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Journal of Pediatric Hematology/oncology May 2022Primary extrarenal Wilms tumors are rare neoplasms that are presumed to arise from metanephric or mesonephric remnants outside of the kidney. Their pathogenesis is...
Primary extrarenal Wilms tumors are rare neoplasms that are presumed to arise from metanephric or mesonephric remnants outside of the kidney. Their pathogenesis is debated but has not been studied, and there are no reports of genomic descriptions of extrarenal Wilms tumors. We describe a diffusely anaplastic extrarenal Wilms tumor that occurred in the lower abdomen and upper pelvis of a 10-year-old boy. In addition to the clinical, histopathologic, and radiologic features, we describe the cytogenetic changes and exomic profile of the tumor. The tumor showed loss of the tumor suppressor AMER1, loss of chromosome regions 1p, 16q, and 22q, gain of chromosome 8, and loss of function TP53 mutation-findings known to occur in renal Wilms tumors. This is the first description of the exomic profile of a primary extrarenal Wilms tumor. Our data indicate that primary extrarenal Wilms tumors may follow the same pathogenetic pathways that are seen in renal Wilms tumors. Finally, we describe the establishment of first ever tumor models (primary cell line and patient-derived xenograft) from an extrarenal Wilms tumor.
Topics: Child; Female; Humans; Kidney; Kidney Neoplasms; Male; Mutation; Wilms Tumor
PubMed: 35129140
DOI: 10.1097/MPH.0000000000002413 -
Diagnostics (Basel, Switzerland) Jan 2022Mesonephric adenocarcinoma (MA) of the female genital tract is a rare but distinct entity, exhibiting unique morphological, immunophenotypical, and molecular...
Mesonephric adenocarcinoma (MA) of the female genital tract is a rare but distinct entity, exhibiting unique morphological, immunophenotypical, and molecular characteristics. Vaginal MA is hypothesized to arise from the mesonephric remnants located in the lateral vaginal wall. A 52-year-old woman presented with vaginal bleeding. Physical examination revealed a protruding mass in the left vaginal wall. Pelvic magnetic resonance imaging revealed a 2.5-cm mass arising from the left upper vagina and extending posterolaterally to the extravaginal tissue. The punch biopsy was diagnosed as poorly differentiated adenocarcinoma. She received radical surgical resection. Histologically, the tumor displayed various architectural patterns, including compactly aggregated small tubules, solid cellular sheets, endometrioid-like glands and ducts, intraluminal micropapillae, cribriform structure, and small angulated glands accompanied by prominent desmoplastic stroma. The tubules and ducts possessed hyaline-like, densely eosinophilic intraluminal secretions. The tumor extended to the subvaginal soft tissue and had substantial perineural invasion. Immunostaining revealed positivity for the mesonephric markers, including GATA3, TTF1, and PAX2, while showing very focal and weak positivity for estrogen receptor and negativity for progesterone receptor. Additionally, we observed a complete absence of p53 immunoreactivity. Targeted sequencing analysis revealed that the tumor harbored both activating p.G12D mutation and truncating p.E286* mutation. A thorough review of the previous literature revealed that 4.5% (3/67) of vaginal/cervical MAs and 0.9% (1/112) of uterine/ovarian mesonephric-like adenocarcinomas harbor mutations, indicating that this is very uncommon in malignant mesonephric lesions. In summary, we presented a rare case of vaginal MA uniquely harboring pathogenic mutation, resulting in p53 aberration.
PubMed: 35054285
DOI: 10.3390/diagnostics12010119 -
Hypertension (Dallas, Tex. : 1979) Mar 2022The renin-angiotensin system is highly conserved across vertebrates, including zebrafish, which possess orthologous genes coding for renin-angiotensin system proteins,...
BACKGROUND
The renin-angiotensin system is highly conserved across vertebrates, including zebrafish, which possess orthologous genes coding for renin-angiotensin system proteins, and specialized mural cells of the kidney arterioles, capable of synthesising and secreting renin.
METHODS
We generated zebrafish with CRISPR-Cas9-targeted knockout of renin () to investigate renin function in a low blood pressure environment. We used single-cell (10×) RNA sequencing analysis to compare the transcriptome profiles of renin lineage cells from mesonephric kidneys of with zebrafish and with the metanephric kidneys of and mice.
RESULTS
The larvae exhibited delays in larval growth, glomerular fusion and appearance of a swim bladder, but were viable and withstood low salinity during early larval stages. Optogenetic ablation of renin-expressing cells, located at the anterior mesenteric artery of 3-day-old larvae, caused a loss of tone, due to diminished contractility. The mesonephric kidney exhibited vacuolated cells in the proximal tubule, which were also observed in mouse kidney. Fluorescent reporters for renin and smooth muscle actin ()), revealed a dramatic recruitment of renin lineage cells along the renal vasculature of adult fish, suggesting a continued requirement for renin, in the absence of detectable angiotensin metabolites, as seen in the YFP mouse. Both phenotypes were rescued by alleles lacking the potential for glycosylation at exon 2, suggesting that glycosylation is not essential for normal physiological function.
