Plasmablastic lymphoma (PBL) is an uncommon but aggressive subtype of diffuse, large, B-cell lymphoma. The diagnosis of PBL is difficult because its features overlap with myeloma and lymphoma. The primary organs involved are usually the gastrointestinal system, lymph nodes, oral mucosa and sometimes the skin. It has a very aggressive disease course comprising relapses and refractoriness to chemotherapy. PBL is a very rare diagnosis, and hence there is no established standard to treat PBL.
It is more prevalent in patients with human immunodeficiency virus (HIV) and Ebstein-Barr virus (EBV) infections and patients with a suppressed immune system (such as patients on immunosuppressive medications). In the literature, there are rare cases of PBL described in patients who harbor none of these infections.
The actual incidence of HIV positive and HIV negative PBL is unknown. It is estimated that PBL comprises 2% of all HIV-related lymphoma cases. There is a male predominance in the HIV-positive population, while the HIV-negative population has a female predominance. The median age of diagnosis in HIV-positive patients is 42 years and 55 years of age in the HIV-negative population.
The pathophysiology is incompletely understood, but the plasmablast is known to be the cell of origin. The plasmablast is an activated B cell that has undergone somatic hypermutation and class switching recombination and is becoming a plasma cell. It is also proposed that in PBLs in which EBV is one of the risk factors, EBV leads to prevention of apoptosis of B cells by several mechanisms.
It is a high-grade neoplasm combining features of B-cell and plasma-cell neoplasms under the microscope. It appears as large cells with an immunoblastic appearance, with moderately abundant cytoplasm, central oval nuclei with prominent nucleoli. The immunophenotype for plasmablastic lymphoma is similar to that in plasma cell neoplasms, positive for CD79a, IRF-4/MUM-1, BLIMP-1, CD38, and CD138. The neoplastic cells are negative for B-cell markers CD19, CD20, and PAX-5; however, may be weakly positive for CD45. Few cases express T-cell markers CD2 or CD4. MYC is also expressed in half of the cases of PBL. Ki-67 proliferation index is usually high in most cases. EBV can be detected by EBV coded RNA expression, which is the most sensitive means to detect an EBV infection.
Patients usually present with B symptoms: fevers, weight loss, and night sweats. Since the oral cavity and the gastrointestinal (GI) tract are the most common sites of disease, weight loss is the most common presenting symptom. Lymphadenopathy is not commonly seen in these patients.
An evaluation includes a complete blood count (CBC), complete metabolic panel (CMP), lactate dehydrogenase (LDH), uric acid, hepatitis panel, HIV testing, EBV RNA testing, and a bone marrow biopsy to evaluate the bone marrow involvement.
Since PBL is very uncommon, it has been very difficult to establish a chemotherapy regimen which would be the standard of care. CHOP (Cyclophosphamide, Vincristine, Doxorubicin, and Prednisone) is considered inadequate due to the highly aggressive nature of the lymphoma. Other regimens such as dose-adjusted EPOCH or cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate (CODOX-M)/ alternating with ifosfamide, etoposide and high-dose cytarabine (IVAC) or hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine (hyper-CVAD) can be considered as treatment options for this highly aggressive lymphoma. Chemotherapy usually involves 6 to 8 cycles of these regimens. Most experts believe that EPOCH should be regarded as first in the treatment of PBL. A meta-analysis confirmed the benefit of EPOCH over CHOP in HIV-positive PBL. Intrathecal chemotherapy is not well-studied in these cases and can be offered on a case to case basis. In the literature, intrathecal methotrexate and high-dose cytarabine have been used in patients in the past. In the refractory setting other chemotherapeutic options such as bortezomib in combination with doxorubicin or lenalidomide can be considered although they are not well studied in this setting. They work well for myeloma, and since PBL has some of those immunophenotypic markers, these agents can be used as a last resort. Patients whose disease is chemosensitive should also be considered for an autologous stem cell transplant in first remission. Patients with HIV should begin or continue their anti-retroviral therapy under direction from an infectious disease specialist.
Anaplastic or plasmablastic multiple myeloma, diffuse, large, B-cell lymphoma
There is no role for surgery for PBL. Surgery has not been the desired treatment for any lymphomas, including PBL.
The use of radiation therapy in PBL is limited to case reports and single-institution studies. Radiation therapy can be used in the refractory setting but is seldom used in the up-front treatment of PBL.
As described above, various chemotherapy regimens have been studied for PBL and most experts at this time prefer EPOCH, at least in HIV-positive individuals.
The Ann Arbor staging system is used for staging PBL.
The prognosis is usually dismal for patients with PBL with a median overall survival ranging from 3 to 5 months. HIV-positive patients have a decreased overall survival compared to their HIV-negative counterparts.
These patients when undergoing chemotherapy have a high risk of complications such as immunosuppression, cytopenias, neutropenic fever along with other chemotherapy-induced toxicities such as nausea, vomiting, gastrointestinal (GI) side effects, hair loss, among others.
Patients undergoing chemotherapy treatment might benefit from a rehabilitation program focused on physical and occupational therapy to stay active while undergoing treatment.
Radiation oncology and infectious disease specialists can work alongside the medical oncologist and provide meaningful insight into the care of these very complicated patients. Palliative care specialists should also be consulted early on during the treatment of PBL. Studies have shown that involving palliative care soon improves the quality of life in most cancer patients.
Patients should be educated about the dismal prognosis and the possible adverse side effects from the intensive chemotherapeutic regimes before beginning treatment. They should be provided with the options of less intensive chemotherapy options such as CHOP versus more intensive, and the higher side effect profile of options such as EPOCH or CODOX-M or hyper-CVAD and a combined decision between the physician and the patient should be made weighing all risks and benefits.
PBL is a very aggressive lymphoma. It is a very hard condition to diagnose and treat. No chemotherapy regimen is considered a standard of care for PBL. Regardless of treatment, the prognosis is dismal averaging 3 to 5 months in most cases.
Plasmablastic lymphoma is a very aggressive lymphoma that is very difficult to diagnose and treat. It requires an interprofessional team with a medical oncologist, infectious disease physician, pharmacist, and oncology nurse for treatment in the form of chemotherapy. It should also be noted that palliative care should also be involved as early as possible to help patients transition their care, if needed, to the hospice setting due to a very high rate of death with this lymphoma. It should be a goal to provide patient-centered care with all the teams involved to enhance outcomes and patient safety.