Primary Effusion Lymphoma

• Primary Effusion Lymphoma (PEL) is a rare, aggressive non-Hodgkin lymphoma that primarily grows in body cavities.
• It is strongly linked to human herpesvirus 8 (HHV-8) infection, particularly in immunocompromised individuals.
• Symptoms often involve fluid accumulation in body cavities, leading to swelling and organ dysfunction.
• Diagnosis relies on analyzing these effusions for lymphoma cells and detecting HHV-8.
• Treatment typically involves chemotherapy, though prognosis can be challenging due to its aggressive nature.

What is Primary Effusion Lymphoma (PEL)?

Primary Effusion Lymphoma (PEL) is a distinct and aggressive subtype of B-cell non-Hodgkin lymphoma characterized by its unique presentation. Unlike most lymphomas that form solid tumors, PEL primarily grows as malignant effusions within body cavities, such as the pleural (lungs), peritoneal (abdomen), and pericardial (heart) spaces, without forming a detectable solid mass in lymph nodes or other organs at presentation. This rare malignancy is almost universally associated with infection by the human herpesvirus 8 (HHV-8), also known as Kaposi’s Sarcoma-associated Herpesvirus (KSHV). It predominantly affects individuals with severe immunodeficiency, such as those with HIV/AIDS, but can also occur in other immunocompromised states or, rarely, in immunocompetent individuals. According to the Lymphoma Research Foundation, PEL accounts for less than 1% of all non-Hodgkin lymphomas.

Symptoms and Causes of Primary Effusion Lymphoma

The presentation of primary effusion lymphoma symptoms often relates directly to the accumulation of malignant fluid in various body cavities. These symptoms can be non-specific and may include:

• Shortness of breath (due to pleural effusion)
• Abdominal swelling and discomfort (due to peritoneal effusion)
• Chest pain or palpitations (due to pericardial effusion)
• Fatigue and weight loss
• Fever and night sweats (B symptoms)
• Edema (swelling) in the extremities

The primary underlying factor for primary effusion lymphoma causes is infection with human herpesvirus 8 (HHV-8), also known as Kaposi’s Sarcoma-associated Herpesvirus (KSHV). This virus is responsible for several other conditions, including Kaposi’s sarcoma and multicentric Castleman disease. While HHV-8 infection is necessary for PEL development, it is not sufficient on its own; additional factors, particularly severe immunosuppression, are crucial for the malignant transformation of B-cells. For instance, individuals with advanced HIV infection are at a significantly higher risk of developing PEL, as their compromised immune systems cannot effectively control the viral infection or prevent the proliferation of HHV-8-infected B-cells.

Diagnosing Primary Effusion Lymphoma

The primary effusion lymphoma diagnosis typically involves the analysis of the accumulated fluid from the affected body cavity. This fluid is aspirated and examined for the presence of malignant lymphoma cells. Pathologists look for characteristic large, anaplastic lymphoid cells that often have plasmablastic features. Immunophenotyping of these cells is crucial, as they usually express B-cell markers (like CD45) but often lack pan-B-cell markers (like CD20) and T-cell markers. A definitive diagnosis also requires the detection of HHV-8 in the lymphoma cells, which can be identified through immunohistochemistry for the HHV-8 latency-associated nuclear antigen (LANA-1) or by molecular techniques such as polymerase chain reaction (PCR) for HHV-8 DNA. Imaging studies, such as CT scans or PET scans, may be used to assess the extent of effusions and rule out solid masses, although PEL is defined by the absence of such masses at presentation. Bone marrow biopsy may also be performed to check for involvement, though it is often negative.