Histiocytic Sarcoma With CCND1 Gene Rearrangement Clonally Related and Transdifferentiated From Mantle Cell Lymphoma

Abstract

Abstract Objectives Histiocytic neoplasms demonstrate shared gene translocations and clonal immunoglobulin gene rearrangements in cases of associated B-cell lymphomas. However, the evolution of these related disease processes remains largely uncertain, especially in the setting of a prior mantle cell lymphoma. Methods We describe a unique case of a histiocytic sarcoma that transdifferentiated from blastoid mantle cell lymphoma after extensive therapy. Cytogenic and molecular studies were performed and provided evidence for clonal progression. Results We present the first reported case of a patient with blastoid mantle cell lymphoma harboring a CCND1 rearrangement that progressed despite multiple therapeutic regimens and ultimately transdifferentiated into histiocytic sarcoma. The histiocytic sarcoma demonstrated a CCND1 rearrangement and targeted next-generation sequencing showed a pathogenic variant in NRAS, a gene involved in the RAS/MAPK pathway, known to play a role in the pathogenesis of histiocytic sarcomas. TP53, NOTCH2, CREBBP, and NFKBIE variants were also identified, which are often seen in B-cell lymphomas, while rarely described in histiocytic sarcoma. Conclusions To our knowledge, this is the first report to provide evidence for clonal evolution of histiocytic sarcoma from blastoid mantle cell lymphoma based on cytogenic and molecular findings. The patient’s protracted therapeutic course may have acted as an evolutionary driver promoting this transdifferentiation process.