. The patient was treated with 4 additional courses of TC therapy after surgery, and has had no recurrence in 13 months. We report a first case of response to neoadjuvant chemotherapy with TC regimen in a patient with mesonephric carcinoma of the cervix.

Cervical Mesonephric Adenocarcinoma With Novel FGFR2 Mutation.

Mesonephric adenocarcinoma is a rare tumor, accounting for <1% of cervical cancers. Well-differentiated mesonephric adenocarcinoma can be difficult to distinguish from diffuse mesonephric hyperplasia. Herein, we report a case of well-differentiated mesonephric adenocarcinoma with an FGFR2 mutation not previously reported in the literature. Nonselective tyrosine kinase inhibitors or FGFR2 inhibitors may represent options for targeted therapy.

Mixed Mesonephric Adenocarcinoma and High-grade Neuroendocrine Carcinoma of the Uterine Cervix: Case Description of a Previously Unreported Entity With Insights Into Its Molecular Pathogenesis.

Human papillomavirus (HPV)-negative cervical carcinomas are uncommon and typically encompass unusual histologic subtypes. Mesonephric adenocarcinoma is one such subtype. Mesonephric tumors in the female genital tract are thought to arise from Wolffian remnants, and are extremely rare tumors with widely variable morphology. Sarcomatoid dedifferentiation has been previously described in a few cases, but other forms of dedifferentiation have not been reported. Neuroendocrine carcinoma of the cervix (e.g. small cell carcinoma) is associated with HPV infection, typically HPV 18. These tumors often arise in association with a conventional epithelial component such as squamous cell carcinoma or usual-type endocervical adenocarcinoma. We describe a case of mesonephric adenocarcinoma of the uterine cervix associated with an HPV-negative high-grade neuroendocrine carcinoma at the morphologic and immunophenotypic level, for which we performed targeted massively parallel sequencing analysis of the 2 elements. Both components shared identical mutations in U2AF1 p.R156H (c.467G>A) and GATA3 p.M422fs (c.1263dupG), as well as MYCN amplification. In addition, the neuroendocrine carcinoma harbored TP53 and MST1R mutations not present in the mesonephric carcinoma. Our data suggest a clonal origin of the 2 components of this rare entity, rather than a collision tumor.

Malignant mesonephric tumor of the cervix with an initial manifestation as pulmonary metastasis: case report and review of the literature.

Malignant mesonephric tumor (MMT) is a relatively uncommon malignancy of the female genital tract. The diagnosis of metastatic MMT is difficult because cytological, pathological, immunohistochemical characteristics of MMT are under-recognized. The authors present a 55-year-old female with metastatic pulmonary nodules. The bronchial washing cytology revealed three dimensional clusters of bland epithelial cells with slight nuclear grooves. A corresponding lung histology had ductal or tubular clusters of epithelial cells with intraglandular eosinophilic materials. These epithelial cells were positive for immunohistochemical stain of CD10, suggesting metastasis from MMT. The cervical smear showed clusters of bland, gland-forming epithelial cells with intraglandular eosinophilic materials. On histologic examination, mesonephric adenocarcinoma with papillary and solid proliferation was identified in the uterine cervix. A review of the literature for 72 cases of MMT is also included. Clinical and cytopathological features of MMT are herein made available.

Differential patterns of PAX8, p16, and ER immunostains in mesonephric lesions and adenocarcinomas of the cervix.

