Primary Mediastinal Large B-Cell Lymphoma
Primary mediastinal large B-cell lymphoma is a rare and aggressive form of cancer that develops in the chest, primarily affecting young adults and showing a unique tendency to occur more often in women than men.
Table of contents
- What is Primary Mediastinal Large B-Cell Lymphoma?
- Who is Affected by This Disease
- Signs and Symptoms
- How the Disease is Diagnosed
- Treatment Options
- Outlook for Patients
What is Primary Mediastinal Large B-Cell Lymphoma?
Primary mediastinal large B-cell lymphoma (PMBCL) is a rare type of non-Hodgkin lymphoma (a group of cancers that affect the immune system). It makes up only 2 to 4 percent of all non-Hodgkin lymphomas[2][3]. This cancer develops from B lymphocytes (also called B cells), which are white blood cells that normally help fight infections.
The cancer forms in an area called the mediastinum, which is the space in the middle of the chest between the lungs[2][3]. The thymus (a small organ that helps the immune system develop) is also located in this area. PMBCL cells are thought to come from thymic B cells that develop in the thymus[2][5].
Although PMBCL is classified as a form of non-Hodgkin lymphoma, it shares many features with another type of cancer called classical Hodgkin lymphoma[2][7]. Under a microscope, the cancer cells from PMBCL can resemble those found in Hodgkin lymphoma[2][3]. Because of its unique characteristics, the World Health Organization now recognizes PMBCL as a separate and distinct disease entity[2][7].
mediastinal B-cell lymphoma, mediastinal (thymic) large B-cell lymphoma, primary thymic mediastinal lymphoma
- Mediastinum
- Thymus
- Lymph nodes in the chest
- Lungs
- Chest wall
- Pleura
- Pericardium
Who is Affected by This Disease
Primary mediastinal large B-cell lymphoma mainly affects young adults, with most patients being diagnosed in their third or fourth decade of life. The average age at diagnosis is around 35 to 37 years[2][7][8]. This makes it particularly common among adolescents and young adults (often abbreviated as AYA)[2][16].
Unlike many other types of cancer, PMBCL has a clear female predominance, meaning it occurs more often in women than in men[2][7][8]. While the disease can also affect children, this is less common[2][3].
Signs and Symptoms
Most of the symptoms of PMBCL are caused by a rapidly growing mass in the chest that presses on nearby organs and tissues[2][3][7]. The majority of people with PMBCL have what doctors call bulky disease, meaning the tumor is greater than 10 centimeters in diameter[2][3].
Common symptoms include:
- Persistent coughing[2][3][13]
- Shortness of breath or rapid breathing[2][3][13]
- Difficulty swallowing (called dysphagia)[2][3]
- Chest pain or ache[2][4]
- Blood clots in the veins[2][3]
- Hoarseness[2][7]
Some people experience superior vena cava syndrome, a serious condition that occurs when the large vein carrying blood to the heart becomes compressed. This can cause difficulty breathing, swelling of the face and abdomen, and large visible veins in the chest[2][3][7].
Patients may also experience what doctors call B symptoms, which include fever, night sweats, and unintended weight loss[2][7].
The cancer can spread to nearby structures such as the lungs, chest wall, pleura (the lining around the lungs), or pericardium (the sac around the heart)[2][5][16]. Enlarged lymph nodes are typically found only within the mediastinum, not in other parts of the body[2][3].
Fluid can also accumulate around the lungs, a condition called pleural effusion, which is common in PMBCL[2][3][13].
How the Disease is Diagnosed
Diagnosing PMBCL involves several different tests and procedures. The process is important because the disease shares features with other types of lymphoma, and accurate diagnosis helps determine the best treatment[2].
Biopsy: A tissue sample must be taken from the affected area in the chest so it can be examined under a microscope. This can be done through a surgical biopsy (removing an entire lymph node) or a needle biopsy (removing a portion of tissue)[2][3]. The cancer cells express certain markers on their surface, including CD19, CD20, CD22, and CD79a, which are characteristic of B cells[2][7][16]. The cells often show weak CD30 expression and are negative for CD15[2][7][16].
Imaging tests: CT scans (computed tomography) and PET-CT scans (positron emission tomography combined with CT) are used to create detailed pictures of the chest and see the characteristic mass in the mediastinum[2][3]. These scans can also detect pleural effusion[2][3].
Blood tests: Blood samples are taken to measure blood cell counts and check levels of a protein called lactate dehydrogenase, which may be higher than normal in people with PMBCL[2][3].
