Lymphomas are a heterogeneous group of malignancies that originate from neoplastic transformation of a lymphocyte that has undergone mutations that confer growth and survival advantages compared with their normal cellular counterparts. These neoplasms usually originate in lymph nodes or lymphatic tissue in other sites (extranodal lymphoma) and can be localized or widespread at the time of diagnosis. Men are affected more frequently than women, and the risk of acquisition of most lymphomas increases logarithmically with age. There is considerable variation in incidence depending on geographical region and racial origin. The reported incidence of non-Hodgkin lymphomas rose dramatically between 1975 and 1995 and has since been relatively stable. It is not clear to what extent this relates to improved diagnostics. Although most lymphomas arise without an evident cause, certain occupations are associated with increased risk, and environmental toxins probably are implicated. Radiation exposure can be lymphomagenic. A number of infections are also implicated in lymphomagenesis. Human T-cell leukemia/lymphoma virus 1 (HTLV-1), Epstein-Barr virus (EBV), hepatitis C virus and human herpes virus-8 infections, as well as infections with the bacteria Helicobacter pylori and perhaps Chlamydophila psittaci, either are established as causal (eg, HTLV-1) or have very strong associations with lymphoma incidence (hepatitis C virus). HIV is permissive by inducing severe immunodeficiency and setting the stage for an EBV-induced or human herpes virus-8–induced lymphoma. Genome-wide association studies have revealed multiple loci predisposing to lymphoma; some predispose to all lymphomas, and others are restricted to limited lymphoma subtypes. The specific pathologic diagnosis is usually established by the appearance of the histopathology in tissue sections, the immunophenotypic profile of cluster differentiation antigens expressed on affected lymphocytes, specific cytogenetic findings, especially translocations (eg, t[11;14]), immunocytochemical markers (eg, cyclin D1), and the specific tissue location (eg, mucosa-associated lymphatic tissue). Determination of the anatomical extent of the lymphoma is largely determined from a thorough history, examination, and imaging, usually by positron emission tomography/computerized tomography. Therapy and recommendations for follow-up depend on the precise histologic entity, the anatomical stage, and patient comorbidities. Primary extranodal lymphoma may involve virtually any tissue or organ, and depending on the site, specific therapies may be required.
Acronyms and Abbreviations
ALCL, anaplastic large cell lymphoma; BMI, body mass index; CBC, complete blood count; CD, cluster differentiation; CI, confidence intervals; CLL, chronic lymphocytic leukaemia; CNS, central nervous system; CR, complete remission; CRu, complete remission unconfirmed; CT, computed tomography; DLBCL, diffuse large B-cell lymphoma; EBV, Epstein-Barr virus; FDG, 2-fluorodeoxyglucose; GWAS, genome wide association studies, HHV8, human herpes virus-8; HLA, human leukocyte antigen; HL, Hodgkin lymphoma; HR, hazard ratio; HIV, human immunodeficiency virus; HTLV-1, human T-cell leukemia/lymphoma virus-1; HL, Hodgkin lymphoma; Ig, immunoglobulin; ILSG International Lymphoma Study Group; IWG, International Working Group; MALT, mucosa-associated lymphoid tissue; MZL, marginal zone lymphoma; MRI, magnetic resonance imaging; NCCN, National Comprehensive Cancer Network; NCI National Cancer Institute; NHL, non-Hodgkin lymphoma; NK, natural killer; OR, observed risk; PET, positron emission tomography; PTCL, peripheral T-cell lymphoma; R-CHOP, ...