Increased expression of S100A6 in malignant granular cell tumours.

Granular cell tumours (GCT) are rare mesenchymal soft tissue neoplasms that may arise throughout the body. Most tumours are benign and solitary but approximately 2% of tumours are malignant (1). It is difficult to differentiate between benign and malignant GCT. We present a case of malignant GCT with inguinal meta stases in which the initial lesions could not be diagnosed as malignant. Interestingly, the S100A6 protein, which is expressed in Schwann cells (2), was seen both in the initial and metastatic tumours. A 61-year-old Japanese woman with a one-year history of subcutaneous tumours on the right thigh (4.0 cm in diameter) and right abdominal wall (1.0 cm in diameter) was referred to our hospital. Magnetic resonance imaging revealed that the lesions were located in the subcutaneous tissue and did not involve deep structures (Fig. 1A). Both lesions were excised. Histopathological staining revealed oval to round cells with abundant eosinophilic granular cytoplasm in both tumours. Partial tumour necrosis, focal pleomorphism, and mitotic figures (1/10 high-power fields) were observed in the thigh tumour (Fig. 1B), but not in the abdominal tumour. The tumour cells in both lesions were immuno-positive for the S100 protein, neuron-specific enolase, and CD68, but immunonegative for CD34, keratin AE1/AE3, and human melanoma black-45. The MIB-1 labelling index was 5% in the thigh tumour, compared to 3% in the abdominal tumour. We diagnosed these lesions as GCT and carefully followed up the patient. After 20 months, a right inguinal tumour was noticed, which developed rapidly over 6 months. Physical examination revealed an elastic, hard, and painless mass, 6.5 cm in diameter. The tumour consisted of nests of spindle and oval to round cells with abundant eosinophilic granular cytoplasm, accompanied by necrosis. These cells included vesicular nuclei with large nucleoli, a high nuclear-to-cytoplasmic ratio, and cytologic pleomorphism. Mitotic figures were also occasionally observed (4/10 high-power fields) (Fig. 2A, B). The tumour cells were immunopositive for the S100 protein and CD68. The MIB-1 labelling index was 17%. Cytoplasmic staining of S100A6 and receptor for advanced glycation endproducts, a multi-ligand receptor that binds a variety of proteins including S100 family proteins, was observed in the abdominal, the thigh and the inguinal tumours (Fig. 2C). Staining for other subtypes of S100 (S100A2, A4, A7, and P) was negative. We resected the right thigh tumour with a wide 2-cm margin and performed right inguinal dis-section. Two of the 6 lymph nodes were metastatic. Six …