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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 -
Modern Pathology : An Official Journal... Jan 2023Given the association of mesonephric adenocarcinoma (MA) of the uterine cervix with florid mesonephric hyperplasia, one would expect MAs to rarely arise in other...
Given the association of mesonephric adenocarcinoma (MA) of the uterine cervix with florid mesonephric hyperplasia, one would expect MAs to rarely arise in other anatomical locations that harbor mesonephric remnants. In contrast, mesonephric-like adenocarcinoma (MLA) is thought to arise from Müllerian origin without an association with mesonephric remnants. The current case series characterizes 4 cases of MA arising in the urinary bladder (1 woman and 3 men), 1 case of MA in the perirenal region (woman), and 1 case of MLA in the ureter (woman). All cases displayed morphologic features similar to MA of the uterine cervix and MLA of the ovary and endometrium, characterized by predominant tubular and focal glandular/ductal architecture. Mesonephric remnants in the bladder wall were closely associated with adjacent MA in cases 1 and 4. MLA in case 6 was associated with mesonephric-like proliferations and endometriosis. All cases (6/6) were diffusely positive for Pax8, and all displayed a luminal pattern of CD10 staining, except case 4 for which CD10 immunostain was not available for review. Gata3 was either focally positive (cases 1, 2, and 6), negative (case 3), or diffusely positive (case 5). TTF-1 was diffusely expressed in cases 1 and 3 and negative in cases 2, 5, and 6. Although a KRAS G12C somatic mutation was detected in case 6, hotspot mutations in KRAS, NRAS, and PIK3CA were not present in other tested cases. Our study demonstrates that MAs and MLAs of the urinary tract share similar histopathogenesis, morphology, and immunophenotype to their counterparts in the female genital tract. We propose that, in the urinary tract, MA might be classified as a distinctive tumor that arises from mesonephric remnants or presumed Wolffian origin if they are not related to Müllerian-type precursors. The tumor displaying similar morphology and immunoprofile to MA but associated with Müllerian-type precursors should be classified as MLA.
Topics: Male; Female; Humans; Uterine Cervical Neoplasms; Proto-Oncogene Proteins p21(ras); Adenocarcinoma; Mesonephroma; Urinary Tract
PubMed: 36788068
DOI: 10.1016/j.modpat.2022.100031 -
Organogenesis Jan 2016Gonadal differentiation has a determinative influence on sex development in human embryos. Disorders of sexual development (DSD) have been associated with persistent... (Review)
Review
Gonadal differentiation has a determinative influence on sex development in human embryos. Disorders of sexual development (DSD) have been associated with persistent embryonal differentiation stages. Between 1998 and 2015, 139 female patients with various (DSD) underwent operations at the Scientific Center of Obstetrics, Gynaecology and Perynatology in Moscow, Russia. Clinical investigations included karyotyping, ultrasound imaging, hormonal measurement and investigations of gonadal morphology. The male characteristics in the embryo are imposed by testicular hormones. When these are absent or inactive, the fetus may be arrested at between developmental stages, or stay on indifferent stage and become phenotypically female. A systematic analysis of gonadal morphology in DSD patients and a literature review revealed some controversies and led us to formulate a new hypothesis about sex differentiation. Proliferation of the mesonephric system (tubules and corpuscles) in the gonads stimulates the masculinization of gonads to testis. Sustentacular Sertoli cells of the testes are derived from mesonephric excretory tubules, while interstitial Leydig cells are derived from the original mesenchyme of the mesonephros. According of the new hypothesis, the original mesonephric cells (tubules and corpuscles) potentially persist in the ovarian parenchyma. In female gonads, some mesonephric excretory tubules regress and lose the tubular structure, but form ovarian theca interna and externa, becoming analogous to the sustentacular Sertoli cells in the testis. The ovarian interstitial Leydig cells are derived from intertubal mesenchyme of the mesonephros, similar to what occurs in male gonads (testis). Surprisingly, the leading determinative factor in sexual differentiation of the gonads is the mesonephros, represented by the embryonic urinary system.
Topics: Disorders of Sex Development; Female; Gonads; Humans; Male; Sex Determination Processes; Sex Differentiation
PubMed: 26950283
DOI: 10.1080/15476278.2016.1145318 -
Surgical Pathology Clinics Jun 2022This article presents features of uncommon high-grade endometrial carcinomas that often pose a significant diagnostic challenge. An update on undifferentiated and... (Review)
Review
This article presents features of uncommon high-grade endometrial carcinomas that often pose a significant diagnostic challenge. An update on undifferentiated and dedifferentiated endometrial carcinoma is first provided, followed by discussions on more recently defined entities such as mesonephric-like carcinoma of the endometrium and gastric-type endometrial carcinomas. Finally, endometrial carcinoma with germ cell or trophoblastic-like components is discussed.
Topics: Biomarkers, Tumor; Carcinoma; Carcinoma, Endometrioid; Endometrial Neoplasms; Endometrium; Female; Humans; Hyperplasia; Immunohistochemistry
PubMed: 35715163
DOI: 10.1016/j.path.2022.02.007 -
The Veterinary Clinics of North... Jan 2020The number of fish as pets far exceeds the populations of any other companion animal. As our knowledge of aquatic animal species and aquatic animal medicine continues to... (Review)
Review
The number of fish as pets far exceeds the populations of any other companion animal. As our knowledge of aquatic animal species and aquatic animal medicine continues to expand, veterinary expertise is becoming more critical to the client, researcher, fisheries biologist, aquarist, farmer, and fish hobbyist. Similar to other vertebrates, fish are susceptible to infectious and noninfectious renal disease. This article compares vertebrate renal anatomy and physiology and highlights some renal disease examples.
Topics: Animals; Fish Diseases; Fishes; Kidney; Kidney Diseases; Vertebrates
PubMed: 31759450
DOI: 10.1016/j.cvex.2019.09.006