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Journal of Clinical Medicine Jul 2023Mesonephric adenocarcinoma (MA) of the vagina is a rare tumor that arises from mesonephric remnants (Wolffian) in the female genital tract. It is a neoplasm with no... (Review)
Review
BACKGROUND
Mesonephric adenocarcinoma (MA) of the vagina is a rare tumor that arises from mesonephric remnants (Wolffian) in the female genital tract. It is a neoplasm with no significant evidence about its diagnosis, treatment, follow-up and prognosis.
METHODS
Systematic research of the literature was conducted in Scopus, PubMed/MEDLINE, ScienceDirect and the Cochrane Library, including observational prospective and retrospective studies, case series and case reports. We collected data regarding studies related to diagnosis and treatment options evaluating the following aspects: study design, population, treatment type, rate of surgical complications and fertility outcome. We further included a case report of laparoscopic management of MA with pictorial assays.
RESULTS
Thirteen cases of MA of the vagina are available in the literature, including our case report. The median age at diagnosis was 52 years old; the majority of patients reported vaginal bleeding as a symptom (38%); and ultrasound, followed by a magnetic resonance and CT scan were the diagnostic tools most used. In 54% of the cases, a surgical biopsy was performed, and 92% of the patients underwent upfront surgery with an open access or vaginal resection except one case fully managed by minimally invasive surgery. Most of the patients (68%) received adjuvant treatment with chemotherapy or radiotherapy or a combination of them. The mean follow-up period was 6 years.
CONCLUSIONS
Despite the rarity of this cancer and bizarre location, a minimally invasive approach seems feasible after multidisciplinary evaluation. According to the rarity of this tumor, any future case and follow-up data must be reported in the literature in order to enlarge the knowledge about it.
PubMed: 37510961
DOI: 10.3390/jcm12144846 -
Gynecologic Oncology Mar 2024Mesonephric (MA) and mesonephric-like (MLA) adenocarcinomas are rare cancers, and data on clinical behavior and response to therapy are limited. We sought to report...
OBJECTIVES
Mesonephric (MA) and mesonephric-like (MLA) adenocarcinomas are rare cancers, and data on clinical behavior and response to therapy are limited. We sought to report molecular features, treatment, and outcomes of MA/MLA from a single institution.
METHODS
Patients with MA (cervix) or MLA (uterus, ovary, other) treated at Memorial Sloan Kettering Cancer Center (MSK) from 1/2008-12/2021 underwent pathologic re-review. For patients with initial treatment at MSK, progression-free survival (PFS1) was calculated as time from initial surgery to progression or death; second PFS (PFS2) was calculated as time from start of treatment for recurrence to subsequent progression or death. Overall survival (OS) was calculated for all patients. Images were retrospectively reviewed to determine treatment response. Somatic genetic alterations were assessed by clinical tumor-normal sequencing (MSK-Integrated Mutation Profiling of Actionable Cancer Targets [MSK-IMPACT]).
RESULTS
Of 81 patients with confirmed gynecologic MA/MLA, 36 received initial treatment at MSK. Sites of origin included cervix (n = 9, 11%), uterus (n = 42, 52%), ovary (n = 28, 35%), and other (n = 2, 2%). Of the 36 patients who received initial treatment at MSK, 20 (56%) recurred; median PFS1 was 33 months (95% CI: 17-not evaluable), median PFS2 was 8.3 months (95% CI: 6.9-14), and median OS was 87 months (95% CI: 58.2-not evaluable). Twenty-six of the 36 patients underwent MSK-IMPACT testing, and 25 (96%) harbored MAPK pathway alterations.
CONCLUSION
Most patients diagnosed with early-stage disease ultimately recurred. Somatic MAPK signaling pathway mutations appear to be highly prevalent in MA/MLA, and therapeutics that target this pathway are worthy of further study.
Topics: Humans; Female; Retrospective Studies; Adenocarcinoma; Mutation; Ovary; Cervix Uteri
PubMed: 38246044
DOI: 10.1016/j.ygyno.2024.01.015 -
Clinical Cancer Research : An Official... Apr 2024We aimed to describe RAS mutations in gynecologic cancers as they relate to clinicopathologic and genomic features, survival, and therapeutic implications.
BACKGROUND
We aimed to describe RAS mutations in gynecologic cancers as they relate to clinicopathologic and genomic features, survival, and therapeutic implications.
METHODS
Gynecologic cancers with available somatic molecular profiling data at our institution between February 2010 and August 2022 were included and grouped by RAS mutation status. Overall survival was estimated by Kaplan-Meier method, and multivariable analysis was performed using Cox proportional-hazards model.
