OBJECTIVETo investigate the clinicopathologic features of malignant granular cell tumor (MGCT) and evaluate the histologic criteria for diagnosis of malignancy.

METHODSThe clinical and pathologic profiles of 10 MGCT cases were evaluated. Immunohistochemical study was performed on paraffin sections of 9 cases. Electron microscopy was carried out in 3 cases with available fresh or formalin-fixed tissues. The biologic behavior was analyzed with follow-up data.

RESULTSFour patients were males and six were females. Their age ranged from 27 to 73 years (mean = 46 years). The main presenting symptom was a painless nodule or mass located in the subcutis or deep soft tissue. One case had peripheral nerve symptoms. Three of the tumors occurred in the lower extremity, two in the breast, two in the nuchal region, and one each in the chest wall, neck, and peritoneal cavity. The tumor size ranged from 2 to 11 cm (mean size = 4.8 cm). Microscopically, the tumor was composed of nests or sheets of polygonal cells which possessed abundant eosinophilic granular cytoplasm and closely resembled its benign counterpart. After careful assessment, 9 cases exhibited at least 3 of the following suspicious features: enlarged vesicular nuclei with prominent nucleoli, nuclear pleomorphism, high nuclear-to-cytoplasmic ratio, spindling of tumor cells, appreciable mitotic activity, and tumor necrosis. In addition, a hitherto undescribed feature characterized by multinucleated tumor cells was observed in 1 case. The remaining case demonstrated benign-appearing features but behaved in a malignant fashion. Immunohistochemical study showed positive staining for S-100 protein (9/9), neuron specific enolase (9/9) and CD68 (7/9). Electron microscopy demonstrated abundant intracytoplasmic autophagic vacuoles. Follow-up information available in 7 patients revealed local recurrence in 5, metastasis in 4 and tumor-related deaths in 2 patients.

CONCLUSIONSThe histologic criteria for malignancy in GCTs established in 1998 by Fanburg-Smith et al. are reproducible in most instances. In exceptional circumstances, however, the diagnosis relies on clinicopathologic correlation. Based on the current study and literature review, a modified criterion of mitotic count (> 5/50 HPF instead of > 2/10 HPF) is recommended. Wide local excision with regional lymph node dissection remains the mainstay of treatment. Chemotherapy and radiotherapy however have not been shown to significantly improve the clinical course of the disease. The morphologic spectrum of MGCT also includes a rare multinucleated variant.