title: Leiomyoma of the gastrointestinal tract with interstitial cells of Cajal: a mimic of gastrointestinal stromal tumor.
abstract: Leiomyomas (LMs) of the gastrointestinal tract arise within the muscularis mucosae (superficial) and muscularis propria (deep). There are isolated reports of KIT-positive cells, presumed interstitial cells of Cajal (ICCs), within gastrointestinal LMs. We have encountered esophageal LMs with a high proportion of KIT-positive and DOG1-positive spindle-shaped cells, an appearance that mimicked gastrointestinal stromal tumor. Our aim was to explore the prevalence of ICCs in LMs of the gastrointestinal tract and the etiopathogenic significance of these cells in this benign neoplasm. We identified 34 esophageal LMs (28 deep, 6 superficial), 8 gastric LMs, and 5 small-bowel LMs (all lesions in muscularis propria). We performed immunohistochemical staining studies for desmin, DOG1, and KIT on these neoplasms. We also evaluated 12 superficial colonic LMs. ICCs were distinguished from mast cells on the basis of morphology (elongated and occasionally branching spindle-shaped cells) and the presence of DOG1 reactivity. Four cases were screened for mutations in PDGFRA exons 12, 14, and 18 and KIT exons 9, 11, 13, and 17. ICCs were identified in all deep esophageal LMs and constituted an average of 20% of the lesional cells; focally, these cells comprised >50% of cells. The density of these cells was significantly higher than the background muscularis propria, and hyperplasia of ICCs was not identified in the adjacent muscle. ICCs were identified in 6 of 8 gastric LMs and 1 of 5 small-bowel LMs and were entirely absent in all superficial esophageal and colonic/rectal LMs. There were no mutations in KIT or PDGFRA. ICCs are universally present in deep esophageal LMs, and thus these neoplasms could be mistaken for gastrointestinal stromal tumors, particularly on biopsy samples, an error associated with adverse clinical consequences. ICCs are also identified in gastric and intestinal LMs, albeit in a smaller proportion of cases. Colonization and hyperplasia by non-neoplastic ICCs likely account for this phenomenon.
authors.affiliation: *Department of Pathology and Laboratory Medicine, Boston Medical Center ‡Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA †Department of Pathology, Oregon Health & Science University, Portland, OR.
authors.forename: Anita
authors.initials: A
authors.lastname: Deshpande
authors.forename: Dylan
authors.initials: D
authors.lastname: Nelson
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Corless
authors.forename: Vikram
authors.initials: V
authors.lastname: Deshpande
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Brien
mesh_terms: D000075369:Anoctamin-1; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D001706:Biopsy; D049109:Cell Proliferation; D018118:Chloride Channels / Q000032:analysis; D004252:DNA Mutational Analysis; D003893:Desmin / Q000032:analysis; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D005091:Exons; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D056885:Interstitial Cells of Cajal / Q000737:chemistry / Q000473:pathology*; D007414:Intestinal Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D007889:Leiomyoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000032:analysis; D011237:Predictive Value of Tests; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D013274:Stomach Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D014408:Biomarkers, Tumor; D018118:Chloride Channels; D003893:Desmin; D009363:Neoplasm Proteins; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha