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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 -
Frontiers in Oncology 2022Mesonephric-like adenocarcinoma (MLA) is a recently characterized, rare, and aggressive neoplasm that mostly arises in the uterine corpus and ovary. MLA shows...
BACKGROUND
Mesonephric-like adenocarcinoma (MLA) is a recently characterized, rare, and aggressive neoplasm that mostly arises in the uterine corpus and ovary. MLA shows characteristic pathological features similar to mesonephric adenocarcinoma of the cervix. The origin of MLA is still controversial and recognition of it remains challenging for pathologists. The aim of this study was to enrich the clinicopathological features of MLA in the uterine corpus and explore its molecular alterations by targeted next-generation sequencing (NGS).
METHODS
Four cases of MLA were identified among a total of 398 endometrial carcinomas diagnosed in our institution between January 2014 and December 2021. Immunohistochemistry and targeted NGS spanning 437 cancer-relevant genes were performed.
RESULTS
The most common symptom was abnormal vaginal bleeding, and the average age was 68 years. Histologically, the tumors showed a mixture of varied growth patterns including papillary, glandular, tubular, cribriform, solid, and slit-like architectures, which were lined by columnar to cuboidal cells with overlapping vesicular nuclei and sometimes nuclear grooves. Intraluminal eosinophilic colloid-like secretions were focally evident in three of the four cases. Immunohistochemically, the MLAs were positive for GATA3 (4/4), TTF-1 (3/3), luminal CD10 (3/3), calretinin (2/3), and patchy P16 (3/3) and were negative for ER (0/4) and PR (0/4). The expression of P53 was "wild type" (4/4). By targeted NGS, 3/4 (75%), 2/4 (50%), and 1/4 (25%) cases harbored , , and mutations, respectively. None of the tumors had mutations in DNA mismatch repair genes, , , , , or . At the time of diagnosis, three were presented with FIGO IB stage and one with IIIC stage. Two patients received postoperative chemotherapy and radiotherapy and they were alive without evidence of disease at 8 and 56 months follow-up, respectively. One patient developed pulmonary metastasis 13 months after surgery and chemotherapy, and one was dead of the disease 24 months after the operation without adjuvant therapy.
CONCLUSIONS
MLA is a rare and aggressive malignancy, representing approximately 1% of all endometrial carcinomas. It exhibits mixed architectures associated with distinctive immunophenotype and recurrent and mutations, supporting classified as of Müllerian origin with mesonephric differentiation.
PubMed: 35865471
DOI: 10.3389/fonc.2022.911695 -
Archives of Pathology & Laboratory... Jan 2022Female adnexal tumor of probable Wolffian origin (FATWO) often is a diagnostic challenge given its rarity, histologic heterogeneity, and lack of specific immunoprofile.
CONTEXT.—
Female adnexal tumor of probable Wolffian origin (FATWO) often is a diagnostic challenge given its rarity, histologic heterogeneity, and lack of specific immunoprofile.
OBJECTIVE.—
To further understand the clinicopathologic and immunohistochemical features of this rare entity.
DESIGN.—
We studied the clinical, morphologic, and immunohistochemical features of a cohort of 11 FATWO cases from our institute.
RESULTS.—
Patients' age ranged from 25 to 76 years (mean, 55 years). Tumor size ranged from 0.5 to 18 cm (mean, 2.7 cm). Histopathologically, most tumors presented with low-grade cytologic features with low mitotic activity and lack of necrosis. Three main growth patterns were appreciated: solid, tubular, and sievelike patterns. Higher-grade nuclear atypia, increased mitotic activity, and focal necrosis were seen in 2 cases. These 2 cases were clinically considered malignant FATWO mainly because of their extra-adnexal involvement. Immunohistochemical studies found that tumor cells were positive for CD10 (11 of 11, 100%), AE1/3 (8 of 8, 100%), CAM 5.2 (4 of 5, 80%), and cytokeratin 7 (CK7; 7 of 10, 70%), and focally positive for calretinin (4 of 10, 40%), inhibin (4 of 10, 40%), epithelial membrane antigen (EMA; 3 of 9, 33%), and steroidogenic factor-1 (SF-1; 2 of 8, 25%). Lack of immunoreactivity to PAX8 and GATA3 in almost all cases indicates that FATWO is different from the tumors derived from the Müllerian or mesonephric origins. All patients with available follow-up had favorable prognosis.
CONCLUSION.—
The broad spectrum of clinical presentation, various morphologic features, and overlapping immunophenotype suggest that FATWO is a diagnosis of exclusion until it is further defined at the molecular and immunohistochemical levels.
Topics: Adenoma; Adnexal Diseases; Biomarkers, Tumor; Female; Humans; Neoplasms, Adnexal and Skin Appendage; Prognosis
PubMed: 34133728
DOI: 10.5858/arpa.2020-0432-OA -
Anticancer Research Sep 2021Ovarian endometrioid carcinoma (EC) and high-grade serous carcinoma (HGSC) may exhibit various growth patterns and mimic mesonephric-like adenocarcinoma (MLA). We... (Comparative Study)
Comparative Study
Mesonephric-like Differentiation of Ovarian Endometrioid and High-grade Serous Carcinomas: Clinicopathological and Molecular Characteristics Distinct from Those of Mesonephric-like Adenocarcinoma.
BACKGROUND/AIM
Ovarian endometrioid carcinoma (EC) and high-grade serous carcinoma (HGSC) may exhibit various growth patterns and mimic mesonephric-like adenocarcinoma (MLA). We investigated the clinicopathological and molecular features of ovarian carcinomas with mesonephric-like differentiation (MLD).
PATIENTS AND METHODS
We analyzed the electronic medical records and pathology slides of two EC-MLD and three HGSC-MLD patients, and conducted immunostaining and targeted sequencing of their samples.
RESULTS
All cases showed architectural diversity, compactly aggregated small tubules and ducts, and eosinophilic intraluminal secretions, indicating the possibility of an ovarian MLA. However, the following histological and immunophenotypical features confirmed the diagnoses of EC-MLD and HGSC-MLD: squamous, tubal, and sertoliform differentiation; serous tubal intraepithelial carcinoma; solid, endometrioid, transitional (SET) feature; solid, transitional, endometrioid, mucinous-like (STEM) feature; diffuse expression of hormone receptors and Wilms tumor 1; mutant p53 immunostaining pattern; and wild-type v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog gene.
CONCLUSION
A subset of ovarian ECs and HGSCs can display MLD and mimic an MLA. A thorough histological examination combined with ancillary tests is crucial to differentiate between these ovarian neoplastic entities.
Topics: Adult; Biomarkers, Tumor; Carcinoma, Endometrioid; Cystadenocarcinoma, Serous; Diagnosis, Differential; Electronic Health Records; Female; Humans; Middle Aged; Neoplasm Grading; Ovarian Neoplasms; Proto-Oncogene Proteins p21(ras); Retrospective Studies; Tumor Suppressor Protein p53; WT1 Proteins; Wolffian Ducts
PubMed: 34475087
DOI: 10.21873/anticanres.15272 -
Cancer Genomics & Proteomics 2022This study aimed to investigate the clinicopathological, prognostic and molecular characteristics of uterine mesonephric-like carcinosarcoma (MLCS).
Mesonephric-like Carcinosarcoma of the Uterine Corpus: Clinicopathological, Molecular and Prognostic Characteristics in Comparison With Uterine Mesonephric-like Adenocarcinoma and Conventional Endometrial Carcinosarcoma.
BACKGROUND/AIM
This study aimed to investigate the clinicopathological, prognostic and molecular characteristics of uterine mesonephric-like carcinosarcoma (MLCS).
PATIENTS AND METHODS
We collected clinical, pathological, and genetic information from 12 MLCS patients, and analyzed their differences from mesonephric-like adenocarcinoma (MLA) and conventional endometrial carcinosarcoma (CECS).
RESULTS
The epithelial component was exclusively MLA in all MLCS cases. Metastatic and recurrent tumors consisted predominantly or exclusively of MLA in the majority of MLCS cases. Patients with MLCS and MLA presented with more advanced-stage disease than those with CECS. They also exhibited post-treatment recurrence and lung metastases more frequently than CECS. Disease-free survival rates of MLCS and MLA were shorter than those of CECS. Tumor protein 53 gene mutations were detected in four MLCS cases.
CONCLUSION
The predominance or exclusive presence of MLA in metastatic and recurrent tumors highlights the possibility that MLA may determine the clinical outcomes of patients with MLCS. Further studies are required to provide direct molecular evidence of the monoclonal origin of uterine MLCS.