RESULTS
Of 3328 gynecologic cancers, 523 (15.7%) showed any RAS mutation. Patients with RAS-mutated tumors were younger (57 vs 60 years non-mutated), had higher prevalence of endometriosis (27.3% vs 16.9%), and lower grades (grade 1/2, 43.2% vs 8.1%, all p<0.0001). Highest prevalence of KRAS mutation was in mesonephric-like endometrial (100%, n=9/9), mesonephric-like ovarian (83.3%, n=5/6), mucinous ovarian (60.4%), and low-grade serous ovarian (44.4%) cancers. After adjustment for age, cancer type, and grade, RAS mutation was associated with worse overall survival (HR=1.3, p=0.001). Specific mutations were in KRAS (13.5%), NRAS (2.0%), and HRAS (0.51%), most commonly KRAS G12D (28.4%) and G12V (26.1%). Common co-mutations were PIK3CA (30.9%), PTEN(28.8%), ARID1A (28.0%), and TP53 (27.9%), of which 64.7% were actionable. RAS+MAPK pathway-targeted therapies were administered to 62 patients with RAS-mutated cancers. While overall survival was significantly higher with therapy (8.4 years [95%CI 5.5-12.0] vs 5.5 years [95%CI 4.6-6.6], HR=0.67, p=0.031), this effect did not persist in multivariable analysis.
CONCLUSION
RAS mutations in gynecologic cancers have a distinct histopathologic distribution and may impact overall survival. PIK3CA, PTEN, and ARID1A are potentially actionable co-alterations. RAS pathway-targeted therapy should be considered.
PubMed: 38687597
DOI: 10.1158/1078-0432.CCR-23-2819 -
Journal of Ovarian Research Mar 2024Mesonephric-like adenocarcinoma is a new class of rare subtypes of the female reproductive system. Its clinical symptoms are similar to other types of ovarian tumors....
Mesonephric-like adenocarcinoma is a new class of rare subtypes of the female reproductive system. Its clinical symptoms are similar to other types of ovarian tumors. The diagnosis is based on pathological and immunohistochemical methods. The main treatment option is surgery combined with chemotherapy. Few cases have been reported at home and abroad. We reported a case of a 45-year-old woman with a cystic solid mass in the left adnexa. The postoperative pathological diagnosis was mesonephric-like adenocarcinoma of the left ovary and mature cystic teratoma (partial infiltration of the small intestine). This case had no specific clinical symptoms. Immunohistochemical findings showed positive results of GATA3, TTF1, CD10, ER, and PR. Paclitaxel and carboplatin chemotherapy were given after the operation. Currently, no specific criteria are available for diagnosis and treatment of the disease. This article aims to improve the understanding of clinicians in this disease and create a basis for clinical diagnosis and treatment.
Topics: Female; Humans; Middle Aged; Ovarian Neoplasms; Adenocarcinoma; Pelvis; Carboplatin
PubMed: 38444000
DOI: 10.1186/s13048-024-01383-7 -
The Journal of Pathology Jan 2024Mesonephric-like adenocarcinoma (MLA) of the female genital tract is an uncommon histotype that can arise in both the endometrium and the ovary. The exact cell of origin...
Mesonephric-like adenocarcinoma harbours characteristic copy number variations and a distinct DNA methylation signature closely related to mesonephric adenocarcinoma of the cervix.
Mesonephric-like adenocarcinoma (MLA) of the female genital tract is an uncommon histotype that can arise in both the endometrium and the ovary. The exact cell of origin and histogenesis currently remain unknown. Here, we investigated whole genome DNA methylation patterns and copy number variations (CNVs) in a series of MLAs in the context of a large cohort of various gynaecological carcinoma types. CNV analysis of 19 MLAs uncovered gains of chromosomes 1q (18/19, 95%), 10 (15/19, 79%), 12 (14/19, 74%), and 2 (10/19, 53%), as well as loss of chromosome 1p (7/19, 37%). Gains of chromosomes 1q, 10, and 12 were also identified in the majority of mesonephric adenocarcinomas of the uterine cervix (MAs) as well as subsets of endometrioid carcinomas (ECs) and low-grade serous carcinomas of the ovary (LGSCs) but only in a minority of serous carcinomas of the uterine corpus (USCs), clear cell carcinomas (CCCs), and tubo-ovarian high-grade serous carcinomas (HGSCs). While losses of chromosome 1p together with gains of chromosome 1q were also identified in both MA and LGSC, gains of chromosome 2 were almost exclusively identified in MLA and MA. Unsupervised hierarchical clustering and t-SNE analysis of DNA methylation data (Illumina EPIC array) identified a co-clustering for MLAs and MAs, which was distinct from clusters of ECs, USCs, CCCs, LGSCs, and HGSCs. Group-wise comparisons confirmed a close epigenetic relationship between MLA and MA. These findings, in conjunction with the established histological and immunophenotypical overlap, suggest bona fide mesonephric differentiation, and support a more precise terminology of mesonephric-type adenocarcinoma instead of MLA in these tumours. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Topics: Female; Humans; Cervix Uteri; DNA Copy Number Variations; DNA Methylation; Carcinoma, Endometrioid; Cystadenocarcinoma, Serous; Carcinoma, Ovarian Epithelial; Ovarian Neoplasms
PubMed: 37850576
DOI: 10.1002/path.6217 -
Asian Journal of Surgery Dec 2023
Topics: Female; Humans; Adenocarcinoma; Endometrium
PubMed: 37730504
DOI: 10.1016/j.asjsur.2023.09.029 -
CRSLS : MIS Case Reports From SLS 2023Endometriosis originating in mesonephric cyst is unusual and with unknown prevalence. Endometriotic lesion in vestigial remnant of wolffian duct (mesonephric cyst) is... (Review)
Review
OBJECTIVES
Endometriosis originating in mesonephric cyst is unusual and with unknown prevalence. Endometriotic lesion in vestigial remnant of wolffian duct (mesonephric cyst) is exceptional. In the extended literature review only three cases have been reported in animal studies, and our case reported here is the first in human beings. We present a case of mesonephric cyst endometrioma in a 37-year-old patient who was referred for severe dysmenorrhea, long duration pelvic and back pain, subfertility, severe dyspareunia, and groin discomfort. The patient underwent laparoscopic removal and we performed a literature review to gain insight about the origin and surgical management of an atypical site endometriosis.
