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

• Gastric Mantle Cell Lymphoma
• MCL of Stomach
• Primary Gastric Mantle Cell Lymphoma

What is Mantle Cell Lymphoma of Stomach? (Definition/Background Information)

• Mantle Cell Lymphoma of Stomach is an extremely rare and aggressive B-cell non-Hodgkin’s lymphoma typically affecting older adults. There are a few variants of mantle cell lymphoma (MCL) and these include the diffuse, nodular, mantle, and blastoid variants. Amongst these, the blastoid variant is the most aggressive type
• It is reported that a mantle cell lymphoma first involves the intestine and spleen most commonly, which then typically affects lymph nodes of the stomach. Thus, a Primary Gastric Mantle Cell Lymphoma, when the stomach is involved first, is highly uncommon
• The cause of Mantle Cell Lymphoma of Stomach may be due to certain genetic mutations. No underlying conditions, such as inflammatory bowel disease (Crohn’s disease) or gastrointestinal adenocarcinoma, have been identified as being predisposing factors for lymphoma formation
• The signs and symptoms include abdominal pain, diarrhea, gastrointestinal tract bleeding, swollen stomach, and other general signs and symptoms, such as anemia, fatigue, and appetite loss. Mantle cell lymphomas frequently involve the lymph nodes, bone marrow, liver, and other regions of the gastrointestinal tract
• Chemotherapy, radiation therapy, or targeted therapy may be employed in case of significant symptoms. Nevertheless, no treatment protocols have been adequately established to treat the condition, due to its rarity. The prognosis of Mantle Cell Lymphoma of Stomach is generally 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. Mantle Cell Lymphoma of Stomach 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 Mantle Cell Lymphoma of Stomach? (Age and Sex Distribution)

• Mantle Cell Lymphoma of Stomach is an extremely uncommon malignancy that is generally observed in elderly adults
• Both males and females are affected; mantle cell lymphomas are typically more common in males
• It can occur worldwide and all racial and ethnic groups may be affected, although Gastric Mantle Cell Lymphomas are very rare

What are the Risk Factors for Mantle Cell Lymphoma of Stomach? (Predisposing Factors)

No specific risk factors have been identified for Mantle Cell Lymphoma of Stomach. In general, there are certain risk factors that may contribute towards lymphoma formation and development such as:

• Family history of immune disease
• 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

International Prognostic Index: According to some scientists, the International Prognostic Index may not be very helpful in evaluating lymphomas. However, some scientists believe that it is helpful in some cases, to determine the prognosis. However, in the specific case of Gastric Mantle Cell Lymphoma, the index is not particularly helpful.

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, such as AIDS, is a high risk factor
• Those infected with Epstein-Barr virus

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s 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 Mantle Cell Lymphoma of Stomach? (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 causative factors of Mantle Cell Lymphoma of Stomach, which is a non-Hodgkin’s lymphoma, are unknown. It may be caused by genetic mutations. Also, there may be 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
• Genetic abnormality:
  • Chromosomal translocation, namely t(11;14)(q13;32), is observed in a majority of individuals with mantle cell lymphoma
  • Occasionally, the overexpression of SOX11 gene is noted in some individuals

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 Mantle Cell Lymphoma of Stomach?

The signs and symptoms of Mantle Cell Lymphoma of Stomach may include:

• Presence of a single polypoid tumor may be noted
• Bloating and feeling of fullness
• Burning sensation in the stomach
• Constipation, diarrhea
• Stomach ulcer
• Gastrointestinal tract bleeding
• Vomiting (with blood sometimes), nausea
• Unintentional weight loss; changes in appetite
• High temperatures and excessive night sweats (may be recurrent)
• Fatigue and weakness, headache
• Anemia (low red blood cell count)
• Frequent infections
• Low blood pressure
• In many individuals, the condition may be asymptomatic during early stages of the disease

Typically, 1 in 3 individuals (about 35%) with mantle cell lymphoma have ‘B’ symptoms, which refer to the following:

• Fever over 35 deg. C; the fevers come and go
• Excessive sweating; especially in the evenings or nights
• 10% or more weight loss which cannot be explained due to any other reason. The 10% weight loss should occur within a period of 6 months or less

Apart from the above, systemic conditions affect the entire body and the following general symptoms of MCL may be manifested:

