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The American Journal of Surgical... Apr 2021Mesonephric adenocarcinoma (MA) and mesonephric-like adenocarcinoma (MLA) are uncommon neoplasms of the gynecologic tract that have until recently been poorly...
Mesonephric adenocarcinoma (MA) and mesonephric-like adenocarcinoma (MLA) are uncommon neoplasms of the gynecologic tract that have until recently been poorly understood. Although their morphologic, immunohistochemical, and molecular profiles have been recently defined, little is known about their clinical behavior. Small studies have demonstrated inconsistent findings and no large studies have examined the clinical behavior of these adenocarcinomas. In this multi-institutional study, representing the largest and most stringently defined cohort of cases to date, we examined the clinicopathologic features of 99 MAs and MLAs (30 MAs of the uterine cervix, 44 MLAs of the endometrium, and 25 MLAs of the ovary). Only tumors with characteristic mesonephric morphology and either immunohistochemical or molecular support were included. Our results demonstrate that the majority of mesonephric neoplasms presented at an advanced stage (II to IV) (15/25 [60%] MA of the cervix, 25/43 [58%] MLA of the endometrium, and 7/18 [39%] MLA of the ovary). The majority (46/89 [52%] overall, 12/24 [50%] MA of the cervix, 24/41 [59%] MLA of the endometrium, and 10/24 [42%] MLA of the ovary) developed recurrences, most commonly distant (9/12 [75%] MA of the cervix, 22/24 [92%] MLA of the endometrium, and 5/9 [56%] MLA of the ovary). The 5-year disease-specific survival was 74% (n=26) for MA of cervix, 72% (n=43) for MLA of endometrium, and 71% (n=23) for MLA of ovary. Our results confirm that mesonephric neoplasms are a clinically aggressive group of gynecologic carcinomas that typically present at an advanced stage, with a predilection for pulmonary recurrence.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Databases, Factual; Endometrial Neoplasms; Female; Humans; Lung Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; North America; Northern Ireland; Ovarian Neoplasms; Progression-Free Survival; Registries; Time Factors; Uterine Cervical Neoplasms; Wolffian Ducts
PubMed: 33165093
DOI: 10.1097/PAS.0000000000001612 -
Virchows Archiv : An International... Nov 2019Endocervical adenocarcinomas (ECAs) are currently classified according to the 2014 World Health Organization (WHO) system, which is predominantly based on descriptive... (Review)
Review
Endocervical adenocarcinomas (ECAs) are currently classified according to the 2014 World Health Organization (WHO) system, which is predominantly based on descriptive morphologic characteristics, considers factors bearing minimal etiological, clinical, or therapeutic relevance, and lacks sufficient reproducibility. The 2017 International Endocervical Adenocarcinoma Criteria and Classification (IECC) system was developed by a group of international collaborators to address these limitations. The IECC system separates ECAs into two major groups-those that are human papillomavirus-associated (HPVA) and those that are non-HPV-associated (NHPVA)-based on morphology (linked to etiology) alone, precluding the need for an expensive panel of immunohistochemical markers for most cases. The major types of HPVA ECA include the usual (with villoglandular and micropapillary architectural variants) and mucinous types (not otherwise specified [NOS], intestinal, signet-ring, and invasive stratified mucin-producing carcinoma). Invasive adenocarcinoma NOS is morphologically uninformative, yet considered part of this group when HPV positive. NHPVA ECAs include gastric, clear cell, endometrioid, and mesonephric types. The IECC system is supported by demographic and clinical features (HPVA ECAs develop in younger patients, are smaller, and are diagnosed at an earlier stage), p16/HPV status (almost all HPVA ECAs are p16 and/or HPV positive), prognostic parameters (NHPVA ECAs more often have lymphovascular invasion, lymph node metastases, and are Silva pattern C), and survival data (NHPVA ECAs are associated with worse survival). A move from the morphology-based WHO system to the IECC system will likely provide clinicians with an improved means to diagnose and classify ECAs, and ultimately, to better personalize treatment for these patients.
