Case 98-3

History/Physical Findings:

Laboratory findings:

Microscopic examination of pleural fluid:

Flow cytometric analysis of pleural fluid:

Immunohistochemically, the neoplasm is is negative for LCA (Figure 2A). It is positive for epithelial membrane antigen (Figure 2B). It

Further evaluation showed no evidence of lymphadenopathy or mass lesions. A bone marrow biopsy showed an active cellular marrow and no evidence of malignancy.

What is your diagnosis?

Discussion:

Microscopic examination of the pleural fluid showed a predominance of very large, pleomorphic lymphocytes with enlarged nuclei, prominent, frequently multiple nucleoli, and moderate to abundant deeply basophilic cytoplasm which often contained vacuoles (Figure 1A-1C). By flow cytometry, the cells were negative for CD 45 (leucocyte common antigen), the B-cell marker CD 19 and the T-cell marker CD 5. The cells were positive for the activation markers HLA-DR, CD 38, CD 71 and CD 30. Paraffin-based immunohistochemical stains performed on cell block material demonstrated positivity for CD 30 and epithelial membrane antigen (Figure 2B), and absence of staining for CD 45 (Figure 2A), the B-cell markers L26 (CD 20), 4kb5 (CD 45RA), and the T-cell markers CD3p and UCHL-1 (CD 45RO).

Southern blot analysis was used to assess the immunoglobulin heavy chain gene for evidence of clonal rearrangement using three separate restriction enzymes. A single abnormal band was identified with each enzyme. However, the band was heavier than the germ line band, and thus the possibility that this was a result of partial digestion of the DNA, rather than a gene rearrangement, could not be excluded. Southern blot analysis demonstrated no evidence of clonal rearrangement of the T-cell receptor beta gene. PCR analysis for the presence of EBV and KSHV demonstrated the presence of KSHV and the absence of EBV in the tumor cells.

The clinical, morphologic and immunophenotypic findings are indicative of AIDS-related primary effusion lymphoma (PEL).^2,3 Typically, these lymphomas express LCA both by immunocytochemistry and flow cytometry and activation antigens, but are negative for B- and T-cell markers by flow cytometry and paraffin immunohistochemistry. Rearrangement of immunoglobulin genes can usually be detected via Southern blot analysis, indicating the B-cell nature of these neoplasms. The lack of B-cell surface antigens and expression of activation antigens most closely resembles the immunophenotype of B-cells in the process of transformation to plasma cells among the normal hematopoietic cell types. Unusual findings in this case include the lack of positivity for LCA and EBV. These lymphomas occur almost exclusively in men, and particularly homosexual men, with advanced AIDS. These epidemiologic findings are very similar to those for Kaposi's sarcoma. Kaposi's sarcoma is present in about one-third of patients, and was present in this case. There is often no other evidence of disease, and these lymphomas usually stay confined to body cavities without disseminating to other sites. Median survival in the largest series was five months (range: 12 days - 14 months), and did not seem influenced by chemotherapy.

PELs should be distinguished from Burkitt-type lymphomas (Figure 3B) that also occur in AIDS patients². In contrast to the marked cellular pleomorphism of PELs, Burkitt-type lymphomas are relatively monomorphic. In addition, the cells are smaller, with less prominent (and more often multiple) nucleoii, and the cytoplasmic vacuoles are more frequently seen. Burkitt-type lymphomas will also frequently have a B-cell immunophenotype and express surface immunoglobulin. At the molecular level, Burkitt-type lymphomas show amplification of the c-myc oncogene and rearrangement of the bcl-6 oncogene, both of which are absent in PELs. Finally, PELs contain KSHV sequences which are not present in Burkitt-type lymphomas.

The patient refused chemotherapy for treatment of the lymphoma. One year later, a biopsy of his axillary lymph node was reported as follicular hyperplasia. Two years later, the patient developed a pericardial effusion and enlarged groin lymph nodes. The microscopic examination of the pericardial fluid reveals lymphoma cells similar to those in his previous pleural fluid. Flow cytometry of the pericardial effusion is shown below.

Flow cytometric analysis of pericardial fluid:

Diagnosis:

References:

1. Walts AE, Shintaku P, Said JW. Diagnosis of malignant lymphoma in effusions from patients with AIDS by gene rearrangement. Am J Clin Pathol 1990;94:170-175.
2. Nador RG, Cesarman E, Chadburn A, et al. Primary effusion lymphoma: A distinct clinicopathologic entity associated with the Kaposi's sarcoma-associatated herpes virus. Blood 1996;88:645-656.
3. Ansari MQ, Dawson DB, Nador R, et al. Primary body-cavity-based AIDS-related lymphomas. Am J Clin Pathol 1996;105:221-229.

Contributors:

Mark H. Stoler, M.D.
Department of Pathology
University of Virginia Health System

Questions should be addressed to: