Version May 2024
| Entity | Histology | Immunophenotype | Genetic features/other | |
| Peripheral blood | Spleen and bone marrow | |||
| Splenic marginal zone lymphoma | Tumor cell resembles a lymphocyte with a round nucleus, condensed chromatin, and abundant basophilic cytoplasm with short surface "villous" projections that are often unevenly distributed around the circumference of the cell. | In the white pulp, the neoplastic cells occupy both the mantle and marginal zones, usually with a central residual germinal center, which may be either atrophic or hyperplastic. The red pulp demonstrates both a diffuse and micronodular pattern of involvement with sinus infiltration. Nodular pattern of marrow involvement. | Express surface immunoglobulin (eg, IgM+, IgD+), B cell antigens (CD19, CD20, CD22) and BCL-2. Expression of CD20 and surface immunoglobulin is bright. Frequently CD11c positive, subset is CD5 positive. Do not express CD25, CD103, or annexin A1. | No specific translocations or genetic abnormalities; deletions of 7q relatively frequent compared with other lymphoproliferative disorders. |
| Follicular lymphoma | Overt involvement of the blood is unusual. When present, circulating cells have notches or clefts, and correspond to centrocytes. | Follicular lymphoma cells are most often found in the white pulp and consist of a mixture of centrocytes and centroblasts. | Unlike splenic marginal zone lymphoma, follicular lymphoma cells express CD10 and BCL-6. | t(14;18) |
| Mantle cell lymphoma | Can have a leukemic phase with variable morphology. | Monomorphous small to medium-sized B lymphocytes infiltrate both the red and white pulp. | Typically positive for IgM, IgD, CD20 and CD5 and negative for CD23. Express cyclin D1. | t(11;14) |
| Hairy cell leukemia, classic | Commonly demonstrates circulating mononuclear cells one to two times the size of a mature lymphocyte with abundant pale blue cytoplasm. The cytoplasmic outline is indistinct with varying numbers of projections. The nuclei are often eccentric, lack prominent nucleoli, and have a reticular chromatin pattern. | Spleen is markedly enlarged with diffuse expansion of the red pulp and atrophy of the white pulp. The cords and sinuses of the red pulp are infiltrated by a monotonous population of tumor cells with a "fried egg" appearance. Dilated sinuses may form "blood lakes." | Most cases of hairy cell leukemia express CD20, CD22, CD11c, CD103, CD123, and CD25. Usually positive for annexin A1 and cyclin D1. Expression of CD20 and surface immunoglobulin is bright. Rare cases express CD5 or CD10. | Nearly 100 percent have BRAF V600E mutation. Lacks the t(11;14) despite cyclin D1 positivity. |
| Hairy cell leukemia, variant | May show greater nuclear irregularity, more variation in cell size, larger cell size, prominent nucleoli. | Similar to classic form of hairy cell leukemia. | Typically lack one or more markers that characterize classic forms of hairy cell leukemia (eg, CD25, annexin A1). | Lack the BRAF V600E mutation; approximately 50 percent have activating mutations in MEK1. |
| Chronic lymphocytic leukemia (CLL) | Circulating tumor cells are typically small, mature appearing lymphocytes with a dense nucleus, partially aggregated chromatin, and without discernible nucleoli. There is a narrow border of clear to slightly basophilic cytoplasm. | Most cases demonstrate diffuse infiltration of both the red and white pulp with effacement of the follicles. Some cases appear micronodular and involve the marginal zones of the white pulp. In difficult cases identification of proliferation centers (pathognomonic for CLL, best seen in lymph nodes) may be helpful. | Express CD23, CD43, CD5, IgD and/or IgM, BCL-2. | Diverse genetic lesions, none specific for CLL; trisomy 12 and deletions of 11q, 13q, and 17p most common abnormalities. |
| Lymphoplasmacytic lymphoma | Circulating malignant cells often have a plasmacytoid appearance with an oval shape, abundant basophilic cytoplasm, a round eccentrically located nucleus with "clock-face" chromatin, absent nucleoli, and a perinuclear hof. | Both the red and white pulp of the spleen may be infiltrated. The pattern is usually diffuse, without a distinct marginal zone or nodularity in the red pulp. | Express high levels of surface immunoglobulin, usually of IgM type; surface IgD is usually lacking. Express pan B cell antigens (CD19, CD20, CD22, CD79a). Subset is CD5 positive. The plasma cells express CD138. | Monoclonal immunoglobulin spike common, usually IgM. |
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