Abstract

A 56-year-old healthy man presented with new onset, innumerable, reddish brown, dome-shaped papules on the face, scalp, neck, chest, back, and shoulders. The lesions were mildly pruritic, but otherwise asymptomatic. Punch biopsy demonstrated a well-circumscribed nodular infiltrate with sheets of histiocytes, Touton giant cells, and rare bizarre multinucleated giant cells with foci of emperipolesis. The initial differential diagnosis included generalized eruptive histiocytosis, progressive nodular histiocytosis, and Erdheim-Chester disease. The histiocytes were positive for CD68 and ALK immunohistochemical stains, and negative for S100 and CD1a. BRAF mutational testing was negative. Imaging demonstrated diffuse bony sclerotic activity, most severe in the appendicular skeleton; there were also nodules in the peritoneal and retroperitoneal fat. Molecular testing demonstrated the presence of a DCTN1-ALK fusion, leading to the diagnosis of ALK-positive non-Langerhans cell histiocytosis. Patient was started on an anti-ALK antibody (alectinib) for treatment. ALK-positive histiocytosis is a rare histiocytosis with a wide clinicopathologic spectrum. Most cases are reported in infants and children, but cases have rarely been reported in patients as old as 51. Neurologic involvement is common, as is involvement of the liver, lung, bone, and skin. Cutaneous lesions often mimic xanthogranulomas, with nodular proliferations of foamy histiocytes with Touton giant cells. Immunohistochemical staining is positive for CD68 and ALK, and negative for S100 and CD1a. Multiple ALK-fusion proteins have been reported, with KIF5B-ALK being the most common. DCTN1-ALK, present in our case, has been reported in one other case in the literature. Treatment with ALK inhibitors can be effective in about half of cases. This is a recently described clinicopathologic entity with few reports in the literature, and recognition and awareness is crucial, as it has direct impact on therapeutic management.

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