In this study, we uncovered activating mutations in CSF1R and rearrangements in RET and ALK that conferred dramatic responses to selective inhibition of RET (selpercatinib) and crizotinib, respectively, in patients with histiocytosis.
The clinicopathological spectrum of ALK-positive histiocytosis is broader than originally described, and this entity is characterized by frequent presence of KIF5B-ALK gene fusion.
Our 2 cases highlight previously unrecognized diversity of ALK-positive histiocytosis in clinical manifestation, organ involvement, and cytomorphologic features and further elucidate the diagnostic challenges of this rare entity.