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Primary Mediastinal Large B-Cell Lymphoma

Last updated Dec. 20, 2018

Approved by: Maulik P. Purohit MD, MPH

Primary Mediastinal Large B-Cell Lymphoma (PMBCL) is a rare and aggressive non-Hodgkin’s B-cell lymphoma that usually arises from the thymus gland (lymphoid organ located in the chest cavity). PMBCL is mostly observed in young men and women.


What are the other Names for this Condition? (Also known as/Synonyms)

  • PMBCL (Primary Mediastinal Large B-Cell Lymphoma)
  • Primary Mediastinal (Thymic) Large Cell Lymphoma
  • Primary Thymic Mediastinal Lymphoma

What is Primary Mediastinal Large B-Cell Lymphoma? (Definition/Background Information)

  • Primary Mediastinal Large B-Cell Lymphoma (PMBCL) is a rare and aggressive non-Hodgkin’s B-cell lymphoma that usually arises from the thymus gland (lymphoid organ located in the chest cavity). PMBCL is mostly observed in young men and women
  • This type of lymphoma first involves the thymus gland and later can involve other parts of the body including the lymph nodes and bone marrow. Primary Mediastinal Large B-Cell Lymphoma may be present as a mediastinal mass
  • Currently, no risk factors for Primary Mediastinal Large B-Cell Lymphoma have been identified. The cause of the condition is also unknown, though genetic mutations have been implicated
  • The condition can cause chest pain, breathing difficulties, fatigue, and other general signs and symptoms, such as fever, weight loss, and appetite loss. In case of severe complications, the lungs and heart may be affected
  • Chemotherapy, surgery, radiation therapy, and other treatment measures may be used for treating Primary Mediastinal Large B-Cell Lymphoma based on the assessment of the physician
  • The prognosis depends on many factors including the subtype and stage of lymphoma, progression of the condition, response to treatment, and overall health of the individual. In general, the prognosis of Primary Mediastinal Large B-Cell Lymphoma is guarded

General information on lymphoma and lymphocytes:

  • Lymphoma is a type of cancer stemming from uncontrollably dividing lymphocytes (type of white blood cells). There are two types of lymphomas:
    • Hodgkin lymphoma
    • Non-Hodgkin lymphoma
  • Lymphocytes are the main white blood cells found in the lymph, which is the fluid of the lymphatic system; just as blood is the fluid of the circulatory system. Lymphocytes are made in bone marrow, and can develop into either B-cells or T-cells
  • Lymph results from filtration of blood as it travels to and from tissues. Lymph is colorless because it lacks red blood cells; instead, it contains lymphocytes. It is central to the immune system
  • There are 3 different kinds of lymphocytes:
    • T-lymphocytes or T cells: They help combat infections and abnormalities within the cells (cell-mediated immunity). They fight viruses and cancerous cells
    • B-lymphocytes or B cells: They produce antibodies that are bodily defense proteins, which target foreign invaders outside the cells (humoral immunity). They fight bacterial cells, cell fragments, and other immunogenic elements
    • Natural killer cells or NK cells: They perform diverse functions related to both cell-mediated and humoral immunity. They also scout for cancer cells, a process called immune surveillance

Who gets Primary Mediastinal Large B-Cell Lymphoma? (Age and Sex Distribution)

  • Primary Mediastinal Large B-Cell Lymphoma occurs infrequently. It constitutes about 2-4% of all non-Hodgkin lymphomas
  • It is generally seen in younger adults in the age group 20-40 years; median age at presentation is 35 years
  • Both males and females can be affected, though females are affected more than males in a 2:1 ratio
  • It can occur worldwide and all racial and ethnic groups may be affected

What are the Risk Factors for Primary Mediastinal Large B-Cell Lymphoma? (Predisposing Factors)

No specific risk factors have been identified for Primary Mediastinal Large B-Cell Lymphoma. However, the following general factors may contribute towards lymphoma formation and development:

  • Advanced age; older individuals commonly have a higher risk
  • Individuals with weak immune system (due to various health conditions)
  • Family history of immune disease
  • The presence of any systemic disease
  • Smoking
  • Exposure to radiation and industrial chemicals
  • Chemotherapy
  • Viruses (in some rare cases); Epstein-Barr virus infection
  • X-ray, CT scan exposure
  • Profession involving radiation exposure, which may include nuclear plant workers, pilots, astronauts, etc.
  • Certain medications and drugs

International Prognostic Index: According to some scientists, the International Prognostic Index may not be very helpful in evaluating Primary Mediastinal Large B-Cell Lymphoma. However, some scientists believe that it is helpful in some cases, to determine the prognosis.

The International Prognostic Index, for aggressive non-Hodgkin lymphoma, lists a few factors that determine the overall risk:

  • Age over 60 years
  • Elevated level of serum lactate dehydrogenase - LDH (a type of enzyme)
  • Performance status, i.e. the overall health condition of the individual, which could range from being fully active (low risk) to being completely disabled (very high risk)
  • Individual, who have already suffered from lymphoma, or other types of blood cancers, may have a relapse or a recurrence
  • Presence of an immunodeficiency syndrome, like AIDS, is a high risk factor
  • Those infected with Epstein-Barr virus are also prone to this lymphoma type

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Primary Mediastinal Large B-Cell Lymphoma? (Etiology)

Lymphocytes are a type of white blood cells that are responsible for providing immunity in the human body. B-cells and T-cells are the two different types of lymphocytes. When under certain circumstances, the lymphocytes grow and multiply abnormally, it leads to a condition called as lymphoma, which is a most common type of cancer. There are 2 types of lymphoma:

  • Hodgkin lymphoma
  • Non-Hodgkin lymphoma

The exact cause of Primary Mediastinal Large B-Cell Lymphoma, a non-Hodgkin’s lymphoma, is unknown. There may be certain genetic defects, such as translocation, which is a juxtaposition of regions of the chromosomes. This may result in:

  • Change of regulatory elements of certain cancer-causing genes called as oncogenes, which can lead to increased production of their mRNA (overexpression), thus increasing their protein levels
  • Exchange of protein coding regions of gene, giving rise to new proteins that can stimulate the inappropriate growth of cells

It is believed that the abnormal development of lymphocytes gives rise to cancerous cells leading to the formation of this condition. Nevertheless, how this occurs and the factors that cause it remain under investigation.

What are the Signs and Symptoms of Primary Mediastinal Large B-Cell Lymphoma?

Primary Mediastinal Large B-Cell Lymphoma may be present as a mediastinal mass (arising from the thymus gland) that may cause the following signs and symptoms:

  • Cough
  • Chest pain
  • Breathing difficulties
  • Loss of appetite
  • ‘B’ symptoms that may include fever, night sweats, and 10% weight loss over a period of 6 months
  • Generally, these tumors are large bulky tumors, often greater than 10 cm in size

The tumor can spread to the surrounding structures such as the lung, covering of the heart (pericardium), covering of lungs (pleura), and even the chest wall. Involvement of the bone marrow is uncommon.

Additionally, there may also be the following general signs and symptoms:

  • Fatigue and weakness, headache
  • Anemia (low red blood cell count)
  • Frequent infections
  • Low blood pressure
  • Pain in the abdomen, bones
  • Itchy skin rashes
  • Enlarged lymph nodes that may be painless

When the involvement of other organs occurs, the signs and symptoms may be based on the specific organs that are affected.

How is Primary Mediastinal Large B-Cell Lymphoma Diagnosed?

Primary Mediastinal Large B-Cell Lymphoma diagnosis is generally performed by obtaining biopsy samples from the affected region and examining them under a microscope to detect the cancerous cells. However, in order to establish a diagnosis, the following criteria should be met:

  • Absence of lymphoma at the following locations:
    • Lymph nodes
    • Bone marrow
    • Any other part of the body (other than the mediastinum)

Tests and procedures that could help in the diagnosis of PMBCL include:

  • A thorough physical examination and a complete medical history, which is very important
  • Blood tests that may include:
    • Complete blood cell count (CBC) blood test
    • Absolute lymphocyte count on peripheral blood
    • Liver function blood test (LFT)
    • Lactate dehydrogenase (LDH) blood test
    • Blood chemistry study
  • Angiography of the chest region
  • Pulmonary function tests (if necessary) can help determine the extent of lung damage and help the healthcare provider to assess the ability of lungs, to deliver oxygen to the body
  • Tissue biopsy from the mediastinal mass, the thymus gland, or affected region:
    • A biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
    • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
    • Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, flow cytometric analysis and very rarely, electron microscopic studies, to assist in the diagnosis
  • The biopsy may be performed through any of the following procedures:
    • Mediastinoscopy: A medical instrument called a mediastinoscope is inserted into the chest wall to examine and remove samples
    • Fine needle aspiration biopsy (FNAB): A device called a cannula is used to extract tissue or fluid from the gland, or surrounding lymph nodes
  • Radiological imaging may be performed specific to location of the involved organ, and to determine the extent of lymphoma in the body including:
    • X-ray of the chest
    • Ultrasound scan of the lungs
    • Pulmonary computerized tomography (CT) scan
    • MRI scan of the lungs
    • Vascular radiological studies
    • Whole body bone scan
    • Whole body CT-PET scans to determine how far the lymphoma has spread, by checking the size and metabolic rate (a reflection of uncontrolled growth) of lymph nodes, throughout the body. This can also help determine, if the cancer has spread to other organ systems
    • Brain MRIs are used if neurological symptoms are present, which can help determine if the cancer has spread to the brain, or to tissues that cover the brain
  • Bone marrow aspiration and biopsy is performed and sent to a laboratory for a pathological examination, to determine if the bone marrow is involved. Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, histochemical stains, molecular testing, and very rarely electron microscopic studies. However, a bone marrow biopsy is not needed in the early stages of the condition
  • Flow cytometry to identify cells as they flow through an instrument, called a flow cytometer. Flow cytometry measures the number and percentage of cells in a blood sample, and cell characteristics such as size, shape, and the presence of biomarkers on the cell surface. This method helps to sub-classify the condition and also to detect residual levels of disease after treatment. This tool can help in diagnosing relapse and restart treatment as needed
  • Fluorescence in situ hybridization (FISH): It is a test performed on the blood or bone marrow cells to detect chromosome changes (cytogenetic analysis) in blood cancer cells. The test helps in identifying genetic abnormalities that may not be evident with an examination of cells under a microscope
  • Immunophenotyping to identify a specific type of cell in a sample, which can help determine the best treatment course to be followed
  • Polymerase chain reaction (PCR): It is used to measure the presence of certain biomarkers in blood or bone marrow cells. The test is ultrasensitive and detects extremely low amounts of biomarkers remaining in blood, which can be missed by cytogenetic methods, such as FISH, karyotype, or flow cytometry. PCR allows a more sensitive follow-up of patients in remission and can help determine whether additional treatment is necessary
  • Exploratory laparoscopy (diagnostic laparoscopy) may be required, if gastrointestinal symptoms are present. In this procedure, the abdomen is examined using a minimally-invasive technique, and a tissue biopsy and tissue for culture obtained. Minimally-invasive approaches help decrease complications and the length of stay at the hospital. A diagnostic laparoscopy is also helpful in staging of the tumor. Nevertheless, this procedure is not very much used

Note:

  • Differential diagnoses, to eliminate other tumor types are often considered, before arriving at a definitive diagnosis
  • Often times, a Primary Mediastinal (Thymic) Large Cell Lymphoma can be confused with Hodgkin lymphoma, and hence, a careful examination by the pathologist is important

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Primary Mediastinal Large B-Cell Lymphoma?

