Track: Case Reports

Topic: Lymphoproliferative Disorders

Abstract:

Adult-onset xanthogranuloma (AXG) is usually a solitary and benign lesion without genetic alterations. Multiple AXGs, however, behaves like disseminated juvenile xanthogranuloma, which represents a distinct histiocytic neoplasm exclusive to the pediatric population. We present a 50-year-old male with a 3-year history of asymptomatic but persistent skin-colored to red-brown papules and nodules on the face, neck, trunk, and extremities, unresponsive to isotretinoin. Multiple skin biopsies demonstrated well-circumscribed nodular dermal proliferations of histiocytes with bland nuclei and abundant foamy cytoplasm admixed with touton-type giant cells, suggestive of AXGs. The lesional cells were positive for histiocytic markers (CD68, CD163), S100, cyclinD1 (diffuse), and were negative for ALK, OCT2, and CD1a. Next generation sequencing on skin biopsy revealed no pathogenic mutations, but, RNA sequencing identified a novel LRCH1-FLT3 fusion, suggestive of clonal histiocytosis. Rearrangements of FLT3, a receptor tyrosine kinase with role in cell proliferation, is common in myeloid neoplasms with response to tyrosine kinase inhibition. Although rare, FLT3 fusions can occur in ~3% of histiocytic neoplasms. This patient was subsequently initiated on targeted therapy with FLT3-inhibitor (sorafenib) with remarkable improvement in skin lesions. This case emphasizes the significance of comprehensive workup for xanthogranuloma lesions. Diffuse cyclinD1 expression is well documented in histiocytic neoplasms, and the finding suggests MAPK pathway activation even in the absence of identifiable pathogenic mutations. Given the complexity of the work up required to diagnose and effectively treat this emerging class of disorders, a multidisciplinary approach and monitoring with dermatology, hematology, pathology, and radiology is imperative.

Gaurav Goyal

Affiliation

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Multiple Adult Onset Xanthogranulomas associated with LRCH1-FLT3 Fusion with Response to Sorafenib