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Journal of Cancer Research and Clinical... Nov 2023Mesonephric-like adenocarcinomas (MLA) of the female genital tract represent a rare and relatively recently described neoplasm exhibiting characteristic morphologic and... (Review)
Review
Mesonephric-like adenocarcinoma of the female genital tract: possible role of KRAS-targeted treatment-detailed molecular analysis of a case series and review of the literature for targetable somatic KRAS-mutations.
PURPOSE
Mesonephric-like adenocarcinomas (MLA) of the female genital tract represent a rare and relatively recently described neoplasm exhibiting characteristic morphologic and immunohistochemical findings commonly associated with a KRAS-mutation. Most cases display an aggressive clinical behavior, but knowledge about treatment approaches is limited, especially for targeting KRAS.
METHODS
We report a series of eight cases with a detailed molecular analysis for KRAS. These cases as well as the data of previously published cases with detailed information regarding KRAS-mutational events were reviewed for a potential targeted approach and its prognostic impact.
RESULTS
Both the uterine and ovarian MLA harbor a somatic KRAS-mutation in about 85% of the reported cases, affecting the hotspot codons 12 and 13. 15.7% of the endometrial and 15.6% of ovarian MLA are wild type for KRAS. A p.G12A-alteration was seen in 5.6% (5/89) of the endometrial and in 6.2% (2/32) of the ovarian tumors, for p.G12C in 7.9% and 6.2%, for p.G12D in 32.6% and 34.5% and for p.G12V in 36% and 37.5%, respectively. Very limited data are available regarding the prognostic impact of different mutational sites within the KRAS-gene without significant prognostic impact.
CONCLUSION
Because of a specific p.G12C-KRAS somatic mutation, only the minority of MLA (7.9% with uterine and 6.2% with ovarian primary) are potentially targetable by sotarasib in that rare but aggressive subtype of adenocarcinoma of the female genital tract. Until now, the different location of a somatic KRAS-mutation is of no prognostic impact.
Topics: Humans; Female; Proto-Oncogene Proteins p21(ras); Adenocarcinoma; Mutation; Prognosis; Genitalia, Female
PubMed: 37668797
DOI: 10.1007/s00432-023-05306-9 -
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 -
Histopathology Jun 2023To report novel observations in five mesonephric-like adenocarcinomas (MLAs) of the female genital tract.
Mesonephric-like adenocarcinoma of the female genital tract: novel observations and detailed molecular characterisation of mixed tumours and mesonephric-like carcinosarcomas.
AIMS
To report novel observations in five mesonephric-like adenocarcinomas (MLAs) of the female genital tract.
METHODS AND RESULTS
We report two endometrial MLAs in association with endometrioid carcinoma and atypical hyperplasia and three (one endometrial, two ovarian) cases with a sarcomatoid component (mesonephric-like carcinosarcoma). Pathogenic KRAS mutations, which are characteristic of MLA, were identified in all cases although interestingly, in one of the mixed carcinomas, this was confined to the endometrioid component. The concurrent MLA, endometrioid carcinoma and atypical hyperplasia components in one case harboured identical EGFR, PTEN and CCNE1 mutations, suggesting that the atypical hyperplasia gave rise to a Müllerian carcinoma with both endometrioid and mesonephric-like components. The carcinosarcomas all contained a component of MLA and a sarcomatous component with chondroid elements. In the ovarian carcinosarcomas, the coexisting epithelial and sarcomatous components shared some mutations including KRAS and CREBBP, suggesting that they are clonally related. Furthermore, in one case CREBBP and KRAS mutations detected in the MLA and sarcomatous components were also detected in an associated undifferentiated carcinoma component, suggesting that it was clonally related to the MLA and sarcomatous components.
CONCLUSIONS
Our observations provide additional evidence that MLAs have a Müllerian origin and characterise mesonephric-like carcinosarcomas in which chondroid elements appear to be characteristic. In reporting these findings, we provide recommendations for distinction between a mesonephric-like carcinosarcoma and a MLA with a spindle cell component.
Topics: Female; Humans; Carcinoma, Endometrioid; Hyperplasia; Proto-Oncogene Proteins p21(ras); Adenocarcinoma; Carcinosarcoma; Endometrium
PubMed: 36860193
DOI: 10.1111/his.14892 -
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 -
Diagnostic Cytopathology Jun 2021Recently we encountered two cases with mesonephric features, mesonephric-like carcinoma (MLC) of the ovary, and female adnexal tumor of probable Wolffian origin (FATWO)....
