Microscopic pathological image of a section of the spleen showing non-Hodgkin's lymphoma.
What are other names for this condition? (alias/synonyms)
- lymphoma of the marginal zone of the spleen
- SMZL (marginal zone lymphoma of the spleen)
- Milz MZL
What is splenic marginal zone lymphoma? (definition/basic information)
- Marginal zone lymphoma (MZL) is a slow-growing B-cell non-Hodgkin's lymphoma that affects adults. Marginal zone lymphomas are usually not very aggressive and have a better prognosis compared to other B-cell lymphomas.
- They make up about 10% of all B-cell lymphomas. There are 3 types of MZL, including:
- Nodal marginal zone lymphoma
- Extranodal Marginal Zone Lymphoma
- Splenic marginal zone lymphoma
- Splenic marginal zone lymphoma (SMZL) is a rare type of B-cell non-Hodgkin lymphoma that affects the spleen, as the name suggests. It is a slow growing tumor that mostly occurs in older adults.
- The cause and risk factors for splenic marginal zone lymphoma are generally unknown, although certain genetic factors may be involved. SMZL can be associated with several other disorders such as Waldenstrom's macroglobulinemia, viral infection and weak immunity.
- Most people may not have signs or symptoms of marginal zone lymphoma of the spleen. Others may have other enlarged spleens and general symptoms such as fatigue, weight loss, and frequent infections.
- Your doctor may suggest a "wait and see" approach to monitoring the progress of marginal zone spleen lymphoma if you remain asymptomatic. However, if symptoms are significant, surgery and, if necessary, chemotherapy, radiotherapy, or targeted therapy may be used.
- Prognosis depends on many factors, including the type of lymphoma, disease progression, response to treatment, and the patient's overall health. In general, with proper management, the prognosis for splenic marginal zone lymphoma is good.
General information about lymphomas and lymphocytes:
- Lymphoma is a type of cancer that begins with the uncontrolled division of lymphocytes (a type of white blood cell). There are two types of lymphoma:
- Hodgkin lymphoma
- non-Hodgkin's lymphoma
- Lymphocytes are the main white blood cells of the lymph, the fluid of the lymphatic system; just as blood is the fluid of the circulatory system
- Lymphocytes are produced in the bone marrow and can become B cells or T cells. Splenic marginal zone lymphoma arises from cancerous B cells
- Lymph results from the filtration of blood on its way to and from tissues. Lymph is colorless because it lacks red blood cells; instead, it contains lymphocytes. It is essential for the immune system.
- There are 3 different types of lymphocytes:
- T lymphocytes or T cells: help fight infections and abnormalities within cells (cell-mediated immunity). They fight viruses and cancer cells.
- B lymphocytes or B cells: Produce antibodies, which are the body's own defense proteins that attack foreign invaders outside cells (humoral immunity). They fight bacterial cells, cell fragments and other immunogenic elements.
- Natural killer cells or NK cells: They perform various functions related to cellular and humoral immunity. They also look for cancer cells, a process called immune surveillance.
Who has marginal zone lymphoma of the spleen? (distribution by age and sex)
- Splenic marginal zone lymphoma is a rare condition that accounts for approximately 1% of all B-cell non-Hodgkin lymphomas.
- This type of lymphoma usually affects older adults; The average age at diagnosis is 65 years.
- Both men and women can be affected.
- It can occur worldwide and all racial and ethnic groups can be affected.
What are the risk factors for splenic marginal zone lymphoma? (predisposing factors)
No specific risk factors for splenic marginal zone lymphoma have been identified. However, the condition is known to be associated with the following factors:
- Waldenstrom's macroglobulinemia; another type of B-cell non-Hodgkin lymphoma
- Hepatitis C virus (HCV) infection.
- Advanced age; Older people are generally at greater risk
- Individuals with weakened immune systems (due to various health conditions)
In addition to the above, the following general factors may contribute to the onset and development of lymphoma:
- Family history of immune disorders
- The presence of a systemic disease.
- from smoking
- Exposure to radiation and industrial chemicals
- Viruses (in some rare cases); Epstein-Barr virus infection
- X-ray exposure, CT scan
- Radiation exposure occupations which may include nuclear power plant workers, pilots, astronauts, etc.