Topics: Female; Humans; Prognosis; Carcinosarcoma; Endometrial Neoplasms; Adenocarcinoma
PubMed: 36316041
DOI: 10.21873/cgp.20357 -
Abdominal Imaging Oct 2015Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare congenital anomaly of the female urogenital tract that associates Müllerian duct anomalies with mesonephric duct... (Review)
Review
Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare congenital anomaly of the female urogenital tract that associates Müllerian duct anomalies with mesonephric duct anomalies. The triad of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis characterizes this syndrome. Patients generally present with non-specific symptoms after menarche. Pelvic pain, dysmenorrhea, and palpable mass due to hematocolpos or hematometra are the most common findings. Pyohematocolpos and pyosalpinx may appear as acute complications, while endometriosis and pelvic adhesions constitute potential long-term complications. When a prenatal diagnosis of unilateral renal agenesis in newborn girls is known, a gynecological imaging study should be performed to exclude uterine and vaginal abnormalities. These patients should be followed up to ensure that a timely surgical correction is performed. The diagnosis of HWWS is difficult due to the lack of specific symptoms or findings upon physical examination. An accurate imaging description of these congenital anomalies is crucial to guide patients toward surgical treatment, relieving acute complications, and preserving the normal fertility. The authors provide a pictorial review of the magnetic resonance imaging and ultrasonography findings of the HWWS with correlation to embryological, clinical, and surgical features.
Topics: Congenital Abnormalities; Female; Humans; Kidney; Kidney Diseases; Magnetic Resonance Imaging; Mullerian Ducts; Postoperative Complications; Preoperative Care; Syndrome; Ultrasonography; Urogenital Abnormalities; Wolffian Ducts
PubMed: 25852048
DOI: 10.1007/s00261-015-0421-0 -
Frontiers in Cell and Developmental... 2021The conduits of life; the animal oviducts and human fallopian tubes are of paramount importance for reproduction in amniotes. They connect the ovary with the uterus and... (Review)
Review
The conduits of life; the animal oviducts and human fallopian tubes are of paramount importance for reproduction in amniotes. They connect the ovary with the uterus and are essential for fertility. They provide the appropriate environment for gamete maintenance, fertilization and preimplantation embryonic development. However, serious pathologies, such as ectopic pregnancy, malignancy and severe infections, occur in the oviducts. They can have drastic effects on fertility, and some are life-threatening. Despite the crucial importance of the oviducts in life, relatively little is known about the molecular drivers underpinning the embryonic development of their precursor structures, the Müllerian ducts, and their successive differentiation and maturation. The Müllerian ducts are simple rudimentary tubes comprised of an epithelial lumen surrounded by a mesenchymal layer. They differentiate into most of the adult female reproductive tract (FRT). The earliest sign of Müllerian duct formation is the thickening of the anterior mesonephric coelomic epithelium to form a placode of two distinct progenitor cells. It is proposed that one subset of progenitor cells undergoes partial epithelial-mesenchymal transition (pEMT), differentiating into immature Müllerian luminal cells, and another subset undergoes complete EMT to become Müllerian mesenchymal cells. These cells invaginate and proliferate forming the Müllerian ducts. Subsequently, pEMT would be reversed to generate differentiated epithelial cells lining the fully formed Müllerian lumen. The anterior Müllerian epithelial cells further specialize into the oviduct epithelial subtypes. This review highlights the key established molecular and genetic determinants of the processes involved in Müllerian duct development and the differentiation of its upper segment into oviducts. Furthermore, an extensive genome-wide survey of mouse knockout lines displaying Müllerian or oviduct phenotypes was undertaken. In addition to widely established genetic determinants of Müllerian duct development, our search has identified surprising associations between loss-of-function of several genes and high-penetrance abnormalities in the Müllerian duct and/or oviducts. Remarkably, these associations have not been investigated in any detail. Finally, we discuss future directions for research on Müllerian duct development and oviducts.
PubMed: 33763415
DOI: 10.3389/fcell.2021.605301 -
The American Journal of Surgical... Apr 2021The current World Health Organization (WHO) classification of adenocarcinoma of the urinary tract including the urethra includes uncommon Müllerian-derived carcinomas...