The complications due to Primary Mediastinal Large B-Cell Lymphoma may include:

  • Involvement of local and distant organs: It can lead to systemic or disseminated disease in some cases
  • Loss of function of the organ/area to which cancer has spread due to systemic involvement
  • It can compress the trachea and bronchus causing associated breathing/talking problems
  • If the lymphoma grows to large sizes, it can obstruct the functioning of the heart
  • PMBCL can cause superior vena cava syndrome
  • Deep vein thrombosis of arms
  • Invasion to nearby sites such as chest wall, lungs, pleura, and pericardium. This can result in pleural and pericardial effusion
  • In case of a relapse, this lymphoma is known to affect several organs such as the central nervous system (CNS), kidney, breast, GI tract, and liver (extranodal locations)
  • Weakened immune system (or immunosuppression) can be a complication, which can become more severe during treatment. Due to this, individuals are more vulnerable to infections; there is an increased risk of developing serious complications from such infections
  • Occasionally, the tumor can transform into a more aggressive form or subtype of lymphoma

There may be complications related to chemotherapy used in treating the condition, which may include:

  • Side effects such as dizziness, vomiting, appetite loss, mouth ulcers, and hair loss
  • By damaging healthy cells, the individual is more open or vulnerable to secondary infections
  • The treatment can also cause infertility in men and women. Hence, measures to protect the individual’s fertility must be considered, before starting chemotherapy

The treatment measures can also give rise to secondary cancers, such as skin cancer.

How is Primary Mediastinal Large B-Cell Lymphoma Treated?

A combination of measures may be used to treat Primary Mediastinal Large B-Cell Lymphoma. The treatment also depends upon the stage, overall health, age, and subtype of lymphoma.

  • Chemotherapy: This approach uses a combination of drugs to kill the cancerous cells and can be used in patients, for all stages of the tumor
    • There can be severe side effects including fatigue, nausea, hair loss, anemia, high risk of infection, and drug-specific reactions
    • Many lymphomas can be resistant to chemotherapy. It can also damage healthy cells
    • Chemotherapy can be administered as a pill, liquid, shot, or intravenously

Note: Men and women in child-bearing age would greatly benefit from counseling regarding fertility issues. Some chemotherapy agents can cause infertility in both men and women. There can be permanent damage to the testicles and ovaries, harming their ability to produce sperms or ova. In men, sperm banking can be considered before initiating therapy. In women, in many cases, due to urgency of starting chemotherapy, it is often difficult to perform ovum banking. However, if there is sufficient time prior to chemotherapy, ovum banking may be performed. The healthcare provider may help assess the risk-benefit analysis, depending upon each individual’s specific circumstances.

  • Radiation: Radiation therapy is the use of high-energy radiation waves to kill cancer cells, by destroying their DNA
    • This treatment modality is generally used for early stage lymphomas. It is most commonly used in combination with chemotherapy
    • The radiation may be administered by a machine placed outside the body, or by placing a radioactive material inside the body
    • The side effects of radiation therapy include nausea, vomiting, fatigue, pain, risk of cancer later in life, and risk of heart disease
    • Radiation can damage healthy cells in addition to cancer cells, causing further complications
  • Surgical removal of the lymphoma from the chest cavity, if required
  • Undertaking treatment of underlying conditions/disorders, as warranted
  • Supportive treatment: Steroids, blood transfusions, anti-nausea medications, and antibiotics, may be used as supportive therapy. In combination with other treatment measures, these can help combat the symptoms of immunodeficiency

If Primary Thymic Mediastinal Lymphoma is not fully responsive to treatment, or if the chance of recurrence is high, then bone marrow transplantation or stem cell transplantation can be considered.

  • Bone marrow transplantation: Typically systemic cases may be treated by administering high doses of chemotherapy or radiotherapy. But, high doses of chemotherapy drugs will also damage the bone marrow, preventing it from making any blood cells. Hence, before starting high-dose chemotherapy, the physicians may take out some of the patient’s bone marrow and freeze/preserve it. Collecting the bone marrow is called a bone marrow harvest. The bone marrow is then stored. After high dose chemotherapy or radiation, the bone marrow is thawed and injected back into patient through a drip (transfusion). This is called an autologous bone marrow transplant. Sometimes bone marrow donated by another matching person (usually a brother or sister) is used, if the condition recurs following transplant using one’s own cell. This is called as allogeneic bone marrow transplant
  • Stem cell transplantation: This procedure is similar to bone marrow transplantation and involves the transplantation of healthy blood-forming stem cells into the body. The procedure is also called hematopoietic progenitor cell transplantation. Stem cells can be collected from the bone marrow, circulating (peripheral) blood, and umbilical cord blood. It may either involve an autologous stem cell transplantation, where stem cells are harvested from individuals before treatment and transplanted back into the patient after treatment, or involve an allogeneic stem cell transplantation, where stem cells donated by another matching person (usually a brother or sister) is used, if the condition recurs after stem cell transplant using one’s own cell. This is called as allogeneic stem cell transplant

