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General and Comparative Endocrinology Jan 2024In non-avian reptiles, the onset of sexual dimorphism of the major structures of the urogenital tract varies temporally relative to gonadal differentiation, more so than...
In non-avian reptiles, the onset of sexual dimorphism of the major structures of the urogenital tract varies temporally relative to gonadal differentiation, more so than in other amniote lineages. In the current study, we used tonic-release implants to investigate the effects of exogenous testosterone (T) on postnatal development of the urogenital tract in juvenile Eastern Fence Lizards (Sceloporus undulatus) to better understand the mechanisms underlying the ontogeny of sexual differentiation in reptiles. We examined gonads, mesonephric kidneys and ducts (male reproductive tract primordia), paramesonephric ducts (oviduct primordia), sexual segments of the kidneys (SSKs), and hemiphalluses to determine which structures were sexually dimorphic independent of T treatment and which structures exhibited sexually dimorphic responses to T. To better understand tissue-level responsiveness to T treatment, we also characterized androgen receptor (AR) expression by immunohistochemistry. At approximately 4 months after hatching in control animals, gonads were well differentiated but quiescent; paramesonephric ducts had fully degenerated in males; mesonephric kidneys, mesonephric ducts, and SSKs remained sexually undifferentiated; and hemiphalluses could not be everted in either sex. Exogenous T caused enlargement, regionalization, and secretory activity of the mesonephric ducts and SSKs in both sexes; enlargement and regionalization of the oviducts in females; and enlargement of male hemipenes. The most responsive tissues exhibited moderate but diffuse staining for AR in control lizards and intense nuclear staining in T-treated lizards, suggestive of autoregulation of AR. The similarity between sexes in the responsiveness of the mesonephric ducts and SSK to T indicates an absence of sexually dimorphic organizational effects in these structures prior to treatment, which was initiated approximately 2 months after hatching. In contrast, the sex-specific responses in oviducts and hemipenes indicate that significant organization and/or differentiation had taken place prior to treatment.
Topics: Female; Animals; Male; Testosterone; Androgens; Receptors, Androgen; Lizards
PubMed: 38036014
DOI: 10.1016/j.ygcen.2023.114418 -
Cancer Reports (Hoboken, N.J.) Jan 2024Mesonephric carcinoma (MC) is a very rare tumor with less than 70 cases had been reported. The rarity of MC has restricted its research, resulting in the lack of...
Identification of characteristics and construction of nomogram to predict the survival probability of mesonephric carcinoma patients: A population-based analysis and a case report.
BACKGROUND
Mesonephric carcinoma (MC) is a very rare tumor with less than 70 cases had been reported. The rarity of MC has restricted its research, resulting in the lack of published guidelines.
OBJECTIVE
To summarize the characteristics and construct an external-validated nomogram to predict the survival of MC patients.
METHOD
Sixty-four qualified patients derived from the Surveillance, Epidemiology, and End Results Plus database, and one patient from the Guangzhou Red Cross Hospital were enrolled. The entire cohort was randomly divided into a development (70%) and a validation cohort (30%). The Kaplan-Meier method and univariate and multivariate Cox regression analyses were applied. Two nomograms were established to predict the 3-to-8-year survival probability of MC patients, which were evaluated by C-index, ROC curves, DCA curves, and calibration plots.
RESULTS
The average survival time of MC patients was 84.22 ± 50.66 months. No significant difference was shown among different groups of race, primary site, tumor differentiated grade, and FIGO stages, while different SEER stages did distinguish patients' survival time, which indicated that the SEER stage standards might be a better staging system in the MC patients than FIGO stage (p = .0835). Additional survival analyses showed that MC patients benefited from shorter waiting times to begin treatment, accepting surgery, regional lymph node examination, radiotherapy, and chemotherapy. Two nomograms were established, both of which got satisfied scores in C-index, ROC curves, DCA curves, and calibration plots.
CONCLUSION
Sufficient regional lymph nodes examined, and applying radiotherapy in high-risk patients are recommended in MC patients. Nomograms established in the present study had good predicting and discriminating capabilities, which would be helpful in patients' individual risk estimation, management, counseling, and follow-up.
