Abstract
•Rare coexistence of HCL and aggressive B-cell lymphoma documented.•BRAF V600E mutation found only in HCL clone, not in lymphoma.•Concurrent HLH diagnosis complicated clinical management.•Immunophenotyping revealed two distinct B-cell populations.•Patient developed secondary HLH with rapid clinical decline.
Hairy cell leukemia (HCL) is a rare, indolent B-cell lymphoma that is highly responsive to the purine analog cladribine. A defining feature of classical HCL is the presence of the BRAF V600E mutation, which is almost universally present. The transformation of HCL to an aggressive large B-cell lymphoma is extremely rare. Here, we report a case of intercurrent presentation of worsening classical HCL with a rapidly evolving BRAF V600E-negative aggressive large B-cell lymphoma and associated hemophagocytic lymphohistiocytosis (HLH). The contiguous presentation of these three entities posed significant diagnostic and therapeutic challenges. Despite treatment with cladribine, the patient’s condition deteriorated, leading to a palliative focus. This case underscores the challenges of managing multiple intercurrent hematologic malignancies manifesting with overlapping symptoms and sites of organ involvement but non-overlapping treatments. The presence of HLH as a complication in patients with malignancy further complicates the clinical picture and requires early recognition and prompt intervention. Further research is needed to better understand the pathophysiological links between HCL, large cell transformation, and HLH. Additionally, registry or other cross-sectional studies with larger numbers of HCL patients could clarify the exact frequency of these rare but fatal complications.