Topics: Adenocarcinoma; Cervix Uteri; Female; Humans; Lymphatic Metastasis; Papillomaviridae; Papillomavirus Infections; Prognosis; Reproducibility of Results; Uterine Cervical Neoplasms
PubMed: 31209635
DOI: 10.1007/s00428-019-02601-0 -
The Journal of Pathology Apr 2021Endometrial carcinoma (EC) is classified into a wide range of morphological variants; this list has expanded over the past decade with the inclusion of mesonephric-like... (Review)
Review
Endometrial carcinoma (EC) is classified into a wide range of morphological variants; this list has expanded over the past decade with the inclusion of mesonephric-like and dedifferentiated carcinoma as EC variants in the fifth edition of the WHO Classification of Female Genital Tumours, and recognition that carcinosarcoma is a biphasic carcinoma rather than a sarcoma. Each EC variant has distinct molecular abnormalities, including TCGA-based molecular subtypes, allowing further subclassification and adding complexity. In contrast to this rapid progress in understanding EC, there are only two recognized EC precursor lesions: endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (EAH/EIN) and serous intraepithelial carcinoma, a situation that has not changed for many years. Diagnosis of EC precursors is a cornerstone of surgical pathology practice, with early diagnosis contributing to the relatively favorable prognosis of EC. In this review we relate the precursor lesions to each of the EC morphological variants and molecular subtypes, discuss how successful early diagnosis is for each variant/molecular subtype and how it might be improved, and identify knowledge gaps where there is insufficient understanding of EC histogenesis. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Topics: Early Diagnosis; Endometrial Neoplasms; Female; Humans; Precancerous Conditions
PubMed: 33368243
DOI: 10.1002/path.5608 -
Journal of Clinical Medicine Feb 2021Mesonephric-like adenocarcinoma is a recently described rare neoplasm occurring in the uterine corpus and ovary. This under-recognized subtype of carcinoma can be very... (Review)
Review
Mesonephric-like adenocarcinoma is a recently described rare neoplasm occurring in the uterine corpus and ovary. This under-recognized subtype of carcinoma can be very challenging to diagnose. In mesonephric adenocarcinoma a variety of growth patterns can be present within the same tumor, as a result of which they can be misinterpreted and diagnosed as low-grade endometrioid adenocarcinoma, clear cell carcinoma, or even serous carcinoma and carcinosarcoma. We report a case of mesonephric-like adenocarcinoma misdiagnosed as a low-grade endometrioid endometrial adenocarcinoma that had an early local recurrence and metastasized to the liver and the lungs. Histopathological, immunohistochemical and molecular analysis were performed and compared to published literature, providing a comprehensive overview of the current knowledge. Databases (Pubmed, Web of Science, Google Scholar) were searched with a combination of the following search terms: mesonephric-like, mesonephric, adenocarcinoma, carcinoma, uterine body, uterine corpus, endometrium. Mesonephric-like adenocarcinoma is a difficult-to-diagnose entity. Advanced diagnostics, including improved morphologic, immunohistochemical and molecular knowledge can help develop new therapeutic strategies against this specific subtype of endometrial cancer with an aggressive clinical behavior.
PubMed: 33670088
DOI: 10.3390/jcm10040698 -
Histopathology Jan 2020Cervical adenocarcinoma is a heterogenous group of tumours with various aetiologies, molecular drivers, morphologies, response to treatment and prognosis. It has become... (Review)
Review
Cervical adenocarcinoma is a heterogenous group of tumours with various aetiologies, molecular drivers, morphologies, response to treatment and prognosis. It has become evident that human papillomavirus (HPV) infection does not drive all adenocarcinomas, and appropriate classification is critical for patient management, especially in the era of the HPV vaccine and HPV-only screening. Identified as one of the most important developments in gynaecological pathology during the past 50 years, the separation of cervical adenocarcinomas into HPV-associated (HPVA) and HPV-independent has resulted in a transformation of the classification system for cervical adenocarcinomas. HPVA has been traditionally subclassified by morphology, such as usual type (UEA), mucinous and villoglandular, etc. However, it has become evident that cell type-based histomorphological classification is not clinically meaningful, and the newly proposed International Endocervical Adenocarcinoma Criteria and Classification (IECC) is a necessary and relevant break from this prior system. Non-HPV-associated adenocarcinomas can be divided by their distinct morphology and molecular genomics with very different responses to standard therapies and potential for future targeted therapies. These include gastric-type, clear-cell, mesonephric and endometrioid adenocarcinomas. So-called 'serous' carcinomas of the cervix probably represent morphological variants of UEA or drop metastases from uterine or adnexal serous carcinomas, and the existence of true cervical serous carcinomas is in question. This review will discuss the advances since WHO 2014, and how HPV status, pattern of invasion as described by Silva and colleagues, histological features and molecular markers can be used to refine diagnosis and prognostication for patients with cervical adenocarcinoma.
