Transformed Nodular Lymphocyte-Predominant Hodgkin Lymphoma: Histologic Features and Relationship to T-Cell/Histiocyte–Rich Large B-Cell Lymphoma

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon variant of Hodgkin lymphoma, with a generally indolent course in low-stage presentations. Recurrences can demonstrate features of the diffuse variant, resembling T-cell/histiocyte–rich large B-cell lymphoma (THRLBCL). Transformation can additionally occur, either THRLBCL-like lesion or a diffuse large B-cell lymphoma (DLBCL). Transformation to DLBCL may be detected concurrently with NLPHL, prior to NLPHL, or years to decades later. The prognosis of such transformation is controversial, but thought to be worse than NLPHL and similar to that of de novo DLBCL. T-cell/histiocyte–rich large B-cell lymphoma–like transformation is histologically indistinguishable from primary THRLBCL, reflecting significant histologic and genetic overlap between NLPHL and THRLBCL. We present a patient with NLPHL and transformation to DLBCL at 7 years after initial diagnosis, who ultimately developed a therapy-related myeloid neoplasm. We review the histologic spectrum of transformed NLPHL, its relationship with THRLBCL, and recent developments in its molecular pathogenesis. Cases of transformation may prove valuable in understanding complex biologic relationships between a spectrum of overlapping lymphoma entities and may ultimately help refine therapy and improve prognosis.