Clonal relationship between juvenile xanthogranuloma and juvenile myelomonocytic leukaemia: insights from a PTPN11...

Juvenile xanthogranuloma (JXG) is typically a benign non-Langerhans cell histiocytosis, but it has been rarely associated with juvenile myelomonocytic leukaemia (JMML). Mutations in the RAS-MAPK (mitogen-activated protein kinase) pathway are implicated in both conditions, suggesting a shared genetic basis. However, only one prior case has demonstrated a clonal relationship. We report the case of 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.226G>A) variant in both peripheral blood (32.6%) and skin lesions (27.2%). The early identification of this mutation prompted urgent haemato-oncological 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.