Clinical meaning
Lymphomas are clonal proliferations of lymphocytes arrested at specific stages of differentiation. Hodgkin lymphoma (HL) is characterized by the presence of Reed-Sternberg (RS) cells, which are large binucleated or multinucleated cells derived from germinal center B lymphocytes that have lost the ability to express immunoglobulin due to crippling mutations in the Ig gene variable region. RS cells constitute only 1-2% of the tumor mass; the remainder is a reactive inflammatory infiltrate of T cells, eosinophils, macrophages, and plasma cells recruited by cytokines (IL-5, IL-13, CCL5) secreted by RS cells. RS cells evade apoptosis through constitutive NF-kB activation and express CD15 and CD30 surface markers (targetable by brentuximab vedotin). HL spreads predictably along contiguous lymph node chains, which is why radiation fields follow anatomical nodal stations. Non-Hodgkin lymphoma (NHL) encompasses over 60 subtypes arising from B cells (85%), T cells, or NK cells. Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive NHL, characterized by rapid proliferation of large transformed B cells that efface normal nodal architecture. Follicular lymphoma, the most common indolent NHL, results from the t(14;18) translocation that juxtaposes BCL2 with the IgH promoter, producing constitutive BCL-2 overexpression that blocks apoptosis, allowing malignant follicular center cells to accumulate. The Ann Arbor staging system classifies disease extent: Stage I (single nodal region), Stage II (two or more regions on the same side of the diaphragm), Stage III (both sides of the diaphragm), Stage IV (extranodal dissemination to bone marrow, liver, lung). B symptoms (fever >38C, drenching night sweats, >10% weight loss in 6 months) confer worse prognosis and are appended as suffix B to the stage.