Co-occurrence of clonally related follicular lymphoma and histiocytic sarcoma

Histiocytic sarcoma (HS) is a rare and aggressive malignancy thought to be derived from mononuclear phagocytic cells. No standard therapy exists for this disease, and the median overall survival is 6 months [ 1 ]. HS may also occur as a secondary cancer in the setting of a prior hematologic malignancy [ 2 , 3 , 4 , 5 , 6 ]. HS has been described in patients with follicular lymphoma (FL) [ 7 , 8 , 9 ]. In some of these cases, clonal rearrangements of B cell receptor genes, and IGH-BCL2 translocations, which occur early in FL pathogenesis [ 10 ], have established a shared clonal origin of FL and HS. Two evolutionary pathways are possible: (1) a common progenitor clone that can differentiate either into FL or HS [ 7 , 11 ] or ii) transdifferentiation from a malignant lymphoid clone to HS [ 8 ]. Understanding how a B cell malignancy can develop into a myeloid one would yield insights into the fundamental biology of both diseases. Here, we present single-cell analyses of samples from a patient with FL who developed HS and provide a comprehensive genetic and transcriptional analysis of both malignancies and their clonal relationships.