SUBCLASSIFICATION OF GASTROINTESTINAL STROMAL TUMORS BASED ON EVALUATION BY ELECTRON-MICROSCOPY AND IMMUNOHISTOCHEMISTRY

Fifty-six gastrointestinal stromal tumors (GIST) were subclas sified b y ultrastructural examination and by immunophenotypic analysis using a panel of 13 antibodies. Eighty percent of the tumors originated in th e stomach and small intestines. The neoplasms were classified as follo ws: 42.9% smooth muscle tumors (4 leiomyomas, 9 spindle cell and 8 epi thelioid leiomyosarcomas, and 3 mixed spindle cell and epithelioid lei omyosarcomas); 37.5% gastrointestinal autonomic nerve tumors (GANT), 4 7.6% of which arose in the small intestines; 8.9% mixed leiomyosarcoma /neurogenic tumors; and 10.7% undifferentiated GIST, not otherwise spe cified. The muscle common actin antibody HHF-35, variably reactive wit h tumor cells composing 23 of 24 smooth muscle tumors, was found to be the most sensitive marker of leiomyocyte differentiation. One immunop henotypically questionable spindle cell leiomyosarcoma was diagnosed b y electron microscopy. Since neuron specific enolase positive cells we re found in 1/3 of the leiomyosarcoma cases, the ultrastructural demon stration of synapse-like structures and neurosecretory granules was re quired for diagnosing GANTs. The immunophenotype of the ultrastructura lly undifferentiated GIST was vimentin and CD34+. Variable numbers of ultrastructurally undifferentiated cells also were found in all of the tumors except 2 leiomyomas. CD34 was also expressed in smooth muscle (54%) and GAN (62%) tumors. Despite their similar light microscopic ap pearance, GIST are phenotypically heterogeneous, requiring both ultras tructural and immunohistochemical studies for accurate characterizatio n.