Diffuse Large B-Cell Lymphoma of Liver
Diffuse Large B-Cell Lymphoma (DLBCL) of Liver is a rare, B-cell non-Hodgkin’s lymphoma that affects older men and women. It is the most common subtype of lymphoma of liver.
What are the other Names for this Condition? (Also known as/Synonyms)
- DLBCL of Liver
- Hepatic DLBCL
- Hepatic Lymphoma, Diffuse Large B-Cell Type
What is Diffuse Large B-Cell Lymphoma of Liver? (Definition/Background Information)
- Diffuse Large B-Cell Lymphoma (DLBCL) of Liver is a rare, B-cell non-Hodgkin’s lymphoma that affects older men and women. It is the most common subtype of lymphoma of liver
- In majority of cases, the lymphoma is a secondary type of non-Hodgkin lymphoma. This means that it is a lymphoma that involves other parts of the body first, such as peripheral blood, lymph nodes, bone marrow, and other organs; liver (hepatic) involvement occurs later
- DLBCL of Liver may be associated with autoimmune disorders and viral infections, such as occurring due to hepatitis and EBV. However, the cause of the condition is unknown, and it is researched that certain genetic factors may be involved
- The lymphoma can cause abdominal pain, nausea and vomiting, weight loss, and other general signs and symptoms, such as fever, fatigue, and appetite loss
- Systemic therapy for Diffuse Large B-Cell Lymphoma of Liver is employed when there is the involvement of other organs. The treatment modality may include chemotherapy, radiation therapy, and targeted therapy as necessary
- The prognosis depends on many factors including the progression of the condition, response to treatment, and overall health of the individual. In general, the prognosis of Diffuse Large B-Cell Lymphoma of Liver is guarded and is mainly based on the stage of the tumor
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. Diffuse Large B-Cell Lymphoma of Liver 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 Diffuse Large B-Cell Lymphoma of Liver? (Age and Sex Distribution)
- Diffuse Large B-Cell Lymphoma of Liver is a rare type of lymphoma. It generally affects middle-aged and older adults; median age at presentation is 50 years
- Both males and females can be affected, but there is a male predilection observed (male-female ratio is 2:1)
- All races and ethnic groups can be affected and DLBCL of Liver may be observed worldwide
What are the Risk Factors for Diffuse Large B-Cell Lymphoma of Liver? (Predisposing Factors)
No specific risk factors have been identified for Diffuse Large B-Cell Lymphoma of Liver. However, the condition may be associated with the following factors:
- Autoimmune disorders
- Epstein-Barr virus infection
- Infection by hepatitis B virus (HBV) and hepatitis C virus (HCV): More than 50% of primary hepatic lymphomas are associated with HCV infection
- Advanced age; older individuals commonly have a higher risk
- Individuals with weak immune system due to various health conditions such as HIV infection, organ transplant, etc.
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
- 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 DLBCL of Liver. However, some scientists believe that it is helpful in some cases, to determine the prognosis.
The International Prognostic Index, for aggressive non-Hodgkin lymphoma, lists a few factors that determine the overall risk:
- Age over 60 years
- Elevated level of serum lactate dehydrogenase - LDH (a type of enzyme)
- Performance status, i.e. the overall health condition of the individual, which could range from being fully active (low risk) to being completely disabled (very high risk)
- Individual, who have already suffered from lymphoma, or other types of blood cancers, may have a relapse or a recurrence
- Presence of an immunodeficiency syndrome, like AIDS, is a high risk factor
- Those infected with Epstein-Barr virus are also prone to this lymphoma type
It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.
Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.
What are the Causes of Diffuse Large B-Cell Lymphoma of Liver? (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
Diffuse Large B-Cell Lymphoma of Liver is a type of non-Hodgkin lymphoma of unknown cause. It is known to be associated with certain viral infections. It may be caused by certain genetic defects, such as translocation, which is a juxtaposition of regions of chromosomes that 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 Diffuse Large B-Cell Lymphoma of Liver?