- Certain medications and drugs
International Prognostic Index: According to some experts, the International Prognostic Index may not be very helpful in evaluating marginal zone splenic lymphoma. However, some scientists believe that in some cases it is useful in determining the prognosis.
The International Prognostic Index for Aggressive Non-Hodgkin Lymphoma lists some factors that determine overall risk:
- Age over 60 years
- Elevation of serum lactate dehydrogenase - LDH (a type of enzyme)
- performance state, d. h The person's overall health, which can range from fully active (low risk) to fully disabled (very high risk).
- People who have already had lymphoma or other blood cancers may experience a recurrence or recurrence
- The presence of an immunodeficiency syndrome, such as AIDS, is a high risk factor
- Individuals infected with the Epstein-Barr virus
It is important to note that having a risk factor does not mean you will have the disease. Having a risk factor increases the chance of getting a disease compared to someone without risk factors. Some risk factors are more important than others.
The absence of a risk factor also does not mean that a person will not have the condition. It is always important to discuss the impact of risk factors with your doctor.
What are the causes of lymphoma of the marginal zone of the spleen? (Etiology)
Lymphocytes are a type of white blood cell responsible for providing immunity in the human body. B cells and T cells are the two different types of lymphocytes. When lymphocytes grow and multiply abnormally under certain circumstances, it results in a condition called lymphoma, which is one of the most common types of cancer. There are 2 types of lymphoma:
- Hodgkin lymphoma
- non-Hodgkin's lymphoma
The causative factors of splenic marginal zone lymphoma are unknown. It can be caused by genetic mutations. There may also be certain genetic defects, such as
- Alteration of regulatory elements of certain cancer-causing genes, called oncogenes, which can lead to increased production of their mRNA (overexpression) and therefore increased protein levels
- Swapping regions of protein-coding genes, creating new proteins that can stimulate inappropriate cell growth.
It is believed that the abnormal development of lymphocytes gives rise to cancerous cells, leading to the formation of this condition. However, how this happens and what factors cause it is still being investigated.
What are the signs and symptoms of lymphoma of the marginal zone of the spleen?
In many individuals, the condition can be asymptomatic. In other cases, signs and symptoms of marginal zone lymphoma of the spleen may include:
- Enlarged spleen (splenomegaly)
- In SMZL, the hilar lymph nodes of the spleen and the lymph nodes surrounding the spleen may be affected
- 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 detected by a blood test
- frequent infections
- difficult breathing
- low blood pressure
- back pain
- leg swelling
- abdominal pain and bloating; cold
- frequent urination
When other organs and parts of the body are affected, specific signs and symptoms may appear, such as:
- Associated autoimmune disorders that can cause joint and muscle pain, heat intolerance, recurrent skin rashes, abdominal pain, and a general feeling of being unwell
- When the brain is involved, neurological symptoms such as the following may be seen:
- Tinnitus (ringing in the ears)
- hearing and visual impairment
- When the gastrointestinal (GI) tract is affected, GI tract symptoms such as the following may be seen:
- gastrointestinal bleeding
- enlarged liver
- If the joints are affected, joint swelling and fluid accumulation (oedema) may occur.
How is lymphoma of the marginal zone of the spleen diagnosed?
A diagnosis of marginal zone lymphoma of the spleen can be made by taking biopsy samples from the affected spleen and examining them under a microscope to look for cancer cells. Other methods to support the study may include:
- A complete physical exam and a complete medical history, which is very important
- Blood tests, which may include:
- Complete blood count (CBC) blood test
- Absolute lymphocyte count in peripheral blood; Malignant peripheral blood lymphocytes can be detected.
- Liver function blood test (LFT)
- Lactate dehydrogenase (LDH) blood test
- chemistry table
- serum calcium levels
- HIV tests
- Biopsy of the affected area (spleen):
- A biopsy of the tumor is taken and sent to a laboratory for pathologic evaluation. A pathologist examines the biopsy under a microscope. After collecting the clinical findings, special tissue tests (if necessary), and microscopic findings, the pathologist arrives at a definitive diagnosis. Microscopic examination of the biopsy by a pathologist is considered the gold standard for a definitive diagnosis.
