XI. Non- Hodgkin's Lymphomas

• A. Malignancies of the lymphoid system in which the primary manifestations of disease occur outside the bone marrow, at the sites of normal lymphoid homing
  • 1. Lymph nodes
  • 2. Spleen
  • 3. M.A.L.T.
  • 4. Anywhere
  • 5. (Lymphomas outside lymph nodes and spleen are referred to as extranodal lymphomas)
• B. Approximately 40, 000 cases per year, 20,000 deaths
• C. Composed of cells frozen at a single stage of normal lymphoid maturation/differentiation
• D. Recapitulate the biologic behavior and immunophenotype of normal cell they mimic
• E. Since there are several cytologically and immunologically recognizable stages of normal lymphoid maturation, there are several subtypes of lymphoma
• F. All are clonal malignancies, derived from a single cell that has undergone a malignant transformation, mutation
• G. Best initially conceptualized as two major clinical types
  • 1. Indolent lymphomas
  • 2. Aggressive lymphomas
• H. Indolent lymphomas
  • 1. Lymphomas frozen at stages which are not normally replicating, but may be circulating
  • 2. Often widespread throughout the body at diagnosis
  • 3. Prolonged natural history, median survivals greater than 5 years
  • 4. Will usually respond very well to chemo- or radiation therapy
  • 5. Will usually relapse, and currently incurable unless
    • a. Localized disease (see below) or
    • b. Marrow ablation with some type of stem cell transplant
  • 6. Classification of indolent lymphomas- see below
• I. Aggressive lymphomas
  • 1. Lymphomas frozen at stages normally characterized by replication and accelerated growth
  • 2. More often localized at presentation than indolent lymphomas; more often extranodal
  • 3. Short natural history; median survival </= 2 years
  • 4. Require more aggressive forms of chemotherapy to achieve "clinical remission"- disappearance of all detectable disease
  • 5. Despite aggressive natural history, approximately 30-40% of adults curable with aggressive therapy, 50-80% children
• J. Subtyping within these two common clusters is necessary, because they have distinct clinical presentations, can require different therapy, and have differing prognoses, reflecting different mechanisms of molecular pathogenesis.
• K. Classification of lymphomas
  • 1. Rarely unanimous acceptance of any one classification scheme.
  • 2. Often changing terminology, reflecting classifier bias and new information
  • 3. Often lags behind advances in immunology, research pathology
  • 4. From 1982-1994, the classification used in the United States was called the Working Formulation for Clinical Usage.
    • a. Based on the dominant cytologic cell type observed under the microscope
    • b. Presence or absence of "follicularity" - mimicking of normal lymphoid follicle formation
    • c. The observed clinical history of 1200 patients classified according to the terminology below
      
      

Table 1: Working Formulation for Clinical Usage

• d. Divided into three "grades" of lymphoma-low, intermediate and high
  • 1). Low grade = indolent
  • 2). Intermediate and high = aggressive
• e. Microscopic features of malignant lymphomas
  • 1) Low power
    • a) Loss of normal architectural organization
    • b) Presence of absence of aberrant follicle formation
  • 2) High power
    • a) Replacement of cellular heterogeneity by a dominant cell type

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Pathology of Lymph Nodes Outline I-V. Goals, etc Outline VI. Big Picture Outline VII-IX Normal immune development Outline X Pathology Outline XI NHL1- Non-Hodgkin's lymphomas Outline XI NHL2- continued Outline XII NHL3- Ancillary diagnostic studies Outline XIII NHL4- Clinical features Outline XIV Hodgkin's lymphoma Outline XV Additional figures Self assessment