ABSTRACT
PURPOSE: Sebaceous carcinoma is the third most common nonkeratinocyte skin cancer in the United States with 1,000 cases per year. The clinicopathologic features of sebaceous carcinoma and benign sebaceous neoplasms (adenomas, sebaceomas) can overlap, highlighting the need for molecular biomarkers to improve classification. This study describes the genomic and transcriptomic landscape of sebaceous neoplasms in order to understand tumor etiology and biomarkers relevant for diagnosis and treatment. EXPERIMENTAL DESIGN: We performed whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS) of sebaceous neoplasms from six academic and two federal healthcare facilities in the United States diagnosed between January 1, 1999, and December 31, 2021. RESULTS: We evaluated 98 sebaceous neoplasms: 64 tumors (32 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 25 carcinomas) had sufficient material for WGS, 96 tumors (42 adenomas, 11 sebaceomas, 8 atypical sebaceous neoplasms, 35 carcinomas) had sufficient material for WTS, and 62 tumors (31 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 24 carcinomas) had sufficient material for combined WGS and WTS. Overall, we found decreased cholesterol biosynthesis and increased TP53 mutations, copy number gains (chromosome 6, 8q, and/or 18), and tumor mutation burden-high (>10 mutations/MB) in carcinomas compared to adenomas. Although diminished compared to adenomas, most carcinomas still had higher cholesterol biosynthesis than nonmalignant skin. Multiomics profiling also supported a precancerous model of tumor evolution with sebaceomas and atypical sebaceous neoplasms being likely intermediate lesions. CONCLUSIONS: The study findings highlight key diagnostic biomarkers for sebaceous carcinoma and suggest that immunotherapy and modulation of cholesterol biosynthesis could be effective treatment strategies.
ABSTRACT
ABSTRACT: Periodic acid-Schiff (PAS) stain is a commonly used ancillary test for inflammatory and infectious dermatoses, yet infrequently changes the diagnosis. Previous studies have shown that clinical suspicion and histopathologic features are poor predictors of PAS positivity. Current appropriate use criteria from the American Society of Dermatopathology supports PAS staining when histopathologic features could be consistent with a dermatophyte infection. At the authors' institution, PAS stains are preordered on biopsies of inflammatory and infectious diagnoses to aid in a timelier sign out. Our aim was to reduce the percentage of PAS stains preordered on all dermatology specimens over a 6-month period without reducing the percentage of fungal infections identified. Review of a 12-month preintervention period found that our laboratory received 6104 biopsies for which PAS stain was preordered on 616 (10.1%). Based on a review of the preintervention period, preordering PAS on cases with clinical suspicion for cutaneous T-cell lymphoma was stopped unless there was clinical suspicion for eczematous dermatitis, vesiculobullous disorders, or fungal infection. The proposed intervention resulted in a 3.7% reduction in the number of PAS stains ordered while PAS-positivity rate remained unchanged. The described quality improvement process may be used as a model for other laboratories.
Subject(s)
Quality Improvement , Skin Neoplasms , Humans , Periodic Acid , Coloring Agents , Staining and LabelingABSTRACT
With increasing access to electronic health records, patients may encounter dermatopathology reports more readily. Dermatopathologists should consider their impact and interactions with transgender patients, who may face specific health and healthcare inequities. Rendering accurate diagnosis for skin diseases requires accurate information about patient's sex assigned at birth and gender identity. Understanding how sex and gender identity data flow between electronic health records, laboratory information systems, insurance billing systems, and patients will be important to avoid patient misgendering, to render accurate diagnoses, to maintain consistency in dermatopathology reports, and to avoid insurance billing denials. Dermatopathologists have important roles to build patient trust in the healthcare system and to help dermatologists diagnose, treat, and characterize skin diseases in transgender populations.
Subject(s)
Skin Diseases , Transgender Persons , Infant, Newborn , Humans , Male , Female , Gender Identity , Delivery of Health CareABSTRACT
Kaposi sarcoma is a vascular endothelial neoplasm caused by human herpesvirus 8. Although it is a well-studied disease, little is known about the specific characteristics or epidemiology of Kaposi sarcoma in Afghanistan. The data consist primarily of anecdotal reports and epidemiological studies extrapolated from neighboring countries. In this case series, we summarize existing data about Kaposi sarcoma in Afghanistan and present seven histologically confirmed cases with associated clinical features to shed light on the characteristics of Kaposi sarcoma in this unique geographic setting.