A 59-year-old HIV positive man developed worsening shortness of breath over the previous six months. Chest radiography revealed a left-sided pleural effusion on which thoracentesis was performed. The aspirate and cell block demonstrated discohesive sheets of large cells with pleomorphic nuclei and abundant pale to basophilic cytoplasm that was often vacuolated (see Figures 1 and 2). There were frequent reactive histiocytes associated with abundant apoptotic debris.
Initial workup demonstrated the pleomorphic cells lacking staining for CD3, CD5, CD10, CD19, CD20, CD21, CD30, CD45, CD79a, CD138, BCL2, BCL6, Cyclin-D1, Pan-Keratin, S100, EBV-LMP1, OCT2, MPO, and PAX5. The pleomorphic cells were positive for EMA, MUM1, HHV8, CD38 (Figure 3), and EBV-ish.
The correct answer is ...
The correct answer is: Primary effusion lymphoma (PEL).
Primary effusion lymphoma (PEL) is a rare form of lymphoma which usually occurs within the body cavities of individuals with AIDS. It usually does not form a solid tumor mass. The neoplastic cells in PEL are large and pleomorphic/anaplastic, often with plasmacytoid cytology. The neoplastic cells are infected with HHV8, which is the virus culpable for Kaposi sarcoma (not usually seen in these individuals). Staining for HHV8 is necessary for a diagnosis of PEL. Additionally, these neoplastic cells are often infected with EBV, as are many lymphomas in patients with AIDS. The prognosis is poor for individuals with PEL; survival is usually around one year. The neoplastic cells are technically B-cells based on molecular studies and usually express the common leukocyte antigen, CD45, and lack B-cell markers like PAX-5, CD20, and CD19. They do, however, stain like terminally differentiated B-cells with positivity for CD138, CD38, and MUM-1 as well as EMA. Rarely PEL can occur in sites outside of body cavities, termed extracavitary PEL, and have a similar morphology and immunophenotype, except they are more likely to express pan-B cell markers.
Plasmablastic lymphoma can resemble PEL in terms of cytology but will have a more consistent plasmacytoid appearance. In contrast, PEL can demonstrate plasmacytoid morphology, but will be more varied in appearance with more anaplastic appearing morphology than plasmablastic lymphoma. Plasmablastic lymphomas will stain for plasma cell antigens like CD138 and CD38 similar to PEL, but will be negative for HHV8. This is another rare lymphoma that arises also in AIDS patients and can also be associated with EBV, but again will be HHV-8 (-). These lymphomas are often seen in the oral cavity and can involve lymph nodes, but are less likely to involve body cavities. Similar to PEL, they weakly stain for pan B-cell antigens like CD20 and the common leukocyte antigen, CD45.
DLBCL’s make up a significant proportion of AIDS-related lymphomas and retain a similar morphology to their immunocompetent-related counterparts. Similar to other lymphomas in immunodeficient individuals, EBV can be frequently identified, specifically in DLBCLs of the CNS. However, in contrast to PEL, they stain with both EBV-ISH and LMP-1, while PEL characteristically does not stain for EBV-LMP-1. This is why in the above case EBV-ISH was positive but EBV-LMP-1 was negative. Similar to other variants of DLBCL, they stain with pan-B cell markers, including CD19, CD20, CD79a, PAX-5; conversely PEL do not stain for B-cell markers and will more consistently stain more for postgerminal center markers.
Peripheral T-cell lymphomas including ALCL are much less common in immunodeficient conditions. ALCL can be ALK (+) or ALK (-), but ALCL consistently stains for CD30 regardless of ALK reactivity. As a T-cell lymphoma they will stain for T-cell markers, but commonly lose CD3, CD5, CD7 and CD8. CD4 and CD43 are more likely to retain reactivity in ALCL. A lack of CD30 staining effectively rules out ALCL in this case. ALCL is most likely to show up in a seroma in the case of breast-implant associated ALCL. Like the name implies, it usually (not always) occurs in individuals with breast implants and is diagnosed in a peri-implant effusion. These cases are usually negative for ALK. These patients have a better prognosis than systemic or nodal ALCL.
Casey Gleue, M.D.
Resident, Anatomic and Clinical Pathology
William Macon, M.D.
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science