Pathophysiology
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...