Version July 2025
| Entity | Histology | Immunophenotype | Genetic features/Other |
| 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. | t(11;14) must be excluded. No associated paraproteinemia. |
| 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. "Prolymphocytes" may be present, but are <55 percent of circulating cells. | Typically express CD5 and CD23. Expression of CD20 and surface immunoglobulin is dim. | Trisomy 12, deletions of 6q, 11q, 13q, and 17p |
| T cell prolymphocytic leukemia | Similar morphologic appearance to B-PLL. | Expresses pan-T cell antigens (CD2, CD3, CD5, CD7). | inv(14q) |
| Mantle cell lymphoma | Can have a leukemic phase that mimics B-PLL morphologically. | Typically CD20 and CD5 positive and CD23 negative. Express cyclin D1. | t(11;14) |
| Follicular lymphoma | Circulating centrocytes have highly irregular or cleaved nuclear contours. | Typically expresses CD10. | t(14;18) |
| Lymphoplasmacytic lymphoma | Occasionally associated with circulating malignant cells with a plasmacytoid appearance. | Often associated with a paraproteinemia. | |
| Hairy cell leukemia variant | Circulating tumor cells with morphology intermediate between hairy cells and prolymphocytes. | Express CD103 and CD11c. | Associated with mutations in MAP2K1 |
