An ALK Immunohistochemical Pitfall: ALK-Positive Histiocytosis Versus Angiomatoid Fibrous Histiocytoma

The proliferation of recognized neoplasms related to related to rearrangements involving kinase genes, arising in diverse somatic tissue lineages, poses an increasing challenge in surgical pathology. For instance, ALK rearrangements have been observed in diverse neoplasms of epithelial, connective tissue, and hematolymphoid lineages, many of which are associated with overexpression of ALK by immunohistochemistry as a useful biomarker. An even higher order challenge and pitfall would be the scenario where a tumor without an ALK rearrangement nonetheless overexpresses the protein, thereby simulating an ALK-defined neoplasm. Herein, we present this exact scenario, where an angiomatoid fibrous histiocytoma, exhibiting the recently-described phenomenon of its overexpression of ALK, clinically, histologically, and immunophenotypically simulated ALK-positive histiocytosis.