Abstract

Xanthogranulomas are characterized by accumulation of histiocytes with bland nuclear features and abundant foamy (xanthomatous) cytoplasm, frequently admixed with touton-type giant cells. When such lesions present in pediatric population, they are classified as juvenile xanthogranuloma (JXG), a distinct histiocytic neoplasm per the WHO classification of hematopoietic tumors. Adult-onset XG (AXG) lesions, however, are considered to be benign and typically present as a solitary lesion. We present a 62-year-old female with persistent xanthelasma-like lesions in bilateral periorbital regions and right earlobe. Due to the anatomic site of involvement, differential diagnosis of histiocytic neoplasm, specifically Erdheim-Chester disease (ECD) was considered, but imaging studies were negative for systemic involvement. Histopathology of right earlobe showed dermal infiltrate of bland appearing histiocytes with positive staining for CD163, Factor 13a, cyclinD1 (diffuse) and ALK (nuclear and cytoplasmic), and these were negative for CD1a, OCT2, and S100. Next generation sequencing was pursued and was negative for ALK fusions, excluding ALK-positive histiocytosis. DNA sequencing revealed a pathogenic KRAS G12A (VAF: 11.3%), suggestive of clonal histiocytosis, necessitating treatment with a MEK inhibitor (Cobimetinib), an FDA-approved targeted therapy for histiocytic neoplasms.

AXG lesions should prompt a thorough workup to effectively identify cases with clonal histiocytosis amenable to targeted therapies. While these are classified under the ‘xanthogranuloma family’ per the 2016 Histiocyte Society classification, larger scale studies are needed to elucidate the evolution of these XG lesions, specifically in adults. Further, these XG lesions significantly overlap with ECD and a multidisciplinary approach is necessary for prompt diagnosis and effective management.