Topics: Adenocarcinoma; Biomarkers, Tumor; Cervix Uteri; Female; Humans; Papillomavirus Infections; Uterine Cervical Neoplasms
PubMed: 31846527
DOI: 10.1111/his.13995 -
European Journal of Case Reports in... 2021Zinner syndrome is a developmental anomaly of the urogenital tract. This condition is defined by the triad of unilateral renal agenesis, ipsilateral seminal vesicle cyst...
UNLABELLED
Zinner syndrome is a developmental anomaly of the urogenital tract. This condition is defined by the triad of unilateral renal agenesis, ipsilateral seminal vesicle cyst and ipsilateral ejaculatory duct obstruction. The syndrome is due to malformation of the mesonephric duct during embryogenesis. The condition used to be rare but is now frequently encountered due to the advent of MRI and CT. MRI confirms the diagnosis by revealing the seminal vesicle cyst and its contents, and the ejaculatory duct obstruction, while CT confirms renal agenesis. We report the case of a young patient with Zinner syndrome.
LEARNING POINTS
Zinner syndrome consists of the triad of renal agenesis, seminal vesicle cyst and ejaculatory duct obstruction.Any insult during embryogenesis of the mesonephric duct in men can result in Zinner syndrome.Pelvic MRI is the gold standard to confirm the diagnosis of Zinner syndrome.
PubMed: 34268266
DOI: 10.12890/2021_002628 -
Seminars in Diagnostic Pathology Jan 2022This review provides an update on immunohistochemistry applications-diagnostic, prognostic, and predictive-in the pathology evaluation of gynecologic carcinomas. The 5th... (Review)
Review
This review provides an update on immunohistochemistry applications-diagnostic, prognostic, and predictive-in the pathology evaluation of gynecologic carcinomas. The 5th edition of the WHO Classification of Female Genital Tumors introduced important changes in the diagnostic classification of lower genital tract, endometrial, and ovarian carcinomas, with major influence on the routine pathology practice. Lower genital tract carcinomas and their precursor lesions are now classified based on their human papillomavirus (HPV)-associated and HPV-independent pathogenesis, reflecting the clinically significant prognostic differences and impacting the therapeutic decision-making. Immunohistochemical markers have an increasing role in the pathology evaluation of endometrial carcinomas: in addition to their traditional use in the differential diagnosis and histologic subtyping, they have also been recently advocated for prognostic classification as surrogates for the TCGA (The Cancer Genome Atlas) molecular groups. New entities - mesonephric-like adenocarcinoma and gastric (gastrointestinal)-type mucinous adenocarcinoma of the endometrium - have also been added and often require immunostains for diagnostic confirmation. Ovarian carcinomas frequently show overlapping morphologic patterns and heterogeneous appearance within the same tumor, necessitating immunohistochemical work-up. Beyond diagnostic applications, there is increasing clinical demand for screening of inherited cancer syndromes, prediction of prognosis and guiding targeted therapy. Practical issues and pitfalls related to mismatch repair protein immunohistochemistry, HER2, and PD-L1 testing are also discussed.