Recently we encountered two cases with mesonephric features, mesonephric-like carcinoma (MLC) of the ovary, and female adnexal tumor of probable Wolffian origin (FATWO). They are thought to be related to mesonephric remnants (or Wolffian duct remnants). Herein we describe the cytohistolgical features, differential diagnoses, and potential pitfalls in diagnosis of these neoplasms. On cytological examination, the case of MLC showed tight 3-dimensional clusters of overlapping round cells, corresponding to solid growth pattern seen on histological examination. Tubular architecture and papillary formations composed of neoplastic cells of medium size with scant cytoplasm were readily identified. Intraluminal eosinophilic secretions were better seen on histological examination. Additionally, areas resembling features of papillary thyroid carcinoma were noted. Mitoses and apoptotic bodies were not identified on cytology but seen on histological sections. The neoplastic cells were positive for CK7, CD10, PAX-8, TTF-1, and GATA-3, and negative for ER, PR, and WT-1 immunostains. In contrast to MLC, cytological examination of FATWO showed smaller oval to spindle monotonous cells without mitotic figures. Some cells contained paranuclear vacuoles and were arranged individually or in loose cohesive clusters. Other cells were closely associated with pericellular hyalinized basement membrane-like material and they were arranged in cohesive clusters as well. On histological examination, similar to MLC, the FATWO had areas with thyroid-like features, such as, intraluminal eosinophilic secretions, paranuclear vacuoles, in the background of collagenous stroma. The neoplastic cells were positive for CK AE1/AE3, calretinin, WT-1, inhibin, and CD10, and negative for CK7, PAX-8, GATA-3, ER, PR, and C-kit immunostains.
Topics: Adenoma; Adnexal Diseases; Adult; Carcinoma; Female; Humans; Middle Aged; Ovarian Neoplasms
PubMed: 33296554
DOI: 10.1002/dc.24675 -
Zhonghua Bing Li Xue Za Zhi = Chinese... Oct 2022To investigate the clinicopathological features of proliferations with mesonephric features (PMF) of the gynecologic tract. A retrospective analysis was performed on...
To investigate the clinicopathological features of proliferations with mesonephric features (PMF) of the gynecologic tract. A retrospective analysis was performed on the clinical and pathological data of 16 cases with PMF that were diagnosed from October 2016 to January 2022 at a single institution. The relevant literature was reviewed. Among the 16 cases, with an average of 53 years (31-68 years), there were 5 cases of mesonephric hyperplasia, 4 cases of mesonephric adenocarcinoma and 7 cases of mesonephric-like adenocarcinoma. The five cases of mesonephric hyperplasia were located in the lateral wall of the cervix and composed of simple tubules with growth patterns of diffuse or lobular clusters, without obvious stromal reaction. Four cases of mesonephric adenocarcinoma consisted of a mixture of papillary, cribriform, solid and other architectures, the nuclei resembling these of papillary thyroid carcinoma, and strong fibroproliferative reaction. They were located deep in the cervical and vaginal stroma. One of the tumors showed atypical mesonephric hyperplasia adjacent to the tumor. Five uterine and two ovarian mesonephric-like adenocarcinoma cases had similar histological morphology with mesonephric adenocarcinoma, but no mesonephric remnants/mesonephric hyperplasia were found near the tumors. In addition, four (4/5) uterine mesonephric-like adenocarcinoma cases originated from the endometrium with secondary involvement of myometrium, including one case with clear demarcation between the normal endometrium and the neoplastic glands. One (1/5) uterine mesonephric-like adenocarcinoma case was mainly located in the deep myometrium, along with adenomyosis around the tumor, without mesonephric remnants. Two ovarian mesonephric-like adenocarcinoma cases were associated with endometriotic cyst/endometrioid cystadenoma, including one case with an abrupt transition between normal epithelium and atypical mesonephric cells within the single individual cyst directly adjacent to tumor. All mesonephric hyperplasia and mesonephric adenocarcinoma cases were positive for GATA3, PAX8 and CD10 in a varying degree, and negative for ER, PR and TTF1. Although mesonephric-like adenocarcinoma showed a considerable overlap of immunohistochemical expression with mesonephric adenocarcinoma, seven mesonephric-like adenocarcinoma cases were positive for TTF1 and negative for GATA3. PMF is a class of rare proliferative lesions with morphological and immunophenotypic characteristics of mesonephric duct. Its commonly involved site, microscopic morphology, associated benign and/or atypical lesions, and immunophenotype may contribute to its diagnosis and differential diagnosis.
Topics: Adenocarcinoma; Biomarkers, Tumor; Cervix Uteri; Diagnosis, Differential; Female; Humans; Hyperplasia; Precancerous Conditions; Retrospective Studies
PubMed: 36207913
DOI: 10.3760/cma.j.cn112151-20220209-00088 -
Revista Brasileira de Ginecologia E... Apr 2021Malignant mesonephric tumors are uncommon in the female genital tract, and they are usually located where embryonic remnants of Wolffian ducts are detected, such as...
