Hairy Cell Leukemia and Its Mimics: A Case-Based Exploration of Diagnostic Complexity

Hairy cell leukemia (HCL) is a rare but well-characterized B-cell malignancy with distinct immunophenotypic and genetic features. Advances in molecular diagnostics, particularly the identification of the BRAF V600E mutation, have significantly enhanced diagnostic precision and informed targeted treatment strategies. However, the HCL variant and other HCL-like syndromes continue to present substantial diagnostic challenges due to their absence of BRAF mutations, atypical immunophenotypic profiles, and divergent clinical courses. This case report provides an overview of the morphological, immunophenotypic, molecular, and histopathological features of HCL, as well as its differential diagnoses, with a focus on the utility of flow cytometry and emerging molecular diagnostic markers. To underscore the practical implications of these diagnostic complexities, we present a case report that reinforces the challenges in distinguishing HCL from its mimics and highlights the role of contemporary integrated diagnostic methodologies.