Lymphomas Also Occurring in Immunocompetent Patients

HIV-related Burkitt lymphomas (BL) include cases exhibiting the features of classical BL, those showing plas-macytoid differentiation, and those exhibiting features of atypical Burkitt or Burkitt-like lymphoma. Translocation of MYC into one of the immunoglobulin loci is considered by some to be a prerequisite for classification of a lymphoma as BL or atypical BL. The most common translocation is a t(8;14), involving the MYC and immunoglobulin heavy-chain (IGH) genes, but in 10% the translocation involves MYC and one of the light-chain (IGL) genes. It is thought that this translocation leads to deregulated expression of the MYC gene. Mutation of the MYC locus also occurs in Burkitt lymphoma and also may lead to abnormal MYC expression.

Diffuse large B-cell lymphoma (DLBCL) can be divided into centroblastic (CB) and immunoblastic (IB) categories. The IB type is more frequently associated with EBV infection, and patients with these lymphomas usually have significant immunosuppression, with low CD4 counts (median <100 x 106/L), and approximately one third have been previously diagnosed with an AIDS-defining illness. This degree of immune dysfunction allows EBV to be the driving proliferative force, with expression of the onco-genic but also immunogenic LMP1 and EBNA2 proteins.

Primary effusion lymphomas (PEL) are characterized by the presence of Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8) within the tumor cells. PEL are rare tumors, accounting for only approximately 3% of all HIV-related NHLs. These neoplasms usually present as an effusion involving one or more of the pleural, peritoneal, and pericardial spaces. While the majority lack an associated tissue mass at presentation, in about one third of the cases dissemination to extracavitary sites occurs. In addition, KSHV-associated lymphomas can occur as primary solid tumor masses without an effusion. Some lymphomas first diagnosed as IB lymphoma have been found to contain KSHV, with immunophenotypic and molecular features similar to those of PEL.

Plasmablastic lymphomas, associated with multicentric Castleman's disease, occur in HIV-positive patients. While these plasmablastic lymphomas are KSHV positive, they differ from PEL in a number of ways. Plasmablastic lymphomas are EBV negative, do not contain mutations in the immunoglobulin genes, and are thought to arise from naive IgM lambda-expressing B cells rather than terminally differentiated B cells. Polymorphic B-cell lymphomas (PTLD-like) are extremely rare lesions but morphologically resemble polymorphic PTLD (see PTLD section below).

Table 34-2. Major Categories of HIV-Associated Lymphomas and Approximate Frequencies

Lymphomas Also Occurring in Immunocompetent Patients

Burkitt and Burkitt-like lymphoma

30%

Diffuse large B-cell lymphoma

Centroblastic

25%

Immunoblastic

22%

Lymphomas Occurring Primarily in HIV-Positive Patients

Primary effusion lymphoma

3%

KSHV-positive extracavity lymphoma

Unknown

Polymorphic B-cell lymphoma (PTLD-like)

Rare

Plasmablastic lymphoma of oral cavity

Rare

Primary CNS lymphomas

10-15%

Table 34-4. Correlation of Morphology and Genotype in HIV-

Related Lymphomas

Genetic

Lesion BL CB IB PEL Poly PCNSL

Table 34-4. Correlation of Morphology and Genotype in HIV-

Related Lymphomas

Genetic

Lesion BL CB IB PEL Poly PCNSL

IGH/IGL R

>95%

>95%

>95%

>95%

80%

>95%

BCL6 R

<5%

20%

15%

0%

0%

0%

BCL6 M

50-60%

70%

50%

80%

10%

50%

MYC R

>95%

30%

25%

Rare

0%

0%

RAS M

23%

Rare

Rare

0%

0%

ND

TP53 M

40-60%

10%

10%

Rare

20%

ND

BCL1,

0%

0%

0%

0%

ND

BL, Burkitt and Burkitt-like lymphoma; CB, centroblastic diffuse large B-cell lymphoma;IB, immunoblastic diffuse large B-cell lymphoma; PEL, primary effusion lymphoma; Poly, polymorphic B-cell lymphoma (PTLD-like);PCNSL, primary CNS lymphoma;M, mutations; R, rearrangements; ND, not determined.

BCL2 R

BL, Burkitt and Burkitt-like lymphoma; CB, centroblastic diffuse large B-cell lymphoma;IB, immunoblastic diffuse large B-cell lymphoma; PEL, primary effusion lymphoma; Poly, polymorphic B-cell lymphoma (PTLD-like);PCNSL, primary CNS lymphoma;M, mutations; R, rearrangements; ND, not determined.

Table 34-5. Major Differences Between PTLDs in Solid Organ

Transplantation and Allogeneic Bone Marrow Transplantation

Solid

Allogeneic Bone

Organ

Marrow

Transplantation

Transplantation

Usual origin of PTLD

Recipient

Donor

Course

Variable

Usually aggressive

Incidence

More common

Less common

(0.3-12.5%)

(~1%)

Prognostic association

Yes

No

of molecular

abnormalities,

including

BCL6 mutations

Primary CNS lymphomas differ from systemic DLBCL, as noted in Tables 34-3 and 34-4, with the majority of cases exhibiting IB morphology and EBV-positivity. Plasmablas-tic lymphoma of the oral cavity, a recently described distinct entity, has features similar to IB lymphomas, but is less heterogeneous and polymorphic. Approximately 50% of cases are associated with EBV infection.

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