CONCLUSIONS
Phenotypic similarities and transcriptional variations between mouse and zebrafish renin knockouts suggests evolution of renin cell function with terrestrial survival.
Topics: Animals; Animals, Genetically Modified; Blood Pressure; Clustered Regularly Interspaced Short Palindromic Repeats; Kidney; Mice; Mice, Knockout; Renin; Renin-Angiotensin System; Transcriptome; Zebrafish
PubMed: 35000430
DOI: 10.1161/HYPERTENSIONAHA.121.18600 -
Diagnostics (Basel, Switzerland) Nov 2021Mesonephric-like adenocarcinoma (MLA) of the uterine corpus is a rare but distinct malignant tumor of the female genital tract, demonstrating a characteristic morphology...
Mesonephric-like adenocarcinoma (MLA) of the uterine corpus is a rare but distinct malignant tumor of the female genital tract, demonstrating a characteristic morphology and unique immunohistochemical profiles and molecular alterations. We conducted immunohistochemical staining (IHC) to make precise differential diagnoses of uterine MLAs from common histological subtypes of endometrial carcinomas. We collected 25 uterine MLAs and performed IHC for GATA3, TTF1, CD10, ER, PR, p16, p53, and HER2. Seventeen cases (68.0%) showed at least moderate nuclear GATA3 immunoreactivity in ≥25% of tumor cells. Most cases expressed TTF1 (17/21, 81.0%) and CD10 (luminal; 17/21, 81.0%). Heterogeneous TTF1 expression was noted in 12 cases. An inverse pattern of GATA3 and TTF1 staining was observed in eight cases (32.0%). Three cases (12.0%) showed moderate-to-strong ER expression in ≥25% of tumor cells, and two cases (8.0%) showed moderate-to-strong PR expression in ≥5% of tumor cells. These hormone receptor-positive MLAs varied in intensity and proportion of GATA3 staining. None of the 25 cases exhibited either diffuse and strong p16 expression or aberrant p53 expression. Five cases (20.0%) showed equivocal HER2 immunoreactivity (score 2+), but FISH confirmed that none of them exhibited gene amplification. In summary, a small subset of uterine MLAs displayed atypical IHC results: focal but strong expression of ER or PR, the complete absence of GATA3 immunoreactivity, the concurrent expression of mesonephric and hormone receptors, and the inverse pattern of GATA3 and TTF1 staining. These unusual immunophenotypes may complicate the differential diagnosis of MLA. Moreover, pathologists should be encouraged to interpret the IHC results cautiously.
PubMed: 34829389
DOI: 10.3390/diagnostics11112042 -
The Indian Journal of Radiology &... Jul 2021Zinner syndrome is a rare congenital anomaly of the urogenital system resulting from an in utero insult during the first trimester. This entity comprises a triad of...
A Triad of Unilateral Renal Dysgenesis with Ipsilateral Seminal Vesical and Ejaculatory Duct Obstruction: An Uncommon Urogenital Congenital Anomaly, Zinner Syndrome-A Case Report.
Zinner syndrome is a rare congenital anomaly of the urogenital system resulting from an in utero insult during the first trimester. This entity comprises a triad of unilateral renal agenesis/dysgenesis with ipsilateral seminal vesical and ejaculatory duct obstruction. This combination of urinary and genital abnormalities occurs because of the closely related embryological origin of these structures from the distal mesonephric (Wolffian) duct. Nearly 200 cases of seminal vesical cysts with ipsilateral renal agenesis have been reported in the literature. The affected person generally presents in early adulthood when the reproductive activity commences. In this report, we present a case of a 22-year-old male with complaints of painful ejaculation.
PubMed: 34790319
DOI: 10.1055/s-0041-1735503 -
In Vivo (Athens, Greece) 2021We describe a rare case of ovarian mesonephric-like adenocarcinoma (MLA) involving the fimbria and mimicking serous tubal intraepithelial carcinoma (STIC).
Ovarian Mesonephric-like Adenocarcinoma With Multifocal Microscopic Involvement of the Fimbrial Surface: Potential for Misdiagnosis of Tubal Intraepithelial Metastasis as Serous Tubal Intraepithelial Carcinoma Associated With Ovarian High-grade Serous Carcinoma.
BACKGROUND/AIM
We describe a rare case of ovarian mesonephric-like adenocarcinoma (MLA) involving the fimbria and mimicking serous tubal intraepithelial carcinoma (STIC).
