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Diagnostics (Basel, Switzerland) Aug 2021When diagnosing endometrial carcinoma cases, we encountered histological features that strikingly resembled uterine mesonephric-like adenocarcinoma (MLA), but the...
Mesonephric-like Differentiation of Endometrial Endometrioid Carcinoma: Clinicopathological and Molecular Characteristics Distinct from Those of Uterine Mesonephric-like Adenocarcinoma.
When diagnosing endometrial carcinoma cases, we encountered histological features that strikingly resembled uterine mesonephric-like adenocarcinoma (MLA), but the differential diagnosis remained challenging after performing immunostaining. Considering the aggressive biological behavior and poor prognosis of uterine MLA, we believe that the accurate recognition of mesonephric-like differentiation (MLD) is important in the diagnosis of endometrial carcinoma. We aimed to investigate the clinicopathological and molecular characteristics of such cases and compared them with those of uterine MLAs. Five patients diagnosed with endometrioid carcinoma (EC) with MLD were included in this study. Histological evaluation, immunostaining, and targeted sequencing were performed. All five tumors showed typical morphological features of MLA, including densely aggregated tubular structures, deep basophilia under low-power magnification microscopy, eosinophilic intraluminal secretions, and diverse growth patterns. Immunostaining revealed moderate-to-strong nuclear immunoreactivity for estrogen and progesterone receptors in more than 50% tumor cells. The staining intensities and proportions of PAX2 and GATA3 were variable. None of the tumors harbored mutations. Considering the prognostic implications, ancillary tests, including immunostaining and targeted sequencing, should be performed to accurately differentiate between endometrial EC-MLD and uterine MLA.
PubMed: 34441384
DOI: 10.3390/diagnostics11081450 -
International Journal of Gynecological... Jul 2017Immunohistochemistry is widely used to support a pathology diagnosis of cervical adenocarcinoma despite the absence of a systematic review and meta-analysis of the... (Meta-Analysis)
Meta-Analysis Review
Tissue-based Immunohistochemical Biomarker Accuracy in the Diagnosis of Malignant Glandular Lesions of the Uterine Cervix: A Systematic Review of the Literature and Meta-Analysis.
Immunohistochemistry is widely used to support a pathology diagnosis of cervical adenocarcinoma despite the absence of a systematic review and meta-analysis of the published data. This systematic review and meta-analysis was performed to investigate the sensitivity and specificity of immunohistochemistry biomarkers in the tissue-based diagnosis of cervical adenocarcinoma histotypes compared with normal endocervix and benign glandular lesions. The systematic review and meta-analysis used a PICOT framework and QUADAS-2 to evaluate the quality of included studies. The literature search spanned 40 years and ended June 30, 2015. Abstracts of identified records were independently screened by 2 of the authors who then conducted a full-text review of selected articles. Sensitivity and specificity of immunohistochemistry expression in malignant glandular lesions of the cervix classified per WHO 2003 compared with 5 benign comparators (normal/benign endocervix, and benign endocervical, endometrioid, gastric, and mesonephric lesions) were calculated. Of 902 abstracts screened, 154 articles were selected for full review. Twenty-five articles with results for 36 biomarkers were included. The only biomarker with enough studies for a meta-analysis was p16 and the definition of positive p16 staining among them was variable. Nevertheless, any positive p16 expression was sensitive, ranging from 0.94 to 0.98 with narrow confidence intervals (CIs), for adenocarcinoma in situ (AIS) and mucinous adenocarcinomas in comparison with normal/benign endocervix and benign endocervical and endometrioid lesions. Specificity for AIS and mucinous adenocarcinomas was also high with narrow CIs compared with benign endocervical lesions. The specificity was high for AIS, 0.99 (0.24, 1.0), and mucinous adenocarcinoma, 0.95 (0.52, 1.0), compared with normal/benign endocervix but with wider CIs, and low with very wide CIs compared with benign endometrioid lesions: 0.31 (0.00, 0.99) and 0.34 (0.00, 0.99), respectively. Results from single studies showed that p16, p16/Ki67 dual stain, ProExC, CEA, ESA, HIK1083, Claudin 18, and ER loss in perilesional stromal cells were useful with high (≥0.75) sensitivity and specificity estimates in ≥1 malignant versus benign comparisons. None of the biomarkers had highly useful sensitivity and specificity estimates for AIS, mucinous adenocarcinomas, or minimal deviation adenocarcinoma/gastric adenocarcinoma compared with benign gastric or mesonephric lesions or for mesonephric carcinoma compared with normal/benign endocervix, benign endocervical, endometrial, or mesonephric lesions. Any expression of p16 supports a diagnosis of AIS and mucinous adenocarcinomas in comparison with normal/benign endocervix and benign endocervical lesions. The majority of studies did not separate mosaic/focal p16 staining from diffuse staining as a distinct pattern of p16 overexpression and this may have contributed to the poor performance of p16 in distinguishing AIS and mucinous adenocarcinomas from benign endometrioid lesions. Single studies support further investigation of 8 additional biomarkers that have highly useful sensitivity and specificity estimates for ≥1 malignant glandular lesions compared with ≥1 of the 5 benign comparators.
