Plasmablastic lymphoma (PBL) is a rare, aggressive form of non-Hodgkin lymphoma (NHL). It is recognized as a distinct subtype of large B-cell lymphoma, characterized by rapid progression and typically poor prognosis. The disease is most frequently observed in individuals with compromised immune systems, making it a significant concern in certain patient populations. Understanding the unique cellular features, associated risk factors, and complex treatment protocols is the first step toward managing this serious diagnosis.
The Unique Pathology of Plasmablastic Lymphoma
Plasmablastic lymphoma is defined by malignant cells that resemble plasmablasts, which are B-lymphocytes actively differentiating into mature plasma cells. This cellular origin gives PBL its distinctive pathological profile, showing features of both a B-cell lymphoma and a plasma cell neoplasm.
The cancer cells display a plasmacytic phenotype, meaning they have characteristics similar to plasma cells, which are responsible for producing antibodies. Histologically, the lymphoma typically presents as large sheets of cells with a high rate of proliferation, often exhibiting a Ki-67 index exceeding 80% to 90%.
PBL is known for its tendency toward extranodal involvement, meaning it presents outside of traditional lymph nodes. While other lymphomas often begin in the lymph nodes, PBL commonly first appears in the oral cavity, such as the gums or palate, or in the gastrointestinal tract. Involvement of the lymph nodes without extranodal masses is uncommon.
Critical Underlying Risk Factors
The development of plasmablastic lymphoma is strongly linked to states of significant immunodeficiency. The most prevalent risk factor is infection with the Human Immunodeficiency Virus (HIV), particularly in cases where the immune system is severely suppressed. Historically, PBL was first described primarily in the context of advanced AIDS.
Many cases of PBL are also associated with co-infection by the Epstein-Barr Virus (EBV). EBV is a common herpesvirus that can contribute to the development of several lymphoproliferative disorders. The presence of EBV is thought to play a role in preventing the natural death of B-cells, allowing the malignant transformation to occur.
PBL can also arise in patients with other causes of immunosuppression. This includes individuals who have received solid organ transplants and are taking immunosuppressive medications to prevent rejection. Elderly patients may also be at higher risk due to age-related declines in immune function.
Clinical Presentation and Diagnostic Testing
The clinical signs of plasmablastic lymphoma can vary widely depending on the primary site of involvement. A common initial presentation is a quickly enlarging, painful mass in the oral cavity, which may be ulcerated or bleeding. When the gastrointestinal tract is affected, patients might experience symptoms such as abdominal pain, obstruction, or internal bleeding.
Patients may also suffer from non-specific systemic symptoms, often referred to as “B symptoms,” which include unexplained fevers, drenching night sweats, and significant unintentional weight loss. Patients frequently present with advanced-stage disease, meaning the cancer has already spread to multiple sites throughout the body.
Diagnosis requires an excisional or core needle biopsy of the tumor tissue for pathological examination. The distinguishing feature of PBL is its unique immunophenotype, which is determined through immunohistochemistry staining. The malignant cells typically express plasma cell markers such as CD138 and CD38, and a transcription factor called MUM1, reflecting their terminal B-cell differentiation.
Crucially, PBL cells show a lack of or weak expression of the standard B-cell marker CD20. This CD20-negative profile is a major diagnostic challenge and has implications for treatment. Diagnostic workup is completed with staging scans, such as a PET-CT, and a bone marrow biopsy to determine the full extent of the disease.
Current Management and Treatment Protocols
The management of plasmablastic lymphoma must be aggressive. Intensive multi-agent chemotherapy regimens are the foundation of therapy. The National Comprehensive Cancer Network (NCCN) recommends using more intensive protocols than standard chemotherapy, such as dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin).
Another intensive regimen frequently employed is Hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high-dose methotrexate and cytarabine). The lack of CD20 expression means that the antibody rituximab, a standard component in most B-cell lymphoma treatments, is generally ineffective and not included in the regimen.
For patients who are HIV-positive, optimizing their antiretroviral therapy (ART) is a simultaneous and equally important component of the treatment plan. Effective ART management can help restore immune function. This requires careful coordination between the oncology and infectious disease teams to manage potential drug interactions and overlapping toxicities.
The role of targeted therapies is also being explored, particularly the use of proteasome inhibitors, such as bortezomib, which are commonly used in plasma cell disorders like multiple myeloma. For patients who achieve a complete response to initial chemotherapy, consolidation therapy with an autologous stem cell transplant may be considered to reduce the risk of relapse.