Topics: Humans; Nomograms; Databases, Factual; Lymph Nodes; Carcinoma
PubMed: 38030392
DOI: 10.1002/cnr2.1940 -
Biomedicines Nov 2023Microcystic, elongated, and fragmented (MELF) pattern of invasion has seldom been documented in endocervical adenocarcinoma (EAC). The aim of this study was to analyze...
Endocervical Adenocarcinoma Showing Microcystic, Elongated, and Fragmented (MELF) Pattern of Stromal Invasion: A Single-Institutional Analysis of 10 Cases with Comprehensive Clinicopathological Analyses and Ki-67 Immunostaining.
Microcystic, elongated, and fragmented (MELF) pattern of invasion has seldom been documented in endocervical adenocarcinoma (EAC). The aim of this study was to analyze the clinicopathological characteristics of EAC showing MELF pattern. We collected the clinicopathological information of 10 cases of EAC with the MELF pattern and conducted polymer-based immunostaining for Ki-67 (dilution 1:200, clone MIB-1) on these cases. Ki-67 expression was assessed using the average estimation within the hotspot method. All tumors were human papillomavirus-associated EAC with Silva pattern C. All except one tumor exceeded 3 cm in size. Five tumors involved the entire thickness of the cervical stroma, and four tumors extended into the parametrium. Lymphovascular space invasion was identified in six cases. Two patients developed metastatic recurrences in the para-aortic lymph nodes and lungs, respectively. The MELF area showed significantly lower Ki-67 labelling index than that of a conventional tumor area. We confirmed our previous observation that the MELF area displayed lower proliferative activity than the conventional tumor area of EAC. We also demonstrated that patients with EAC showing MELF pattern had several adverse clinicopathological characteristics reflecting aggressive behavior. On the other hand, since the frequencies of post-operative recurrence and disease-related mortality that occurred during the follow-up period were relatively low, further investigations are warranted to clarify the prognostic value of MELF pattern in EAC patients.
PubMed: 38002025
DOI: 10.3390/biomedicines11113026 -
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 -
Asian Journal of Surgery Feb 2024
Topics: Female; Humans; Brenner Tumor; Ovarian Neoplasms; Pelvis; Cysts
PubMed: 37981498
DOI: 10.1016/j.asjsur.2023.11.033 -
FEBS Open Bio Jan 2024Male and female reproductive tracts develop from anterior intermediate mesoderm with similar differentiation processes. The anterior intermediate mesoderm develops into...
Male and female reproductive tracts develop from anterior intermediate mesoderm with similar differentiation processes. The anterior intermediate mesoderm develops into the mesonephros, and the Wolffian duct initiates by epithelialization in the mesonephros. The Müllerian duct invaginates from the coelomic epithelium of the cranial mesonephros for ductal formation and is then regionalized into proximal to caudal female reproductive tracts. In this study, we focused on the epithelialization of the Wolffian duct, initiation of the Müllerian duct, and the regionalization step of the Müllerian ducts as a continuous process. By using intermediate mesodermal cells from mouse pluripotent stem cells, we identified that inhibition of SMAD2/3 signaling might be involved in the differentiation into mesenchymal cells, after which mesonephric cells might be then epithelialized during differentiation of the Wolffian duct. Aggregation of coelomic epithelial cells might be related to initiation of the Müllerian duct. Transcriptomic analysis predicted that consensus sequences of SMAD3/4 were enriched among highly expressed genes in the proximal Müllerian duct. SMAD2/3 signaling to regulate differentiation of the Wolffian duct was continuously activated in the proximal Müllerian duct and was involved in proximal and oviductal regionalization. Therefore, SMAD2/3 signaling may be finely tuned to regulate differentiation from initiation to regionalization steps.
Topics: Mice; Animals; Male; Female; Wolffian Ducts; Mullerian Ducts; Cell Differentiation; Epithelial Cells; Signal Transduction
PubMed: 37953493
DOI: 10.1002/2211-5463.13729 -
Radiology Case Reports Dec 2023Herlyn-Werner-Wunderlich (HWW) syndrome is a rare anomaly of the female urogenital tract characterized by the combination of uterine didelphys, obstructed hemivagina,...
