Oluwole Fadare

Characterization of gastric/gastrointestinal-like immunophenotypes in endometrial endometrioid adenocarcinomas, including endometrioid adenocarcinomas with mucinous differentiation

Endometrial mucinous carcinoma of the gastric [gastrointestinal] type (MCG) is a rare, possibly aggressive subtype of endometrial cancer that should be distinguished from its potential mimics, including endometrioid carcinoma (EEC). Herein, we assess the frequency of gastric and gastrointestinal immunophenotypes in EEC without any discernible gastric/gastrointestinal-type morphology. Immunohistochemical analyses for KRT(CK)7, KRT20, CDX2, ER, SATB2, MUC6, PAX8, and HIK1083 were performed on 81 EEC, inclusive of consecutively archived low grade [with (n = 22) and without (n = 47) mucinous differentiation] and high grade (n = 12) cases. None displayed gastric-type morphology or goblet cells. Expression levels were semi-quantified as H-scores (combining intensity and extent of staining) on a standardized 0-300 scale. Among the gastric/gastrointestinal-type markers, 56%, 62%, 23%, 25%, and 0% of cases expressed MUC6, CDX2, KRT20, SATB2, and HIK1083 respectively. The expression levels for positive cases were generally limited, with average H-scores being 49.5 [range 1-250] for MUC6, 33.7 [1-285] for CDX2, 24.0 [1-270] for CK20, and 30.5 [2-220] for SATB2. Ten (12.35%) cases showed high expression (H ≥ 200) of at least 1 gastric/gastrointestinal-type marker, including 1, 2, 2 and 6 cases that were high positive for KRT20, SATB2, CDX2 and MUC6 respectively. Immunoreactive foci were generally indistinguishable from background at the morphologic level. There was no statistically significant correlation between the expression of any of the gastric/gastrointestinal-type markers and ER, KRT7 or PAX8 expression. In summary, gastric/gastrointestinal-type proteins are not uncommonly expressed at low levels in EEC. As such, positivity for these markers cannot be the sole basis for distinguishing EEC from MCG.

Endometrial Polyp-Like Lesions Arising From Adenomyosis: Report of 5 Cases

Endometrial Mesonephric-Like Carcinoma With Prominent Clear Cell Carcinoma-Like Features

This report details findings from a morphologic, immunohistochemical, and molecular analysis of an example of endometrial mesonephric-like adenocarcinoma (MLA) with prominent clear cell carcinoma (CCC)-like features, with an assessment of whether such tumors represent mixed MLA/CCC or a morphologic subtype of MLA. Approximately 40% of an otherwise prototypical MLA was comprised of spatially discrete zones with prominent CCC-like morphology. The MLA-like nuclear features of both components were similar, as were their immunoreactivity patterns for estrogen receptor, progesterone receptor, SOX17, and calretinin (all negative), GATA3, and TTF1 (patchy positive). Diffuse immunoreactivity for CD10 and Napsin-A was limited to the CCC-like areas. Next generation sequencing of each macro-dissected component showed both to display the same KRAS variant (G12V), with similar variant allelic frequencies (42.5% [MLA]; 48.2% [CCC-like]). Although KRAS G12V lacks specificity for MLA, the totality of findings supports the interpretation that the CCC-like areas represent morphologic mimicry of CCC by MLA. Additional supportive factors include the similarity in nuclear features between the 2 components, absence of other architectural patterns of CCC in the CCC-like areas, co-expression of GATA3 and TTF1, as well as negativity for SOX17 in both components. This tumor highlights the potential for MLA to display striking CCC-like morphology, possibly leading to misclassification in a sampling specimen, and adds to the emerging literature on the potential for MLA to express Napsin-A.

High-Grade Endometrioid Carcinoma of the Endometrium With a GATA-3-Positive/PAX8-Negative Immunophenotype Metastatic to the Breast: A Potential Diagnostic Pitfall

This report describes clinicopathologic findings from the case of a patient with a breast mass that was ultimately diagnosed as a metastatic high-grade endometrioid carcinoma of endometrial origin. The breast lesion as well as the solid areas of the endometrial lesion displayed a similar immunoprofile: GATA3-positive; synaptophysin positive; negative for mammaglobin, gross cystic disease fluid protein-15, chromogranin, estrogen receptor, progesterone receptor, and HER2/neu; and intact expression of the DNA mismatch repair proteins MLH1, MSH2, MSH6, and PMS2. The breast lesion was negative for PAX-8, whereas the solid areas of the endometrial lesion showed focal weak positivity. A review of the literature on GATA-3 expression in endometrial carcinomas found a reported frequency of expression that ranged from 0% to 13% of cases, typically in a patchy, focal, and generally restricted pattern. However, GATA-3 may be diffusely expressed in high-grade endometrial carcinomas. Since the potential for PAX-8 expression to be lost in high-grade endometrioid carcinomas is well known, a GATA-3-positive/PAX8-negative immunoprofile may be encountered in high-grade endometrioid carcinomas of the endometrium, and this composite immunoprofile is a potential diagnostic pitfall when such a lesion is being evaluated in a breast metastasis.

Ovarian Fibroma With Bizarre Nuclei: A Rare Finding

High-grade Squamous Intraepithelial Lesion of the Vulva with Obscuring Edema: A Potential Diagnostic Pitfall in Vulvar Biopsies

Pathologic Determination of Multifocality in pT1a1 Squamous Cell Carcinoma of the Cervix: A Retrospective Analysis

When more than one focus of stromal invasion is present in a superficially invasive cervical squamous cell carcinoma (SCC), determination of the tumoral lateral extent/horizontal extension, and hence tumor-nodes-metastases (TNM) staging, can be problematic. In recent years, a diagnostic approach to distinguish multifocal pT1a1 from pT1b cases has gained increased attention. These criteria call for classifying SCC as multifocal when invasive foci are separated by blocks of uninvolved cervical tissues, and/or are located on separated cervical lips in a tumor that is discontinuous, and/or are situated far apart (≥2 mm) from each other. In this study, we assess our experience with multifocal stage pT1a1 cervical SCC that was retrospectively classified as such using these criteria. Slides from the loop electrosurgical excision or conization specimens, comprising 212 pT1a1, 173 pT1a2, and 206 pT1b cases, were reviewed. Twenty-four (11%) of the 212 pT1a1 cases were classified as multifocal after review. The 24 multifocal pT1a1 cases were compared with the 188 unifocal pT1a1 cases regarding a variety of clinicopathologic parameters. Notably, these 2 groups showed no significant differences regarding all parameters that were evaluated, including patient age, recurrence rate, primary tumoral features in the primary excision specimen (rate of positive margins, median depth of stromal invasion, frequency of lymphovascular invasion), and frequency of residual disease in additional excisions. In summary, we demonstrate comparably favorable patient outcomes in both unifocal and multifocal cases of pT1a1 SCC of the cervix, and, accordingly, we conclusively affirm the validity of the aforementioned criteria for establishing multifocality.