Note: Allogeneic bone marrow and allogeneic stem cell transplants may have more side effects and complications, and this treatment may not be suitable for every individual. If allogeneic transplants come from a healthy donor with no malignant cells, then the chances of recurrence of the condition may be reduced.

  • In order to prevent infections because the immune system is weakened by PMBCL or by its treatment, the patient is kept in an isolated ward and treated with appropriate antibiotics
  • Nowadays, targeted therapies are being developed, that can selectively kill the lymphoma/leukemia cells. Many of them are in the stage of clinical trials
  • Clinical trials: There may be some newer treatment options, currently on clinical trials, which can be considered for some patients depending on their respective risk factors

Your healthcare provider will determine the best course of treatment depending on your individual circumstances. Also, follow-up care with regular screening and check-ups are important post-treatment.

How can Primary Mediastinal Large B-Cell Lymphoma be Prevented?

Currently, it is not possible to prevent Primary Mediastinal Large B-Cell Lymphoma. However, controlling certain factors may help lower one’s risk for the condition.

  • Healthy diet and exercise, as well as avoidance of unnecessary exposure to chemicals, may help decrease its risk
  • Avoiding smoking
  • Using appropriate protective gear while working with x-rays and other radioactive source
  • In order to avoid a relapse, or be prepared for a recurrence, the entire diagnosis, treatment process, drugs administered, etc. should be well-documented and follow-up measures initiated

Regular medical screening at periodic intervals with blood tests, scans, and physical examinations, are mandatory. Often several years of active vigilance are crucial and necessary.

What is the Prognosis of Primary Mediastinal Large B-Cell Lymphoma? (Outcomes/Resolutions)

  • Primary Mediastinal Large B-Cell Lymphoma is a slow-growing malignancy with a generally good prognosis with early diagnosis and treatment
  • Primary Mediastinal Large B-Cell Lymphoma is a subtype of diffuse large B-cell lymphoma. The cure rate of PMBCL is similar to the cure rate of DLBCL and the 5 year survival rate is 50%
  • In general, the prognosis depends upon a set of several factors, which include:
    • Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
    • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
    • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
    • The size of the tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
    • Individuals with bulky disease have a poorer prognosis
    • Involvement of vital organs may complicate the condition
    • The surgical respectability of the tumor (meaning, if the tumor can be removed completely) - it is a rare option
    • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
    • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
    • Progression of the condition makes the outcome worse (progressive Primary Mediastinal Large Cell Lymphoma)
  • The combination chemotherapy drugs used, may have some severe side effects (such as cardio-toxicity). This chiefly impacts the elderly adults, or those who are already affected by other medical conditions. Tolerance to the chemotherapy sessions is a positive influencing factor
  • Progression to bone marrow failure is usually associated with short survival

Additional and Relevant Useful Information for Primary Mediastinal Large B-Cell Lymphoma:

  • Treatment for Primary Mediastinal Large B-Cell Lymphoma can cause physical and emotional distress; supportive care and encouragement, help positively and can bring a measure of relief to the patients

The following article link will help you understand leukemia and lymphoma (blood cancer):

http://www.dovemed.com/diseases-conditions/leukemia-and-lymphoma/

What are some Useful Resources for Additional Information?


References and Information Sources used for the Article:


Helpful Peer-Reviewed Medical Articles:


Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: March 18, 2016
Last updated: Dec. 20, 2018