- Biopsy specimens are first examined with hematoxylin and eosin stains. The pathologist then decides on further studies depending on the clinical situation.
- Sometimes the pathologist may perform special studies that may include immunohistochemical staining, molecular testing, flow cytometry analysis, and, very rarely, electron microscopy studies to aid in diagnosis.
- Lymphoma can affect the lymph nodes. In these cases, biopsies of the enlarged lymph nodes are taken and examined in the laboratory to determine whether the cells are cancerous or benign. Biopsies can be performed under general or local anesthesia. Typically, the entire lymph node is removed to determine the lymphoma subtype.
- X-ray images may be done specifically to locate the affected organ and to determine the extent of lymphoma in the body, including:
- X-ray of the affected region
- Ultrasound examination of the affected region.
- Computed tomography of the spleen
- Vascular radiological exams
- Whole body bone scan
- Whole-body positron emission computed tomography (PET-CT) 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 whether the cancer has spread to other organ systems.
- Brain MRIs are used when there are neurological symptoms, which can help determine whether the cancer has spread to the brain or tissues overlying it.
- A bone marrow aspiration and biopsy is performed and sent to a laboratory for pathological evaluation to determine if the bone marrow has been affected. Sometimes the pathologist can perform special studies that may include immunohistochemical staining, histochemical staining, molecular testing, and, very rarely, electron microscopy. However, a bone marrow biopsy is not necessary in the early stages of the disease.
- 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, as well as cell characteristics such as size, shape, and the presence of biomarkers on the cell surface. This method helps to subclassify the condition and also to detect residual disease after treatment. This tool can help diagnose a relapse and resume treatment if necessary.
- Fluorescent in situ hybridization (FISH): This is a test done on blood or bone marrow cells to look for chromosomal changes (cytogenetic analysis) in blood cancer cells. The test helps identify genetic abnormalities that may not be apparent when cells are examined under a microscope.
- Immunophenotyping to identify a specific cell type in a sample that can help determine the best course of treatment
- Polymerase Chain Reaction (PCR): Used to measure the presence of certain biomarkers in blood or bone marrow cells. The test is ultrasensitive and detects extremely low levels of residual biomarkers in the blood that may be missed by cytogenetic methods such as FISH, karyotyping or flow cytometry. CRP allows for more sensitive monitoring of patients in remission and can help determine if further treatment is needed.
- GI endoscopy: may be done to assess the extent of tumor spread
- Multiple acquisition scanning (MUGA) or echocardiography to identify cardiotoxicity secondary to chemotherapy
- Lumbar puncture to determine if the brain is involved
- In addition, cerebrospinal fluid (CSF) can be collected by inserting a needle into the spine and subjecting it to microscopic, flow cytometric, PCR, and biochemical analysis to diagnose central nervous system (CNS) involvement, if present.
- Exploratory laparoscopy (diagnostic laparoscopy) may be needed if gastrointestinal symptoms are present. In this procedure, the abdomen is examined in a minimally invasive way, a tissue biopsy is taken, and the tissue is removed for culture. Minimally invasive approaches help reduce complications and length of stay. Diagnostic laparoscopy is also useful for tumor staging. Despite this, this method is not used very often.
Note: Differential diagnoses to rule out other tumor types are often considered before making a definitive diagnosis.
Many clinical conditions can have similar signs and symptoms. Your doctor may perform additional tests to rule out other medical conditions to reach a definitive diagnosis.
What are the possible complications of lymphoma of the marginal zone of the spleen?
Complications of splenic marginal zone lymphoma can include:
- Involvement of local and distant organs: can spread from the lymph nodes to other parts of the body, resulting in loss of function of the organ/area where the cancer has spread.
- lymphoma recurrence
- A weakened immune system (or immunosuppression) can be a complication that can become more serious during treatment. Because of this, people are more susceptible to infection. There is an increased risk of serious complications from such infections.
- As the condition spreads to the brain and central nervous system, it can result in:
- Inflammation of the meninges or brain (can be fatal)
- seeing changes
- numbness in the face
- If the abdomen is affected, it can lead to bowel obstruction, leading to blockage of urine flow and damage to the kidneys.
