Abstract
Hairy cell leukemia (HCL) is a disease with distinctive clinical findings, as well as a unique morphology and immunophenotype. These features typically allow for a reliable and reproducible diagnosis in nearly all situations. However, certain morphological features of HCL, such as villous cytoplasmic projections or characteristic tissue specific infiltrative patterns, including red pulp expansion with pseudosinuses, may be seen in other B-cell lymphoproliferative disorders. A methodical and thorough approach evaluating the clinical, cytological, histological, architectural, and immunophenotypic features is described and will aid in rendering the appropriate diagnosis. This is paramount as current data indicate that hairy cell leukemia - variant and other splenic B-cell lymphomas must be distinguished from HCL, as the response to therapy differs in these disorders.