Topics: Adenocarcinoma; Adenocarcinoma in Situ; Adenocarcinoma, Mucinous; Biomarkers, Tumor; Cervix Uteri; Cyclin-Dependent Kinase Inhibitor p16; Female; Humans; Immunohistochemistry; Ki-67 Antigen; Sensitivity and Specificity; Uterine Cervical Neoplasms
PubMed: 27801764
DOI: 10.1097/PGP.0000000000000345 -
Mechanisms of Development Feb 2019This study utilizes morphological and mechanistic endpoints to characterize the onset of bilateral atresia of the vas deferens in a recently derived cystic fibrosis (CF)...
This study utilizes morphological and mechanistic endpoints to characterize the onset of bilateral atresia of the vas deferens in a recently derived cystic fibrosis (CF) rat model. Embryonic reproductive structures, including Wolffian (mesonephric) duct, Mullerian (paramesonephric) duct, mesonephric tubules, and gonad, were shown to mature normally through late embryogenesis, with involution of the vas deferens and/or epididymis typically occurring between birth and postnatal day 4 (P4), although timing and degree of atresia varied. No evidence of mucus obstruction, which is associated with pathology in other CF-affected tissues, was observed at any embryological or postnatal time point. Reduced epididymal coiling was noted post-partum and appeared to coincide with, or predate, loss of more distal vas deferens structure. Remarkably, α smooth muscle actin expression in cells surrounding duct epithelia was markedly diminished in CF animals by P2.5 when compared to wild type counterparts, indicating reduced muscle development. RNA-seq and immunohistochemical analysis of affected tissues showed disruption of developmental signaling by Wnt and related pathways. The findings have relevance to vas deferens loss in humans with CF, where timing of ductular damage is not well characterized and underlying mechanisms are not understood. If vas deferens atresia in humans begins in late gestation and continues through early postnatal life, emerging modulator therapies given perinatally might preserve and enhance integrity of the reproductive tract, which is otherwise absent or deficient in 97% of males with cystic fibrosis.
Topics: Actins; Animals; Cystic Fibrosis; Epididymis; Female; Male; Mucus; Pregnancy; Rats; Vas Deferens
PubMed: 30391480
DOI: 10.1016/j.mod.2018.10.002 -
International Journal of Clinical and... 2014Mesonephric carcinomas are rare in the female genital tract and usually are found in sites where embryonic remnants of wolffian ducts are usually detected, such as the...
Mesonephric carcinomas are rare in the female genital tract and usually are found in sites where embryonic remnants of wolffian ducts are usually detected, such as the uterine cervix, broad ligament, mesosalpinx and exceptionally rarely in the uterine corpus. To date, only four cases of mesonephric carcinomas arising in the uterine corpus have been described in literature. Here we report two cases of mesonephric carcinomas arising in a deep intramural location of the uterine corpus in a 55-year-old woman and a 62-year-old woman in Chinese populations. It is believed to be the first report in China. Both cases presented with a little postmenopausal bleeding. Before hospitalized, uterine curettages were programmed for both cases. The pathology reports were mesonephric adenocarcinoma. A total hysterectomy and bilateral salpingo-oophorectomy were performed. On gross examination, the tumors of both cases were confined to the myometrium. Microscopic examination found both tumors of these two cases were adenocarcinomas mixed with spindle cell component. The most primary histologic patterns of the mesonephric adenocarcinomas were tubular glands that varied in size and were lined by one to several layers of columnar cells. Immunohistochemically, the tumor cells expressed positive with CD10, calretinin, vimentin, cytokeratin (AE1/AE3) and epithelial membrane antigen (EMA); but expressions of ER and PR were completely negative. The peculiar location of mesonephric carcinoma of the uterine corpus may be misinterpreted as other histological type neoplasms. Awareness of this rare phenomenon and immunostaining for markers of mesonephric carcinoma can prevent from making a false diagnosis.
