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Healthcare (Basel, Switzerland) Jul 2022We report the case of a 29-year-old patient with low-grade squamous intraepithelial lesion (L-SIL), negative human papilloma virus (HPV), positive p16/Ki-67...
We report the case of a 29-year-old patient with low-grade squamous intraepithelial lesion (L-SIL), negative human papilloma virus (HPV), positive p16/Ki-67 dual-staining and colposcopy suggestive for severe dysplastic lesion. The patient underwent a loop electrosurgical excision procedure (LEEP), the pathology report revealing mesonephric hyperplasia and adenocarcinoma. The patient also opted for non-standard fertility-sparing treatment. The trachelectomy pathology report described a zone of hyperplasia at the limit of resection towards the uterine isthmus. Two supplementary interpretations of the slides and immunohistochemistry (IHC) were performed. The results supported the diagnosis of mesonephric adenocarcinoma, although with difficulty in differentiating it from mesonephric hyperplasia. Given the discordant pathology results that were inconclusive in establishing a precise diagnosis of the lesion and the state of the limits of resection, the patient was referred to a specialist abroad. Furthermore, the additional interpretation of the slides and IHC were performed, the results suggesting a clear cell carcinoma. The positive p16/Ki-67 dual-staining prior to LEEP, the non-specific IHC and the difficulties in establishing a diagnosis made the case interesting. Given the limitations of cytology and the fact that these variants are independent of HPV infection, dual staining p16/Ki-67 could potentially become useful in the diagnosis of rare adenocarcinoma variants of the cervix, however further documentation is required.
PubMed: 36011067
DOI: 10.3390/healthcare10081410 -
Diagnostics (Basel, Switzerland) Aug 2022Some ovarian mucinous tumors are thought to originate from Brenner tumors and teratomas; however, data are limited on what could be the origin for the remaining tumors....
Some ovarian mucinous tumors are thought to originate from Brenner tumors and teratomas; however, data are limited on what could be the origin for the remaining tumors. We report a new case of ovarian mucinous borderline tumor/atypical proliferative mucinous tumor (MBT/APMT) co-existing with a mesonephric-like proliferation (MLP)/mesonephric-like hyperplasia (MLH). The patient was a 58-year-old woman who presented with a pelvic mass and abdominal pain. Pathology demonstrated an 11 cm MBT/APMT in the left ovary. In addition, the tumor contained one focal area (<1% of total tumor volume) of MLP/hyperplasia adjacent to, or intimately admixed with, mucinous epithelium, with an immunophenotype of diffuse Pax8 and Gata3 expression and negative TTF-1, ER, and PR staining. Pax8 was also weakly positive in the MBT/APMT component. Some mesonephric-like glands partially exhibited gastrointestinal-type mucinous metaplasia/differentiation. A polymerase chain reaction (PCR)-based Sanger sequencing demonstrated that a KRAS G12V mutation was present in both MLP/MLH and MBT/APMT components, providing further evidence to support their clonal relationship. We previously reported a series of similar cases and demonstrated a novel association between MLP, mesonephric-like adenocarcinoma and ovarian mucinous tumor. It is conceivable that benign MLPs may have ability to differentiate to lineage-specific mucinous lesions, and, as such, they may serve as a possible new origin of some ovarian mucinous neoplasms; in particular, Pax8-positive tumors. The current case provides additional evidence to support this theory.
PubMed: 36010251
DOI: 10.3390/diagnostics12081901 -
Gynecologic Oncology Reports Aug 2022Mesonephric-like adenocarcinoma (MLA) is a recently described histologic tumor subtype of the Müllerian tract. MLA can arise in association with Müllerian lesions that...
Somatic mutation analysis of Mesonephric-Like adenocarcinoma and associated putative precursor Lesions: Insight into pathogenesis and potential molecular treatment targets.
AIMS
Mesonephric-like adenocarcinoma (MLA) is a recently described histologic tumor subtype of the Müllerian tract. MLA can arise in association with Müllerian lesions that share common mutations. We report three MLAs and hypothesize that concurrent endometriosis and cystadenofibroma with focal borderline changes might also carry common mutations.
METHODS AND RESULTS
We searched "mesonephric" in our database from 2015 to mid-2021 to retrieve MLA cases. Somatic mutation analysis was performed on tumors and on associated benign proliferative lesions. All MLAs (2 ovarian and 1 uterine) harbored G12D or G12 V mutations. A alteration (H1047Q) was detected in one MLA and in the associated cystadenofibroma with focal borderline changes. The molecular profile of MLA-associated Müllerian lesions (endometriosis and seromucinous cystadenofibroma with focal borderline changes) was similar to concurrent adenocarcinoma. However, tumor contamination could not be excluded in the endometriotic lesion. Patients presented at various stages, with no evidence of post-operative recurrence after 15 months (FIGO IC) and 33 months (FIGO IIA2). One patient (FIGO IIIA1) died of disease 32 months after surgery.
CONCLUSIONS
mutations commonly characterize MLA. At least some MLA-associated Müllerian lesions show MLA-like genetic profiles, suggesting a precursor role. As far as we are aware, we describe for the first time in MLA the potentially actionable H1047Q variant of .
PubMed: 35880223
DOI: 10.1016/j.gore.2022.101049 -
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 -
Annals of Medicine and Surgery (2012) Jul 2022and importance: Zinner syndrome is a rare congenital malformation of the seminal vesicles and the homolateral upper urinary tract. While the majority of patients remain...
INTRODUCTION
and importance: Zinner syndrome is a rare congenital malformation of the seminal vesicles and the homolateral upper urinary tract. While the majority of patients remain asymptomatic and are discovered incidentally, others present symptoms such as micturition or ejaculatory difficulties, or pain. We report a case of Zinner syndrome in a 32-year-old patient with painful ejaculation and discuss the diagnosis and treatment difficulties.
CASE PRESENTATION
A 32-year-old married patient was consulted for pelvic pain associated with painful ejaculation that had been evolving for six months. The clinical examination was normal. Routine laboratory studies of blood and urine were normal. The patient was explored by ultrasound which showed the absence of the right kidney and the presence of a 7 cm right lateral prostatic cystic mass. On MRI, the right kidney was not visualized. Multiple cysts were seen in the right seminal vesicle. Surgical excision of the cyst by laparotomy was performed. The patient had an uneventful recovery and was discharged on the third postoperative day.
CLINICAL DISCUSSION
Congenital malformations of the seminal vesicles are often associated with those of the ipsilateral upper urinary tract, as the ureteral and seminal vesicle buds originate from the mesonephric duct. The syndrome often occurs in the second and third decades of life, especially after the onset of sexual activity. The most common symptoms were dysuria, perineal pain, epididymitis, and painful ejaculation. Diagnostic modalities include ultrasound, MRI, and cystoscopy. In patients with symptoms, the therapeutic management of the cyst includes ultrasound-guided aspiration and laparoscopic or open surgical excision.
CONCLUSION
Seminal vesicle cysts associated with homolateral renal agenesis or hypoplasia are a rare urologic anomaly. The treatment depends on the patient's symptoms. surgical excision of seminal vesicle cysts may be needed for large cysts causing obstructive symptoms.
PubMed: 35860150
DOI: 10.1016/j.amsu.2022.103982 -
Nature Jul 2022Gonadal development is a complex process that involves sex determination followed by divergent maturation into either testes or ovaries. Historically, limited tissue...
Gonadal development is a complex process that involves sex determination followed by divergent maturation into either testes or ovaries. Historically, limited tissue accessibility, a lack of reliable in vitro models and critical differences between humans and mice have hampered our knowledge of human gonadogenesis, despite its importance in gonadal conditions and infertility. Here, we generated a comprehensive map of first- and second-trimester human gonads using a combination of single-cell and spatial transcriptomics, chromatin accessibility assays and fluorescent microscopy. We extracted human-specific regulatory programmes that control the development of germline and somatic cell lineages by profiling equivalent developmental stages in mice. In both species, we define the somatic cell states present at the time of sex specification, including the bipotent early supporting population that, in males, upregulates the testis-determining factor SRY and sPAX8s, a gonadal lineage located at the gonadal-mesonephric interface. In females, we resolve the cellular and molecular events that give rise to the first and second waves of granulosa cells that compartmentalize the developing ovary to modulate germ cell differentiation. In males, we identify human SIGLEC15 and TREM2 fetal testicular macrophages, which signal to somatic cells outside and inside the developing testis cords, respectively. This study provides a comprehensive spatiotemporal map of human and mouse gonadal differentiation, which can guide in vitro gonadogenesis.
Topics: Animals; Cell Lineage; Chromatin; Female; Germ Cells; Granulosa Cells; Humans; Immunoglobulins; Macrophages; Male; Membrane Glycoproteins; Membrane Proteins; Mice; Microscopy, Fluorescence; Ovary; PAX8 Transcription Factor; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Receptors, Immunologic; Sex Differentiation; Single-Cell Analysis; Testis; Transcriptome
PubMed: 35794482
DOI: 10.1038/s41586-022-04918-4 -
Cureus May 2022Cervical cancer is one of the leading causes of cancer mortality in women. However, there have been great advances in its prevention and treatment. Nevertheless, there...
Cervical cancer is one of the leading causes of cancer mortality in women. However, there have been great advances in its prevention and treatment. Nevertheless, there are certain rare forms of this cancer that are under-recognized, underreported, and have a paucity of evidence in terms of treatment. Mesonephric adenocarcinoma (AC) is one such rare disease, with less than 50 cases reported in the literature so far. We report a case of mesonephric AC of the cervix in a 73-year-old female who presented with abnormal vaginal bleeding. Our case is unique in that the patient had recurrence with lung metastases as well as fibroblast growth factor receptor 2 (FGFR2) mutation on genetic sequencing. She responded well to platinum-based chemotherapy and is currently on maintenance therapy with lenvatinib and bevacizumab. We aim to bring this patient's disease course and treatment options chosen to the attention of the medical community as this is only the second reported case of mesonephric AC with FGFR2 mutation, and probably the first one to be treated with tyrosine kinase inhibitors and immunotherapy with a favorable response.
