Objectives: The objective of this study was to evaluate SOX17, a transcription factor from the Sry high-mobility group-related box superfamily, as a diagnostic marker to determine site of origin using both whole-tissue sections and tissue microarrays (TMAs).
Methods: SOX17 immunohistochemistry was performed on gynecologic and nongynecologic tissues (N = 1004) using whole-tissue sections and both internally constructed and commercially available TMAs. SOX17 nuclear reactivity was scored as positive or negative on the whole-tissue sections and using the semiquantitative H score method on TMAs.
Triple-negative breast cancer (TNBC) refers to an estrogen receptor-negative, progesterone receptor-negative, and HER2-negative breast cancer. Although accepted as a clinically valid category, TNBCs are heterogeneous at the histologic, immunohistochemical, and molecular levels. Gene expression profiling studies have molecularly classified TNBCs into multiple groups, but the prognostic significance is unclear except for a relatively good prognosis for the luminal androgen receptor subtype.
View Article and Find Full Text PDFBackground: Breast magnetic resonance imaging (MRI) is an important imaging tool for the management of breast cancer patients and for screening women at high risk for breast cancer.
Objectives: To examine long-term trends in the distribution of histologic diagnoses obtained from MRI-guided breast biopsies.
Design: Retrospective analysis.
Cold Spring Harb Mol Case Stud
December 2022
Myoepithelial carcinomas (MECs) of soft tissue are rare and aggressive tumors affecting young adults and children, but their molecular landscape has not been comprehensively explored through genome sequencing. Here, we present the whole-exome sequencing (WES), whole-genome sequencing (WGS), and RNA sequencing findings of two MECs. Patients 1 and 2 (P1, P2), both male, were diagnosed at 27 and 37 yr of age, respectively, with shoulder (P1) and inguinal (P2) soft tissue tumors.
View Article and Find Full Text PDFBackground: Autoimmune encephalitis (AE) is a rare collection of disorders that present with a diverse and often nebulous set of clinical symptoms. Indiscriminate use of multi-antibody panels decreases their overall utility and predictive value. Application of a standardized scoring system may help reduce the number of specimens that generate misleading or uninformative results.
View Article and Find Full Text PDFIntroduction: Molecular testing has helped clinicians and cytopathologists to further categorize indeterminate thyroid fine needle aspiration (FNA) specimens. The purpose of the present study was to evaluate the accuracy of commercially available molecular tests, review their effects on patient treatment, and correlate the molecular alterations with the histologic findings.
Materials And Methods: A pathology laboratory information system search identified thyroid FNAs performed at our institution between January 1, 2015 and June 30, 2020.
Low-grade, low-stage endometrioid carcinomas (LGLS EC) demonstrate 5-yr survival rates up to 95%. However, a small subset of these tumors recur, and little is known about prognostic markers or established mutation profiles associated with recurrence. The goal of the current study was to identify the molecular profiles of the primary carcinomas and the genomic differences between primary tumors and subsequent recurrences.
View Article and Find Full Text PDFBackground: The Bethesda System for Reporting Thyroid Cytopathology contains an atypia of undetermined significance (AUS) category with heterogeneous and distinct inclusion criteria. The purpose of this study was to investigate differences in malignancy rates and molecular alterations based on the presence of different criteria.
Methods: A laboratory information search was conducted to identify thyroid fine-needle aspiration specimens signed out as AUS.
The prevalence and biological consequences of deleterious germline variants in urothelial cancer (UC) are not fully characterized. We performed whole-exome sequencing (WES) of germline DNA and 157 primary and metastatic tumors from 80 UC patients. We developed a computational framework for identifying putative deleterious germline variants (pDGVs) from WES data.
View Article and Find Full Text PDFMixed endometrial carcinomas are defined as a combination of 2 or more distinct histologic subtypes, one of which must be a type II tumor comprising at least 5% of the tumor volume. The oncogenesis of these tumors remains unclear, particularly in light of the increasingly appreciated morphologic overlap among subtypes, as well as evolving molecular data. We evaluated 8 cases of mixed endometrial carcinoma, including 4 endometrioid (EC)/serous (SC), 1 SC/clear cell (CC), and 3 EC/CC cases, to study the underlying molecular features and oncogenic mechanisms at play.
View Article and Find Full Text PDFAcral fibromyxoma (AF) is a slow growing benign soft tissue tumor with predilection to subungal and periungal region of the hands or feet. CD34 is consistently expressed whereas very recently loss of Rb1 expression was described as a possible driver molecular event for this entity. Herein we present two additional cases of AF with loss of Rb1 expression by IHC and subsequent confirmation of loss of the RB1 gene locus by fluorescence in situ hybridization (FISH).
View Article and Find Full Text PDFAdenomyoepitheliomas (AMEs) of the breast are uncommon and span the morphologic spectrum of benign, atypical, in situ, and invasive forms. In exceptionally rare cases, these tumors metastasize to regional lymph nodes or distant sites. In the era of genomic characterization, data is limited regarding AMEs.
View Article and Find Full Text PDFRecently, a new variant of ILC with papillary architecture has been described, which may mimic solid and encapsulated papillary carcinomas of the breast. We report the fifth case of ILC with a solid papillary-like growth pattern, which was initially misdiagnosed as an encapsulated papillary carcinoma. Subtle discohesion in the tumor cells, coupled with the presence of classic invasive lobular carcinoma infiltrating beyond the capsule of the papillary tumor, prompted evaluation with E-cadherin, confirming the diagnosis.
View Article and Find Full Text PDFPurpose: We developed a precision medicine program for patients with advanced cancer using integrative whole-exome sequencing and transcriptome analysis.
Patients And Methods: Five hundred fifteen patients with locally advanced/metastatic solid tumors were prospectively enrolled, and paired tumor/normal sequencing was performed. Seven hundred fifty-nine tumors from 515 patients were evaluated.
Background: Magnetic resonance imaging/ultrasound-guided fusion biopsy (FBx) is more accurate at detecting clinically significant prostate cancer than conventional transrectal ultrasound-guided systematic biopsy. However, learning curves for attaining accuracy may limit the generalizability of published outcomes.
Objective: To delineate and quantify the learning curve for FBx by assessing the targeted biopsy accuracy and pathological quality of systematic biopsy over time.
Histologic transformation to small cell neuroendocrine prostate cancer occurs in a subset of patients with advanced prostate cancer as a mechanism of treatment resistance. Rovalpituzumab tesirine (SC16LD6.5) is an antibody-drug conjugate that targets delta-like protein 3 (DLL3) and was initially developed for small cell lung cancer.
View Article and Find Full Text PDFsomatic mutations occur in ∼10% of diffuse large B-cell lymphomas (DLBCL) but are of unknown significance. Herein, we show that TET2 is required for the humoral immune response and is a DLBCL tumor suppressor. TET2 loss of function disrupts transit of B cells through germinal centers (GC), causing GC hyperplasia, impaired class switch recombination, blockade of plasma cell differentiation, and a preneoplastic phenotype.
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