Topics: Adenocarcinoma; Biomarkers, Tumor; Biopsy; China; Diagnosis, Differential; Female; Humans; Hysterectomy; Immunohistochemistry; Middle Aged; Ovariectomy; Predictive Value of Tests; Salpingectomy; Uterine Neoplasms; Wolffian Ducts
PubMed: 25400789
DOI: No ID Found -
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 -
Urology Case Reports Jul 2022Primary mesonephric adenocarcinoma of the bladder is a very rare lesion. Only 9 cases have been reported since 1968, when it was first described. Due to its...
Primary mesonephric adenocarcinoma of the bladder is a very rare lesion. Only 9 cases have been reported since 1968, when it was first described. Due to its morphological diversity and variable immunohistochemical profile, mesonephric adenocarcinoma presents a diagnostic challenge, especially when seen in male patients, due to the rarity this entity in men. Here we present a rare case of a 63-year-old man who was found to have a bladder tumor and diagnosed with mesonephric adenocarcinoma of the bladder.
PubMed: 35520026
DOI: 10.1016/j.eucr.2022.102096 -
Iranian Journal of Pathology 2021Mesonephric adenocarcinoma of the uterine cervix is an extremely rare tumor of the female genital tract which derives from the remnants of embryonic mesonephric ducts...
Mesonephric adenocarcinoma of the uterine cervix is an extremely rare tumor of the female genital tract which derives from the remnants of embryonic mesonephric ducts and its prognosis, diagnosis and treatment is rather challenging. We report a case of a 46-year-old woman with history of abnormal uterine bleeding and an enlarged uterine cervix on physical examination without obvious mass lesion. She was clinically underdiagnosed with cervical myoma and mesonephric hyperplasia. After simple hysterectomy, stage IB2 mesonephric adenocarcinoma was diagnosed. Despite adjuvant chemoradiation, she presented with peritoneal and locoregional recurrence in less than a year. So, in the presence of abnormal bleeding and cervical mass, mesonephric hyperplasia in cervical biopsy specimen should be suspected for adenocarcinoma. Radical hysterectomy and complete staging with or without salpingo-oophorectomy is the mainstay of treatment. Despite all ambiguities, due to the small number of reported cases, the overall prognosis seems to be less favorable than conventional cervical adenocarcinoma.
PubMed: 33936235
DOI: 10.30699/IJP.2020.125459.2375 -
PeerJ 2021The giant anteater belongs to the supraorder Xenarthra which occupies a systematically isolated position among placental mammals. The species is categorized as...
BACKGROUND
The giant anteater belongs to the supraorder Xenarthra which occupies a systematically isolated position among placental mammals. The species is categorized as Vulnerable by the International Union for Conservation of Nature, and understanding its reproductive characteristics is critical for future conservation efforts.
METHODS
Gross and microscopic anatomy of the genital organs of 23 male and 21 female adult and young roadkill giant anteaters in Brazil were studied.
RESULTS
Male giant anteaters presented a short conical penis, intraabdominal testes, and prostate, vesicular and bulbourethral glands. A tubular remnant of the partially fused Müllerian ducts extended from the seminal colliculus through the prostate gland, continued cranially in the genital fold, bifurcated, and attached with one elongation each to the left and right epididymal corpus. The structure presented a total length of up to 10 cm and contained a yellowish liquid in its lumen. Histologically, the caudal section of this structure resembled the female vagina, the middle portion corresponded to the uterus, and the extensions showed characteristics of uterine tubes. In adult female giant anteaters, ovoid ovaries with occasional seminiferous cord-like structures were observed. The animals possessed a simple uterus, which was directly continuous with the vaginal canal. The caudal portion of the vagina had two lumina, separated by a longitudinal septum and opening into two apertures into the vaginal vestibule, cranial to the urethral opening. In the urethral and the lateral vestibular wall, glandular structures with characteristics of male prostate and bulbourethral glands, respectively, were found. The vestibule opened through a vertical vulvar cleft to the exterior. A pair of well-differentiated Wolffian ducts with a central lumen originated ventrally at the vaginal opening into the vestibule and passed in a cranial direction through the ventral vaginal and uterine wall. Each duct extended highly coiled along the ipsilateral uterine tube until the lateral pole of the ovaries where it merged with the rete ovarii.
DISCUSSION
The reproductive morphology of giant anteaters reveals characteristics shared with other Xenarthrans: intraabdominal testes, a simple uterus, and a double caudal vagina. The persistence of well-differentiated genital ducts of the opposite sex in both males and females, however, singles them out among other species. These structures are the results of an aberration during fetal sexual differentiation and possess secretory functions. The possibility of a pathological degeneration of these organs should be considered in reproductive medicine of the species.
