Epithelioid gastrointestinal stromal tumor of the stomach with liver metastases in a 12-year-old girl: Aspiration cytology and molecular study

Gastrointestinal stromal tumor (GIST), a stromal tumor of the gastrointestinal tract defined as CD117 (c-kit)-positive neoplasm, occurs primarily in adults. GIST with CD117 (c-kit) mutation and certain cytogenetic abnormalities is associated with malignancy, though a definite relationship between prognosisand molecular alterations remains to be elucidated. We report the cytologic features of an epithelioid GIST arising in the stomach of a child and metastatic to the liver, and the molecular mutational analysis of both the primary gastric tumor and the liver metastasis. Literature of pediatric GISTs was also reviewed. Fine needle aspiration of the liver metastasis, processed by Ultrafast Papanicolaou stain, showed fragments of cohesive small epithelioid cells with bland oval nuclei and unipolar cytoplasm transected by capillaries. Immunohistochemically, all nodules in the stomach and liver expressed CD117 (c-kit). Interestingly, some of the gastric tumor clusters were uniformly CD34 positive, whereas others were uniformly CD34 negative, suggesting heterogeneity of tumor clones. The presence of neurosecretory granules further subtyped the tumor into gastric autonomic nerve tumor (GANT). Molecular mutational analysis, performed in both the gastric tumor and the liver metastasis, showed no sequence abnormality in exons 9, 11, and 13 of CD117 (c-kit). Cytogenetic study revealed normal karyotype. These features might suggest a different molecular mechanism leading to malignancy in certain GISTs arising in children.