Definition

Malignant granular cell tumor (MGCT) is a malignant neoplasm classified among the nerve sheath tumors due to its origin from Schwann cells. A benign counterpart exists (→ see Chap. 114).

Epidemiology and Presentation

MGCT is an extremely rare neoplasm which accounts for less than 2% of all granular cell tumors. It occurs in a wide age range (mean of 40 years), with a female predominance. Despite a Schwann cell phenotype, the origin from a nerve cannot be usually identified.

The most frequent sites of involvement are the soft tissue of the thigh, proximal arm, trunk, and then distal extremities. Less commonly it affects the head and neck. The lesion is 1–20 cm in diameter (median: 4 cm) and usually locates in subcutaneous or intramuscular tissues.

Pathology

MGCT is a sarcoma composed of malignant granular cells characterized by abundant cytoplasmic lysosomes filled with amorphous granular material (hence the name). Most cases have high-grade spindle or polygonal cell morphology with eosinophilic granular cytoplasm, high mitotic rate (>2 mitoses per 10 HPF), geographic necrosis, marked pleomorphism, and high nucleus-to-cytoplasm ratio.

A minority of cases are morphologically bland and not overtly malignant in appearance, although they still behave aggressively (i.e., give rise to metastasis). Some investigators argue that metastasis remains the only definite criterion for malignancy.

Biomarkers

Like the benign counterpart, MGCT stain is strongly and diffusely positive for S100 and CD68.

Prognosis

MGCT is highly aggressive with metastatic disease in up to 50% of patients (about 12% to lymph nodes, the remaining to distant sites). Larger primary tumor size, local disease recurrence, metastasis, and older patient age are adverse prognostic factors.

Therapy

Surgery is the treatment of choice for localized primary tumor. Due to the rarity of the disease, no standard therapy exists for metastatic disease; besides conventional chemotherapy, target therapy (e.g., pazopanib) has been utilized in anecdotal cases.