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Primary Effusion Lymphoma

Last updated Dec. 19, 2018

Approved by: Krish Tangella MD, MBA, FCAP

Primary Effusion Lymphoma (PEL) is a rare and aggressive non-Hodgkin’s lymphoma that is generally associated with HIV infection and other immunocompromised states.


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

  • PEL (Primary Effusion Lymphoma)

What is Primary Effusion Lymphoma? (Definition/Background Information)

  • Primary Effusion Lymphoma (PEL) is a rare and aggressive non-Hodgkin’s lymphoma that is generally associated with HIV infection and other immunocompromised states. The condition may arise from a B-cell or T-cell (lymphocytes); however, typically it develops from a B-cell
  • Unlike other lymphomas that generally affect the lymph nodes or body organs, the Primary Effusion Lymphoma affects the body fluids at various body cavities, such as the pleura, pericardium, or peritoneum. The tumor cells are found in the fluid in the affected body cavity
  • Only one cavity is affected at a single time, in a majority of cases; it does not spread from one body fluid to another. This can lead to signs and symptoms that are based on the affected cavity, such as the pleural cavity, pericardial cavity, or peritoneal cavity. However, very rarely, other body cavities may be also involved
  • The cause of Primary Effusion Lymphoma is unknown, but it is strongly linked to human herpes viral infection. Immunocompromised individuals, such as AIDS patients and organ transplant recipients, have a high risk for PEL
  • The treatment of Primary Effusion Lymphoma may involve a combination of chemotherapy, radiation therapy, and targeted therapy. However, it has been observed that the response of PEL affected individuals to treatment is generally poor
  • Primary Effusion Lymphoma is an aggressive malignancy that has a poor prognosis. But, in the context of HIV infection, the outcome is even poorer

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. Primary Effusion Lymphoma arises from cancerous B-cells or even from 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 Effusion Lymphoma? (Age and Sex Distribution)

  • Primary Effusion Lymphoma is a rare condition that generally affects elderly adults who are immunocompromised
  • However, when it is observed in association with AIDS, PEL is reported in much younger adults
  • Both males and females can be affected
  • All races and ethnic groups can be affected
  • This condition constitutes approximately 4% of HIV-associated non-Hodgkin lymphoma

What are the Risk Factors for Primary Effusion Lymphoma? (Predisposing Factors)

Various research studies have identified the following risk factors for Primary Effusion Lymphoma:

  • Human herpes virus (HHV) infection:
    • There is a very strong association of PEL with HHV infection
    • It is more prevalent in certain parts of Africa
    • The infection is more common in men who have sex with other men
  • Immunocompromised individuals, such as those with advanced HIV infection (or AIDS), organ transplantation, etc. PEL is very commonly seen in HIV-infected individuals who have advanced immunosuppression (or AIDS)
  • Association with Epstein-Barr virus (EBV) infection
  • Very elderly adults with decreased immune system due to age

Besides the above, the following factors may also contribute towards lymphoma formation and development:

  • Family history of immune disease
  • Age 60 years and older
  • The presence of any systemic disease
  • Smoking
  • Exposure to radiation and industrial chemicals
  • Chemotherapy
  • X-ray, CT scan exposure
  • Profession involving radiation exposure, which may include nuclear plant workers, pilots, astronauts, etc.
  • Certain medications and drugs

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 PEL

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

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 Effusion 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 Effusion Lymphoma, a rare non-Hodgkin lymphoma, is unknown.

  • It is associated with health conditions involving immunodeficiency in individuals
  • PEL is also strongly associated with human herpes virus (HHV 8), which can be secreted in the saliva and through genital fluids during sex. But, the exact mechanism of how this viral infection influences PEL is currently under investigation

Moreover, Primary Effusion Lymphoma may also be caused by certain genetic defects, such as translocation, which is a juxtaposition of regions of chromosomes resulting 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 Effusion Lymphoma?

Primary Effusion Lymphoma affects the various body cavities such as the pleural cavity (space in the chest), pericardial cavity (around the heart), and peritoneal cavity (in the abdomen), resulting in accumulation of fluids at these locations; a condition termed as effusion. However, majority of the times, only one body cavity is affected and the signs and symptoms are based upon the involved cavity.

Pleural effusion can lead to:

  • Chest pain
  • Rapid breathing and shortness of breath
  • Fever and cough, if caused by an infection
  • Hiccups

Pericardial effusion can lead to:

  • Chest pain or tightness
  • Trouble breathing
  • Fever
  • Abnormalities in heart rhythm

Peritoneal effusion can lead to:

  • Abdominal pain and tenderness
  • Abdominal trauma
  • Fever
  • Fatigue
  • Nausea and vomiting
  • Bloating of abdomen

Besides the above, there may be general signs and symptoms that may include:

  • Unintentional weight loss; changes in appetite
  • Fatigue and weakness, headache
  • High temperatures and excessive night sweats (may be recurrent)
  • Anemia (low red blood cell count)
  • Frequent infections
  • Low blood pressure
  • Back pain
  • Swelling of the legs
  • Frequent urination 

When there is an involvement of other organs and body parts in case of widespread disease, then organ-specific signs and symptoms may be observed such as the following:

  • Non-painful swelling of lymph nodes in the neck, armpits, or groin
  • There may be associated autoimmune disorders, which can cause joint and muscle pain, heat intolerance, recurrent rashes, abdominal pain, and a general feeling of illness
  • If the brain is involved, then neurological symptoms such as the following may be observed:
    • Confusion
    • Tinnitus (ringing in the ears)
    • Hearing and visual impairment
  • If the gastrointestinal (GI) tract is involved, then GI tract symptoms such as the following may be observed:
    • Ulcers
    • Diarrhea
    • Inflammation
    • GI bleeding
  • Liver and spleen enlargement
  • Joint inflammation and fluid accumulation (edema) can occur, if the joints are affected

How is Primary Effusion Lymphoma Diagnosed?

Primary Effusion Lymphoma diagnosis is performed by testing the malignant fluid from the involved body cavity. The presence of HHV8 in the body fluid is mandatory for a definitive diagnosis of PEL. This can be established through a polymerase chain reaction (PCR) test.

The testing of fluids may involve the following procedures:

  • Pleural tap (known as thoracentesis)
  • Pericardial tap (known as percardiocentesis)
  • Peritoneal tap (known as paracentesis)

Tissue biopsy samples from the affected region may be taken for further examination under a microscope to detect the cancerous cells. Since the condition involves either B-cells or T-cells, the diagnosis can be very challenging for a pathologist.

Other diagnostic methods used in the study may 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
    • Chemistry panel
    • Serum calcium levels
    • Serum albumin levels
    • HIV testing
  • Biopsy samples from the affected area:
    • 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
  • If the lymphoma involves the lymph nodes then, biopsies of enlarged lymph nodes are taken and examined in a lab to determine if the cells are malignant or benign. The biopsies may be performed under general or local anesthesia. Normally, the entire lymph node is removed to help determine the subtype of lymphoma
  • Radiological imaging may be performed to determine the extent of lymphoma in the body including:
    • X-ray of the affected region
    • Ultrasound scan of the affected region
    • Computerized tomography (CT) scan of the affected region
    • 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
  • GI endoscopy: It may be performed to assess the extent of tumor spread
  • Multigated acquisition (MUGA) scan or echocardiography to identify cardiotoxicity as a result of chemotherapy
  • Lumbar puncture to determine if the brain is involved
  • In addition, the cerebrospinal spinal fluid (CSF) may be collected by inserting a needle in the spine and subjected to microscopic, flow cytometric, PCR, and biochemical analysis, to diagnose central nervous system (CNS) involvement, if any
  • 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:

  • Approximately, 1-5% of the general population may test positive for HHV 8 (that can be established through a blood test)
  • Differential diagnoses, to eliminate other tumor types are often considered, before arriving at a definitive diagnosis

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 Effusion Lymphoma?

