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Medicine Sep 2021Mesonephric adenocarcinoma (MNAC) is a very rare tumor that originates from mesonephric duct remnants of the female genital tract. Only a few cases were reported in the...
Mesonephric adenocarcinoma (MNAC) is a very rare tumor that originates from mesonephric duct remnants of the female genital tract. Only a few cases were reported in the literature, and most of them occurred in the cervix, extremely rare in the uterine body and ovary. MNAC was rarely reported to arise in the uterine corpus, but never was reported in the ovary. Mesonephric-like adenocarcinomas are recently suggested to describe these neoplasms arising from the uterine corpus and ovary. Due to the rareness of the disease, little is known regarding clinical characteristics, pathological diagnosis, prognosis, and optimal management strategy of MNAC in the female reproductive system. We report a series of MNACs arising from the vagina, cervix, uterine corpus, ovary, and fallopian tube, to summarize the clinical characteristics, pathological diagnosis, treatment, and prognosis.We retrospectively analyzed all MNACs in the female genital tract derived from our institute from January 2010 till January 2020. Patients' clinical details and follow-up were obtained from hospital records and scans were obtained from picture archiving and communication system.A total of 11 patients were included. The median age of onset of symptoms was 52 years. All patients underwent total hysterectomy and bilateral salpingo-oophorectomy, and lymph node dissections were performed in 7/11 (63.6%) patients. Two/eleven (18.2%) received neoadjuvant chemotherapy before surgery and 7/11 (63.6%) received adjuvant chemotherapy after primary surgery. Of the 11 patients, only 1 patient received adjuvant radiation therapy. One patient died at the end point of this study, 9 patients (81.8%) survived and 1 patient was lost to follow-up. The mean follow-up duration was 33.5 months.Although there is no consensus for the optimal treatment of this rare disease, radical surgery is considered to be the initial choice for localized lesion. Given the high malignancy, the majority of MNAC or mesonephric-like adenocarcinoma patients who underwent adjuvant chemotherapy received 4 to 8 cycles of carboplatin/paclitaxel as a first-line treatment after primary surgery with a median progression-free survival of 12 months. Treatment for recurrent disease in these patients included gemcitabine, carboplatin, and paclitaxel. Radiation was very limited in the treatment of the disease.
Topics: Adenocarcinoma; Adult; Aged; China; Female; Genital Neoplasms, Female; Genitalia, Female; Humans; Mesonephroma; Middle Aged; Retrospective Studies
PubMed: 34477176
DOI: 10.1097/MD.0000000000027174 -
International Urogynecology Journal Jun 2015Cystoscopy is frequently performed by gynecologists to ensure ureteral patency and to prevent bladder injury when performing concomitant gynecological procedures....
INTRODUCTION AND HYPOTHESIS
Cystoscopy is frequently performed by gynecologists to ensure ureteral patency and to prevent bladder injury when performing concomitant gynecological procedures. Generally, there are no additional findings on cystoscopy; however, when abnormalities arise, they may require either observation or intervention. Our aim was to create a visual library of benign, malignant, and foreign-body pathological conditions incidentally encountered on cystoscopy.
METHOD
Cystoscopic findings were videotaped at the time of routine surgical care. Regarding Institutional Review Board approval, individual consent was waived as the videos were de-identified and collected for educational purposes.
RESULTS
Benign pathological conditions: squamous metaplasia, duplicated ureteral orifice, ureterocele, Hutch diverticulum, bladder trabeculation, urachal cyst, interstitial cystitis with and without Hunner's lesion, endometriosis in the bladder, port-wine stain due to Klippel-Trénaunay-Weber syndrome, nephrogenic (mesonephric) metaplasia, and cystitis glandularis (intestinal metaplasia). Malignant pathological conditions: papillary urothelial neoplasm of low malignant potential (PUNLMP), carcinoma in situ (CIS), high-grade urothelial carcinoma, and urachal cancer. Foreign-body pathological conditions: edema from ureteral stents and stone-encrusted mesh.
CONCLUSION
This video is intended to educate the audience on some incidental bladder findings seen on female cystoscopy. Many pathological conditions can be biopsied or treated immediately during the procedure; hence, early urology consultation is encouraged for most abnormalities.
Topics: Cystitis, Interstitial; Cystoscopy; Female; Foreign Bodies; Gynecologic Surgical Procedures; Humans; Incidental Findings; Intraoperative Complications; Urethra; Urinary Bladder; Urinary Bladder Diseases; Urinary Bladder Neoplasms
PubMed: 25619539
DOI: 10.1007/s00192-014-2614-4 -
Radiology Case Reports Jan 2023Zinner syndrome is a rare congenital malformation of the mesonephric duct comprising of seminal vesicle cyst, ipsilateral renal agenesis, and ejaculatory duct...
