Non-Hodgkin Lymphoma
Summary of Key Points
Incidence
• Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy; more than 70,000 were estimated to be diagnosed in the United States in 2012. Diffuse large B-cell (DLBCL) and follicular lymphoma (FL) are the most common subtypes, each comprising approximately one third of cases in the Western Hemisphere.
• In the Western hemisphere, approximately 85% of lymphomas are of B-cell origin and 15% are of T-cell/natural killer-cell origin. T-cell lymphomas have a higher incidence in parts of Asia.
Etiology and Biology
• Etiology of most lymphomas is complex and multifactorial. Defects in host immunity that increase the risk and infections associated with NHL include Helicobacter pylori, Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), human T-cell leukemia/lymphoma virus type I (HTLV-I), hepatitis C, and human herpesvirus–8 (HHV-8).
• Specific genetic abnormalities associated with lymphomas include translocations of BCL-2 (t(14;18)) in FL and DLBCL; BCL-6 (t(3;16)) in DLBCL; BCL-10 (t(11;18)) in mucosa-associated lymphoid tissue lymphoma; MYC (t(8;14), t(2;8), t(8;22) in Burkitt lymphoma and subsets of DLBCL; BCL-1 (t(11;14)) in mantle cell lymphoma (MCL); and ALK (t(2;5)) in anaplastic lymphoma kinase (ALK) + anaplastic large T-cell lymphoma (ALCL).
• Gene expression profiling can subdivide the largest group of lymphomas, DLBCL, into three subtypes with distinct pathogenetic mechanisms and decidedly different prognoses.
Differential Diagnosis
• Excisional biopsy is preferred for initial diagnosis and should be reviewed by an experienced hematopathologist. Fresh-frozen tissue should be collected for additional studies.
• World Health Organization (WHO) Classification of Lymphoid Malignancies recognizes lymphomas that may be unclassifiable with morphologic features alone. Clinical and molecular features are essential for subclassification of lymphomas.
Staging Evaluation
• Staging evaluation includes patient history and physical examination; complete blood cell count and chemistry studies including lactate dehydrogenase; computed tomography (CT) of chest, retroperitoneum, and pelvis; and bone marrow biopsy. Positron emission tomography (PET) aids in the detection of extranodal disease and is more sensitive than CT alone.
Primary Therapy
• Rituximab, a chimeric monoclonal antibody against CD20, is an essential component of the front-line and relapsed treatment of B-cell lymphomas.
• Treatment of indolent lymphomas such as follicular lymphoma, marginal zone lymphoma, and lymphoplasmacytic lymphoma is for palliative benefit and is not curative; treatment is frequently curative for DLBCL, ALK+ ALCL, Burkitt lymphoma, and lymphoblastic lymphoma; and proper dose-intensity of therapy is essential.
• MCL demonstrates remarkable clinical heterogeneity; no curative therapy exists, but a subset of patients can have a long indolent course without therapy.
• Peripheral T-cell lymphomas (PTCLs) other than ALK+ ALCL have a poor prognosis and are difficult to cure with standard therapy.