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.
Topics: Diagnosis, Differential; Female; Humans; Hysterectomy; Mesonephroma; Middle Aged; Neoplasm Invasiveness; Radiotherapy, Adjuvant; Uterine Cervical Neoplasms
PubMed: 33784759
DOI: 10.1055/s-0041-1725051 -
Modern Pathology : An Official Journal... Aug 2021Mesonephric carcinoma of the cervix is a rare tumor derived from Wolffian remnants. Mesonephric-like carcinomas of the ovary and endometrium, while morphologically...
Mesonephric carcinoma of the cervix is a rare tumor derived from Wolffian remnants. Mesonephric-like carcinomas of the ovary and endometrium, while morphologically similar, do not have obvious Wolffian derivation. Here, we sought to characterize the repertoire of genetic alterations in primary mesonephric and mesonephric-like carcinomas, in the distinct histologic components of mixed cases, as well as in matched primary tumors and metastases. DNA from microdissected tumor and normal tissue from mesonephric carcinomas (cervix, n = 8) and mesonephric-like carcinomas (ovarian n = 15, endometrial n = 13) were subjected to sequencing targeting 468 cancer-related genes. The histologically distinct components of four cases with mixed histology and four primary tumors and their matched metastases were microdissected and analyzed separately. Mesonephric-like carcinomas were underpinned by somatic KRAS mutations (25/28, 89%) akin to mesonephric carcinomas (8/8, 100%), but also harbored genetic alterations more frequently reported in Müllerian tumors. Mesonephric-like carcinomas that lacked KRAS mutations harbored NRAS (n = 2, ovary) or BRAF (n = 1, endometrium) hotspot mutations. PIK3CA mutations were identified in both mesonephric-like (8/28, 28%) and mesonephric carcinomas (2/8, 25%). Only mesonephric-like tumors harbored CTNNB1 hotspot (4/28, 14%) and PTEN (3/13, 23%) mutations. Copy number analysis revealed frequent gains of chromosomes 1q and 10 in both mesonephric (87% 1q; 50% chromosome 10) and mesonephric-like tumors (89% 1q; 43% chromosome 10). Chromosome 12 gains were more frequent in ovarian mesonephric-like carcinomas, and losses of chromosome 9 were more frequent in mesonephric than in mesonephric-like carcinomas (both p = 0.01, Fisher's exact test). The histologically distinct components of four mixed cases were molecularly related and shared similar patterns of genetic alterations. The progression from primary to metastatic lesions involved the acquisition of additional mutations, and/or shifts from subclonal to clonal mutations. Our findings suggest that mesonephric-like carcinomas are derived from a Müllerian substrate with differentiation along Wolffian/mesonephric lines.
Topics: Adult; Aged; Female; Genital Neoplasms, Female; Humans; Mesonephroma; Middle Aged; Mutation
PubMed: 33772212
DOI: 10.1038/s41379-021-00799-6 -
BMJ Case Reports Jun 2023Mesonephric remnants (MRs) are embryonic vestiges most commonly found in female pathology specimens from the lateral wall of the cervix. The highly regulated genetic...
Mesonephric remnants (MRs) are embryonic vestiges most commonly found in female pathology specimens from the lateral wall of the cervix. The highly regulated genetic programme of mesonephric duct development has been well characterised in animals based on traditional surgical castration and knockout mouse experiments. However, the process is incompletely understood in humans. MRs are believed to give rise to mesonephric neoplasms, which are rare tumours with uncertain pathophysiology. There is a dearth of molecular studies on mesonephric neoplasms in part due to their rarity. Here, we report the results of next-generation sequencing of MR, which identified amplification of the androgen receptor gene for the first time to the best of our knowledge and discuss the potential implications in the context of the literature.
Topics: Animals; Mice; Humans; Female; Receptors, Androgen; Cervix Uteri; Epithelium; Uterine Cervical Neoplasms
PubMed: 37295813
DOI: 10.1136/bcr-2022-251741 -
Surgical Pathology Clinics Jun 2022This article presents features of uncommon high-grade endometrial carcinomas that often pose a significant diagnostic challenge. An update on undifferentiated and... (Review)
Review
This article presents features of uncommon high-grade endometrial carcinomas that often pose a significant diagnostic challenge. An update on undifferentiated and dedifferentiated endometrial carcinoma is first provided, followed by discussions on more recently defined entities such as mesonephric-like carcinoma of the endometrium and gastric-type endometrial carcinomas. Finally, endometrial carcinoma with germ cell or trophoblastic-like components is discussed.
Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Endometrioid; Endometrial Neoplasms; Endometrium; Female; Humans; Hyperplasia; Immunohistochemistry
PubMed: 35715163
DOI: 10.1016/j.path.2022.02.007