The current World Health Organization (WHO) classification of adenocarcinoma of the urinary tract including the urethra includes uncommon Müllerian-derived carcinomas such as clear cell and endometrioid adenocarcinomas. The concept of primary mesonephric (Wolffian-derived) adenocarcinoma (MA) in the urethra (and urinary tract in general) is currently regarded as controversial as the term "mesonephric" had been also inaccurately applied in the past to label Müllerian-derived carcinomas, particularly clear cell adenocarcinoma. Further, pathologically well-documented or bona fide urethral MAs have not yet to be reported. Herein, we describe 2 examples of MA in elderly females that primarily presented in the urethra and manifested clinically with obstructive lower urinary tract symptoms. Both tumors exhibited histology similar to those in MAs of the female genital tract including the distinctive tubular proliferations with luminal eosinophilic materials. The first case, in addition, showed a variety of patterns including ductal (glandular), solid, fused/sieve-like tubules, dilated tubules, and spindled cells. The second case also showed a transition to the more irregular and poorly formed tubular proliferation of cells with greater nuclear atypia and with a desmoplastic response. Both tumors showed positivity for PAX8, GATA3, and luminal CD10, and 1 tumor analyzed harbored KRAS and ARID1A mutations. One patient received neoadjuvant chemotherapy and underwent resection but had local tumor recurrence and metastasis to the lungs and lumbar spine 12 months after presentation. In conclusion, MA, similar to those occurring in the female genital tract and distinct from the recognized Müllerian-derived carcinomas, may present primarily as urethral tumors. MA in the urethra probably shares a common pathogenesis with vaginal MA as both may originate from the same caudal loci of mesonephric remnants along the closely apposed anterior vaginal and posterior urethral walls. MA should be considered in future classifications for urethral tumors and we recommend that the confusing term "mesonephroid adenocarcinoma" should no longer be used.
Topics: Adenocarcinoma; Aged; Biomarkers, Tumor; Chemotherapy, Adjuvant; Female; Humans; Neoadjuvant Therapy; Treatment Outcome; Urethral Neoplasms; Urologic Surgical Procedures; Wolffian Ducts
PubMed: 33284194
DOI: 10.1097/PAS.0000000000001635 -
Der Pathologe Sep 2018Ectopias of female genital tissues are a common event in routine pathology. Mostly they derive from paramesonephric tissues displaced during embryonal development or... (Review)
Review
Ectopias of female genital tissues are a common event in routine pathology. Mostly they derive from paramesonephric tissues displaced during embryonal development or later. However, gonadal-, mesonephric-, or mesothelial-derived tissues may also appear in unusual localizations in and outside the female genital tract. They may be the source of benign and malignant tumors or tumor-like lesions. This review aims to provide an overview of possible tissue ectopias and to improve the developmental understanding of tumorous diseases of the female genital tract. Ectopias of primarily extragenital tissues in the female genital tract are also reviewed.
Topics: Choristoma; Female; Genitalia, Female; Humans; Urogenital System
PubMed: 30155695
DOI: 10.1007/s00292-018-0477-z -
Clinical Anatomy (New York, N.Y.) Sep 2018Variations of testicular vessels are more common than supposed. The testicular artery varies because of abnormal regression of the lateral mesonephric arteries in the... (Meta-Analysis)
Meta-Analysis Review
Variations of testicular vessels are more common than supposed. The testicular artery varies because of abnormal regression of the lateral mesonephric arteries in the fetus, whereas variations in the testicular vein are due to abnormalities in the involution of the intersubcardinal anastomosis. Such variations are usually found incidentally during surgical procedures around the renal pedicle and they often lead to complications. Several authors have attempted to classify them. However, these attempts have not been comprehensive. Therefore, the aim of this study is to provide a simple yet comprehensive classification of variations of the testicular vessels. The PubMed database was searched using keywords pertaining to the testicular vessels. The results were subjected to the Anatomical Quality Assessment (AQUA) tool analysis and were screened for appropriateness for inclusion in this study. The screening procedure yielded 31 original articles, 83 case reports, and 1 review article. Both testicular arterial and venous variations were more common on the left side (20.73% and 24.61%) than the right (12.69% and 18.4%, respectively). We classified the testicular arteries on the basis of their number (N), site of origin (O), and course (C). Similarly, the testicular veins were classified on the basis of their number (N) and site of drainage (D). The proposed classification facilitates identification, understanding, and reporting of variations of the testicular vessels by radiologists. It will also help surgeons to enhance the quality of their treatment. Clin. Anat. 31:854-869, 2018. © 2018 Wiley Periodicals, Inc.
Topics: Aorta, Abdominal; Arteries; General Surgery; Humans; Male; Testis; Veins
PubMed: 29737575
DOI: 10.1002/ca.23204