Mesonephric remnants, usually located deep in the lateral cervical wall, may become hyperplastic resulting in a florid proliferation. These can be misinterpreted as malignant and confused with endocervical adenocarcinomas. Recent data have shown that PAX2 is diffusely expressed in mesonephric remnants and hyperplasias. PAX8 is a related transcription protein that is expressed in tissues of müllerian and wolffian origin. In this study, we have investigated the utility of an immunohistochemical panel comprising of PAX8, estrogen receptor (ER), and p16 in the differential diagnosis between mesonephric proliferations and cervical adenocarcinomas. A database search was conducted for cases of mesonephric remnants/hyperplasia/carcinoma of cervix and invasive cervical adenocarcinomas. Immunohistochemical stains for PAX8, ER, and p16 were performed using the avidin-biotin peroxidase technique on the most representative tissue. The search yielded 28 cases of mesonephric proliferations of cervix (15 mesonephric remnants, 12 mesonephric hyperplasias, and 1 mesonephric adenocarcinoma) and 16 cases of cervical adenocarcinomas (15 usual type and 1 adenoma malignum). Immunohistochemically, all the mesonephric proliferations, regardless of being benign or malignant, displayed a consistent staining pattern-diffusely and strongly positive for PAX8, negative for ER, and patchy cytoplasmic staining for p16. The usual type cervical adenocarcinomas exhibited a variable staining pattern with PAX8 and ER but all were strongly and diffusely positive for p16. The case of adenoma malignum was PAX8 positive, ER negative, and showed weak and patchy staining with p16. Our study suggests that a panel of immunohistochemical stains composed of PAX8, p16, and ER is useful in the distinction between mesonephric proliferations and cervical adenocarcinomas.

A rare case of primary ovarian mesonephric adenocarcinoma and a review of the literature.

OBJECTIVE: Are reported in the cervix in the female genital tract, has been reported in very few studies in the literature. In this report, we aimed to present a case with mesonephric carcinoma, which was detected in the ovary and is very rarely seen. CASE REPORT: In a case since the frozen section results of the left adnexal mass were reported as malignant. CONCLUSION: Ovarian mesonephric carcinoma is very rare and exhibits very different morphological patterns. Therefore, immunohistochemical and morphological findings should be evaluated together. If the pathological picture does not fit the common carcinomas of ovarian origin and this entity must be brought to mind, because, if these tumors with different molecular developmental pathways are diagnosed correctly, treatment schemes will change and targeted therapies will be developed too. KEY WORDS: Mesonephric carcinoma, Mesonephric like carcinoma, Ovarian carcinoma.

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 cervix but 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, 155 EC, 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 & FATWO but 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.

Cervical Mesonephric Adenocarcinoma: A Case Report of a Rare Gynecological Tumor from Embryological Remains of the Female Genital Tract.

INTRODUCTION: Malignant mesonephric tumors are uncommon in the female genital tract, and they are usually located where embryonic remnants of Wolffian ducts are detected, such as the uterine cervix. The information about these tumors, their treatment protocol, and prognosis are scarce. CASE REPORT: A 60-year-old woman with postmenopausal vaginal bleeding was initially diagnosed with endometrial carcinoma. After suspicion co-testing, the patient underwent a loop electrosurgical excision of the cervix and was eventually diagnosed with mesonephric adenocarcinoma. She was subjected to a radical hysterectomy, which revealed International Federation of Gynecology and Obstetrics (FIGO) IB1 stage, and adjuvant radiotherapy. The follow-up showed no evidence of recurrence after 60 months. CONCLUSION: We present the case of a woman with cervical mesonephric adenocarcinoma. When compared with the literature, this case had the longest clinical follow-up without evidence of recurrence, which reinforces the concept that these tumors are associated with a favorable prognosis if managed according to the guidelines defined for the treatment of patients with cervical adenocarcinomas. Though a rare entity, it should be kept in mind as a differential diagnosis for other cervical cancers.

Cytologic features of upper gynecologic tract adenocarcinomas exhibiting mesonephric-like differentiation.

