Distinguishing Gastrointestinal Leiomyomas From Muscularis Propria in Biopsy Specimens by Differential Expression of S100 Immunohistochemical Stain

Abstract Objectives Interpreting small biopsy specimens or fine-needle aspirations of gastrointestinal tract (GI) smooth muscle lesions may be challenging when the differential diagnosis includes leiomyoma vs muscularis propria (MP). We evaluated the utility of S100 staining in distinguishing GI leiomyomas from MP. Methods A search was conducted in our laboratory information system for cases of leiomyomas arising within the GI tract (2004-2021). Site-matched controls containing MP were selected (2018-2020). Five high-power fields (hpf) were counted on S100 immunohistochemical stains by two pathologists in the resections and by three different blinded pathologists in the biopsy specimens and analyzed. Results The median S100 count was 2.5/5 hpf in leiomyoma resection cases (n = 38), which was significantly lower than the median count of 548/5 hpf in MP (n = 19) with a P value of