Zinner syndrome is a rare congenital malformation of the mesonephric duct comprising of seminal vesicle cyst, ipsilateral renal agenesis, and ejaculatory duct obstruction. Clinical presentation varies with perineal pain, painful ejaculation, hematospermia and infertility common presenting complaints. Here, we present a case of Zinner syndrome in a 35-year-old male with a rare clinical presentation of only abdominal discomfort. The purpose of this case report is to highlight the challenging clinical presentation of Zinner syndrome and the use of imaging modalities in diagnosing the condition.
PubMed: 36353249
DOI: 10.1016/j.radcr.2022.10.006 -
The Journal of Obstetrics and... Dec 2021Mesonephric-like adenocarcinoma (MLA) is a rare tumor that occurs in the uterine endometrium and ovary. It morphologically and immunohistochemically resembles cervical... (Review)
Review
Mesonephric-like adenocarcinoma (MLA) is a rare tumor that occurs in the uterine endometrium and ovary. It morphologically and immunohistochemically resembles cervical mesonephric adenocarcinoma (MA). Here, we present a case of MLA of the ovary along with a literature review. An asymptomatic 84-year-old woman presented with a pelvic mass, detected by computerized tomography. Magnetic resonance imaging demonstrated a polycystic mass with a solid component in the left adnexal region. The solid component showed low signal intensity on T2-weighted imaging and high signal intensity on diffusion-weighted imaging. We strongly suspected an ovarian malignant tumor; therefore, surgical resection of the uterus and adnexa was performed. Macroscopically, the tumor was predominantly solid with yellowish-tan cut surface. Microscopically, it showed a tubular pattern with intraluminal colloid-like material resembling MA. The tumor cells were negative for estrogen receptor, calretinin, and CD10 and positive for PAX8 and TTF-1. These findings are consistent with those of MLA.
Topics: Adenocarcinoma; Aged; Aged, 80 and over; Endometrium; Female; Humans; Ovarian Neoplasms; Uterine Cervical Neoplasms
PubMed: 34580958
DOI: 10.1111/jog.15035 -
International Journal of Environmental... Nov 2022Mesonephric-like adenocarcinomas (MLA) are rare neoplasms that arise in the uterine body and ovary and have been added to the World Health Organisation's recent 2020...
Mesonephric-like adenocarcinomas (MLA) are rare neoplasms that arise in the uterine body and ovary and have been added to the World Health Organisation's recent 2020 classification of female genital cancers. The pathogenesis of MLA is unknown and it remains debated whether they represent mesonephric carcinomas (Wolffian) arising in the endometrium/ovary or endometrioid carcinomas (Müllerian) closely mimicking mesonephric carcinomas. Here we report the case of a 57-year-old woman with an initial misdiagnosis of endometrioid adenocarcinoma on diagnostic biopsy. The patient came to our clinical evaluation for the appearance of menometrorrhagia complicated by anemia for several months. Therefore, she underwent pelvic echo-flowmetry, with indication for diagnostic hysteroscopy with endometrial biopsy, which yielded a positive result for endometrioid endometrial adenocarcinoma. Following staging CT scan and targeted examinations on pulmonary findings, the patient underwent surgery with surprise of definitive diagnosis deponent for endometrial MLA. Our intention is to establish a brief review of the scientific evidence in the literature and the tools available for a correct histological diagnosis, in the light of the scant anatomopathological evidence. Our question gives rise to the motive for the publication: is immunohistochemistry the right way to resolve the diagnostic error at histology, which is usually the only source of diagnostic certainty? This case is intended to alert of diagnostic error that risked having the patient treated as a neoplasm with a favorable prognosis and low degree of aggressiveness instead of for a very aggressive and poor prognosis tumor such as MLA.
Topics: Humans; Female; Middle Aged; Adenocarcinoma; Carcinoma, Endometrioid; Immunohistochemistry; Endometrium; Biomarkers, Tumor
PubMed: 36361332
DOI: 10.3390/ijerph192114451 -
Biochimica Et Biophysica Acta. Gene... 2021The homeoboxB9 (HOXB9) gene is necessary for specification of the anterior-posterior body axis during embryonic development and expressed in various types of cancer....
