of the preceding structural gene changes. Potentially important examples include: 1) overexpression of the APOBEC3B gene whose protein product (termed "probable DNA dC->dU-editing enzyme APOBEC-3B") contributes to the regulation of cell growth; 2) missense mutations in the IRAK1 gene which causes overactivation of its product protein, interleukin-1 receptor-associated kinase 1, and thereby overactivation of the NF-κB signaling pathway that regulates cell proliferation and survival; 3) overexpression of the AQP3 gene whose protein product, aquaporin 3, is a water channel that when overexpressed is thought to promote the progression and spread of various types of cancers; 4) overexpression of the P-selectin glycoprotein ligand-1 gene whose protein product promotes cell attachment to vascular endothelium; 5) overexpression of the MUC1 gene whose product, the Mucin 1, cell surface associated protein, binds with P53 to inhibit cell death and interacts with beta-catenin to promote the tissue-invasiveness of cancer cells; and 6) overexpression of the MYC gene, whose product, c-Myc, is the cancer-causing MYC proto-oncogene although this overexpression, unlike the c-Myc overexpression occurring in other B-cell lymphomas, is usually not associated with structural abnormalities in its gene but rather is often overexpressed due to the action of the LANA-1 protein made by KSHV/HHV8. The identification of these changes in tissue samples can assist in making the diagnosis of PEL. Diagnosis In classical cavitary cases, the diagnosis of PEL may be suspected based on its presentation as effusions in one or more bodily cavities in individuals with a history of the immunodeficiencies cited above. The diagnosis is supported by microscopic examination of cytologic smears taken from these effusions. 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 Kaposi's 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