Herlyn-Werner-Wunderlich (HWW) syndrome is a rare anomaly of the female urogenital tract characterized by the combination of uterine didelphys, obstructed hemivagina, and ipsilateral renal anomalies. The exact incidence of the syndrome remains unknown, but it has been reported to be 1 per 2000 to 1 per 28,000 women. It is believed that the triad is a mesonephric duct-induced paramesonephric duct anomaly. In majority of the cases with complete hemivaginal obstruction, the pathology is diagnosed after menarche due to retained menstrual flow. While the common clinical presentations are dysmenorrhea, pelvic pain, intermenstrual bleeding, and pelvic mass, it can also manifest itself with unusual gastrointestinal and urinary tract symptoms. We present a case of HWW syndrome with gastrointestinal symptoms like worsening constipation and abdominal fullness. The unusual clinical presentation of this syndrome makes diagnosis more challenging. To solve such medical puzzles and prevent complications, detailed history-taking and radiological guidance are critical.
PubMed: 37929046
DOI: 10.1016/j.radcr.2023.08.117 -
International Journal of Gynecological... Jul 2024Mesonephric-like adenocarcinoma (MLA) of the ovary is a recently recognized, rare malignancy with aggressive clinical behavior, and is thought to originate from...
Mesonephric-like adenocarcinoma (MLA) of the ovary is a recently recognized, rare malignancy with aggressive clinical behavior, and is thought to originate from Mullerian epithelium with mesonephric transdifferentiation. Emerging evidence suggests that MLA may be classified as an endometriosis-associated neoplasm. The presence of a sarcomatous component within MLA is extremely rare, with common differential diagnoses including the spindle cell component of MLA, carcinosarcoma, as well as mixed Mullerian adenocarcinoma and adenosarcoma. Herein, we report a 58-year-old Chinese woman with bilateral ovarian solid-cystic masses. The left ovarian mass comprised a biphasic tumor with a predominantly high-grade sarcomatous component displaying heterologous mesenchymal differentiation, including liposarcoma, rhabdomyosarcoma and chondrosarcoma-like areas, with a null-type p53 expression. The epithelial component ranged from a bland appearance in areas diagnostic of adenosarcoma to a clearly invasive carcinoma, both with mesonephric-like phenotype, being negative for estrogen receptor, progesterone receptor, and Wilms' tumor 1, variably positive for paired box gene 8, GATA binding protein 3, and thyroid transcription factor 1, with a wild-type p53 expression. The differing p53 expression between the epithelial and sarcomatous elements mitigated against a diagnosis of carcinosarcoma. The right ovarian mass showed endometriosis with focal direct evidence of the development of malignancy within a benign endometriotic cyst, exhibiting the identical immunoprofile of MLA but originating as another malignancy. To the best of our knowledge, this case represents the first reported case of synchronous bilateral ovarian MLAs with separate origins, from high-grade Mullerian adenosarcoma and endometriosis respectively, which broadens the morphologic spectrum of MLA and provides further evidence supporting the Mullerian origin theory.
Topics: Humans; Female; Endometriosis; Middle Aged; Adenosarcoma; Ovarian Neoplasms; Adenocarcinoma; Ovary; Diagnosis, Differential; Mixed Tumor, Mullerian
PubMed: 37922943
DOI: 10.1097/PGP.0000000000000997 -
Indian Journal of Nephrology 2023Mesonephric remnants persist as an appendix of epididymis and paradidymis in efferent ductules in males and skene's glands and Gartner's ducts in females. The...
Mesonephric remnants persist as an appendix of epididymis and paradidymis in efferent ductules in males and skene's glands and Gartner's ducts in females. The mesonephric remnant in the renal parenchyma is extremely rare and only a few cases have been reported in the literature. We present a case with a non-functioning atrophic left kidney. Histopathology showed variable-sized ducts filled with colloid-like material surrounded by collagenized stroma. The ureter showed hypertrophied muscle and a few ducts lined by flattened and a few by columnar epithelium resembling epididymis suggestive of mesonephric remnants. IHC for CD10, PAX 8, and GATA3 was positive. A diagnosis of congenital unilateral hypoplasia of kidneys and ureter with mesonephric remnants was given.
PubMed: 37881746
DOI: 10.4103/ijn.IJN_579_20 -
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