BACKGROUND: Mesonephric adenocarcinomas are rare neoplasms which most commonly arise in the lateral cervix and vagina. Tumors with similar morphologic, immunophenotypic, and molecular characteristics recently have been described in the uterine corpus and ovary. Herein, the authors sought to characterize the cytomorphologic features of adenocarcinomas exhibiting mesonephric-like differentiation arising in the upper gynecologic tract. METHODS: Institutional databases were queried retrospectively for tumors of the upper gynecologic tract described as a "tumor of Wolffian origin" or "with mesonephric features" between 2007 and 2017. All available cytologic material was reviewed. Cytomorphologic characteristics were evaluated by 3 pathologists. RESULTS: The current study cohort consisted of 8 cases taken from 7 patients. Primary sites included the ovary (3 cases); endometrium (4 cases); and pelvis, not otherwise specified (1 case). All cases demonstrated tight 3-dimensional clusters of overlapping cells. Additional architectural features included tubular (5 of 8 cases; 63%) and papillary (3 of 8 cases; 38%) formations. Cells were small with scant (7 of 8 cases; 88%) to moderate (1 of 8 cases; 12%) cytoplasm. Three of the 8 cases (38%) demonstrated extracellular hyaline globules. Nuclei were uniform in size (6 of 8 cases; 75%) or showed mild anisonucleosis (2 of 8 cases; 25%). Nuclear grooves and indentations were observed in all cases. Mitoses (5 of 8 cases; 63%) and apoptotic bodies (4 of 8 cases; 50%), when present, were rare. No necrosis was noted. CONCLUSIONS: Adenocarcinomas exhibiting mesonephric-like differentiation show a monotonous population of small cells with scant to moderate cytoplasm and abundant nuclear grooves arranged in tight, overlapping, 3-dimensional clusters. Occasionally, papillary or tubular architecture, as well as extracellular hyaline globules, may be seen. These features should prompt further testing (eg, immunohistochemistry) to confirm the diagnosis and to exclude potential mimics.

Mesonephric adenocarcinoma of the cervix: a case report with a three-year follow-up, lung metastases, and next-generation sequencing analysis.

BACKGROUND: Mesonephric adenocarcinoma (MNAC) is a rare tumor of the female genital tract, which originates from mesonephric duct remnants. Its diagnosis is pathologically challenging, because MNAC may exhibit a mixture of morphological patterns that complicates the differential diagnosis. CASE PRESENTATION: The patient in this case was a 48-year-old woman with a polypoid mass protruding into the endocervical canal. The patient underwent a total hysterectomy outside the institution. During biopsy, the mass showed a cerebroid aspect. Histological study revealed a tumor with a predominantly tubular and ductal growth pattern. The immunoprofile showed negative staining for calretinin, carcinoembryonic antigen (CEAm), estrogen receptors (ER), and progesterone receptors (PR), and positive staining for CD10, p16, and PAX2. The Ki-67 score was 46%. Using a next-generation sequencing assay, we documented genomic alterations in KRAS and CTNNB1, low tumor mutation burden (TMB), and an absence of microsatellite instability. In addition, gain of the long arm of chromosome 1 (1q) was also documented using chomogenic in situ hybridization (CISH). Three years later, the patient presented pulmonary nodules in the lingula and left basal lobe that were resected by thoracotomy. The histopathologic study of the pulmonary nodules confirmed the presence of metastases. CONCLUSION: Carcinomas of mesonephric origin are among the rarest subtypes of cervical tumors. We report the first case of mesonephric adenocarcinoma of the cervix with lung metastases showing a CTNNB1 gene mutation.

[Mesonephroid carcinoma of the urinary bladder (clear cell carcinoma). Two case reports and review of the literature in a rare variation of the primary adenocarcinoma]. / Das mesonephroide Karzinom der Harnblase (Klarzellkarzinom). Zwei Kasuistiken und Literaturübersicht über eine seltene Variante des primären Adenokarzinoms.

Mesonephroid adenocarcinoma of the bladder may be a malignant form of nephrogenic adenoma or nephroid metaplasia. The lesion is extremely rare in the urinary bladder, and to our knowledge 19 cases have been reported in the literature. We report two cases of mesonephroid adenocarcinoma of the bladder which were treated by radical cystectomy.

Cervical mesonephric adenocarcinoma: A case report of a rare gynecological tumor from embryological remains of the female genital tract / Adenocarcinoma mesonéfrico cervical: Relato de caso de um tumor ginecológico raro de restos embriológicos do trato genital feminino

Abstract Introduction Malignant mesonephric tumors are uncommon in the female genital tract, and they are usually located where embryonic remnants of Wolffian ducts are detected, such as the uterine cervix. The information about these tumors, their treatment protocol, and prognosis are scarce. Case report A 60-year-old woman with postmenopausal vaginal bleeding was initially diagnosed with endometrial carcinoma. After suspicion co-testing, the patient underwent a loop electrosurgical excision of the cervix and was eventually diagnosed with mesonephric adenocarcinoma. She was subjected to a radical hysterectomy, which revealed International Federation of Gynecology and Obstetrics (FIGO) IB1 stage, and adjuvant radiotherapy. The follow-up showed no evidence of recurrence after 60 months. Conclusion We present the case of a woman with cervical mesonephric adenocarcinoma. When compared with the literature, this case had the longest clinical follow-up without evidence of recurrence, which reinforces the concept that these tumors are associated with a favorable prognosis if managed according to the guidelines defined for the treatment of patients with cervical adenocarcinomas. Though a rare entity, it should be kept in mind as a differential diagnosis for other cervical cancers.

