Diffuse large cell lymphoma
The specific molecular aberrations described in patients with AIDS-related diffuse large cell lymphoma appear distinct as well, with recent descriptions of abnormal BCL6 expression in approximately 40% of cases.

Body cavity–based lymphoma/primary effusion lymphoma
This appears to be highly associated with HHV-8 and EBV. The tumor cells stain positive for CD45. The disease appears to occur predominantly in males and may coexist with KS in patients with AIDS.

Signs and symptoms

B symptoms
These events (ie, fever, weight loss, and night sweats) are seen in approximately 80% of patients with systemic AIDS-related NHL. In these patients, it is mandatory to exclude the presence of occult opportunistic infections before ascribing B symptoms to the lymphoma itself.

Extranodal involvement
Advanced-stage disease is expected in the majority of patients, with extranodal involvement reported in 60% to 90% of patients in most series. Common sites of extranodal involvement include the CNS (occurring in approximately 30% of patients), GI tract (25%), and bone marrow (25%). Essentially any other site in the body can also be involved, including the rectum, soft tissue, oral cavity, lungs, and heart.

CNS lymphoma
Patients with primary CNS lymphoma often present with focal neurologic deficits, seizures, and/or altered mental status. Any site in the brain may be involved, and one to four space-occupying lesions are usually seen on MRI or CT scan.

Other sites
Changes in bowel habits, GI bleeding, weight loss, pain, and hepatomegaly are common presenting symptoms in patients with GI involvement. Pancytopenia may indicate bone marrow involvement.

Primary effusion lymphoma
Patients usually present with pleural or pericardial effusion without an identifiable mass. Pain, shortness of breath, and B symptoms are the main initial complaints.

Screening and diagnosis

Diagnosis of NHL in patients with AIDS requires histologic confirmation by biopsy with immunophenotypic and/or molecular gene-rearrangement studies.

Evaluation
A complete staging evaluation should be done. This should include:

• CT or MRI of the head
• positron-emission tomography/CT scan of whole body
• bone marrow aspiration and biopsy
• liver function studies
• spinal fluid analysis.

Assessing spinal fluid for EBV
The presence of EBV DNA in cerebrospinal fluid, as determined by polymerase chain reaction, appears to have a high specificity and sensitivity for the diagnosis of primary CNS lymphoma.

Pathology

Common tumor types
Over 95% of AIDS-related NHL cases are of B-lymphocyte origin. Most AIDS-related NHL tumors are high-grade types, including the immunoblastic and small noncleaved lymphomas. Diffuse large cell lymphoma constitutes up to 30% of AIDS lymphomas.

Less common tumor types
Although not considered part of the AIDS epidemic, several cases of T-cell lymphoma occurring in HIV-infected patients have been described. In addition, cases of Ki-1–positive, large cell anaplastic lymphoma and plasmablastic lymphoma have been reported in HIV-infected patients. The clinical and pathologic characteristics of these forms of lymphoma are similar to those seen in non–HIV-infected individuals.

CNS lymphomas
These are typically of the immunoblastic or large cell type.

GI and oral cavity lymphomas
Large cell or immunoblastic lymphomas are also more likely to involve the GI tract and oral cavity than are small noncleaved lymphomas.

Primary effusion lymphomas
The cells are large and pleomorphic with prominent nucleoli and immunoblastic morphology. Clonal immunoglobulin DNA rearrangement demonstrates clonality of the tumor cells but not surface immunoglobulin expression.