What is Plasmablastic Lymphoma?
Plasmablastic lymphoma (PBL) is a rare, but highly aggressive type of lymphoma – a cancer of the white blood cells. Since its first description in 1997, PBL has remained a difficult disease to diagnose and treat, despite advancements in lymphoma treatment. Many patients suffering from PBL experience growths outside of the lymph nodes, often found in the mouth or digestive system. An occurrence of this disease in the lymph nodes alone, without affecting other parts of the body, is quite rare.
To diagnose PBL, doctors typically use techniques such as histologic evaluation; a process where they closely examine the patient’s cells under a microscope. In some cases, they might also use genetic testing and immunophenotyping – a process of studying the proteins in and on cells. Diagnosing PBL is a challenge because its features are similar to plasmablastic myeloma and other severe types of lymphoma that share a similar appearance.
Chemotherapy is currently the cornerstone treatment for PBL. It involves a team of experts from different medical backgrounds for effective treatment, including oncologists and infectious disease doctors. However, PBL is an aggressive condition that tends to come back after treatment; this often results in poor outcomes despite strong multi-drug chemotherapy and the use of transplantation of a patient’s own stem cells. The rarity of PBL and the lack of extensive trials further complicates these aspects, making it tough to determine the best way to manage this condition.
What Causes Plasmablastic Lymphoma?
The exact cause of Plasmablastic lymphoma (PBL), a type of blood cell cancer, is still not known. However, a lot of research points towards chronic viral infections playing a role. For example, there seems to be a strong link between PBL and HIV, an infection that attacks the body’s immune system.
In one important study by a researcher named Delecluse, it was found that 15 out of 16 patients with PBL were also positive for HIV. This finding has been supported by further studies, with estimates that around two-thirds of people with PBL also have HIV.
That said, PBL has also been found in people who are not infected with HIV but have a weakened immune system for other reasons. These include individuals who have had an organ or bone marrow transplant, or those with underlying autoimmune disorders, which are conditions where the body mistakenly attacks its own healthy cells.
Another viral infection linked with PBL is the Epstein-Barr virus (EBV), often known for causing mononucleosis or ‘mono’. There’s also evidence suggesting that there could be a link between PBL and the HHV-8 virus, though this is still being studied.
Risk Factors and Frequency for Plasmablastic Lymphoma
How often plasmablastic lymphoma (PBL) occurs in HIV-positive and HIV-negative populations isn’t entirely known. That being said, research suggests that PBL makes up about 2% of all lymphoma cases related to HIV. Interestingly, a large US study found that 69% of PBL patients were HIV positive, showing a link between the two conditions. In the HIV-positive group, more males than females have PBL, while in the HIV-negative group, more females than males have PBL. A similar pattern of more males having PBL was also seen in people who had a transplant and in children. However, it’s important to keep in mind that PBL is rare in children and usually occurs in the context of HIV infection.
- The rate of PBL in HIV-positive and HIV-negative individuals isn’t fully known.
- Research estimates that 2% of all lymphomas related to HIV are PBL.
- In a large US study, 69% of PBL patients were found to be HIV positive.
- More males have PBL in the HIV-positive group, and more females have it in the HIV-negative group.
- PBL is also more common in males who have had a transplant and in children.
- PBL is rare in children, but when it does occur, it is usually in those with HIV.
The median age of diagnosis for PBL varies between HIV-positive and HIV-negative individuals. For HIV-positive individuals, the median age of diagnosis is 42 years, and for HIV-negative individuals, it is 55 years. The survival outlook for those with this type of lymphoma is unfortunately poor, with a median survival time of 6 to 11 months.
Signs and Symptoms of Plasmablastic Lymphoma
People who have this condition usually have noticeable tissue masses outside the lymph nodes. These are most commonly found in the oral cavity or the digestive tract. It’s rare for people to have issues with their lymph nodes without these external tissue masses. Other places these masses can show up include the urinary tract, the brain and spinal cord, the lungs, the liver, bones, nasal cavities, and eye sockets. Most of the time, people start seeing these symptoms when their condition is quite advanced, often in stages III or IV. The bone marrow, which is the spongy tissue inside your bones, is usually affected. It is thought that 27% to 40% of individuals with HIV and 25% of individuals without HIV have this bone marrow involvement.
Testing for Plasmablastic Lymphoma
Plasmablastic Lymphoma (PBL), a type of cancer, is primarily diagnosed through a combination of methods including close examination of tissue samples (histologic evaluation), genetics, and a process known as immunophenotyping. PBL shares some features with other severe lymphomas and myelomas, so further tests may be needed to confirm the diagnosis.
Immunophenotyping is a method that helps differentiate PBL from other similar conditions by studying certain proteins going through a process known as staining. On the other hand, genetic analysis can also confirm PBL if a particular mutation in the MYC gene is identified. This process uses a technique known as fluorescence in-situ hybridization (FISH).
PBL diagnosis should proceed the same way as any other severe lymphoma. Your doctor will call for specific laboratory tests, starting with a complete blood count (CBC) which often shows low levels of red blood cells, a condition known as anemia. Other tests, including a complete metabolic panel (CMP), lactate dehydrogenase (LDH), and uric acid levels are done to check for a condition called tumor lysis syndrome, which happens when a large number of cancer cells are killed rapidly, leading to a fast release of the cell contents into the blood.
Additionally, tests for Hepatitis, HIV, and Epstein-Barr virus (EBV) should be done since these infections can be associated with lymphoma. To check if the cancer has spread to the bone marrow, a bone marrow biopsy is performed. A PET CT scan, which is a type of detailed body imaging, can also be used to identify the extent and stage of the cancer in your body.
Treatment Options for Plasmablastic Lymphoma
Chemotherapy, a treatment that uses medication to destroy cancer cells, is the primary strategy to treat Plasmablastic Lymphoma (PBL), a rare type of cancer that affects the immune system. This process involves a team of specialists including oncologists, who specialize in treating cancer, and infectious disease experts, who help deal with any related infections.
Unlike some cancers, surgery is not used to treat PBL. Radiation therapy, a treatment that uses high-energy particles or waves to destroy or damage cancer cells, may be used but only in very specific circumstances, such as reinforcing the effects of chemotherapy in patients who are responding well to the treatment.
Because PBL is quite rare, there is no universally agreed-upon treatment plan. However, a common approach involves using a combination of several drugs, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, that together are known as CHOP. Alternatively, some guidelines suggest using a different combination of drugs known as EPOCH, which includes etoposide in addition to the drugs used in CHOP.
Typically, the chemotherapy treatment involves receiving 6 to 8 cycles, or rounds, of these drugs. Another complementary therapy, called intrathecal chemotherapy, can also be used in selected cases. This procedure involves delivering chemotherapy directly into the spinal canal.
After successful initial chemotherapy – when the cancer doesn’t show signs of being active –, patients might also undergo an autologous stem cell transplant. This procedure involves harvesting healthy blood stem cells from the patient, which are then used to replace blood cells damaged by chemotherapy.
If the patient also has human immunodeficiency virus (HIV), it’s important that they continue to take, or start, their anti-retroviral therapy, a treatment that helps manage HIV infection. Such decisions should be made in consultation with a specialist in infectious diseases.
What else can Plasmablastic Lymphoma be?
In the process of diagnosing PBL, the doctor may consider a few other conditions, all of which have distinguishing characteristics and can look similar under testing:
- Plasmablastic myeloma: Indicated by characteristic ‘plasma cell markers’ such as CD38, CD138, and IRF4/MUM1, as well as an excess of a certain type of protein in the blood, issues with kidney function, and bone damage
- Extraosseous plasmacytoma with plasmablastic morphology: Shows the same ‘plasma cell markers’ as above, but usually lacks a MYC rearrangement (a specific genetic trait) and is negative for EBER (a virus-related indicator)
- Anaplastic large cell lymphoma kinase (ALK) positive large B cell lymphoma: Again displays the ‘plasma cell markers’ noted earlier, features ALK as detected by a particular test, and has the presence of one of two specific genetic combinations
- Extracavitary primary effusion lymphoma: Highlights ‘pan B cell markers’ including CD19, CD20, and PAX5, and is positive for HHV8 (a virus)
- HHV8 positive diffuse large B cell lymphoma: Tests positive for IRF4/MUM1 and HHV8, and is negative for EBER
- Immunoblastic diffuse large B cell lymphoma: Displays ‘pan B cell markers’ including CD19, CD20, and PAX5, typically lacks plasma cell markers, might be positive for EBER, and occasionally features MYC rearrangements
Remember, these are all different conditions that could potentially show similar signs as PBL in medical testing. That’s why it’s crucial for professionals to carefully review all results when making a diagnosis.
Surgical Treatment of Plasmablastic Lymphoma
In the treatment of PBL, a type of lymphoma, surgery is typically not used or recommended. Lymphoma is a type of cancer that originates from your immune cells, and the management is usually focused on therapies other than surgery.
What to expect with Plasmablastic Lymphoma
Plasmablastic lymphoma is a type of cancer that, unfortunately, often has a poor outcome. If left untreated, those with the disease are typically expected to live for a median of 3 months if they have HIV, and 4 months if they do not. However, treatment with drugs to kill the cancer cells (chemotherapy) generally improves survival. On average, the lifespan increases to 10 months for HIV-positive patients, 11 months for HIV-negative patients, and 7 months for patients who received a transplant.
Recent studies that have used a strong chemotherapy regimen called dose-adjusted EPOCH have shown a survival rate of 47.4% at two years, which suggests that the treatment outcomes are improving. Regardless, these survival rates emphasize the urgent need for therapies that are more effective in treating this type of cancer.
Possible Complications When Diagnosed with Plasmablastic Lymphoma
People undergoing chemotherapy often face an increased risk of certain issues. These include a weakened immune system, a decrease in blood cells, fever related to low neutrophil count, hair loss, infertility, nerve damage, and stomach-related problems like feeling nauseous, vomiting, and diarrhea. Usually, these issues get better after the chemotherapy is finished. To lower the risk of complications linked with infections, doctors often use a treatment called pegfilgrastim as a form of support.
Potential Side Effects:
- Weakened immune system
- Decrease in blood cells
- Fever related to low neutrophil count
- Hair loss
- Infertility
- Nerve damage
- Nausea
- Vomiting
- Diarrhea
Recovery from Plasmablastic Lymphoma
People receiving chemotherapy may find a rehabilitation program helpful. This program, focusing on physical and occupational therapy, can provide ways to stay active during treatment.
Preventing Plasmablastic Lymphoma
Patients should be informed that the condition they have been diagnosed with often has a challenging outcome. They should also understand the potential side effects before they start treatment, as the process of using intensive drugs to kill cancer cells can be quite tough. Additionally, if the patients are males or females who might want to have children in the future, they should be given the option to preserve their fertility.
It is equally important for patients to know that this type of lymphoma is commonly linked with HIV infection, so we advise getting tested for HIV. This will allow patients to get the right therapy to control HIV if they test positive. Furthermore, because chemotherapy can make patients more vulnerable to severe infections, we recommend getting flu shots as well as COVID-19 vaccinations and boosters as soon as possible.
However, given the aggressive nature of this lymphoma, the treatment should not be postponed just for vaccinations. The primary goal is to treat the lymphoma as swiftly as possible to maximize the chances of recovery.
