Classification of canine nonangiogenic, nonlymphogenic, gastrointestinal sarcomas based on microscopic, immunohistochemical, and molecular characteristics

Abstract

Canine nonangiogenic, nonlymphogenic, gastrointestinal sarcomas have been previously diagnosed as gastrointestinal stromal tumors (GIST), leiomyosarcomas, or nonspecified spindle cell sarcomas, but diagnostic criteria for each entity are poorly defined. We propose a classification for canine nonangiogenic, nonlymphogenic, gastrointestinal sarcomas based on microscopic, immunohistochemical, and molecular characteristics. Applying the classification to 40 canine nonangiogenic, nonlymphogenic, gastrointestinal sarcomas documented its diagnostic and prognostic value. Eighteen (45%) sarcomas were classified as GIST based on positive KIT immunoreactivity. All GISTs were positive for vimentin, 14 (78%) were positive for S-100, and 6 (33%) were positive for smooth muscle actin (SMA). In contrast to their human counterparts, canine GISTs occurred mainly in the small intestine (67%) but commonly metastasized (5/18) to liver, lymph nodes, and omentum. Six GISTs had an activated KIT mutation in exon 11 of c-Kit, but no mutations were detected in exons 8, 9, 13, and 17. Twelve (30%) sarcomas were classified as leiomyosarcomas based on positive labeling for SMA and negative labeling for KIT. Four of these neoplasms were well differentiated leiomyosarcomas characterized by weak to no labeling for vimentin, and 8 were poorly differentiated leiomyosarcomas characterized by strong labeling for vimentin. None of the leiomyosarcomas metastasized, but poorly differentiated leiomyosarcomas had a higher risk of local invasion. Ten (25%) sarcomas were classified as non-GIST/nonleiomyosarcomas that were negative for KIT and SMA but positive for vimentin and either S-100 and/or PGP 9.5. These neoplasms most likely represent sarcomas of neurogenic differentiation resembling Schwann cells or perineurial or endoneurial fibroblasts, respectively.

Keywords: GIST; c-kit; canine; gastrointestinal; leiomyosarcoma; nonangiogenic; nonlymphogenic; sarcoma.