The homeoboxB9 (HOXB9) gene is necessary for specification of the anterior-posterior body axis during embryonic development and expressed in various types of cancer. Here we show that the Wilms tumor transcription factor WT1 regulates the HOXB9 gene in a bidirectional manner. Silencing of WT1 activates HOXB9 in Wt1 expressing renal cell adenocarcinoma-derived 786-0 cells, mesonephric M15 cells and ex vivo cultured murine embryonic kidneys. In contrast, HOXB9 expression in U2OS osteosarcoma and human embryonic kidney (HEK) 293 cells, which lack endogenous WT1, is enhanced by overexpression of WT1. Consistently, Hoxb9 promoter activity is stimulated by WT1 in transiently transfected U2OS and HEK293 cells, but inhibited in M15 cells with CRISPR/Cas9-mediated Wt1 deletion. Electrophoretic mobility shift assay and chromatin immunoprecipitation demonstrate binding of WT1 to the HOXB9 promoter in WT1-overexpressing U2OS cells and M15 cells. BASP1, a transcriptional co-repressor of WT1, is associated with the HOXB9 promoter in the chromatin of these cell lines. Co-transfection of U2OS and HEK293 cells with BASP1 plus WT1 prevents the stimulatory effect of WT1 on the HOXB9 promoter. Our findings identify HOXB9 as a novel downstream target gene of WT1. Depending on the endogenous expression of WT1, forced changes in WT1 can either stimulate or repress HOXB9, and the inhibitory effect of WT1 on transcription of HOXB9 involves BASP1. Consistent with inhibition of Hoxb9 expression by WT1, both transcripts are distributed in an almost non-overlapping pattern in embryonic mouse kidneys. Regulation of HOXB9 expression by WT1 might become relevant during kidney development and cancer progression.
Topics: Animals; Cell Line, Tumor; Embryo, Mammalian; Gene Expression Regulation, Developmental; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; HEK293 Cells; Homeodomain Proteins; Humans; Kidney; Kidney Neoplasms; Mice; Organ Culture Techniques; Promoter Regions, Genetic; Transcriptional Activation; WT1 Proteins; Wilms Tumor
PubMed: 34508900
DOI: 10.1016/j.bbagrm.2021.194764 -
Clinical Cancer Research : An Official... Apr 2024We aimed to describe RAS mutations in gynecologic cancers as they relate to clinicopathologic and genomic features, survival, and therapeutic implications.
BACKGROUND
We aimed to describe RAS mutations in gynecologic cancers as they relate to clinicopathologic and genomic features, survival, and therapeutic implications.
METHODS
Gynecologic cancers with available somatic molecular profiling data at our institution between February 2010 and August 2022 were included and grouped by RAS mutation status. Overall survival was estimated by Kaplan-Meier method, and multivariable analysis was performed using Cox proportional-hazards model.
RESULTS
Of 3328 gynecologic cancers, 523 (15.7%) showed any RAS mutation. Patients with RAS-mutated tumors were younger (57 vs 60 years non-mutated), had higher prevalence of endometriosis (27.3% vs 16.9%), and lower grades (grade 1/2, 43.2% vs 8.1%, all p<0.0001). Highest prevalence of KRAS mutation was in mesonephric-like endometrial (100%, n=9/9), mesonephric-like ovarian (83.3%, n=5/6), mucinous ovarian (60.4%), and low-grade serous ovarian (44.4%) cancers. After adjustment for age, cancer type, and grade, RAS mutation was associated with worse overall survival (HR=1.3, p=0.001). Specific mutations were in KRAS (13.5%), NRAS (2.0%), and HRAS (0.51%), most commonly KRAS G12D (28.4%) and G12V (26.1%). Common co-mutations were PIK3CA (30.9%), PTEN(28.8%), ARID1A (28.0%), and TP53 (27.9%), of which 64.7% were actionable. RAS+MAPK pathway-targeted therapies were administered to 62 patients with RAS-mutated cancers. While overall survival was significantly higher with therapy (8.4 years [95%CI 5.5-12.0] vs 5.5 years [95%CI 4.6-6.6], HR=0.67, p=0.031), this effect did not persist in multivariable analysis.
CONCLUSION
RAS mutations in gynecologic cancers have a distinct histopathologic distribution and may impact overall survival. PIK3CA, PTEN, and ARID1A are potentially actionable co-alterations. RAS pathway-targeted therapy should be considered.
PubMed: 38687597
DOI: 10.1158/1078-0432.CCR-23-2819 -
International Journal of Gynecological... Sep 2014PAX8 is a useful immunohistochemical marker for the diagnosis of gynecologic tract malignancies. Several studies have described PAX8 expression in a wide variety of...
PAX8 is a useful immunohistochemical marker for the diagnosis of gynecologic tract malignancies. Several studies have described PAX8 expression in a wide variety of epithelial neoplasms, including ovarian and endometrial carcinomas. The goal of this study was to evaluate PAX8 expression in various types of uterine adenocarcinomas and mesonephric proliferations. Ninety-four cases of uterine adenocarcinomas (52 endometrial endometrioid carcinomas, 21 endometrial serous carcinomas, and 21 human papillomavirus-related endocervical carcinomas), 11 cases of benign mesonephric proliferations (remnants/hyperplasia), and normal endometrial and endocervical glandular epithelium in 58 cases were studied. Immunohistochemical staining was performed with the rabbit polyclonal anti-PAX8 antibody. All adenocarcinoma groups demonstrated a high frequency of PAX8 expression but with relatively high variability in the extent of staining among different subtypes. Both serous carcinomas and endometrioid carcinomas were positive in most cases (95% and 96%, respectively), but serous carcinomas displayed a significantly higher level of expression (immunohistochemical composite scores based on combined extent and intensity of expression) compared with endometrioid carcinomas (mean immunohistochemical composite scores: 8.3 vs. 5.3, respectively; P<0.006). Endocervical adenocarcinomas also had a high frequency of PAX8 expression (86% of cases), but the level of expression was significantly less than that of endometrial adenocarcinomas (mean immunohistochemical composite scores: 2.9 vs. 5.3-8.3, respectively; P<0.004). Among benign glandular epithelia, normal endocervical glands exhibited a significantly lower level of expression compared with either normal endometrial glands or benign mesonephric proliferations (mean immunohistochemical composite scores: 2.6 vs. 6.6-11.2, respectively; P<0.0006). We conclude that PAX8 is expressed in the vast majority of uterine adenocarcinomas, including those of both endometrial and endocervical origin, and that the level of expression based on combined extent and intensity is highest in endometrial serous carcinoma and lowest in endocervical adenocarcinoma. However, the high prevalence of PAX8 expression in the various types of uterine adenocarcinomas precludes use of this marker for distinguishing these tumors. In extrauterine sites, PAX8 can serve as a useful marker for adenocarcinomas of uterine origin (also positive in the majority of ovarian carcinomas), being most sensitive for identification of endometrial adenocarcinomas (both serous and endometrioid). The sensitivity for identifying metastatic endocervical adenocarcinomas is likely less and dependent on the degree to which the significantly lower extent of expression in these tumors is maintained in metastatic sites.
Topics: Adenocarcinoma; Biomarkers, Tumor; Female; Humans; Mesonephros; PAX8 Transcription Factor; Paired Box Transcription Factors; Uterine Neoplasms; Uterus
PubMed: 25083965
DOI: 10.1097/PGP.0b013e3182a54afa -
The American Journal of Surgical... Dec 2018Mesonephric carcinomas of the gynecologic tract are neoplasms that are often under-recognized due to their varied morphologic appearances. Recently, GATA3 and TTF1 have... (Comparative Study)
Comparative Study
Mesonephric carcinomas of the gynecologic tract are neoplasms that are often under-recognized due to their varied morphologic appearances. Recently, GATA3 and TTF1 have been reported to be useful immunohistochemical markers for distinguishing mesonephric carcinomas from its morphologic mimics. Herein, we compared the performance of GATA3 and TTF1 to the traditional markers used for mesonephric carcinomas, CD10 and calretinin. We studied 694 cases: 8 mesonephric carcinomas (7 cervical [includes 3 mesonephric carcinosarcomas], 1 vaginal), 5 mesonephric-like carcinomas (4 uterine corpus, 1 ovarian), 585 endometrial adenocarcinomas, and 96 cervical adenocarcinomas. Mesonephric-like carcinomas were defined as tumors exhibiting the classic morphologic features of mesonephric carcinoma, but occurring outside of the cervix and without convincing mesonephric remnants. GATA3 had the highest sensitivity and specificity (91% and 94%) compared with TTF1 (45% and 99%), CD10 (73% and 83%), and calretinin (36% and 89%). GATA3, however, also stained a substantial number of uterine carcinosarcomas (23/113, 20%). TTF1 was positive in 5/5 (100%) mesonephric-like carcinomas and only 1/8 (13%) mesonephric carcinomas. In 4/6 (67%) TTF1 positive cases, GATA3 exhibited an inverse staining pattern with TTF1. In summary, GATA3 was the best overall marker for mesonephric and mesonephric-like carcinomas, but cannot be used to distinguish mesonephric carcinosarcomas from Müllerian carcinosarcomas. The inverse staining pattern between GATA3 and TTF1, suggests that TTF1 may be useful when GATA3 is negative in small biopsies where mesonephric or mesonephric-like carcinoma is suspected. The greater TTF1 positivity in mesonephric-like carcinomas suggests they may be biologically different from prototypical mesonephric carcinomas.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy; Calbindin 2; Carcinosarcoma; Diagnosis, Differential; Endometrial Neoplasms; Female; GATA3 Transcription Factor; Humans; Immunohistochemistry; Middle Aged; Mullerian Ducts; Neprilysin; Predictive Value of Tests; Thyroid Nuclear Factor 1; Tissue Array Analysis; Uterine Cervical Neoplasms; Vaginal Neoplasms; Wolffian Ducts
PubMed: 30148742
DOI: 10.1097/PAS.0000000000001142 -
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