CONCLUSION
Knowledge of the unique reproductive characteristics of the giant anteater is essential for future reproductive management of the species. Additionally, further research on the peculiarities of the persisting genital duct structures might help to understand sexual differentiation in placental mammals in general.
PubMed: 34447632
DOI: 10.7717/peerj.11945 -
Journal of Feline Medicine and Surgery Jun 2020A notable, although relatively uncommon, finding during feline ovariohysterectomy is the presence of parovarian nodules, located proximal to the ovary, near or within...
OBJECTIVES
A notable, although relatively uncommon, finding during feline ovariohysterectomy is the presence of parovarian nodules, located proximal to the ovary, near or within the ovarian vascular bundle. They are usually 2-3 mm in diameter, white-to-tan in color and glandular in appearance. The objective of this study was to either decisively reinforce the existing findings reported in the literature, which suggest that these parovarian nodules are incidental adrenocortical nodules that are clinically and surgically insignificant, or capture any samples that were not ectopic adrenal tissue in order to characterize them histologically.
METHODS
Ninety-one formalin-preserved tissue sections containing parovarian nodules were collected during routine feline elective ovariohysterectomy and evaluated histologically.
RESULTS
Definitive histologic information was obtained from 73/91 (80.2%) submitted samples. Fifty-two of 73 (71.2%) samples were determined to contain accessory adrenal gland cortex. Twenty of 73 (27.4%) samples were determined to contain residual mesonephric structures. While accessory adrenocortical nodules were found bilaterally in cats of all ages, mesonephric structures were predominantly right-sided, and only found in one cat over the age of 1 year. Ectopic or accessory ovarian tissue was not found in any of the samples.
CONCLUSIONS AND RELEVANCE
This study adds to the existing body of data which suggest these nodules are incidental structures that do not need to be removed during surgical sterilization. However, further in vivo studies with larger sample sizes and years of follow-up would be required to more definitively prove this theory.
Topics: Adrenal Cortex; Animals; Cats; Female; Hysterectomy; Ovary
PubMed: 31411532
DOI: 10.1177/1098612X19867166 -
Applied Immunohistochemistry &... Mar 2023A subset of endometrial endometrioid carcinomas (EECs) with low-grade histology recur with poor outcomes. Published evidence suggests that poor outcomes may be...
A subset of endometrial endometrioid carcinomas (EECs) with low-grade histology recur with poor outcomes. Published evidence suggests that poor outcomes may be associated with loss of expression of ER-alpha (ER-α) as well as with β-Catenin-1 ( CTNNB1 ) and Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutations. This study reports on institutional experience with the incidence of recurrence in low-grade EEC and their association with CTNNB1 and KRAS mutations as well as estrogen/progesterone receptor (ER/PR) expression. Forty-eight (8.5%) out of 568 cases of low-grade EEC with biopsy-proven recurrence were identified; and were analyzed by immunohistochemistry for ER, PR, p53, MMR protein, and mutation analysis for exon 3 of the CTNNB1 and exon 2 of KRAS in relation to recurrence type, local or distant metastasis/recurrence. Twenty-three patients (4%) developed local, and 25 patients (4.4%) developed distant metastases/recurrence. Decreased expression or loss of ER/PR was found in 17/44 (38.6%) patients with recurrence. Eighty-four percent of patients with low-grade EEC and local recurrence had CTNNB1 mutations. Seventy-three percent of patients with distant metastasis/recurrence had KRAS mutations. The association of these mutations with the type of recurrence was statistically significant for both. Five cases with the morphology of low-grade EEC were reclassified as mesonephric-like carcinoma and were universally characterized by distant metastasis/recurrence, loss of ER/PR expression, large tumor size, absence of CTNNB1 mutations, and the presence of KRAS mutations. In low-grade EEC, CTNNB1 and KRAS mutations are associated with local recurrence and distant metastasis/recurrence, respectively, suggesting that these 2 different progression types may be conditioned by tumor genotype. ER/PR immunohistochemistry may be helpful in identifying poor performers in low-grade EEC. Furthermore, identification of the decreased expression or loss of ER/PR in tumors with low-grade histology should prompt consideration of mesonephric-like carcinoma, which is a more aggressive tumor than the low-grade EEC. KRAS mutations were associated with distant metastasis/recurrence in tumors with and without mesonephric-like phenotype.
Topics: Female; Humans; Carcinoma, Endometrioid; Endometrial Neoplasms; Receptors, Progesterone; Proto-Oncogene Proteins p21(ras); Catenins; Mutation; Estrogens; Biomarkers, Tumor; beta Catenin
PubMed: 36695555
DOI: 10.1097/PAI.0000000000001102