In Focus: Diffuse Large B-Cell Lymphoma

In non-Hodgkin’s lymphoma, the most common type of general lymphoma, tumors develop from the lymphocytes. Diffuse large B-cell lymphoma (DLBCL) accounts for 30–40 percent of newly diagnosed adult non-Hodgkin’s lymphoma, making it the most prevalent of these cancers. But DLBCL exhibits a key difference to other lymphomas: it rarely presents in the leukemic phase (1).

Lymphoma differs from leukemia by its primary site of disease, which is typically peripheral lymphoid tissue rather than blood or bone marrow. The presence of neoplastic lymphoid cells in lymphoma indicates that the peripheral blood and bone marrow have been infiltrated, ultimately giving rise to the leukemic phase. Although DLBCL patients rarely present with leukemic transformation, those who do frequently exhibit a high tumor burden, involvement of extranodal sites, and high lactate dehydrogenase levels.

DLBCL is microscopically characterized by the presence of large, atypical lymphoid cells; round, irregular vesicular nuclei with prominent nucleoli; and a moderate-to-abundant amount of pale blue cytoplasm. Immunophenotypically, DLBCL is positive for B-lineage markers, such as CD20, and variable immunoglobulins. Germinal center markers, such as CD10 and BCL6, are positive in 40–60 percent of cases; post-germinal center markers, such as CD38 and MUM1, are also expressed.

The basic pathogenesis of leukemic transformation in lymphoma, and the degree to which it occurs among different lymphomas, is still unclear. One possible mechanism for the migration of atypical lymphoid cells to the bloodstream is the expression of adhesion molecules, although this still requires validation.

Patients with DLBCL presenting in the leukemic phase are prone to extranodal and bone marrow involvement. One study of 29 patients uncovered the involvement of spleen in 62 percent, lung in 41 percent, liver in 21 percent, bone in 17 percent, cerebrospinal fluid in 14 percent, and bowel in 7 percent of cases (2). Such patients have a higher chance of early complications and death. Fortunately, treatment with anthracycline- and rituximab-based regimens is effective and associated with a four-year survival of approximately 50 percent.