Porth's Essentials of Pathophysiology, 4e

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Disorders of White Blood Cells and Lymphoid Tissues

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nophenotyping to determine the lineage and clonal- ity. Lymphomas can be grouped according to surface markers or phenotypic markers (e.g., CD20). 43 Staging of the disease is important in selecting a treatment for persons with NHL. Bone marrow biopsy, blood stud- ies, chest and abdominal CT scans, magnetic resonance imaging (MRI), positron emission tomography (PET), gallium scans, and bone scans may be used to determine the stage of the disease. 39 Newer technologies, such as deoxyribonucleic acid (DNA) microarray analysis, which identifies genes that are either overexpressed or underexpressed by tumor cells, may be used to further classify patients into distinct risk groups. Treatment of NHLs depends on the histologic type, stage of the disease, and clinical status of the person. 40 For early-stage disease with single or limited node involve- ment, localized radiation may be used as a single treatment modality. However, because most people who present with indolent lymphomas have disseminated disease at the time of diagnosis, combination chemotherapy, combined adju- vant radiation therapy, or both are recommended. Persons with lymphomas that carry a risk of CNS involvement usually receive CNS prophylaxis with high doses of che- motherapeutic agents or cranial irradiation. Hodgkin Lymphoma Hodgkin lymphoma, previously known as Hodgkin dis- ease, is a specialized form of lymphoma that features the presence of an abnormal cell called a Reed-Sternberg cell. 4,7,39,44 Because of improved treatment methods, death rates have decreased by more than 60% since the early 1970s. Distribution of the disease is bimodal; it occurs more frequently in two separate groups, the first in early adulthood (15 to 40 years) and the second in older adult- hood (55 years of age or older). 39,44 About 10% to 15% of cases are diagnosed in children and teenagers. 44 Hodgkin lymphoma differs from NHLs in many aspects. First, HL usually arises in a single node or chain of nodes and spreads first to anatomically contiguous lymphoid tissues, while NHLs frequently originates at extranodal sites and spreads in an unpredictable fash- ion. Therefore, the staging of HL is much more impor- tant in guiding therapy than it is for NHLs. Second, HL also has distinctive morphological features. It is charac- terized by the presence of large, atypical, mononuclear tumor cells, called Reed-Sternberg cells (Fig. 11-9). These cells release factors that induce the accumulation of reactive lymphocytes, macrophages, and granulo- cytes, which typically make up greater than 90% of the tumor cells. 7 The origin of the neoplastic Reed-Sternberg cell of Hodgkin lymphoma has been difficult to study, in large part because these cells do not express many of the markers found on lymphocytes. It is only recently that methods have been developed that allow for the micro- analysis of these cells and their variants. These stud- ies have shown that the Reed-Sternberg cells of most individual cases harbor identical immunoglobulin genes that show evidence of mutation, establishing the cell of origin as a germinal center or postgerminal center B cell.

remain localized for prolonged periods and to follow an indolent course. Extranodal marginal B-cell lymphomas of the MALT type are curable by radiation or surgery when localized. Mucosa-associated lymphoid tissue lymphomas that occur in the stomach secondary to H. pylori infection often respond to treatment with appro- priate antimicrobial agents. Clinical Manifestations. The manifestations of NHLs depend on lymphoma type (i.e., indolent or aggres- sive) and the stage of the disease. Persons with indo- lent or slow-growing lymphomas usually present with painless lymphadenopathy, which may be isolated or widespread. Involved lymph nodes may be present in the retroperitoneum, mesentery, and pelvis. The indo- lent lymphomas are usually disseminated at the time of diagnosis, and bone marrow involvement is frequent. With or without treatment, the natural course of the disease may fluctuate over 5 to 10 or more years. Many low-grade lymphomas eventually transform into more aggressive forms of lymphoma/leukemia. Persons with intermediate or more aggressive forms of lymphoma usually present with accompanying consti- tutional symptoms such as fever, drenching night sweats, or weight loss. Frequently, there is increased susceptibil- ity to bacterial, viral, and fungal infections associated with hypogammaglobulinemia and a poor humoral antibody response, rather than the impaired cellular immunity seen with Hodgkin lymphoma. Because of their high growth fraction, these lymphomas tend to be sensitive to radiation and chemotherapy. Hence, with intensive combination chemotherapy, complete remis- sion can be achieved in 60% to 80% of cases. 41 Diagnosis and Treatment. A lymph node biopsy is used to confirm the diagnosis of NHLs and immu- FIGURE 11-8. Burkitt lymphoma. A tumor of the jaw distorts this child’s face. (FromValdez R, Zutter M, Dulau FA, et al. Hematopathology. In: Rubin R, Strayer DS, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine. 6th ed. Philadelphia, PA: Wolters Kluwer Health | Lippincott Williams & Wilkins; 2012:1012).