Malignant peripheral nerve sheath tumor (MPNST) is a soft tissue malignancy that can occur sporadically or in association with neurofibromatosis type 1 (NF1). The tumor generally occurs in adults (typically earlier in patients with NF1) and most commonly involves the nerve trunks/plexi of proximal limbs or head and neck. Recurrences and distant metastases occur in approximately half of cases. Surgical resection, with or without adjuvant radiotherapy, offers the best chance for cure or local control.

The tumor is composed of uniform spindled cells arranged in fascicular, storiform, and herringbone patterns. On low power there are areas of hypo-and hypercellularity. The cytoplasm of the cells is long and tapered on either end but difficult to distinguish on H&E staining. Tumor cell nuclei show mild enlargement and hyperchromasia and often retain the wavy contour characteristic of neural differentiation. The stromal background may be myxoid to fibrous. Mitotic figures are often easily found and necrosis is common. By immunohistochemistry MPNST may have focal S100 positivity (approximately 50% of tumors), and may also stain with CD34. This case showed positive staining with S100 and SOX10, but was negative for CD34.

The differential diagnosis includes other tumors with similar architectural patterns, such as synovial sarcoma (may be biphasic and monotonous, EMA occasionally positive, characteristic translocation), leiomyosarcoma (stains for smooth muscle markers instead of S100), dedifferentiated liposarcoma (look for well-differentiated component; has characteristic 12q13-q15 amplification), and undifferentiated pleomorphic sarcoma (diagnosis of exclusion, no NF1 association).

This slide shows H&E stain. See Related Content for S100 and SOX10 stains.