PubMed: 35733501
DOI: 10.7759/cureus.25098 -
Cancer Genomics & Proteomics 2022Uterine mesonephric-like adenocarcinoma (MLA) is a rare malignant tumor of the female genital tract. (Review)
Review
Mesonephric-like Adenocarcinoma of the Uterine Corpus: Comprehensive Analyses of Clinicopathological, Molecular, and Prognostic Characteristics With Retrospective Review of 237 Endometrial Carcinoma Cases.
BACKGROUND/AIM
Uterine mesonephric-like adenocarcinoma (MLA) is a rare malignant tumor of the female genital tract.
PATIENTS AND METHODS
We reviewed 237 endometrial carcinoma cases and investigated the clinicopathological and molecular characteristics of uterine MLA.
RESULTS
We found that 3.0% (7/237) of the endometrial carcinoma cases were MLAs. Compared to endometrial endometrioid carcinoma, MLA showed larger tumor size, deeper myometrial invasion, increasingly advanced-stage disease, and more frequent lymphovascular space invasion. All MLAs exhibited architectural diversity, compactly aggregated small tubules, eosinophilic intraluminal secretions, overlapped and angulated nuclei, scant cytoplasm, and presence of spindle cells. All the MLAs expressed at least two mesonephric markers. All except one MLA harbored activating Kirsten rat sarcoma viral oncogene homolog mutations. All patients with MLA developed postoperative metastases. MLA had the lowest progression-free survival rate among different histological types of endometrial carcinoma.
CONCLUSION
Uterine MLA is a highly aggressive gynecological malignancy, showing unique morphological and molecular features, frequent recurrences and metastases, as well as poor prognosis.
Topics: Adenocarcinoma; Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Humans; Prognosis; Retrospective Studies
PubMed: 35732320
DOI: 10.21873/cgp.20338 -
Cell Reports Jun 2022Leydig cells (LCs) are the major androgen-producing cells in the testis. They arise from steroidogenic progenitors (SPs), whose origins, maintenance, and differentiation...
Leydig cells (LCs) are the major androgen-producing cells in the testis. They arise from steroidogenic progenitors (SPs), whose origins, maintenance, and differentiation dynamics remain largely unknown. Single-cell transcriptomics reveal that the mouse steroidogenic lineage is specified as early as embryonic day 12.5 (E12.5) and has a dual mesonephric and coelomic origin. SPs specifically express the Wnt5a gene and evolve rapidly. At E12.5 and E13.5, they give rise first to an intermediate population of pre-LCs, and finally to fetal LCs. At E16.5, SPs possess the characteristics of the dormant progenitors at the origin of adult LCs and are also transcriptionally closely related to peritubular myoid cells (PMCs). In agreement with our in silico analysis, in vivo lineage tracing indicates that Wnt5a-expressing cells are bona fide progenitors of PMCs as well as fetal and adult LCs, contributing to most of the LCs present in the fetal and adult testis.
Topics: Androgens; Animals; Cell Differentiation; Fetus; Leydig Cells; Male; Mice; Testis
PubMed: 35705036
DOI: 10.1016/j.celrep.2022.110935 -
JNMA; Journal of the Nepal Medical... Jun 2022Obstructed hemivagina and ipsilateral renal anomaly syndrome also known as Herlyn-Werner-Wunderlich syndrome is a rare congenital urogenital anomaly characterised by...
UNLABELLED
Obstructed hemivagina and ipsilateral renal anomaly syndrome also known as Herlyn-Werner-Wunderlich syndrome is a rare congenital urogenital anomaly characterised by Mullerian duct anomalies associated with mesonephric duct anomalies. A 10-year old female presented with acute lower abdominal pain, urinary retention and scanty menstrual flow during her first menstruation. Ultrasonography and contrast computed tomography showed uterine didelphys, hematocolpos, obstructed hemivagina and left renal agenesis. Hemivaginal septal resection and drainage of the hematocolpos were done and operative findings also confirmed the final diagnosis. She was discharged and followed up after 2 weeks and her symptoms had resolved completely. Being a rare entity many clinicians and radiologists are unaware of this disease so this may lead to misdiagnosis whenever these cases present. So strong suspicion and knowledge of this disease entity are essential for a precise diagnosis.
KEYWORDS
case reports; hematocolpos; mullerian ducts; unilateral renal agenesis.
Topics: Abnormalities, Multiple; Child; Congenital Abnormalities; Female; Hematocolpos; Humans; Kidney; Kidney Diseases; Syndrome; Urogenital Abnormalities; Uterus; Vagina
PubMed: 35690980
DOI: 10.31729/jnma.7444