- Blood loss can occur due to frequent or heavy bleeding, which can lead to severe anemia.
- Leukemia cells can grow very large and block blood vessels, which can lead to stroke or blurred vision.
- Complications that may arise from underlying medical conditions, if any.
There can be complications associated with the chemotherapy used to treat the condition, including:
- Side effects such as dizziness, vomiting, loss of appetite, mouth ulcers and hair loss
- By damaging healthy cells, the individual is more open or susceptible to secondary infections.
- The treatment can also cause infertility in both men and women. Therefore, measures to protect fertility should be considered before starting chemotherapy.
- Tumor Lysis Syndrome: This can occur due to chemotherapy treatment and can lead to kidney failure if not caught early.
How is marginal splenic zone lymphoma treated?
Once a definitive diagnosis of marginal zone spleen lymphoma is made, the grading is used to describe how far the cancer has spread. The scenario can help describe:
- How many lymph nodes are affected?
- their locations in the body
- And if other organs are affected
Staging is important because different treatment regimens are needed depending on the progression of the lymphoma. SMZL stages include:
- Stage 1: A group of lymph nodes are affected
- Stage 2: Two or more groups of lymph nodes are affected on one side of the diaphragm
- Stage 3: Lymph nodes on both sides of the diaphragm are affected
- Stage 4 – The condition affects tissues other than lymphoid tissues, such as the spleen, liver, and bone marrow.
For asymptomatic people, the healthcare professional will generally consider a "wait and see" approach. For people with significant signs and symptoms, a combination of treatment measures can be used effectively to manage the condition. Treatment also depends on the stage, general health, age and type of lymphoma.
Surgery to remove the spleen (splenectomy) is the treatment of choice. However, if the person cannot tolerate the surgery, the following treatment options may be considered:
- Chemotherapy: This approach uses a combination of drugs to kill cancer cells and can be used in patients with all stages of cancer.
- Serious side effects such as fatigue, nausea, hair loss, anemia, high risk of infection, and specific drug reactions may occur.
- Many T-cell lymphomas can be resistant to chemotherapy. It can also damage healthy cells.
- Chemotherapy can be given as a pill, liquid, injection or intravenously.
Note: Men and women of reproductive age would greatly benefit from fertility counseling. Some chemotherapy drugs can cause infertility in both men and women. The testes and ovaries can be permanently damaged, affecting their ability to produce sperm or eggs. In men, sperm banking may be considered before starting therapy. In women, it is often difficult to carry out an egg bank in many cases due to the urgency of starting chemotherapy. However, if there is enough time before chemotherapy, an egg bank can be done. The health care provider can help assess the risk-benefit analysis, based on 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 method is generally used for early-stage lymphoma. It is most commonly used in combination with chemotherapy.
- Radiation can be given by a machine placed outside the body or by placing a radioactive material in the body.
- Side effects of radiotherapy include nausea, vomiting, fatigue, pain, subsequent cancer risk, and heart disease risk.
- In addition to cancer cells, radiation can also damage healthy cells and cause other complications.
- Intrathecal chemotherapy for brain involvement
- Supportive Care: Steroids, blood transfusions, anti-nausea medications, and antibiotics can be used as supportive therapy. In combination with other treatment measures, they can help combat the symptoms of immunodeficiency in individual cases.
If marginal zone lymphoma of the spleen does not fully respond to treatment or if there is a high chance of recurrence, bone marrow or stem cell transplantation may be considered.
- Bone marrow transplant: systemic cases can usually be treated by administering high doses of chemotherapy or radiotherapy. But high doses of chemotherapy drugs also damage the bone marrow, preventing it from producing blood cells. Therefore, before starting high-dose chemotherapy, doctors may collect and freeze/preserve some of the patient's bone marrow. The removal of bone marrow is called a bone marrow harvest. The bone marrow is then stored. After a high dose of chemotherapy or radiation, the bone marrow is thawed and reinjected into the patient through a drip (transfusion). This is called an autologous bone marrow transplant. Bone marrow donated by another suitable person (usually a brother or sister) is sometimes used if the condition returns after a transplant with the patient's own cell. This is called an allogeneic bone marrow transplant.
