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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 -
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 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 -
Folia Medica Cracoviensia Dec 2022Hutch Diverticulum (HD) is defined as the protrusion of the mucosal and submucosal layer through the muscle bundles of the underlying detrusor muscle. HD is located at... (Review)
Review
Hutch Diverticulum (HD) is defined as the protrusion of the mucosal and submucosal layer through the muscle bundles of the underlying detrusor muscle. HD is located at the vesicoureteral junction with a backward direction from the homolateral ureteral orifice. As far as its etiology is concerned, HD is caused either by a congenital muscle wall defect at the level where the Waldeyer's fascia occupies the clefts between the vesical part of the homolateral ureter and the detrusor, or is associated with abortive ureteral duplication or defective incorporation of mesonephric duct into the bladder at the site of ureteral hiatus or finally is associated with the development of transient urethral obstruction. HD is usually unilateral and more common in male patients. It may be associated with the Ehlers-Danlos, Williams-Elfin and Menkes syndromes. HD usually occurs in childhood and rarely during adulthood. It is found in 0.2-13% of all children presenting with urinary tract infection. Through this short review article, we attempt to present in detail the most recent bibliographic data concerning this entity, focusing on pathophysiology, diagnostic approach, and treatment strategy.
Topics: Child; Humans; Male; Adult; Urinary Bladder; Fascia; Diverticulum
PubMed: 36854087
DOI: 10.24425/fmc.2022.144083 -
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 -
Biology of Reproduction Jan 2022The vertebrate female reproductive tract has undergone considerable diversification over evolution, having become physiologically adapted to different reproductive... (Review)
Review
The vertebrate female reproductive tract has undergone considerable diversification over evolution, having become physiologically adapted to different reproductive strategies. This review considers the female reproductive tract from the perspective of evolutionary developmental biology (evo-devo). Very little is known about how the evolution of this organ system has been driven at the molecular level. In most vertebrates, the female reproductive tract develops from paired embryonic tubes, the Müllerian ducts. We propose that formation of the Müllerian duct is a conserved process that has involved co-option of genes and molecular pathways involved in tubulogenesis in the adjacent mesonephric kidney and Wolffian duct. Downstream of this conservation, genetic regulatory divergence has occurred, generating diversity in duct structure. Plasticity of the Hox gene code and wnt signaling, in particular, may underlie morphological variation of the uterus in mammals, and evolution of the vagina. This developmental plasticity in Hox and Wnt activity may also apply to other vertebrates, generating the morphological diversity of female reproductive tracts evident today.
Topics: Animals; Biological Evolution; Developmental Biology; Estrogens; Fallopian Tubes; Female; Gene Expression; Genes, Homeobox; Genitalia, Female; Humans; Morphogenesis; Mullerian Ducts; Uterus; Vertebrates; Wnt Signaling Pathway
PubMed: 34494091
DOI: 10.1093/biolre/ioab166 -
International Journal of Gynaecology... Oct 2021This review covers the significant new developments in the pathological classification of gynecological tumors. Many of these were included in the updated World Health... (Review)
Review
This review covers the significant new developments in the pathological classification of gynecological tumors. Many of these were included in the updated World Health Organization Classification of Female Genital Tract Tumours, published in 2020. Topics include the compelling evidence that a large majority of extrauterine high-grade serous carcinomas arise from the fallopian tube; the Cancer Genome Atlas (TCGA) Classification of endometrial carcinomas; the discovery that most so-called synchronous endometrial and ovarian endometrioid carcinomas represent metastasis from the endometrium to the ovary; and the division of cervical, vaginal, and vulval carcinomas into clinically meaningful HPV-associated and HPV-independent types. Newly described tumor types are covered, including endometrial and ovarian mesonephric-like adenocarcinoma, uterine sarcoma types associated with specific molecular abnormalities, and gastric (gastrointestinal)-type adenocarcinomas of the endometrium and vagina. Important molecular events in ovarian sex cord-stromal tumors are also discussed.
Topics: Adenocarcinoma; Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Humans; Ovarian Neoplasms; Uterine Neoplasms
PubMed: 34669206
DOI: 10.1002/ijgo.13871 -
Histopathology Jun 2023
Topics: Humans; Mesonephros; Carcinosarcoma
PubMed: 37191121
DOI: 10.1111/his.14900 -
JNMA; Journal of the Nepal Medical... Mar 2023Herlyn-Werner-Wunderlich syndrome is a rare Mullerian and mesonephric ductal anomaly characterized by a triad of didelphys uterus, obstructed hemivagina, and ipsilateral...
UNLABELLED
Herlyn-Werner-Wunderlich syndrome is a rare Mullerian and mesonephric ductal anomaly characterized by a triad of didelphys uterus, obstructed hemivagina, and ipsilateral renal agenesis complex. This entity is also known as obstructed hemivagina and ipsilateral renal anomaly. We present a case of a 24-year-old nulliparous female with Herlyn-Werner-Wunderlich who presented with dysmenorrhea and intermenstrual bleeding. The diagnosis was initially made through ultrasound and confirmed on magnetic resonance imaging. The nonspecific nature of symptoms and variability in presentation depending on the classification and type of Herlyn-Werner-Wunderlich syndrome often leads to misdiagnosis or a delay in diagnosis. Therefore, a high index of suspicion is required.
KEYWORDS
case reports; mesonephric ducts; mullerian ducts.
Topics: Female; Humans; Young Adult; Adult; Vagina; Kidney; Uterus; Kidney Diseases; Abnormalities, Multiple
PubMed: 37203938
DOI: 10.31729/jnma.8096