Differential Diagnosis

A malignant lymphoproliferative disorder should be suspected when the absolute lymphocyte count is greater than 5000 lymphocytes/^L. The differential diagnosis for patients with lymphocytosis, lym-phadenopathy, and/or organomegaly includes numerous malignant lymphoproliferative disorders (Table 23.1). These include CLL, PLL, adult peripheral T-cell lymphoma, natural killer cell leukemia, mantle cell lymphoma, marginal zone lymphoma (nodal, extran-odal, or splenic), hairy cell leukemia, SLL, lymphoplas-macytic leukemia, and follicular center lymphoma in a leukemic phase. Distinguishing CLL from other lym-phoproliferative disorders is based on morphology and, more importantly, on immunophenotype (Figure 23.1).

Lymphocytosis may be reactive and therefore poly-clonal and benign (Table 23.2). This must be distinguished from the malignant monoclonal lymphopro-liferative disorders. Reactive lymphocytosis may be due to viral or bacterial infections. In addition, individuals may have elevated lymphocyte counts following splenectomy. For B-cell lymphoproliferative diseases, monoclonality is usually established by immunoglobulin (Ig) light-chain restriction.5

Table 23.1 Differential diagnosis for monoclonal B-cell lymphoproliferative disorders

Clonal lymphocyte population Disease

B Cell Chronic lymphocytic leukemia

Mantle cell lymphoma Follicular lymphoma Hairy cell leukemia Splenic marginal zone lymphoma

Splenic lymphoma with villious lymphocytes Lymphoplasmacytoid lymphoma

B-cell prolymphocyte leukemia

T Cell Sezary syndrome

Large granular lymphocyte leukemia Adult T-cell leukemia/lymphoma HTLV-1 + T-cell leukemia T-cell prolymphocytic leukemia

Lymphocytosis Differential Diagnosis
Figure 23.1 Characterization of malignant lymphocytosis by flow cytometry. Lymphoproliferative disorders are characterized by flow cytometry based on T- and B-cell markers. This figure further classifies CD19+ lymphoproliferative diseases based on B-cell markers
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