• Pancytopenia, which includes the following 3 conditions:
  • Anemia causing pale skin, due to lower levels of red blood cells
  • Thrombocytopenia due to decreased platelets, which can cause bleeding disorders and easy bruising
  • Leukopenia or reduced white blood cells
• Unintentional weight loss; changes in appetite
• Fatigue and weakness, headache
• Anemia (low red blood cell count)
• Frequent infections
• Trouble breathing
• Low blood pressure
• Back pain
• Swelling of the legs
• Abdominal pain and swelling; constipation
• Frequent urination

When there is the involvement of other organs and body parts, there may be specific signs and symptoms related to the involved organs. This may include:

• 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 enlargement
• Joint inflammation and fluid accumulation (edema) can occur, if the joints are affected

How is Mantle Cell Lymphoma of Stomach Diagnosed?

A diagnosis of Mantle Cell Lymphoma of Stomach is performed by obtaining biopsy samples from the affected region and examining them under a microscope to detect the cancerous cells. Other methods to aid in the study-diagnosis 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
• Since the lymphoma involves the lymph nodes, 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
• Tissue biopsy from the stomach:
  • 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
• Radiological imaging may be performed to determine the extent of lymphoma in the body including:
  • X-ray of the stomach
  • Ultrasound scan of the stomach/abdomen
  • Upper GI endoscopy: An endoscopic procedure is performed using an instrument called an endoscope, which consists of a thin tube and a camera. Using this technique, the radiologist can have a thorough examination of the insides of the gastrointestinal tract
  • Computerized tomography (CT) scan of the stomach/abdomen
  • 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
• 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
• 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
• 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

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 Mantle Cell Lymphoma of Stomach?

The complications due to Mantle Cell Lymphoma of Stomach may include:

• Involvement to local and distant organs: It can spread from the lymph nodes to other parts of the body, resulting in loss of function of the organ/area to which the cancer has spread
• Recurrence of the lymphoma
• If the abdomen is affected, it can cause intestinal obstruction that results in urine outflow obstruction and kidney damage
• Severe pancytopenia that may result in:
  • Heavy bleeding due to severe thrombocytopenia
  • Severe anemia requiring blood transfusions
  • Severe leukopenia (or leucopenia) leading to recurrent infections
• 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 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
• 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 Mantle Cell Lymphoma of Stomach Treated?

Once a definitive diagnosis of Mantle Cell Lymphoma of Stomach has been made, staging is used to describe how far the cancer has spread. The stage can help describe:

• How many lymph nodes are affected
• Their locations in the body
• And, if other organs are being affected

Staging is important because different treatment regimens are necessary, depending on the progression of the lymphoma. The stages of MCL include:

• Stage 1: One group of lymph nodes are affected
• Stage 2: Two or more groups of lymph nodes on one side of the diaphragm are affected
• Stage 3: Lymph nodes on both sides of the diaphragm are affected
• Stage 4: The condition involves tissues other than lymphoid tissues such as spleen, liver, and bone marrow

In individuals with significant signs and symptoms a combination of treatment measures may be effectively used to treat the condition. The treatment also depends upon the stage, overall health, age, and type of lymphoma. However, with respect to Gastric Mantle Cell Lymphoma, there are no well-established protocols or standard guidelines available to treat the condition.

The treatment may involve the following procedures:

• 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 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 stomach, if necessary
• 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
• Undertaking suitable treatment for underlying infections, diseases, or disorders
• 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

If Mantle Cell Lymphoma of Stomach 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 MCL of Stomach 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 Mantle Cell Lymphoma of Stomach be Prevented?

Presently, the cause of Mantle Cell Lymphoma of Stomach is unknown and there are no known methods to prevent its formation. Eliminating certain risk factors 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
• Undertaking appropriate and early treatment for infections/diseases/disorders that affect the GI tract
• Promptly addressing the cause of concern of immunodeficiency
• 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 Mantle Cell Lymphoma of Stomach? (Outcomes/Resolutions)

• Mantle Cell Lymphoma of Stomach is an aggressive cancer. The prognosis of the condition is typically guarded. In a majority of cases, the condition is usually diagnosed during the later stages, when it has metastasized to local organs and lymph nodes
• 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 resectability 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 MCL of Stomach)
• 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 Mantle Cell Lymphoma of Stomach:

• Treatment for Mantle Cell Lymphoma of Stomach 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 other cancers and benign tumors:

http://www.dovemed.com/diseases-conditions/cancer/