Guidelines on Diagnosis and Treatment of Malignant Lymphomas

Immunodeficiency Associated
Lymphoproliferative Disorders
HUMAN IMMUNODEFICIENCY
VIRUS-RELATED LYMPHOMAS
Definition and Incidence
Lymphomas that develop in HIV-positive patients are
predominantly aggressive B-cell lymphomas. In a proportion of
cases they represent the AIDS-defining illness. These disorders
are heterogeneous and include lymphomas commonly diagnosed
in immunocompetent patients, as well as some seen more
commonly in the setting of HIV infection. The most common
HIV-associated lymphomas include: Burkitt lymphoma (BL),
diffuse large B-cell lymphoma (DLBCL), often involving the
central nervous system, primary effusion lymphoma (PEL) and
plasmablastic lymphoma of the oral cavity and Hodgkin lymphoma.
Clinical Presentation
Clinical presentations are similar to those found in
immunocompetent patients, but usually are more advanced with
bulky disease reflected by a high LDH level. There is a significant
relationship between the subtype of lymphoma and the HIV
disease status. DLBCL usually occurs late in the course of AIDS
with a prior history of opportunistic infection and low CD4 count
usually 200x10 6 . Primary
effusion lymphoma (PEL) and plasmablastic lymphoma of the oral
cavity occur in HIV+ patients almost exclusively. PEL typically
presents with a pleural or peritoneal effusion but can present as a
solid tumour mass. Plasmablastic lymphoma of the oral cavity
presents as a rapidly growing tumour of the jaw or oral cavity.
The incidence of all subtypes of NHL is increased 60-200 fold in
the HIV setting. Before the introduction of HAART, primary CNS
lymphoma and BL had an incidence 1000 fold that of the general
population. The incidence of HL is increased about eight fold.
NHL used to be the AIDS-defining illness in 3-5% of patients,
but this has increased since the introduction of HAART.
This heterogeneous group of diseases reflect several
pathogenetic mechanisms of lymphoma development, notably:
chronic antigen stimulation, cytokine dysregulation and viral
carcinogenesis involving the herpes viruses, EBV and Kaposi
Sarcoma Human Virus (KSHV / HHV8).
ICD – O Codes:
As for cases occurring in the
immunocompetent patient.
Pathology and Genetics
Those diseases which also present in the immunocompetent
patient such as DLBCL, BL and HL will have the usual features.
PEL is associated with both Kaposi sarcoma (KL) and
multicentric Castleman’s disease (MCD) in HIV-positive patients.
In PEL the diagnosis is based on cytology with pleomorphic
cells varying from large immunoblastic or plasmablastic cells to
those with an anaplastic appearance. The PEL immunophenotype
is EMA+ve, CD30+ve, CD38+ve , CD71 +ve and may
express CD3.
Plasmablastic lymphoma of the oral cavity has a diffuse pattern of
growth with interspersed macrophages. The tumour cells are
large, with eccentric nuclei and usually a central, prominent
nucleolus. The cytoplasm is deeply basophilic with a perinuclear
hof. Cyctoplasmic immunoglobin can be detected in about 20%
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