The complications due to Primary Effusion Lymphoma may include: 

  • Loss of function of the organ/area to which the cancer has spread
  • 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
  • If the pleura is affected, then it can result in lung failure and respiratory distress
  • If the pericardium is affected, then it can result in heart attack and sudden death
  • If the peritoneum is affected, then it can result in peritonitis, severe infection, and compression of the abdominal organs leading to their dysfunction
  • If the condition spreads to the brain and central nervous system, it can give rise to:
    • Inflammation of the meninges or brain (that can be lethal)
    • Vision changes
    • Facial numbness
  • If the abdomen is affected, it can cause intestinal obstruction that results in urine outflow obstruction and kidney damage
  • Blood loss may occur due to frequent or heavy bleeding, giving rise to severe anemia
  • The leukemic cells can overgrow and cause clogging of vessels resulting in stroke, or blurring of vision

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
  • Tumor lysis syndrome: This can occur due to chemotherapy treatment and can result in kidney failure, if not recognized promptly

How is Primary Effusion Lymphoma Treated?

There is no standard treatment protocol for Primary Effusion Lymphoma. Moreover, the response to treatment for PEL is generally poor. The following procedures may be used to treat the condition:

  • Chemotherapy: This approach uses a combination of drugs to kill the cancerous cells and can be used in patients, for all stages of the cancer
    • There can be severe side effects including fatigue, nausea, hair loss, anemia, high risk of infection, and drug-specific reactions
    • Many T-cell lymphomas can be resistant to chemotherapy. It can also damage healthy cells
    • Chemotherapy can be administered as a pill, liquid, shot, or intravenously
    • However, chemotherapy is not found to be very effective in treating PEL

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
  • Pleural tap, pericardial tap, and peritoneal tap may be performed in order to relieve the signs and symptoms caused by compression of the lungs, heart, and abdominal organs respectively. The procedure can also help remove any excess fluid formed in these areas
  • Intrathecal chemotherapy, if there is an involvement of the brain
  • 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, on a case-by-case basis
  • In order to prevent infections because the immune system is weakened by T/HRBCL of Skin 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

You 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 Effusion Lymphoma be Prevented?

The cause of Primary Effusion Lymphoma is currently unknown. Hence, there are no known methods to prevent the tumor from occurring. Eliminating certain risk factors for lymphoma development may help in avoiding the condition.

  • Healthy diet and exercise, as well as avoidance of unnecessary exposure to chemicals, may help decrease its risk
  • Avoidance or cessation of smoking
  • 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

A standard recommendation to prevent human herpes virus (HHV 8) infection is not currently available. But, the risk factor for spreading of HHV 8 can be avoided by following certain measures such as:

  • Practicing safe sex
  • Avoiding multiple partners
  • Undergoing periodic sexual health checkups, especially if you are sexually-active
  • Avoiding illegal drug abuse including the sharing of needles
  • Ensuring that blood products and blood transfusion adhere to safety and regulatory standards
  • In case the mother is infected, then child breastfeeding must be discontinued until the mother is completely infection-free

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 Effusion Lymphoma? (Outcomes/Resolutions)

  • Primary Effusion Lymphoma is an aggressive type of cancer. The prognosis of the condition is generally poor
  • If the condition is associated with HIV infection, AIDS, or other immunodeficiency conditions, then the median survival period is 6 months
  • 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
    • 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 PEL)
  • An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment
  • The combination chemotherapy drugs used, may have some severe side effects (like 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

Additional and Relevant Useful Information for Primary Effusion Lymphoma:

  • According to the World Health Organization (WHO), Primary Effusion Lymphoma is a form of diffuse large B-cell lymphoma (DLBCL), another aggressive lymphoma subtype
  • Primary Effusion Lymphoma used to be previously referred to as Body Cavity Lymphoma. This term is not in use anymore
  • Treatment for PEL 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 19, 2016
Last updated: Dec. 19, 2018