PEL in individuals infected by HIV. PEL cells express markers associated with plasma cell differentiation such as CD138, CD38, and MUM1/IRF4. Tumor cells are usually negative for B-cell and T-cell markers (data not shown). (A) In a cell line derived from a classic PEL, tumor cells display features bridging immunoblastic and anaplastic large cell lymphomas and morphologically show a certain degree of plasma cell differentiation. (Inset) In a cell block derived from a primary classic PEL tumor cell are features resembling immunoblastic lymphoma cells. Plasma cell differentiation is confirmed by nuclear immunohistochemical staining for IRF4/MUM1. (B) Immunohistochemical staining for ORF73/LANA detects evidence of KSHV infection. Typically, the staining pattern is speckled. EBER in situ hybridization detects Epstein-Barr virus in tumor cells. The positive nuclei are stained in blue. (C) In a case of extracavitary solid PEL, tumor cells show morphologic features similar to those seen in serous effusion of classic PEL. Immunohistochemical staining for ORF73/LANA is the standard assay to detect evidence of KSHV infection also in tumor tissue. (Inset) Fraction of tumor cells expresses KSHV viral IL6. H&E, hematoxylin-eosin stain; MUM1, ORF73/LANA, v-IL6, immunohistochemistry, hematoxylin counterstain; EBER, in situ hybridization, nuclear fast red counterstaining. Original magnification ×400. Images were taken using a Nikon Eclipse 80i microscope with a Plan Fluor 40×/0.75 objective and Nikon digital sight DS-Fi1 camera equipped with control unit-DS-L2. Images were processed using Adobe Photoshop CS2 V9.0.