CASE REPORT
A 47-year-old woman presented with a 4.4-cm left ovarian mass. Histologically, the ovarian tumor showed papillary and solid architecture, severe nuclear pleomorphism, and increased mitotic activity. Some microscopic foci where the tumor cells spread horizontally along the fimbrial surface epithelium were noted, compatible with STIC. We initially considered the ovarian tumor to be high-grade serous carcinoma accompanied by a fimbrial STIC. However, immunostaining revealed nuclear immunoreactivity for paired box 2 and GATA-binding protein 3, but lacked expression of Wilms tumor 1. A thorough slide review and additional immunostaining revealed architectural diversity, densely eosinophilic intraluminal secretions, and lack of hormone receptor expression, supporting the diagnosis of MLA.
CONCLUSION
Microscopic intraepithelial metastases of the MLA to the fimbria mimic STIC. We recommend ancillary tests, such as immunostaining, in patients with ovarian tumors whenever possible, particularly for those with differential diagnosis of MLA and high-grade serous carcinoma.
Topics: Adenocarcinoma; Carcinoma in Situ; Cystadenocarcinoma, Serous; Diagnostic Errors; Fallopian Tube Neoplasms; Female; Humans; Middle Aged; Ovarian Neoplasms
PubMed: 34697203
DOI: 10.21873/invivo.12667 -
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 -
Urology Case Reports Jan 2022Intratesticular abscess is a rare finding associated with advanced or untreated epididymo-orchitis, often in immunocompromised patients. Implicated pathogens can be...
Intratesticular abscess is a rare finding associated with advanced or untreated epididymo-orchitis, often in immunocompromised patients. Implicated pathogens can be spread hematogenously, by urine reflux in dysfunctional voiders, through aberrant mesonephric duct anatomy, or via a patent processus vaginalis in the setting of an intra-abdominal infection. A testicular-sparing surgical approach is often used in prepubertal populations and is associated with positive outcomes. We present the case of a 6-year-old male with a polymicrobial intratesticular abscess that was successfully managed with antibiotics, operative incision and drainage of abscess cavity, and primary wound closure with drain placement.
PubMed: 34660205
DOI: 10.1016/j.eucr.2021.101873 -
Archives of Pathology & Laboratory... Jun 2022Gender-affirming surgery is part of a multidisciplinary approach in gender transitioning. Deeper histologic examination may strengthen care for transmasculine...
CONTEXT.—
Gender-affirming surgery is part of a multidisciplinary approach in gender transitioning. Deeper histologic examination may strengthen care for transmasculine individuals and increase the understanding of the influence of hormonal therapy in specific organs.
OBJECTIVE.—
To evaluate and catalogue histologic findings of tissue obtained from gender-affirming gynecologic surgery and cervical cytology specimens.
DESIGN.—
This is an institutional review board-approved retrospective study that included transmasculine individuals who underwent gender-affirming gynecologic surgery from January 2015 to June 2020. All surgical gynecologic pathology and cervical cytology slides were reviewed by 2 pathologists.
RESULTS.—
Fifty-five patients were included, which represented 40 uteri, 35 bilateral ovaries, 15 vaginectomy specimens, and 24 cervical cytology results. The median age was 27 years (range, 18-56), and 94% (50 of 53) of patients were receiving testosterone for at least 1 year. Seventy-five percent (30 of 40) of endometria were inactive, while 25% (10 of 40) showed evidence of cycling. Transitional cell metaplasia was the most common finding in the cervix (17 of 40) and vagina (15 of 15), reflecting a high percentage (4 of 24) of unsatisfactory or ASC-US (atypical squamous cells of undetermined significance) cervical cytologies. Prostatic-type glands were identified in 20% (8 of 40) of cervices and 67% (10 of 15) of vaginectomy specimens. Multiple bilateral cystic follicles and evidence of follicular maturation were present in 57% (20 of 35) of cases. Four cases showed paratubal epididymis-like mesonephric remnant hypertrophy.
CONCLUSIONS.—
A comprehensive evaluation of tissue from gender-affirming surgery increases knowledge of the changes following androgen therapy in transmasculine individuals and may contribute to optimal patient care by raising awareness of normal histologic variations in this population.
Topics: Adult; Cervix Uteri; Female; Humans; Male; Metaplasia; Prostate; Retrospective Studies; Uterus
PubMed: 34591101
DOI: 10.5858/arpa.2021-0199-OA -
Medicine and Pharmacy Reports Aug 2021We present the case of a 51-year-old male with Zinner syndrome, which is a rare disease, resulting from an abnormal evolution of the mesonephric (Wolffian) duct. It...
We present the case of a 51-year-old male with Zinner syndrome, which is a rare disease, resulting from an abnormal evolution of the mesonephric (Wolffian) duct. It consists in cystic dilations of one seminal vesicle and/or ejaculatory duct and ipsilateral renal agenesis. It leads to symptoms related to urination, ejaculation, even infertility, and to low-abdomen and perineal pain. The diagnosis is set by ultrasonography, CT scan and, mainly, MRI. Usually it is treated conservatively, but certain cases require surgery, nowadays minimally invasive.
PubMed: 34527910
DOI: 10.15386/mpr-2229