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Modern Pathology : An Official Journal... Jan 2023Given the association of mesonephric adenocarcinoma (MA) of the uterine cervix with florid mesonephric hyperplasia, one would expect MAs to rarely arise in other...
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.
Topics: Male; Female; Humans; Uterine Cervical Neoplasms; Proto-Oncogene Proteins p21(ras); Adenocarcinoma; Mesonephroma; Urinary Tract
PubMed: 36788068
DOI: 10.1016/j.modpat.2022.100031 -
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 -
The American Journal of Surgical... Jun 2023Extrauterine mesonephric-like carcinoma (ExUMLC) shares histologic, immunohistochemical (IHC), and molecular (MOL) features with endometrial mesonephric-like carcinoma...
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=59 y); 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.
Topics: Adult; Aged; Female; Humans; Middle Aged; Adenocarcinoma; Carcinoma; Carcinoma, Endometrioid; Disease-Free Survival; Endometrial Neoplasms; Endometriosis; Mesonephroma; Nuclear Proteins; Ovarian Neoplasms; Repressor Proteins
PubMed: 37026792
DOI: 10.1097/PAS.0000000000002039 -
The American Journal of Surgical... Aug 2022The literature indicates that mesonephric carcinoma (MC) and mesonephric-like adenocarcinoma (MLA) typically lack mucinous and squamous features/differentiation. We...
The literature indicates that mesonephric carcinoma (MC) and mesonephric-like adenocarcinoma (MLA) typically lack mucinous and squamous features/differentiation. We report 4 cases of ovarian mucinous tumors (1 mucinous cystadenofibroma and 3 mucinous borderline tumors/atypical proliferative mucinous tumors [MBT/APMT]) co-existing with mesonephric-like lesions which were highlighted by Gata3 and Pax8 expression. All cases contained benign mesonephric-like proliferations (MLP) which focally displayed gastrointestinal-type mucinous metaplasia/differentiation and some were intimately admixed with mucinous glands associated with the mucinous tumor. Metaplastic mucinous epithelium retained expression of Gata3 and Pax8 in some areas while 1 mucinous cystadenofibroma and 1 MBT/APMT were focally positive for Pax8. Along with these mesonephric components, case 1 exhibited features of mesonephric hyperplasia and in 2 cases, 3 and 4, MLA was identified. In case 4, a KRAS c.35G>T (p.Gly12Val) somatic mutation was detected in both the MBT/APMT and the MLA, indicating a clonal origin. This same mutation was also detected in the benign MLP, indicating that it was likely an early genetic event. A CTNNB1 c.98C>T (p.Ser33Phe) somatic mutation, FGFR2 amplification, and CDKN2A/p16 deletion were only detected in the MLA but not in the MBT/APMT. Our result provides evidence to demonstrate the clonal relationship between these morphologically distinct components. Although speculative, we postulate that benign MLPs may give rise to lineage-specific mucinous and mesonephric-like lesions and propose that the MLPs are a new possible origin of some ovarian mucinous tumors. Whether these MLPs arise through transdifferentiation of Müllerian tissue or represent true mesonephric remnants, however, remains largely unknown.
Topics: Adenocarcinoma; Biomarkers, Tumor; Cell Proliferation; Cystadenofibroma; Female; Humans; Ovarian Neoplasms
PubMed: 35405716
DOI: 10.1097/PAS.0000000000001903 -
The American Journal of Surgical... Jan 2022Mesonephric-like adenocarcinomas (MLA) are rare neoplasms arising in the uterine corpus and ovary which have been added to the recent 2020 World Health Organization...
