Hairy Cell / NHL Differentiation Marker : CD 25

Hairy cell lymphoma shows a characteristic immunophenotype: strong expression of B‑cell markers CD19, CD20 and CD22 plus bright CD11c, CD25, CD103 and CD123. Annexin A1 and TRAP are commonly positive. It is typically negative for CD5, CD10 and CD23. CD200 is often expressed and can aid diagnosis.

CD25 is the alpha chain of the interleukin‑2 receptor (IL‑2Rα). It marks activated T cells and is constitutively expressed at high levels on regulatory CD4+ T cells (CD4+CD25+FoxP3+). CD25 can also appear on activated B and NK cells and is used clinically to indicate immune activation and to help identify certain hematologic malignancies.

Differential diagnosis of hairy cell leukemia includes hairy cell leukemia–variant (HCL‑v), splenic marginal zone lymphoma and other splenic B‑cell lymphomas with villous lymphocytes, chronic lymphocytic leukemia, B‑cell prolymphocytic leukemia, mantle cell and follicular lymphoma with blood involvement, and reactive causes of splenomegaly/cytopenias (viral infections, aplastic or megaloblastic anemia). Diagnosis relies on morphology, flow cytometry/immunophenotype and BRAF V600E testing.

No. Classic hairy cell leukemia is typically CD5‑negative. Its characteristic immunophenotype shows strong B‑cell markers (CD19, CD20, CD22) with CD11c, CD25, CD103 and Annexin A1. CD5 positivity is rare and atypical; when present it prompts consideration of alternative diagnoses or variant forms, so immunophenotyping and molecular testing are used to confirm the diagnosis.

CD19 and CD20 are cell-surface proteins on B lymphocytes used as diagnostic and therapeutic markers. CD19 appears early in B‑cell development and persists through most mature B cells, while CD20 appears later on mature B cells but is absent on early precursors and plasma cells. Both help identify B‑cell populations by flow cytometry and serve as targets for antibody-based therapies in B‑cell disorders.

CD103 (integrin αE) is a cell-surface marker of tissue-resident lymphocytes, especially CD8+ tissue-resident memory T (TRM) cells found in epithelial and mucosal sites. It mediates adhesion to E‑cadherin, promoting retention in tissues. CD103 is also expressed on certain intraepithelial lymphocytes and subsets of dendritic cells, and is used to identify tissue-localized immune cells, including tumor-infiltrating lymphocytes.