- Stem Cell Transplant: This procedure is similar to a bone marrow transplant and involves transplanting healthy blood-forming stem cells into the body. The procedure is also known as a hematopoietic stem cell transplant. Stem cells can be obtained from bone marrow, circulating (peripheral) blood, and cord blood. This could be an autologous stem cell transplant, where stem cells are taken from people before treatment and transplanted back into the patient after treatment, or an allogeneic stem cell transplant, where the stem cells are taken from another suitable person (usually a sibling). sister) to be donated) is used when the condition returns after a stem cell transplant using your own cells. This is called an allogeneic stem cell transplant.
Note: Allogeneic bone marrow and stem cell transplants can have more side effects and complications, and this treatment may not be right for everyone. When the allografts come from a healthy donor with no malignant cells, the chances of the disease coming back can be reduced.
- To prevent infections because SMZL or its treatment weakens the immune system, the patient is placed in an isolation room and treated with appropriate antibiotics.
- Currently, targeted therapies are being developed that can selectively kill lymphoma/leukemia cells. Many of them are in the clinical trial phase.
- Clinical Trials: There may be some newer treatment options currently being tested in clinical trials that may be considered for some patients based on their risk factors.
Your doctor will determine the best course of treatment based on your individual circumstances. Follow-up care with regular exams and check-ups is also an important follow-up treatment.
How can splenic marginal zone lymphoma be prevented?
Currently, the cause of spleen marginal zone lymphoma is unknown and there are no known methods to prevent its formation. Eliminating certain risk factors can help prevent the condition.
- Eating a healthy diet and exercising, as well as avoiding unnecessary exposure to chemicals, can help reduce your risk.
- Avoid or stop smoking
- Provide adequate and prompt treatment for viral infections or other medical conditions.
- Immediate treatment of cause of concern about immunodeficiency
- Use of proper protective equipment when working with X-rays and other radioactive sources
- In order to avoid a relapse or be prepared for a relapse, all diagnoses, course of treatment, medications administered, etc. must be well documented. and follow-up measures should be initiated.
Regular medical examinations at regular intervals with blood tests, scans and physical examinations are mandatory. Several years of active surveillance are often crucial and necessary.
What is the prognosis for marginal zone lymphoma of the spleen? (Results/Resolutions)
- Splenic marginal zone lymphoma is a slow-growing neoplasm with a generally good prognosis. Lymphomas of this type usually do not come back after treatment.
- The prognosis depends on several different factors, including:
- Tumor stage: For lower stage tumors, when the tumor is confined to the site of origin, the prognosis is usually excellent with appropriate therapy. Higher stage tumors such as B. metastatic tumors, the prognosis is poor
- Individual's general health: People with excellent general health have a better prognosis compared to people with poor health.
- Person's age: Older people generally have a worse prognosis than younger people
- Tumor size: people with small tumors do better than those with large tumors
- Those with severe disease have a worse prognosis.
- Vital organ involvement can complicate the condition.
- Surgical resectability of the tumor (i.e. when the tumor can be completely removed): this is a rare option
- Whether the tumor is an early occurrence or a recurrent tumor. Recurrent tumors have a worse prognosis than tumors that do not recur.
- Response to treatment: Tumors that respond to treatment have a better prognosis compared to tumors that do not respond to treatment.
- Disease progression worsens outcome (progressive SMZL)
- Early diagnosis and timely treatment of the tumor often yield better results than late diagnosis and late treatment.
- The combination of chemotherapy drugs used can have some serious side effects (eg cardiotoxicity). It mostly affects older adults or those who are already affected by other medical conditions. The tolerability of chemotherapy sessions is a factor that positively influences
- Progression to bone marrow failure is usually associated with a short survival
Additional useful information relevant to marginal zone lymphoma of the spleen:
- Treatment of marginal spleen lymphoma can cause physical and emotional discomfort; supportive care and encouragement, helps positively and may bring some degree of relief to patients
The following article link will help you understand leukemia and lymphoma (blood cancer):
What are some helpful resources for additional information?
