Abstract

ALK rearrangement represents an important oncogenic mechanism in dermatopathology. ALK fusion represents a common initiating event underlying Spitz nevi and other melanocytic tumors of Spitz lineage, and rearrangement also represents an important trigger of non-neural granular cell tumor, epithelioid dermatofibroma, CD30+ lymphoma, and so-called infantile ALK+ histiocytosis. As a novel expansion of the ALK-associated spectrum, we have encountered 3 examples of non-systemic xanthogranuloma induced by ALK rearrangement. The three tumors presented on the back of a 19-year-old man and on the thigh of a 79-year-old woman. Histopathologic sections demonstrated a nodular infiltrate of foamy histiocytes with admixed Touton-type multinucleated cells. An associated infiltrate of lymphocytes and granulocytes was present. The infiltrate of one tumor was rich in eosinophils, and another tumor showed associated fibrosis. The affected patients were otherwise well. Interestingly, the classic histomorphology of xanthogranuloma is not unique to a single molecular pathway. Rather, our data suggests that the pathogenesis of xanthogranuloma may be diverse, since charactistic histopathology can be triggered both by point mutation (BRAF V600E) and gene rearrangement (ALK).