Bone marrow testing: A doctor may take a sample from the bone marrow through bone marrow biopsy (removing a small tissue sample) or bone marrow aspiration (taking a liquid sample)[2][3].
Spinal tap: Also called a lumbar puncture, this test uses a needle to collect fluid from the spinal canal. It may be performed to check if PMBCL has spread to the nervous system[2][3].
The diagnosis can be challenging because the cells look similar to those found in Hodgkin lymphoma under the microscope[2][16]. However, specific tests examining the markers on the cell surface help doctors distinguish between these diseases.
Treatment Options
Because PMBCL is rare, there are few large clinical trials to guide treatment, and there is no single standard approach used everywhere[2][8][16]. Treatment approaches aim to maximize the chances of cure while minimizing long-term side effects, which is especially important given that most patients are young adults with many years of life ahead[2][16].
Initial Treatment
Chemotherapy with immunotherapy: The main treatment for PMBCL is a combination of chemotherapy drugs (medicines that kill cancer cells) given together with rituximab (Rituxan), which is an antibody that targets cancer cells[2][3][4]. Rituximab is a type of targeted therapy that helps the immune system destroy cancer cells.
The most commonly used treatment combinations are:
- R-CHOP: rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone[2][4][8]
- DA-EPOCH-R: dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab[2][4][10]
DA-EPOCH-R is a more intense regimen that has shown excellent results in studies. One prospective study showed that 5-year survival rates were 93% for event-free survival and 97% for overall survival[2][10]. This regimen has become the preferred treatment at many centers[2][10].
Research suggests that dose-intensive chemotherapy provides a survival benefit compared to standard approaches, with studies showing an 8% improvement in overall survival[2][12].
Radiation Therapy
Radiation therapy uses high-energy rays to destroy cancer cells. It is sometimes used after chemotherapy if there are still areas of cancer remaining in the chest[2][4]. However, the use of radiation in PMBCL is controversial[2][8][16].
Many doctors try to avoid using radiation in this predominantly young, female population because of the risk of long-term side effects. These can include secondary cancers (especially breast cancer), heart problems, and other complications[2][8][12][16]. Studies show that patients treated with dose-intensive chemotherapy need radiation therapy much less often (about 22% of the time) compared to those on standard chemotherapy (about 55% of the time)[2][12].
Treatment for Relapsed or Refractory Disease
If PMBCL comes back after treatment (relapsed) or doesn’t respond to initial treatment (refractory), several options are available[2][4][10]:
Immunotherapy: Drugs that help the immune system fight cancer have shown promising results. Pembrolizumab (Keytruda), which is a checkpoint inhibitor, has demonstrated high and lasting response rates in patients whose disease has stopped responding to at least two other treatments[2][4][10].
Bispecific antibodies are a newer type of immunotherapy that may be used after two or more previous treatments. These include epcoritamab (Epkinly) and glofitamab (Columvi)[2][4].
CAR T-cell therapy: This is an advanced treatment where a patient’s own immune cells are modified in a laboratory to better recognize and attack cancer cells. Axicabtagene ciloleucel (Yescarta) and lisocabtagene maraleucel are two CAR T-cell products used for PMBCL[2][4][10].
Stem cell transplant: A stem cell transplant may be used if the cancer comes back or stops responding to treatment[2][4]. This procedure replaces damaged blood-forming cells with healthy ones. However, outcomes with this approach have not been as good as in other types of lymphoma[2][10].
Outlook for Patients
The outlook for people with PMBCL is generally very good. Most patients are cured of their disease with modern treatments[2][6][16].
With current therapies, the 5-year overall survival rate is greater than 80% in most studies, and some studies report survival rates as high as 90% or more[2][6][11][12]. The event-free survival rate (meaning patients remain free of disease progression or relapse) can be over 90% at 5 years with intensive treatment regimens[2][10].
Most people with PMBCL are diagnosed when the disease is still localized to the chest area, which improves the chances of successful treatment[2][3].
After treatment, patients typically undergo follow-up with PET-CT scans to check how well the treatment worked and to guide decisions about further therapy[2]. However, interpreting these scans can be challenging because inflammation in the chest area after treatment can sometimes be mistaken for remaining cancer[2][11].
While the long-term outlook is excellent for most patients, some people experience relapsed or refractory disease. When the cancer comes back, it may spread to other parts of the body beyond the chest, and the prognosis in these cases is generally poorer[2][7]. However, newer therapies like immunotherapy and CAR T-cell therapy offer hope for patients in this situation[2][10].
