Porth's Essentials of Pathophysiology, 4e

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Hematopoietic Function

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to various lymphoid tissues throughout the body, espe- cially the liver, spleen, and bone marrow. The classification of NHLs remains controversial and is still evolving. A commonly used classification is the World Health Organization (WHO) system 4,7,41 (Chart 11-2). The WHO system classifies lymphomas in terms of cell type (B or T cell), level of maturation (e.g., immature or mature), and anatomic sites (e.g., MALT lymphoma of the stomach). 4 The NHLs are actually a complex group of almost 40 distinct enti- ties, based on the appearance of the lymphoma cells, the presence of surface markers (e.g., antigens, CD markers), and genetic features. 4,5,19 In addition, the specific types of lymphomas are sometimes grouped together into low-grade, aggressive, and very aggres- sive categories. Mature B-Cell Lymphomas. Mature (peripheral) B-cell lymphomas are the most common type of lymphoma in the Western world. The most common of the mature B-cell lymphomas are the follicular lymphomas (22%) and diffuse large B-cell lymphomas (31%). Small lym- phocytic lymphoma, mantle cell lymphoma, periph- eral T-cell lymphoma, and MALT lymphoma together account for 28% of NHLs. 4 Follicular lymphomas are derived from germinal cen- ter B cells and consist of a mixture of centroblasts and centrocytes. Follicular lymphomas are a particularly common neoplasm in the United States, where they con- stitute about one third of all adult NHLs, with a peak incidence at 60 years of age. The lymphoma predomi- nantly affects lymph nodes. Other sites of involvement CHART 11-2   WHO Classification of Selected Non- Hodgkin Lymphomas (most common) B-Cell Lymphomas Precursor B-cell lymphomas B-cell lymphoblastic lymphoma Mature B-cell lymphomas Diffuse large B-cell lymphoma Mediastinal large B-cell lymphoma Follicular lymphoma Small lymphocytic lymphoma Lymphoplasmacytic lymphoma Mantle cell lymphoma Mucosa-associated lymphoid tissue (MALT) lymphoma Burkitt lymphoma T-Cell Lymphomas PrecursorT-cell lymphomas T-cell lymphoblastic lymphoma MatureT- (and natural killer) cell lymphomas Anaplastic large cell lymphoma PeripheralT-cell lymphoma (unspecified) Developed from theWorld Health Organization. Available at: http://www.who.int/classifications/apps/icd/meetings/ tokyomeeting/B_6-3%20Annex1.pdf

include the spleen, bone marrow, peripheral blood, head and neck region, gastrointestinal tract, and skin. Most persons have advanced disease at presentation and an indolent clinical course, with a median survival of 6 to 10 years. 7 Over time, approximately one of three follicu- lar lymphomas transforms into a fast-growing diffuse large B-cell lymphoma. Diffuse large B-cell lymphomas are a heterogeneous group of aggressive germinal or postgerminal center neoplasms. The disease occurs in all age groups but is most prevalent between 60 and 70 years of age. The cause of diffuse large B-cell lymphoma is unknown, but may involve EBV or HIV infections. It is a rap- idly evolving, multifocal, nodal and extranodal tumor. Manifestations are typically seen at the time of presen- tation. As a group, diffuse large B-cell lymphomas are rapidly fatal if untreated. 42 However, with intensive combination chemotherapy, complete remission can be achieved in 60% to 80% of persons and approximately 40% to 50% remain disease free after several years and can be considered cured. 7 Burkitt lymphoma, one of the most rapidly growing tumors of the NHLs, is also a disorder of germinal cen- ter B cells. Endemic Burkitt lymphoma is the most com- mon childhood cancer (peak age 3 to 7 years) in Central Africa, often beginning in the jaw. 4 It occurs in regions of Africa where both EBV and malarial infections are com- mon. Virtually 100% of patients with African Burkitt lymphoma have evidence of previous EBV infection, and their tumors carry the EBV genome and express EBV-encoded antigens. 4 Malarial infections in this pop- ulation have been shown to cause T-cell immunodefi- ciencies, and it is postulated that this association may be the link between EBV infection and the development of lymphoma. A sporadic or nonendemic form of Burkitt lymphoma occurs less frequently in other parts of the world. The classic presentation of endogenous Burkitt lymphoma is a destructive tumor in the jaw and other facial bones (Fig. 11-8), whereas the sporadic form typi- cally presents with abdominal masses. Both forms of Burkitt lymphoma respond to aggressive chemotherapy, with a cure rate of up to 90%. 4 Mantle cell lymphomas constitute less than 10% of NHLs and have their origin in the naive B cell. After the precursor stage, B cells undergo immunoglobulin (Ig) gene rearrangements and develop into surface IgM- and IgD-positive naive B cells. These cells give rise to mantle cell lymphoma. Mantle cell lymphomas do not occur in children, but affect older persons (median age, 60 years). 4,7 They have a rapid rate of progression, and only one in five persons survives at least 5 years. Marginal zone lymphomas involve late-stage memory B cells that reside in the marginal zone or outermost compartment of the lymph node follicle. Variants of marginal node lymphoma include splenic marginal zone lymphoma and MALT lymphomas of the stomach and other mucosal surfaces. Mucosa-associated lymphoid tissue lymphomas constitute 5% to 10% of all B-cell NHLs. 4 Most MALT lymphomas involve the stomach or other mucosal sites, including the respiratory system. Mucosa-associated lymphoid tissue lymphomas tend to