Pulmonary MALT Lymphoma
Marginal Zone Lymphoma of Lung is a Non-Gastric Type of Extranodal Marginal Zone Lymphoma. It affects the lungs in older adults. The condition is also known as Pulmonary MALT Lymphoma or MALT Lymphoma of Lung.
What are the other Names for this Condition? (Also known as/Synonyms)
- Extranodal Marginal Zone Lymphoma of Lung
- MALT Lymphoma of Lung
- Marginal Zone Lymphoma of Lung
What is Pulmonary MALT Lymphoma? (Definition/Background Information)
- Marginal Zone Lymphoma (MZL) is a slow-growing B-cell non-Hodgkin’s lymphoma affecting adults. Marginal Zone Lymphomas are typically not very aggressive and have better prognosis compared to other B-cell lymphomas
- They constitute approximately 10% of all B-cell lymphomas. There are 3 types of MZLs that include:
- Nodal Marginal Zone Lymphoma
- Extranodal Marginal Zone Lymphoma
- Splenic Marginal Zone Lymphoma
- Extranodal Marginal Zone Lymphoma (EMZL) is the most common type of Marginal Zone Lymphoma. It is also known as Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma. Around 1 in 5 MALT lymphoma cases involve the bone marrow
- Generally, Extranodal Marginal Zone Lymphomas do not involve the lymph nodes; they originate/occur outside the lymph nodes. There are 2 types of EMZLs which include:
- Gastric type, which involves the stomach
- Non-gastric type, which develops outside the stomach, such as in the small intestine, thyroid gland, salivary gland, lungs, or eyes
- Marginal Zone Lymphoma of Lung is a Non-Gastric Type of Extranodal Marginal Zone Lymphoma. It affects the lungs in older adults. The condition is also known as Pulmonary MALT Lymphoma or MALT Lymphoma of Lung
- Pulmonary MALT Lymphoma can be associated with Chlamydia psittaci infection (a pathogenic bacterial infection). The condition can cause chest pain, breathing difficulties, fatigue, and other general signs and symptoms, such as fever, weight loss, and appetite loss
- Initially antibiotic therapy is administered to address C. psittaci bacterial infection (if present) and associated signs and symptoms. However, chemotherapy, surgery, and other treatment measures may be used for MALT Lymphoma of Lung based on the assessment of the physician
- The prognosis depends on many factors including the type of lymphoma, progression of the condition, response to treatment, and overall health of the individual. In general, the prognosis of Pulmonary MALT Lymphoma is good
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. Pulmonary MALT Lymphoma arises from cancerous B-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 Pulmonary MALT Lymphoma? (Age and Sex Distribution)
- Pulmonary MALT Lymphoma is an uncommon condition that generally affects older adults
- Both males and females can be affected
- It can occur worldwide and all races and ethnic groups may be affected
What are the Risk Factors for Pulmonary MALT Lymphoma? (Predisposing Factors)
No specific risk factors have been identified for Pulmonary MALT Lymphoma. However, the condition is known to be associated with the following factors:
- Autoimmune disorders
- Chlamydia psittaci infection; bacterial infection that commonly affects birds
- Waldenstrom’s macroglobulinemia; another type of B-cell non-Hodgkin’s lymphoma
- Advanced age; older individuals commonly have a higher risk
- Individuals with weak immune system (due to various health conditions)
Besides the above, the following general factors may contribute towards lymphoma formation and development:
- Family history of immune disease
- The presence of any systemic disease
- Exposure to radiation and industrial chemicals
- 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 MALT Lymphoma of Lung. 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 Pulmonary MALT Lymphoma
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 Pulmonary MALT 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 cause of Pulmonary MALT 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 Pulmonary MALT Lymphoma?
The signs and symptoms of Pulmonary MALT Lymphoma may include:
- Shortness of breath; difficulty in breathing
- Chest pain
- Cough that may be persistent
- 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)
- Low lymphocyte count, established by a blood test
- Frequent infections
- Low blood pressure
In case the condition spreads from the lungs with the involvement of other organs, then the signs and symptoms may be based on specific organs affected. This may include:
- 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:
- Tinnitus (ringing in the ears)
- Hearing and visual impairment
- Liver and spleen enlargement
- Joint inflammation and fluid accumulation (edema) can occur, if the joints are affected
How is Pulmonary MALT Lymphoma Diagnosed?
MALT Lymphoma of Lung diagnosis is generally performed by obtaining biopsy samples from the affected region and examining them under a microscope to detect the cancerous cells. There are other tests and procedures that could help in the diagnosis and these 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
- Pulmonary function tests 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
- Needle biopsy of lung and/or an open lung biopsy: A tissue biopsy is performed and sent to a laboratory for a pathological examination, who 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
- Tissue biopsy 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
- The biopsy may be performed through any of the following procedures:
- Bronchoscopy: A special medical instrument, called a bronchoscope, is inserted through the nose and into the lungs to collect small tissue samples
- Thoracentesis: During thoracentesis, physicians use a special medical device called a cannula, to remove fluid between the lungs and the chest wall for examination
- Thoracoscopy: A medical instrument called a thoracoscope is inserted into the chest through tiny incisions, in order to examine and remove tissue from the chest wall, which is then analyzed further
- Thoracotomy: Thoracotomy is a surgical invasive procedure with special medical instruments to open-up the chest and remove tissue from the chest wall or the surrounding lymph nodes of the lungs
- 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 lungs, 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
- Pulmonary computerized tomography (CT) scan
- 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
- 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: 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 Pulmonary MALT Lymphoma?
