Version May 2024
| Entity | Histology | Immunophenotype | Genetic features/other |
| Hairy cell leukemia | The HCL cell is mononuclear and one to two times the size of a mature lymphocyte. The nuclei are often eccentric, lack prominent nucleoli, and have a reticular chromatin pattern. The cytoplasm is often abundant and pale blue to blue-gray in color. The cytoplasmic outline is indistinct with varying numbers of projections. Characteristically infiltrates the marrow in an interstitial or diffuse pattern; nodular aggregates are absent. | Most cases of HCL express CD20, CD22, CD11c, CD103, CD123, and CD25. Expression of cyclin D1 and annexin A1 is variable. Expression of CD20 and surface immunoglobulin is bright. Rare cases express CD5 or CD10. | Virtually all have BRAF V600E mutation |
| Hairy cell leukemia variant | Variant has circulating tumor cells with morphology intermediate between hairy cells and prolymphocytes. Nucleoli are prominent. | Express CD20, CD22, CD11c, and CD103. Expression of CD123 is dim or negative. Do not express annexin A1 or CD25. Expression of CD20 and surface immunoglobulin is bright. | HCL variants usually lack the BRAF V600E mutation, but are associated with mutations in MAP2K1. Often associated with IGH4-34 rearrangements. |
| Chronic lymphocytic leukemia/small lymphocytic lymphoma | "Typical" CLL cells are small, mature appearing lymphocytes with a dense nucleus, partially aggregated chromatin; no discernible nucleoli; and a narrow border of clear to slightly basophilic cytoplasm. Often involves the marrow as nodular aggregates, sometimes with proliferation centers. | Typically express CD5 and CD23. Expression of CD20 and surface immunoglobulin is dim. Do not express annexin A1. | Trisomy 12, deletions of 6q, 11q, 13q, and 17p. Distinct mutational profile without BRAF mutations. |
| B cell prolymphocytic leukemia | >55 percent (and usually >90 percent) of circulating white cells are "prolymphocytes": medium-sized cells with moderately abundant, slightly basophilic cytoplasm; a round or oval nucleus with moderately condensed chromatin; and a single, prominent nucleolus The bone marrow is infiltrated in an interstitial or nodular pattern by similar cells | Express bright surface IgM +/– IgD and bright CD20 as well as other B cell antigens (CD19, CD22, CD79a, FMC7) CD5 and CD23 expression is usually weak or absent. CD11c, CD103, CD10, CD25, and cyclin D1 are not expressed. Do not express annexin A1. | |
| Splenic marginal zone lymphoma | Splenic MZL cells usually have short polar villi. Both white and red pulp of the spleen are involved. Nodular pattern of marrow involvement. | Do not express CD103 or annexin A1. Expression of CD20 and surface immunoglobulin is bright. | Often associated with deletions of 7q. Distinct mutational profile without BRAF mutations. |
| Splenic diffuse red pulp small B cell lymphoma | Diffuse infiltration of the bone marrow, peripheral blood, and splenic red pulp by small monomorphous lymphocytes, usually with villous projections. | Typically negative for annexin A1, CD25, CD103, CD123, and CD11c | |
| Mantle cell lymphoma | Can have a leukemic phase | Typically positive for IgM, IgD, CD20 and CD5 and negative for CD23. Express cyclin D1. | t(11;14) |
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