Cushing's Warning: Cushing’s Syndrome as first sign of CNS relapse in pediatric acute lymphoblastic leukemia.

Central nervous system (CNS) relapse occurs in 5% of pediatric acute lymphoblastic leukemia (ALL) patients.Cushing syndrome (CS) as its presenting symptom is exceedingly rare.We describe a 4-year-old girl with precursor B-cell ALL (BCP-ALL) who developed CNS relapse, presenting with rapid weight gain and biochemical CS.At relapse she harbored a P2RY8::CRLF2 fusion and JAK2/NRAS mutations absent at diagnosis.Only 14 pediatric patients have presented with CS as the first sign of ALL relapse; all were (very) early BCP-ALL and prognosis was poor.We hypothesize an interplay among CRLF2-rearrangements, adipogenesis and inflammatory cytokines.Vigilance for CNS relapse is advised in overweight or CRLF2-rearranged patients.