Lymphoma Research Foundation (LRF)
115 Broadway, Suite 1301, Nueva York, NY 10006
Phone: (212) 349-2910
Fax: (212) 349-2886
Leukemia and Lymphoma Society (LLS)
1311 Mamaroneck Ave., Suite 310 White Plains, Nueva York 10605
Phone: (914) 949-5213
Toll Free Number: (800) 955-4572
Fax: (914) 949-6691
National Cancer Institute (NCI)
US National Institutes of Health
Public Consultation Office
Building 31, Room 10A03
31 Center Drive, MSC 8322 Bethesda, MD 20892-2580
Phone: (301) 435-3848
Toll Free Number: (800) 422-6237
TTY: (800) 332-8615
American Cancer Society (ACS)
1599 Clifton Road, NE Atlanta, GA 30329-4251
Toll Free Number: (800) 227-2345
TTY: (866) 228-4327
American Academy of Dermatology
930 E. Woodfield Road Schaumburg, IL 60173
Telephone: (866) 503-SKIN (7546)
Fax: (847) 240-1859
References and sources of information used for the article:
http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6300153 (accessed 5/2/16)
http://www.macmillan.org.uk/Cancerinformation/Cancertypes/Lymphomanon-Hodgkin/TypesofNHL/DiffuselargeB-cell.aspx#DynamicJumpMenuManager_6_Anchor_3 (accessed 2/5/16)
Lennert, K. (2013). Histopathology of non-Hodgkin's lymphomas: according to the Kiel classification. Springer Publisher.
Adler, E.M. (2005). Living with lymphoma: a patient guide. Johns Hopkins University Press.
Adler, NE and Page, AE (Eds.). (2008). Whole-patient cancer care: meeting psychosocial health needs. Press of the National Academies.
Carter, J.B., Goyal, A. & Duncan, LM (eds.). (2015). Atlas of cutaneous lymphomas: classification and differential diagnosis. bridge.
Useful peer-reviewed medical articles:
Thieblemont , C. , Davi , F. and Brière , J. (2013). Splenic Marginal Zone Lymphoma. In lymphoma (pp. 127-136). human imprint.
E Fonte, A Agathangelidis, D Reverberi, S Ntoufa, L Scarfò, P Ranghetti, ... & M Ponzoni (2015). Toll-like receptor stimulation in marginal zone lymphoma of the spleen may modulate cell signaling, activation and proliferation. Hematologica, Haematol-2014.
Dimopoulos, K. & Pedersen, M. (2012). Splenic Marginal Zone Lymphoma. Physicians Weekly Magazine, 174(40), 2383-2386.
Rossi, D., Trifonov, V., Fangazio, M., Bruscaggin, A., Rasi, S., Spina, V., ... & Ciardullo, C. (2012). The genome encoding marginal zone lymphoma of the spleen: activation of NOTCH2 and other signaling pathways that regulate marginal zone development. The Journal of Experimental Medicine, 209(9), 1537-1551.
Cohen JM, Nazarian RM, Ferry JA, Takvorian RW. and Carter, J.B. (2015). Rare presentation of secondary cutaneous involvement by marginal zone splenic lymphoma: case report and literature review. The American Journal of Dermatopathology, 37(1), e1-e4.
Bruscaggin, A., Monti, S., Cresta, S., Famà, R., Arcaini, L., Franceschetti, S., ... & Paulli, M. (2013). Molecular lesions of signaling pathway genes in indolent B-cell lymphoproliferation mimicking marginal zone lymphoma of the spleen. Blood, 122(21), 4250-4250.
Chacon, J.I., Mollejo, M., Munoz, E., Algara, P., Mateo, M., Lopez, L., ... & Cruz, MA (2002). Marginal zone splenic lymphoma: clinical features and prognostic factors in a series of 60 patients.blood,100(5), 1648-1654.
Thieblemont C, Felman P, Callet-Bauchu E, Traverse-Glehen A, Salles G, Coiffier B and Berger F (2003). Marginal zone splenic lymphoma: a distinct clinical and pathological entity.Lancet Oncology,4(2), 95-103.
Franco, V., Florena, A.M., & Iannitto, E. (2003). Milk marginal zone lymphoma.blood,101(7), 2464-2472.
Approved by:Maulik P. Purohit MD, MPH
First uploaded: February 24, 2016
Last updated: December 25, 2018