Atypical Neurofibroma with Bizarre Giant Cells

A 27‐year‐old woman presented with a 5 mm papule on her cheek. She had no family history or stigmata of neurofibromatosis. Biopsy showed a diffuse dermal proliferation of spindle cells embedded in a slightly myxomatous stroma which entrapped adnexae. They displayed cytologic atypia with hyperchromatic nuclei and bizarre multinucleated giant cells. No mitosis were identified. Immunohistochemistry showed the spindle cells to be S‐100 and collagen IV positive, but MART‐1 negative. The differential diagnosis included desmoplastic melanoma, malignant peripheral nerve sheath tumor (MPNST) and atypical neurofibroma. Both atypical neurofibroma and desmoplastic melanoma are S‐100 positive, show variable atypia and can have bizarre multinucleated giant cells. However, the lack of epidermal melanocytic hyperplasia, mitosis and the positive collagen type IV staining, favor nerve sheath differentiation. In neurofibromatosis, neurofibromas may undergo malignant degeneration resulting in MPNST. Whether atypical neurofibroma represents a transitional stage is unknown. Mitotic activity and necrosis strongly suggest MPNST. The biologic potential of cutaneous atypical neurofibroma has not been well studied, but they appear to behave in a benign fashion. This case demonstrates the diagnostic challenge of atypia in neurofibromas and highlights the need for further studies on the behavior of these rare variants.