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1574 Part XI: Malignant Lymphoid Diseases Chapter 95: General Considerations for Lymphomas 1575

basin and East and Central Africa. In the latter areas, the HHV-8 sero- Other Bacteria
prevalence can reach 80 percent in the adult population. In the homo- Other bacterial infestations have been found in association with lym-
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sexual population (mainly in the United States and Europe), HHV-8 phomas of MALT. Campylobacter jejuni and Borrelia burgdorferi have
is principally transmitted during repeated sexual contacts, whereas been connected to the onset of immunoproliferative disease of the small
in Africa it is mainly transmitted from mother to child and among intestine and B-cell lymphoma of the skin. 101
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siblings. Saliva seems to play a major role in HHV-8 transmission.
Posttransplantation primary effusion lymphoma is associated with
HHV-8. 76 IMMUNOSUPPRESSION
Inherited
Hepatitis Viruses B and C A number of the rare immunodeficiency syndromes tabulated in
Hepatitis B and C have been implicated in the pathogenesis of lymph- Table 95–2 82,102–123 result from gene mutations leading to deficiencies
oproliferative diseases. In one study, 334 newly diagnosed lymphoma in cellular or humoral immunity or both. These syndromes have a
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patients and 1014 controls had a serologic evaluation for the presence of paradoxically high frequency of autoantibodies but, more relevant to
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prior hepatitis virus B or C infection. The results suggested that hepati- this discussion, an increased probability of developing a lymphoma.
tis B seropositivity was significantly higher in patients with DLBCL and Because these syndromes are so uncommon, reliable assessment of
follicular lymphoma, and seropositivity for hepatitis C was significantly the increased risk of lymphoma often has to be inferred. The increased
higher in DLBCL patients. A similar result was found in another study risk of approximately 0.5 to 10 percent of patients, depending on the
in Taiwan, an area with a high frequency of hepatitis B virus infection. immunodeficiency disease in question, is several orders of magnitude
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In two other studies, seropositivity for hepatitis C was significantly above the risk in the general population (age-adjusted incidence rate in
higher in patients with B-cell lymphomas. 83,84 Hepatitis C virus has a the United States younger than 65 years of age: males = 0.011 percent
predilection for B cells. Hepatitis C virus RNA levels are significantly and females = 0.008 percent). With the exception of common variable
higher in B cells than CD4+ or CD8+ T cells or other cells in infected immunodeficiency, the syndromes present in childhood and because
patients, and the virus is associated with immunopathologic reactions, several are X-chromosome-linked, males are affected more commonly
such as cryoglobulinemia, and, not infrequently, clonality of infected B than females. The lymphomas induced may result from a susceptibility
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lymphocytes. Hepatitis C virus infection may be associated with the to EBV and the lymphoproliferation may initially be polyclonal before
onset of DLBCL, marginal zone lymphoma, and lymphoplasmacytic evolving to a monoclonal tumor. Extranodal involvement appears to be
lymphoma, but not follicular lymphoma. 83 more common than in persons with lymphoma who are immunocom-
petent. The initial manifestations of the immunodeficiency are usually
Helicobacter pylori infections or autoimmune abnormalities, such as immune cytopenias,
Helicobacter pylori can cause marginal zone B-cell MALT lymphomas and lymphoma is a later complication. We have included Li-Fraumeni
of the stomach and probably causes some of the higher-grade lym- syndrome in this cluster for convenience of presentation. This germline
phomas, either from transformation of a MALT or de novo large cell predisposition syndrome does not have an immunodeficiency pheno-
lymphoma. 86–88 This spiral Gram-negative bacillus is the first bacterium type as do all the other entries in Table 95–2. Rather, it is a nonsyndro-
demonstrated to cause a human neoplasm. It had been thought that the mic familial cancer syndrome transmitting susceptibility to mutations
stomach was sterile because of the acid environment, but H. pylori had in p53. The cancers that occur in these families include lymphoma.
evolved to tolerate the environment, perhaps in part, because it secretes
urease, an enzyme that converts urea to ammonia, making the micro- Acquired
environment around the organism less acidic. Although the stomach A variety of types of immunosuppressed individuals develop lym-
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has no endogenous lymphoid tissue, the latter develops in response to phoma. Chapter 81 discusses AIDS-related lymphoma. Posttrans-
the organism, and ultimately the chronic inflammatory reaction can plantation lymphoproliferative diseases generally display B-cell lineage
result in the transformation and selection of a mutant lymphocyte with derivation, involvement of extranodal sites, aggressive histology and
a growth and survival advantage leading to a lymphoma (Chap. 101). clinical behavior, and frequent association with EBV infection. The
Eradication of H. pylori with antibiotics early in the course of gastric occurrence of immunoglobulin (Ig) V mutations in the overwhelming
MALT lymphoma can lead to regression of the lymphoma and perma- majority of posttransplantation lymphoproliferative disease indicates
nent cure of the majority of afflicted patients. 89 that malignant transformation targets germinal center B cells and their
descendants, both in EBV-positive and EBV-negative cases. 125–127 Post-
transplantation T-cell lymphomas may occur and often arise in extran-
Chlamydophila psittaci odal sites, such as skin or central nervous system. 128,129
Ocular adnexal lymphomas are the most common tumor of the The incidence and severity of lymphomas have increased with the
eye. 90,91 The majority of ocular adnexal lymphomas are extranodal, introduction of immunosuppressive agents such as cyclosporine, inflix-
mucosa-associated lymphoid tissue lymphomas and have been linked imab, and etanercept for treatment of autoimmune diseases.
to Chlamydophila psittaci infection in several reports. In one study,
this organism was detected in lymphoma tissue in 75 percent of cases.
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DNA was detected in conjunctional swabs and/or blood mononuclear AUTOIMMUNITY
cells from 50 percent of patients. Mononuclear phagocytes were the Several autoimmune disorders are risk factors for lymphoma, prob-
carriers of C. psittaci in this population of patients. Confirmatory ably as a result of chronic immune stimulation leading to excessive
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reports of the association of C. psittaci with adnexal ocular lymphoma B-cell proliferation as well as depressed regulatory T-cell function.
have been published, 94,95 but other studies report no association. 96–98 The strongest associations are for primary Sjögren syndrome, systemic
These discrepant reports may be explained by the association of differ- lupus erythematosus, and rheumatoid arthritis with relative risks of
20
ent organisms with ocular lymphoma in different geographic regions 18.8, 7.4, and 3.9, respectively. Patients with Sjögren syndrome are
of the world. 99,100 especially susceptible to development of parotid gland marginal zone

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