XII. Ancillary diagnostic studies

• A. Use of immunologic techniques
  • 1. Malignant lymphomas reproduce the immunobiology of their benign counterparts
  • 2. This reproduction may be aberrant, and hence distinguishable from normal
  • 3. Normal lymphoid maturation (within the primary lymphoid organs) requires:
    • a. The production of a unique antigenic receptor on it's surface, through the process of genetic rearrangement of discontinuous segments of the antigen receptor genes
      • 1.) B cells
        • a.) immunoglobulin receptor composed of two heavy and two light chains
        • b.) Selection of only one of two light chains, kappa or lambda
      • 2.) T cells
        • a.) Alpha/Beta heterodimer T cell receptor
        • b.) Gamma/Delta heterodimer T cell receptor
    • b. The expression of several surface proteins necessary for antigen recognition, cell activation, cell-cell communication.
      • 1.) Classified into B, T, activation associated, cytokine receptor thru the CD, clusters of differentiation, numerical system. Now up to CD166. (You'll only be tested on 1-130 though - a joke for you paranoid types.)
  • 4. Expression, normal and aberrant can be used to:
    • a. Determine lineage, B versus T
    • b. Detect clonality- light chain disproportion (normal ratio kappa/lambda light chain expression in B cells= 2/1)
    • c. Suspect malignancy- loss of expression, aberrant expression
    • d. Recognize characteristic patterns associated with certain subtypes of lymphoma
  • 5. Immunologic signals can be detected by
    • a. Flow cytometry-automated fluorescent microscopy
    • b. Immunohistochemistry- in situ detection through the use of enzyme substrate color deposition
  • 6. Examples
    • a. B cell small lymphocytic lymphoma- monoclonal light chain, CD19, CD20, CD5 positive, CD10 negative
    • b. B cell small cleaved lymphoma- monoclonal light chain, CD19, CD20, CD10 positive, CD5 negative
• B. Molecular techniques
  • 1. Detection of antigen receptor clonality
  • 2. Detection of unique cytogenetic rearrangements
  • 3. Examples
    • a. T(14;18) and follicular small cleaved lymphoma- involves immunoglobulin heavy chain gene, ch.14, and bcl2, chr. 18, an "oncogene" normally controlling programmed cell death
    • b. T(8;14) and Burkitt's lymphoma- involves Ig heavy chain gene and myc oncogene, chr.8, which normally controls entry into cell cycle

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