Track

Case Reports

Abstract

Erdheim-Chester disease (ECD) is a rare histiocytic neoplasm often treated with BRAF/MEK inhibitors. A known paradoxical effect of this therapy is the development of sarcoid-like granulomatous reactions. While these reactions are documented, their presentation as a granulomatous tattoo reaction with unusual immunophenotypic changes is not well-described. We present a case of a granulomatous tattoo reaction with aberrant CD163 loss in a patient with ECD on targeted therapy. A 33-year-old male with BRAF V600E-mutated ECD on dabrafenib and trametinib developed new nodules confined to his longstanding tattoos. A skin biopsy showed a dermal granulomatous infiltrate centered on tattoo pigment. Immunohistochemistry revealed histiocytes positive for CD68 and CD4; however, a significant subset of these cells showed a loss of CD163 expression. Rare Langerin-positive, BRAF V600E-positive cells were present, consistent with low-level background of patient's known ECD/Langerhans cell histiocytosis, but the overall features were those of a granulomatous tattoo reaction. Sarcoid-like reactions during BRAF/MEK inhibitor therapy, an increasingly recognized entity in melanoma, are also seen in other conditions treated with these agents, such as ECD. In this case, the reaction is notable for its localization to tattoos and the aberrant loss of the histiocytic marker CD163, likely a direct consequence of the therapy's immunomodulatory effects. It is critical to distinguish this therapy-related reaction from a true progression of ECD. Recognizing this entity prevents misdiagnosis and the unnecessary cessation of effective therapy, as management typically involves continuing the BRAF/MEK inhibitors while monitoring the benign granulomatous process.