INTRODUCTION
Philadelphia chromosome - like acute lymphoblastic leukemia (Ph-like ALL) is defined by a gene expression profile similar to BCR::ABL1ALL.1 and associated with chemotherapy resistance and high risk of relapse.2 The four major subgroups of Ph-like ALL consist of CRLF2 rearrangements, ABL -class fusions, EPOR rearrangements, and JAK2rearrangements.3 In addition, somatic NTRK3 and RAS signaling pathway mutations (IL-7R, KRAS, NRAS) have been identified in a subset of Ph-like ALL.4
Histiocytic disorders are characterized by aberrant accumulation of phagocytes frequently with activating somatic mutations in RAS-MAPK pathway genes.5 Juvenile Xanthogranuloma (JXG) typically presents as a benign self-resolving non-Langerhans-cell histiocytic cutaneous proliferation . Clinical behavior and histology of disseminated JXG overlap with malignant histiocytosis (or histiocytic sarcoma) that can arise as a primary neoplasm or be associated with precursor hematopoietic malignancies, such as juvenile myelomonocytic and acute lymphoblastic leukemia.5-11 Secondary histiocytic neoplasms and their associated hematologic neoplasms share common genetic aberrations suggesting clonal divergence.10
Here we report the first known case of a pediatric patient with refractory Ph-like B-ALL complicated by disseminated JXG and hemophagocytic lymphohistiocytosis (HLH) treated with targeted therapy. This case provides unique insight into the drivers of both Ph-like B-ALL and JXG and illustrates novel use of a targeted MEK inhibitor.