Track

Case Reports

Abstract

A 59-year-old male presented with innumerable yellow to pink papules, nodules, and tumors ranging in size from millimeters to several centimeters, distributed on the head, neck, trunk, and extremities. The lesions initially appeared 10 years prior and progressively grew in size and number. Histopathology demonstrated dermal histiocytes with foamy cytoplasm and admixed Touton-type giant cells. Lesional histiocytes were diffusely positive with CD163 and negative for CD1a and S100, consistent with a diagnosis of xanthogranuloma. Next generation sequencing revealed mutations in BRAF (D594N and G466A) and KRAS (G12D). Laboratory evaluation, including complete blood count, lipids and serum and urine protein electrophoresis, was unremarkable. PET/CT showed multifocal FDG-avid osseous lesions and focal uptake in the pancreas and thyroid, and CT abdomen and pelvis demonstrated a hypoattenuating lesion in the pancreatic neck. Brain MRI demonstrated a hyperintense focus in the left temporal lobe concerning for intracranial xanthogranuloma. The patient’s presentation is best classified as disseminated adult-onset xanthogranuloma (AXG). Verification of multisystem disease is planned to include bone marrow and pancreas biopsies. Mutations in the MAPK pathway suggest susceptibility to therapy with a MEK inhibitor, such as cobimetinib.

AXGs typically present with isolated cutaneous lesions. Less commonly, but increasingly recognized, they can represent an immunohematologic neoplasm. Growing evidence suggests that AXGs, as well as some juvenile xanthogranulomas, harbor mutations in the MAPK pathway and exhibit significant molecular and clinical overlap with other non-Langerhans cell histiocytoses. Consequently, early recognition, genetic analysis, and thorough clinical evaluation for systemic involvement are warranted.