Bulky mesonephric adenocarcinoma of the uterine cervix treated with neoadjuvant chemotherapy and radical surgery: report of the first case.

AIMS AND BACKGROUND: Malignant mesonephric adenocarcinoma of the uterine cervix is a rare occurrence with few cases described in the literature. Although surgery seems to be effective in the treatment of early-stage tumor, no cases describing outcomes of locally advanced stage are available. METHODS: We report the first case of a patient with International Federation of Obstetrics and Gynecologists stage IIB mesonephric adenocarcinoma undergoing neoadjuvant chemotherapy and radical surgery. CONCLUSIONS: Despite the inherent limitation of a single description of a case, our experience supports the utilization of neoadjuvant chemotherapy in patients with malignant mesonephric adenocarcinoma of the uterine cervix. Further prospective multi-institutional studies are needed.

Poorly differentiated carcinoma of unknown primary site: correlation of light microscopic findings with response to cisplatin-based combination chemotherapy.

We have previously reported complete responses and long-term survival in patients with metastatic poorly differentiated carcinoma (PDC) of unknown primary site who received intensive cisplatin-containing chemotherapy regimens. We reviewed the light microscopic specimens from 113 patients with PDC in an attempt to identify common histopathologic features in the chemotherapy-responsive subgroup, and to rule out the presence of previously unrecognized germ cell tumors. Relatively few diagnoses more specific than PDC could be made. We could identify no histopathologic features by light microscopy that distinguished responsive from unresponsive neoplasms. Only one patient was found to have a previously unrecognized yolk sac carcinoma, and in five other patients the possibility of a germ cell neoplasm was considered in the differential diagnosis by at least one reviewer. The remaining tumors had no histologic features suggestive of germ cell neoplasms. Ninety-six patients had received combination chemotherapy (89 with cisplatin-containing regimens); 27 patients (28%) achieved complete remission, and 16 remain free of disease at a median of 65 months after completion of therapy. Patients with PDC of unknown primary site who are responsive to cisplatin-containing chemotherapy regimens cannot be reliably identified by light microscopy. At present, all such patients should be considered for an empiric trial of chemotherapy with cisplatin-based regimens, since cure is achievable in a minority.

Combination cisplatin, vinblastine, and bleomycin chemotherapy (PVB) for malignant germ-cell tumors of the ovary.

Nine women with germ-cell tumors of the ovary (three endodermal sinus tumors, four immature teratomas, and two mixed germ-cell tumors) were treated with cisplatin, vinblastine, and bleomycin (PVB) chemotherapy after cytoreductive operations. Five patients were stage I, three were stage III, and one patient had recurrent disease. All nine women are alive and without evidence of disease with a median follow-up of 31 months from diagnosis and 27 months since completion of PVB. Treatment toxicity although occasionally severe was rapidly reversible.

[Mesonephric carcinoma of the urethra. A case report]. / Das mesonephroide Karzinom der Urethra. Ein Fallbericht.

Mesonephric carcinoma is a tumor entity that rarely develops in the neck of the uterus and vaginal wall and is extremely unusual in the urinary bladder or paraurethral tissue. The tumors arise in the remnants of the wolffian or mesonephric duct. The malignant potential is considered to be lower than in tumors of the urethra with different histologic findings. Anterior pelvic exenteration is recommended in the literature as the treatment of choice. In the case described here, the tumor presented as a space-occupying lesion in a urethral diverticulum exhibiting striking clinical features of macrohematuria and urinary retention with subvesical obstruction of the urethra. In accordance with reports in the literature, cystectomy was performed and a Kock pouch constructed for urinary diversion. Tumors occurring in a diverticulum-and in this case manifesting as the rare tumor form of mesonephric carcinoma-should always be included in the differential diagnosis of macrohematuria in women.