Abstract/Scope of ChapterThis chapter provides an overview of lymphomas and related tumors presenting at extranodal locations. Commonalities and differences in the approach to diagnosis, staging, and their pathogenesis are summarized. Intrinsic tumors of the thymus are also discussed.
Keywords
Overview of Extranodal Lymphomas
General FeaturesThe definition of an extranodal lymphoma is usually one in which the presenting tissue site is the location of primary involvement for at least 3-6 months following diagnosis. However, some extranodal lymphomas show systemic spread much more rapidly (e.g. those in the spleen or tonsils), whereas lymphomas at other sites (e.g. the skin or stomach) can remain localized for many years even without treatment. The general demographic features of extranodal lymphomas are similar to nodal cases, with median age in the fifth to sixth decade at diagnosis, except for those cases with antigen-driven or autoimmune etiology (e.g. MALT lymphomas), which usually present at a slightly younger age.The overall distribution of lymphomas at different extranodal sites is shown in Table 27-1. Several conclusions can be drawn: (1) there are major differences in the types of extranodal lymphomas arising in pediatric and adult patients;[1] (2) geographic differences are noted in the incidence of extranodal lymphomas related to their inciting causes; (3) lymphomas are rare in immune-privileged sites such as the central nervous system (CNS) and testes; and (4) although individual differences in histologic types occur at each site, diffuse large B-cell lymphoma (DLBCL) and marginal zone lymphoma of MALT type (MALT lymphoma) are the most common B-cell lymphomas at most extranodal sites in adult patients, with follicular lymphoma (FL) commonly involving any organ with secondary lymphoid tissue, including bowel mucosa. The most important insight into the development of lymphomas at extranodal sites was the observation that lymphomas sometimes develop from the nonneoplastic mucosa-associated lymphoid tissue (MALT) that arises in inflammatory states. The concept was first developed to explain the emergence of low-grade marginal zone B-cell lymphomas in the small intestine of patients with preceding bacterial infections, but Isaacson and colleagues [2] subsequently expanded the concept to explain the inflammatory-based histogenesis of MALT lymphomas at other extranodal sites . As summarized in Table 27-2, several additional B-cell and T-cell lymphomas have a clear association with preceding inflammatory states, such as mycosis fungoides (MF) arising out of chronic dermatitis ( Fig. 27-1b).Another driver of the extranodal localization of lymphoproliferative disorders is the recruitment of tumor lymphocytes to sites of ongoing inflammation or immune activation. This is particularly common in follicular lymphoma (FL), which homes to germinal centers at any tissue site, and in chronic lymphocytic leukemia/small lymphocyte lymphoma (CLL/SLL), which colonizes sites of preexisting inflammation. As a result, CLL i...
