Clonal Relationship Between Juvenile Xanthogranuloma and Juvenile Myelomonocytic Leukemia: Insights from a PTPN11 Missense Variant.

Abstract

Juvenile xanthogranuloma (JXG) is typically a benign non-Langerhans cell histiocytosis but has been rarely associated with juvenile myelomonocytic leukemia (JMML). Mutations in the RAS-MAPK pathway are implicated in both conditions, suggesting a shared genetic basis; however, only one prior case has demonstrated a clonal relationship. We report a 21-month-old boy with a progressive yellow papulonodular rash, dusky plaques, and recurrent infections. Skin biopsy confirmed JXG, and exome sequencing revealed a somatic PTPN11 (c.226 G>A) variant in both peripheral blood (32.6%) and skin lesion (27.2%). The early identification of this mutation prompted urgent hemato-oncologic evaluation. Two weeks later, the patient developed overt JMML and was successfully treated with chemotherapy and bone marrow transplantation. The shared mutation supports a clonal relationship between JXG and JMML. This case highlights the value of early genetic testing in atypical JXG and represents the second documented case of clonally related, sequential JXG and JMML.