The complications due to Pulmonary MALT Lymphoma may include:
- Involvement of local and distant organs: It can lead to systemic disease in some cases
- Loss of function of the organ/area to which cancer has spread due to systemic involvement
- Collection of fluid in the pleural cavity (pleural effusion)
- Irreversible lung damage such as lung fibrosis
- Development of pneumothorax (collapsed lung)
- Development of pulmonary hypertension, which is indicated by an increased pressure in the arteries of the pulmonary blood vessel system
- 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 abdomen is affected, it can cause intestinal obstruction that results in urine outflow obstruction and kidney damage
- 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
- Occasionally, the tumor can transform into a more aggressive form 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 Pulmonary MALT Lymphoma Treated?
The preliminary treatment for Pulmonary MALT Lymphoma is antibiotic therapy to eliminate Chlamydophila psittaci infection. If it is not responsive to antibiotic treatment, or if the condition recurs following treatment, then chemotherapy, surgical options, and/or targeted therapy may be attempted, as per the decision of the healthcare provider.
A combination of measures may be used to treat this cancer. The treatment also depends upon the stage, overall health, age, and type of lymphoma.
- Antibiotic therapy for Chlamydia psittaci infection
- 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 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
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.
- Surgical removal of the lymphoma from the lungs
- 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
- 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 MALT Lymphoma of Lung 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 Pulmonary MALT Lymphoma 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 cancer 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 Pulmonary MALT Lymphoma be Prevented?
Currently, it is not possible to prevent MALT Lymphoma of Lung. 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
- Undertaking appropriate and early treatment for bacterial infection that affect the lungs and other autoimmune disorders, if any
- 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 Pulmonary MALT Lymphoma? (Outcomes/Resolutions)
- Pulmonary MALT Lymphoma is a slow-growing malignancy with a generally good prognosis. The lymphoma does not typically recur following treatment
- 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 MALT Lymphoma of Lung)
- 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 (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 Pulmonary MALT Lymphoma:
- T-cell lymphomas are less common than B-cell lymphomas
- Treatment for Pulmonary MALT 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):
What are some Useful Resources for Additional Information?
Lymphoma Research Foundation (LRF)
115 Broadway, Suite 1301, New York, NY 10006
Phone: (212) 349-2910
Fax: (212) 349-2886
Leukemia & Lymphoma Society (LLS)
1311 Mamaroneck Ave., Suite 310 White Plains, NY 10605
Phone: (914) 949-5213
Toll-Free: (800) 955-4572
Fax: (914) 949-6691
National Cancer Institute (NCI)
U.S. National Institutes of Health
Public Inquiries Office
Building 31, Room 10A03
31 Center Drive, MSC 8322 Bethesda, MD 20892-2580
Phone: (301) 435-3848
Toll-Free: (800) 422-6237
TTY: (800) 332-8615
American Cancer Society (ACS)
1599 Clifton Road, NE Atlanta, GA 30329-4251
Toll-Free: (800) 227-2345
TTY: (866) 228-4327
American Academy of Dermatology
930 E. Woodfield Road Schaumburg, IL 60173
Phone: (866) 503-SKIN (7546)
Fax: (847) 240-1859
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http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Lymphomanon-Hodgkin/TypesofNHL/DiffuselargeB-cell.aspx#DynamicJumpMenuManager_6_Anchor_3 (accessed on 02/05/16)
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Abramson, J. S., Ferry, J. A., Muse, V. V., & Lanuti, M. (2014). Extranodal Marginal Zone Lymphoma Presenting As Miliary Lung Disease. Journal of Clinical Oncology, JCO-2013.
Rubenstein, J. N., Beatty, C., Kinkade, Z., Bryan, C., Hogg, J. P., Gibson, L. F., & Vos, J. A. (2015). Extranodal Marginal Zone Lymphoma of the Lung: Evolution from an Underlying Reactive Lymphoproliferative Disorder. Journal of clinical & experimental pathology, 5(1).
Khalil, M. O., Morton, L. M., Devesa, S. S., Check, D. P., Curtis, R. E., Weisenburger, D. D., & Dores, G. M. (2014). Incidence of marginal zone lymphoma in the United States, 2001–2009 with a focus on primary anatomic site. British journal of haematology, 165(1), 67-77.
Zinzani, P. L., Pellegrini, C., Gandolfi, L., Casadei, B., Derenzini, E., Broccoli, A., ... & Fanti, S. (2013). Extranodal marginal zone B‐cell lymphoma of the lung: experience with fludarabine and mitoxantrone‐containing regimens. Hematological oncology, 31(4), 183-188.
Olszewski, A. J., & Castillo, J. J. (2013). Survival of patients with marginal zone lymphoma. Cancer, 119(3), 629-638.
Borie, R., Wislez, M., Thabut, G., Antoine, M., Rabbat, A., Couderc, L. J., ... & Bergeron, A. (2009). Clinical characteristics and prognostic factors of pulmonary MALT lymphoma. European Respiratory Journal.
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