Gastrointestinal autonomic nerve tumors. A clinicopathological, immunohistochemical, and ultrastructural study of 12 cases

The gastrointestinal autonomic nerve tumor (GAN tumor) is an uncommon stromal tumor of the intestinal tract and retroperitoneum first described by Herrera and associates in 1984. Distinction of GAN tumors from other gastrointestinal stromal tumors is based on electron microscopic findings. Thus far there have been 12 reported cases. We present an additional 12 GAN tumors, identified by us during 4 years. There were seven male and five female patients and they ranged in age from 10 to 85 years (mean: 58 years). Sites of the tumors were stomach (three), jejunum (two), ileum (four), mesentery (one), and retroperitoneum (two). Eight of the tumors measured > 10 cm in greatest dimension. Usually well circumscribed, the neoplasms were tan to light pink, sometimes hemorrhagic, and soft. There was a variety of histologic patterns including fascicles, palisades, and whorls. Mitotic activity varied from 0 to 23 mitosis per 10 high-power fields (HPF). Using a panel of 10 immunohistochemical stains, only vimentin was consistently positive. There was neuron-specific enolase reactivity in six and S-100 protein reactivity in two cases. All muscle markers were negative. Ultrastructural studies showed neuron-like cells with long axonic cytoplasmic processes ending in bulbous synapse-like structures containing dense-core neurosecretory granules and clear vesicles. Basement membrane was absent. These features are reminiscent of ganglia of the intestinal autonomic nervous system. The patients were followed for 5-125 months (mean of 26 months). Tumor recurred or metastasized to the liver in seven patients (58%) and four patients died with tumor. There were correlations between tumor size (> 10 cm), mitotic count (at least five per 10 HPF), and aggressive behavior.