Disseminated Juvenile Xanthogranuloma with a Novel MYH9-FLT3 Fusion Presenting as a Blueberry Muffin Rash in a Neonate

Abstract

INTRODUCTION: Juvenile Xanthogranuloma (JXG) is a benign proliferative histiocytic disorder of the dendritic cell phenotype. It mostly presents in the pediatric age group as a solitary skin lesion. We describe a rare case of an infant born with disseminated JXG who presented with a blueberry muffin rash at birth. CASE DESCRIPTION: A term infant was noted to have multiple petechiae, purple nodules, and macules (1 mm-2 cm in diameter) and hepatosplenomegaly, at the time of birth. Further investigations revealed thrombocytopenia and direct hyperbilirubinemia and an MRI showed scattered tiny foci of restricted diffusion in multiple areas of the brain. Patient received multiple platelet transfusions in the first few weeks with gradual improvement in thrombocytopenia. Ultimately, a biopsy of one of the lesions revealed the diagnosis of disseminated JXG with notable atypical features. Somatic mutation analysis showed a novel MYH9-FLT3 fusion, but a bone marrow biopsy was negative. The lesions faded over time, relative to patient’s growth and normal neurodevelopment was noted at 18 months of age. CONCULSION: JXG should be considered in the differentials of blueberry muffin rash in an infant. Although, JXG is mostly a self-limited condition, congenital disseminated JXG may be associated with significant morbidity and mortality.

Targeting hyperactive platelet-derived growth factor receptor-β signaling in T-cell acute lymphoblastic leukemia and lymphoma

“… 31 It is the only myosin class II protein that is highly expressed in T cells and has been linked to T-cell motility, 32 as well as immunological synapses and T-cell activation. 33 Fusions involving MYH9 have been found in other disorders and include MYH9::FLT3 , 34 MYH9::ROS1 , 35 and MYH9::USP6 . 36 Similarly, PDGFRB fusion proteins have been described in myeloid disorders and myeloid leukemia 15 , 20 , 37 , 38 and, indeed, aberrant expression of this receptor tyrosine kinase has been described in several cancer entities.…”

Brain imaging in children with neonatal cholestatic liver disease: A systematic review

“…In this heterogeneous group of diseases, some of the findings on brain imaging have been seen in other children with the same disease without cholestasis 94–97 . However, for erythrophagocytic lymphohistiocytosis, juvenile xanthogranuloma, unknown cholestatic liver disease and kernicterus scanned at diagnosis and one case of Kabuki scanned at 6–11 years of not all findings have previously been described in children without cholestasis 98–102 . The findings can be seen in Table 2A and Table S6.…”

“…[94][95][96][97] However, for erythrophagocytic lymphohistiocytosis, juvenile xanthogranuloma, unknown cholestatic liver disease and kernicterus scanned at diagnosis and one case of Kabuki scanned at 6-11 years of not all findings have previously been described in children without cholestasis. [98][99][100][101][102] The findings can be seen in Table 2A and Table S6.…”

Frequent detection of genetic aberrations reveals novel pathogenesis and treatment modalities in systemic juvenile xanthogranuloma

“…Interestingly, upregulation of ALK phosphorylation promoted the phosphorylation of PI3K/AKT, STAT3, and MEK/ERK, indicating that ALK induces cellular hyperplasia through various signaling pathways 5 . Additional studies have identified MRC1‐PDGFRB, RNF11‐BRAF , and MYH9‐FLT3 fusion proteins in SJXG 5,19 …”

“…5 Additional studies have identified MRC1-PDGFRB, RNF11-BRAF, and MYH9-FLT3 fusion proteins in SJXG. 5,19 As recurrent BRAFV600E mutations and ALK translocations have been detected in histiocytosis, we collected 23 cases of SJXG to screen for two common types of genetic abnormalities in a recent study, and the results showed that 34.7% (8/23) of these cases harbored ALK translocations and 17.4% (4/23) carried BRAFV600E mutants. 12 Our study indicates that ALK translocations play an important role in the pathogenesis of SJXG, which is different from BRAFV600E mutations in LCH and ECD.…”