METHODS AND PROCEDURES
Case report presentation rests on information obtained from the patient database. We performed the literature review using a Medline search with the keywords: mesonephric cyst endometriosis, atypical location of endometriosis in vestigial remnant in wolffian duct, and Gartner duct cyst endometrioma.
RESULTS
On physical examination, fullness and tenderness in left adnexa and lateral vaginal wall fullness on left side with restricted mobility of uterus was noted. Based on the examination and imaging the left ovarian cyst and mesonephric cyst were suspected. Surgical exploration revealed the left hemorrhagic cyst with deep infiltrating endometriosis involving left ureter and left uterosacral ligament with mesonephric cyst endometriosis. The review of literature revealed three cases where ectopic endometrial tissue in mesonephric cyst remnant was found in female dogs.
CONCLUSION
Mesonephric cyst endometrioma, although rare, can be a representative of extensive endometriosis. This case highlights an importance of careful clinical examination, correlation of patient symptoms with examination and imaging, and successful laparoscopic management of an atypical location endometriotic lesions. We completed the literature review on successful surgical management of such cases.
Topics: Animals; Dogs; Female; Humans; Adult; Endometriosis; Laparoscopy; Ovarian Cysts; Pelvis; Cysts
PubMed: 37808583
DOI: 10.4293/CRSLS.2023.00029 -
Annales de Pathologie Nov 2023Mesonephric lesions in the female genital tract are uncommon and heterogeneous. Those deriving from the upper tract differ from those developing in the lower tract,... (Review)
Review
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.
Topics: Female; Humans; Carcinoma; Genitalia, Female; Epithelium; Adenoma; Skin Neoplasms
PubMed: 37481413
DOI: 10.1016/j.annpat.2023.07.001 -
International Journal of Surgical... Nov 2023Mesonephric-like adenocarcinoma is a rare neoplasm of the uterine corpus and ovary. Unlike prototypical mesonephric adenocarcinoma of the uterine cervix, which is...
Mesonephric-like adenocarcinoma is a rare neoplasm of the uterine corpus and ovary. Unlike prototypical mesonephric adenocarcinoma of the uterine cervix, which is considered of Wolffian origin, recent evidence suggests that mesonephric-like adenocarcinoma is a Mullerian tumor associated with endometriosis. We report here on a 48-year-old woman with a mixed carcinoma of the ovary that consisted of mesonephric-like adenocarcinoma, clear cell carcinoma, and endometrioid carcinoma, arising from an endometriotic cyst. The mesonephric-like adenocarcinoma consisted of cuboidal cells with vesicular nuclei presenting with a tubular, ductal, papillary, and solid architecture forming nodules. Each component showed distinct immunophenotypes that were consistent with their morphology. The mesonephric-like adenocarcinoma showed diffuse positive staining for paired box 8 and GATA binding protein 3, and negative staining for estrogen and progesterone receptors. A p53 stain exhibited wild-type immunoreactivity. A complete loss of AT-rich interactive domain-containing protein 1A (ARID1A) expression was suggestive of an mutation. Manual macrodissection and Sanger sequencing revealed identical and mutations in all three components. To the best of our knowledge, this is the first report of mesonephric-like adenocarcinoma combined with a clear cell carcinoma and endometrioid carcinoma, which supports the hypothesis that mesonephric-like adenocarcinoma is an endometriosis-associated neoplasm. The report also highlights a potential pitfall in diagnosing mesonephric-like adenocarcinoma combined with clear cell carcinoma.
PubMed: 37994045
DOI: 10.1177/10668969231213390