Massive splenomegaly can be caused by hematologic malignancy, lymphoproliferative disorders such as HLH, ALPS, Castleman disease, and various autoimmune diseases or PID.
We report the case of a 9 years old girl who presented since early childhood with easy bruising and bleeding from her gums with tooth brushing. Otherwise, she was completely asymptomatic with an unremarkable infectious history. After consulting for the first time at 5 years of age, she was discovered to have massive splenomegaly. She had pancytopenia and increased polyclonal immunoglobulins and CRP. A malignancy and storage disorder were excluded. The rest of the investigations were unremarkable, with normal bone marrow biopsy. Her flow cytometry was normal included double negative T-cells.
Finally a whole exome sequencing revealed a heterozygous gain-of-function mutation in the p.G13C KRAS gene, which was somatic (absence of the variants in the cheek swab). The same mutation had been reported by our group before in a patient with Rosai-Dorfman and SLE.
RAS-associated autoimmune leukoproliferative disease (RALD) should be considered in the context of lymphoid organ expansion, cytopenia and autoimmune diseases, in particular in absence of the criteria for ALPS. Our two cases underline the variability of the phenotype in RALD. Despite, the mild form of the present case, a regular follow-up is needed given the risk of development of malignity and autoimmunity. More research should define whether broad-spectrum KRAS inhibitors targeting the KRAS mutations found in malignancy can have some potential applications for RALD.