Topics: Carcinoma; Female; Genital Neoplasms, Female; Humans; Immunohistochemistry; World Health Organization
PubMed: 34750021
DOI: 10.1053/j.semdp.2021.10.006 -
Modern Pathology : An Official Journal... Apr 2023Endometrial carcinoma (EC) can be divided into 4 prognostic molecular subtypes, and no specific molecular profile (NSMP) type is the most commonly occurring type...
Endometrial carcinoma (EC) can be divided into 4 prognostic molecular subtypes, and no specific molecular profile (NSMP) type is the most commonly occurring type (∼50%). Although described as having an intermediate to favorable prognosis, this subtype encompasses pathologically and molecularly diverse tumors. We aimed to identify factors associated with outcomes within the NSMP ECs that might be used to stratify prognosis and direct treatment. Clinicopathologic, immunohistochemical, and genetic features of a large series of NSMP EC were used to identify parameters that could identify the subset associated with a very favorable outcome (disease-specific death rate <5% at 5 years, termed low-risk NSMP). A total of 1110 NSMP ECs were profiled. In a univariate analysis, stage, grade, lymphovascular invasion, estrogen receptor (ER) and progesterone receptor (PR) expression, L1CAM overexpression, and mutations in PIK3CA were associated with disease-specific survival. Two critical features, grade and ER expression, identified a low-risk NSMP subset (grade 1-2, ER-positive [>1%], 84% of cases), which showed a 5-year disease-specific death rate of 1.6% across all stages and 1.4% within stage I. The remaining cases (high-risk NSMPs, grade 3, and/or ER-negative status) were responsible for most of the disease-specific deaths (disease-specific death rate at 5 years, 22.9%; hazard ratio compared with that of low-risk NSMPs: 16.3; 95% CI, 8.4-31.7). Within NSMP EC, the low-risk and high-risk categories were of prognostic significance independent of the stage on a multivariate analysis. Low-grade and ER-positive NSMP ECs are a homogeneous low-risk group associated with an exceptionally favorable prognosis in which de-escalation and/or endocrine therapy strategies can be applied. Grade 3 and/or ER-negative status identifies a high-risk NSMP subset, including rare high-grade histotypes (eg, clear cell, dedifferentiated, and mesonephric-like), responsible for most NSMP-related deaths. Subclassification of NSMPs allows for the category of low-risk EC molecular subtypes to be dramatically expanded because it now includes both POLEmut and the much more common low-risk NSMP EC.
Topics: Female; Humans; Receptors, Estrogen; Endometrial Neoplasms; Prognosis; Risk Factors; Biomarkers, Tumor; Carcinoma, Endometrioid
PubMed: 36788084
DOI: 10.1016/j.modpat.2022.100085 -
Archives of Pathology & Laboratory... Apr 2015Renal dysplasia is an aberrant developmental disease usually diagnosed during the perinatal and childhood years. Prevalence is estimated at 0.1% of infants (via... (Review)
Review
Renal dysplasia is an aberrant developmental disease usually diagnosed during the perinatal and childhood years. Prevalence is estimated at 0.1% of infants (via ultrasound screening) and 4% of fetuses and infants (via autopsy study). Occurrences may be combined with abnormalities in the collecting system or associated with complex syndromes. Histopathology shows primitive tubules surrounded by a fibromuscular collar. The differential diagnosis includes renal dysplasia, hypoplasia, and renal atrophy. Immunohistochemical expression of the paired box genes 2 and 8 (PAX2/8) and Wilms tumor 1 (WT1) is increased in the primitive ducts and fibromuscular collar, respectively. Renal dysplasia pathogenesis is not well understood, but may be caused by a nephron-inductive deficit due to ampullary inactivity or abnormal budding of the ureteric bud from the mesonephric duct. Either the PAX2 mutation only or cross-talk with the p53 pathway is involved in this deficit. Nephrectomy is the treatment of choice for symptomatic renal dysplasia.
Topics: Diagnosis, Differential; Humans; Immunohistochemistry; Kidney; Kidney Diseases; Nephrectomy; PAX2 Transcription Factor; PAX8 Transcription Factor; Paired Box Transcription Factors; WT1 Proteins
PubMed: 25822765
DOI: 10.5858/arpa.2013-0660-RS