Association Between Juvenile Myelomonocytic Leukemia, Juvenile Xanthogranulomas and Neurofibromatosis Type 1: Case Report and Review of the Literature

Abstract

The occurrence of juvenile myelomonocytic leukemia (JMML), juvenile xanthogranuloma (JXG), and neurofibromatosis type 1 (NF1) together is relatively rare. Approximately only 20 cases have been reported in the literature. It is debated whether children with NF1 and JXG are at higher risk of developing JMML than children with NF1 alone. We present the case of a boy primarily diagnosed with NF1 with coexisting JXG who developed JMML at the age of 22 months. The clinical course from initial presentation to final diagnosis is detailed and the genetic features and hematologic characteristics are discussed. We report this case to underscore the importance of close monitoring of blood count and strict clinical follow-up in children presenting with concurrent NF1 and JXG and provide a possible explanation for this association.

Risk of intraocular and other extracutaneous involvement in patients with cutaneous juvenile xanthogranuloma

“…JXG has been associated with neurofibromatosis type 1 (NF1), and it has been suggested that risk of developing juvenile myelomonocytic leukemia is 20‐30 times as great in patients with NF1 and multiple JXGs than in those with NF1 without JXG, although a recent study concluded that JXG lesions are common in NF1 but not associated with greater risk of malignancy …”

Juvenile xanthogranuloma: retrospective analysis of 44 pediatric cases (single tertiary care center experience)

“…Concurrent eruptive JXG with café‐au‐lait spots has been reported, which may be associated with NF1 mutations and NF1 as a clinical diagnosis 7,14‐17 . Although an increased risk of juvenile myelocytic leukemia in patients with JXGs and NF1 mutations has been reported, 6‐8,15 none of the patients in our study with eruptive JXG developed signs or symptoms of hematologic disorders during the period of clinical follow‐up.…”

Juvenile myelomonocytic leukaemia presentation after preceding juvenile xanthogranuloma harbouring an identical somatic PTPN11 mutation

“…The association of juvenile xanthogranuloma (JXG) and juvenile myelomonocytic leukaemia (JMML) has been described in approximately 20 cases in the literature 1‐3 ; however, the pathogenesis underlying the concomitant presentation has never been elucidated in detail. We present the case of a child who developed JXG at the age of 3 months, and 23 months later he was diagnosed with JMML harbouring a somatic PTPN11 p.E76K mutation.…”