Mesonephric-like adenocarcinomas (MLA) are rare neoplasms arising in the uterine corpus and ovary which have been added to the recent 2020 World Health Organization Classification of Female Genital Tumors. They have similar morphology and immunophenotype and exhibit molecular aberrations similar to cervical mesonephric adenocarcinomas. It is debated as to whether they are of mesonephric or Mullerian origin. We describe the clinical, pathologic, immunohistochemical, and molecular features of 5 cases of extrauterine mesonephric-like proliferations (4 ovary, 1 extraovarian), all with novel and hitherto unreported features. These include an origin of MLA in extraovarian endometriosis, an association of ovarian MLA with high-grade serous carcinoma, mixed germ cell tumor and mature teratoma, and a borderline ovarian endometrioid tumor exhibiting mesonephric differentiation. Four of the cases exhibited a KRAS variant and 3 also a PIK3CA variant. In reporting these cases, we expand on the published tumor types associated with MLA and report for the first time a borderline tumor exhibiting mesonephric differentiation. We show the value of molecular testing in helping to confirm a mesonephric-like lesion and in determining the relationship between the different neoplastic components. We provide further evidence for a Mullerian origin, rather than a true mesonephric origin, in some of these cases. We also speculate that in the 2 cases associated with germ cell neoplasms, the MLA arose out of the germ cell tumor.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Differentiation; Cell Proliferation; Class I Phosphatidylinositol 3-Kinases; Female; Humans; Mesocolon; Middle Aged; Mullerian Ducts; Mutation; Ovarian Neoplasms; Peritoneal Neoplasms; Proto-Oncogene Proteins p21(ras); Treatment Outcome; Wolffian Ducts
PubMed: 34183523
DOI: 10.1097/PAS.0000000000001766 -
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 -
Histopathology Sep 2022Mesonephric 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... (Review)
Review
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.
Topics: AMP-Activated Protein Kinase Kinases; Adenocarcinoma; Adenoma; Broad Ligament; Carcinoma, Endometrioid; Female; Genital Neoplasms, Female; Humans; Neoplasms, Adnexal and Skin Appendage; Protein Serine-Threonine Kinases; Wolffian Ducts
PubMed: 35395118
DOI: 10.1111/his.14662 -
Pathology Feb 2018The mesonephric (Wolffian) duct regresses in females during embryological development. Remnants of this duct may persist typically along the lateral walls of the cervix,... (Review)
Review
The mesonephric (Wolffian) duct regresses in females during embryological development. Remnants of this duct may persist typically along the lateral walls of the cervix, vagina, adnexa, and uterine corpus. These mesonephric epithelia may expand into hyperplastic proliferations and rarely form neoplasms. The spectrum of morphology, immunophenotype, clinical presentation, and molecular characteristics of mesonephric lesions is reviewed, with attention to distinction from entities in the differential diagnosis.
Topics: Female; Genital Neoplasms, Female; Humans; Wolffian Ducts
PubMed: 29269124
DOI: 10.1016/j.pathol.2017.11.084 -
International Journal of Surgical... Feb 2017Clear cell urothelial carcinoma (CCUC) is a rare variant of urothelial carcinoma (UC) and its clinical significance has not been well elucidated. Consecutive cases of UC... (Meta-Analysis)
Meta-Analysis
Clear cell urothelial carcinoma (CCUC) is a rare variant of urothelial carcinoma (UC) and its clinical significance has not been well elucidated. Consecutive cases of UC over a period of 5 years were reviewed. Histopathological tumor parameters, including the proportion of tumor cells with clear cell change, and patient outcomes were recorded. Expression of the following immunohistochemical markers was investigated: CK7, CK20, CK5, CD44, and PAX8. We also conducted a review of the literature for case reports/series of CCUC. Ten CCUCs were identified out of a total of 872 cases of UC. The clear cell component was characterized by prominent cytoplasmic membranes and voluminous clear cytoplasm, and accounted for 30% to 90% of the invasive tumor component. Of all the non-CCUC cases reviewed, at least 50% (noninvasive or invasive UC) showed focal areas of clear cell change that accounted for less than 5% of the neoplastic cells. Immunohistochemically, CCUC exhibited positive reactivity for CK5/CD44 (n = 9); CK20 (n = 5), PAX8 (very focal to extensive) (n = 6), and GATA3/CK7 (n = 10). Eight of 10 CCUC were of advanced clinical stage (pT3/pT4) and 6 of 10 experienced tumor recurrence and/or death due to disease. In conclusion, CCUC can be distinguished from non-CCUC by the extensive clear cell change in more than 30% of cells. This variant is associated with rapid progression to muscle invasion and metastasis, with an aggressive clinical course. Expression of CK5/CD44 may represent basal cell features in most CCUC cases, while PAX8 expression is suggestive of mesonephric derivation.
Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Transitional Cell; Female; Humans; Immunohistochemistry; Male; Middle Aged; Urinary Bladder Neoplasms
PubMed: 27422469
DOI: 10.1177/1066896916660195 -
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