These smears typically show plasmablasts and, in some cases, other malignant cells that have the morphology of anaplastic cells (i.e., large pleomorphic cells) or the Reed-Sternberg cells associated with Hodgkin disease. As detected by immunostaining methods, the malignant cells typically express molecular marker proteins such as CD45 (which is not expressed on mature plasma cells) as well as activation and plasma cell marker proteins such as CD30, MUC1, CD38, syndecan 1, and IRF4/MUM1; they do not express B-cell molecular marker proteins such as PAX5, CD19, CD29, or CD79a. The cells may also express many of the structural and non-structural gene abnormalities cited in the Pathophysiology section. By definition, individuals with PEL are infected by Kaposis sarcoma-associated herpesvirus (HHV-8 or KSHV/HHV8) and therefore evidence malignant cells that express products of this virus such as LANA1. In most cases, these individuals are also infected with EBV and therefore evidence malignant cells that express products of this virus such as EBER1/2 nuclear RNAs. Cases associated with HIV/AIDS test positive for antibodies directed against this virus. (PEL occurs in the absence of HHV-8 and HIV, although this is rare.) Individuals with PEL that is associated with cirrosis due to hepatitis evidence positive serum tests for the hepatitis virus B antigen (HBsAg) or one of the various tests for hepatitis C antigen. Extracavitary PEL is diagnosed based on findings that their mass lesions contain the same or very similar types of malignant cells and the same set of blood and serum findings as those that are found in cavitary PEL.
Finally, some studies suggest that EBV cooperates with KSHV/HHV8 to cause PEL, perhaps by enhancing the ability of KSHV/HHV8 to establish their pro-malignant latency phase in infected cells.As a probable result of their excessive proliferation, prolonged survival, and ability to avoid attack by a weakened immune system, the malignant cells in PEL exhibit a high degree of genomic instability, i.e. alterations  in the structure and/or expression of their genetic material which are associated with the development and/or progression of PEL. These alterations include mutations (i.e. changes in nucleic acid sequences), chromosomal rearrangements (i.e. deletions, duplications, inversions, translocations), aneuploidy (i.e. increases or decreases in the number of chromosomes), and the abnormal expression of genes that may or may not be a result of the preceding structural gene changes.