Diagnostic Challenges and Treatment of Hairy Cell Leukemia in a Patient with Sarcoidosis: A Case Report

Introduction: Hairy cell leukemia (HCL) is a rare B-cell malignancy characterized by pancytopenia and susceptibility to infections. We report a case of a patient with sarcoidosis who developed HCL, experienced a relapse, but ultimately achieved complete remission with targeted therapy. Case: A 44-year-old Hispanic male with a history of asthma, sarcoidosis, and anemia (baseline hemoglobin 11.6 g/dL) presented for worsening anemia and thrombocytopenia. Stage III sarcoidosis was diagnosed bronchoscopically in 2009 due to a lung lesion on chest X-ray. The patient had occasional shortness of breath relieved by albuterol and never required treatment. In March 2020, he was hospitalized with symptomatic COVID-19. By February 2021, he developed significant anemia (hemoglobin 10.1 g/dL, MCV 98.1 fl), thrombocytopenia (66 K/uL), and splenomegaly. Peripheral blood smear revealed atypical lymphocytes; manual platelet count was 99 K/uL. ESR was elevated, but anemia workup was negative. The patient was clinically asymptomatic, no treatment was initiated. In June 2021, lab work showed a further decrease in hemoglobin (7.5 g/dL) and platelets (52 K/uL). A blood smear revealed lymphoid cells with hairy projections. Flow cytometry analysis detected 44% lambda monotypic B-cells, expressing CD19, CD20, CD11c, CD103, CD25, CD45, aberrant CD2 expression, consistent with HCL. Next-generation sequencing showed BRAF V600E mutation. Right iliac bone biopsy confirmed the diagnosis. The patient was treated with prednisone, cladribine and rituximab for one cycle. He achieved complete hematologic response with a reduction in spleen size. In January 2022, bone marrow biopsy showed residual leukemia (11% hairy cells by flow), while CBC was normal. In May 2022, peripheral blood flow cytometry showed <1% hairy cells, so he was treated with one more cycle of rituximab. In March 2023, cytopenia worsened, and 8% hairy cells were detected on peripheral blood flow cytometry. He was treated with vemurafenib and rituximab for two cycles and achieved complete hematological response and negative flow cytometry for residual disease by September 2023. As of June 2024, he remains in complete clinical and hematologic response. Discussion: HCL is a rare disease, and coexistence of HCL and sarcoidosis is uncommon. Although overlapping symptoms such as splenomegaly, cytopenia may be attributable to sarcoidosis, hematological diagnosis should always be considered. Asymptomatic HCL may not need immediate treatment. Despite his good response to standard cladribine and rituximab treatment, the patient experienced a relapse but achieved complete remission with vemurafenib and rituximab. The BRAF V600E mutation is a known driver mutation in HCL. Targeted therapy with BRAF inhibitors like vemurafenib has shown significant efficacy, especially in cases where traditional treatments fail or in relapsed/refractory HCL. Conclusion: This case illustrates the treatment outcome of HCL and underscores the importance of thorough evaluation in patients with complex medical histories to differentiate between sarcoidosis sequelae and emerging hematologic malignancies.

No relevant conflicts of interest to declare.