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1576 Part XI: Malignant Lymphoid Diseases Chapter 95: General Considerations for Lymphomas 1577

A B

C D

Figure 95–3. Primary extranodal follicular lymphoma in a parotid gland of a 67-year-old woman. A. Upper right corner shows normal salivary gland
tissue adjacent to a lymphomatous follicular infiltrate with intense fibrosis. B. Lymphoma infiltrate with a vaguely nodular appearance. C. Nodular
appearance better appreciated after immunohistochemical staining for the B-cell marker CD20. D. Lymphomatous follicles display over-expression
for BCL2, which would not be seen in reactive germinal centers. Flow cytometric evaluation showed a monotypic CD10+ B-cell population with λ
light-chain restriction and BCL2 expression on cytoplasmic staining (not shown). (Used with permission from Raymond Felgar, University of Pittsburgh
Medical Center.)

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CHROMOSOMAL TRANSLOCATIONS the BCL-2 protein. The accumulation of the BCL-2 protein permits
accumulation of long-lived centrocytes, because the BCL-2 protein
ASSOCIATED WITH HISTOPATHOLOGIC inhibits programmed cell death (apoptosis), leading to a longer cell life
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SUBTYPE (Chap. 99). The BCL-2 rearrangement can be detected by the
polymerase chain reaction or by iFISH testing (Chap. 99).
Chromosomal abnormalities involving all chromosomes may occur in
lymphomas (Chap. 11). Lymphoid malignancies have a high frequency BURKITT LYMPHOMA
of translocation-inducing fusion genes. Usually they are of two types:
one involving oncogenes that are activated by juxtaposition with IgH In Burkitt lymphoma, the common genetic abnormality is the translo-
or TCR genes, or by formation of chimeric genes that constitutively cation of the MYC oncogene from chromosome 8 to either the immu-
activate mutant kinases or mutant transcription factors. The molecu- noglobulin heavy-chain region on chromosome 14, t(8;14)(q24;q32),
lar alterations leading to translocations involving nonimmune genes or, less commonly, the κ region on chromosome 2, t(2;8)(p13;q24),
are not known, whereas there is strong evidence that mistakes in V(D) or the λ region on chromosome 22, t(8;22)(q24;q11). In the African
J (variable diversity joining) recombinase activity are responsible for endemic cases, the breakpoint on chromosome 14 includes the heavy-
those translocations involving IgH or the TCR genes. 133 chain joining region, suggesting translocation occurs before complete
As in translocations associated with childhood acute lymphocytic immunoglobulin gene rearrangement in an early B cell (Chap. 102).
leukemia and adult chronic myelogenous leukemia (CML) and acute In nonendemic cases, the translocation involves the immunoglobulin
myelogenous leukemia, translocations involving t(14;18)(IgH;BCL-2) heavy-chain switch region, suggesting translocation occurs at a later
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are found in healthy persons. Presumably, additional genetic events are stage of B-cell development. EBV genomes are demonstrated in the
required for transformation of a lymphocyte to occur. Alternatively, tumor cells in most of the African cases, in approximately one-third of
cells containing these translocations may be entering an apoptotic pro- the cases associated with AIDS, 138,139 but less frequently in non-African,
cess, destined to be eliminated. 133 nonimmune-deficient cases (Chap. 102).
FOLLICULAR LYMPHOMA ANAPLASTIC LARGE CELL LYMPHOMA

Approximately 85 percent of follicular lymphomas carry the chromo- The translocation t(2;5)(p23;q35) of anaplastic large cell lymphoma (ALCL)
somal translocation t(14;18)(q32;q21) in which the BCL-2 oncogene involves the nucleophosmin (NPM) gene at 5p35 and the ALCL tyrosine
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on chromosome 18q21 is brought in continuity with the immuno- kinase (ALK) gene at 2p23, leading to expression of the novel fusion
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globulin heavy-chain loci on 14q32, resulting in overexpression of protein p80 that can be identified by immunohistochemical studies.
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