The signs and symptoms of Diffuse Large B-Cell Lymphoma of Liver may include:
- Primary lymphomas are present as a discrete mass, while secondary lymphomas are present as multiple diffuse masses
- Enlargement of the liver, also known as hepatomegaly
- Nausea and vomiting
- Abdominal pain
- Easy bruising or bleeding as a result of liver failure
- 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
- Small tumors may be asymptomatic and the individuals may not have any significant symptoms
When there is an involvement of other organs, the signs and symptoms may be based on specific organs that are 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
- Spleen enlargement
- Joint inflammation and fluid accumulation (edema) can occur, if the joints are affected
How is Diffuse Large B-Cell Lymphoma of Liver Diagnosed?
Diffuse Large B-Cell Lymphoma of Liver diagnosis is often performed by obtaining biopsy samples from the affected region (of liver) 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 - there is no specific blood test to diagnose the condition; however, the following tests may be performed:
- Complete blood cell count (CBC) blood test
- Absolute lymphocyte count on peripheral blood
- Liver function blood test (LFT)
- Lactate dehydrogenase (LDH) blood test
- Tests for viral infections
- Tissue biopsy from the liver:
- 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:
- Fine needle aspiration biopsy (FNAB): A device called a cannula is used to extract tissue or fluid from the affected region, or surrounding lymph nodes
- Core biopsy of the liver
- Open biopsy using wedge liver resections
- 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 abdomen
- CT or MRI scan of the abdomen
- Abdominal ultrasound 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
- 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
- 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 Diffuse Large B-Cell Lymphoma of Liver?
The complications due to Diffuse Large B-Cell Lymphoma of Liver may include:
- Involvement of local and distant organs and loss of function of the organ/area to which the cancer has spread
- Recurrence of the lymphoma
- Portal hypertension if the tumor are large and compress the portal veins
- In some individuals, there may be acute liver failure or complete liver failure
- 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
- In rare cases, 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 Diffuse Large B-Cell Lymphoma of Liver Treated?
A combination of measures may be used to treat Diffuse Large B-Cell Lymphoma of Liver. The treatment also depends upon the stage, overall health, age, and type of lymphoma.
- Chemotherapy: This approach uses a combination of drugs to kill the cancerous cells and can be used in patients, for all stages of the tumor
- There can be severe side effects including fatigue, nausea, hair loss, anemia, high risk of infection, and drug-specific reactions
- Many lymphomas can be resistant to chemotherapy. It can also damage healthy cells
- Chemotherapy can be administered as a pill, liquid, shot, or intravenously
Note: Men and women in child-bearing age would greatly benefit from counseling regarding fertility issues. Some chemotherapy agents can cause infertility in both men and women. There can be permanent damage to the testicles and ovaries, harming their ability to produce sperms or ova. In men, sperm banking can be considered before initiating therapy. In women, in many cases, due to urgency of starting chemotherapy, it is often difficult to perform ovum banking. However, if there is sufficient time prior to chemotherapy, ovum banking may be performed. The healthcare provider may help assess the risk-benefit analysis, depending upon each individual’s specific circumstances.
- Surgical removal of the lymphoma from the liver, if the tumor is easily accessible
- Radiation: Radiation therapy is the use of high-energy radiation waves to kill cancer cells, by destroying their DNA
- Radiation therapy 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
- Undertaking treatment of underlying conditions/disorders, as warranted
If Diffuse Large B-Cell Lymphoma of Liver 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 DLBCL of Liver 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 Diffuse Large B-Cell Lymphoma of Liver be Prevented?
Presently, the cause of Diffuse Large B-Cell Lymphoma of Liver is unknown and there are no known methods to prevent its formation. 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
- Undertaking appropriate and early treatment of various viral infections and 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 Diffuse Large B-Cell Lymphoma of Liver? (Outcomes/Resolutions)
- Diffuse Large B-Cell Lymphoma of Liver is an aggressive and malignant lymphoma that affects the liver. The prognosis of the condition is generally guarded
- 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 Hepatic DLBLC)
- 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 Diffuse Large B-Cell Lymphoma of Liver:
- T-cell lymphomas are less common than B-cell lymphomas
- Treatment for Diffuse Large B-Cell Lymphoma of Liver 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
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http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6300153 (accessed on 02/05/16)
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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Helpful Peer-Reviewed Medical Articles:
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Zhou, Z., Sehn, L. H., Rademaker, A. W., Gordon, L. I., LaCasce, A. S., Crosby-Thompson, A., ... & Nademanee, A. (2014). An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B-cell lymphoma treated in the rituximab era. Blood, 123(6), 837-842.
Chen, K. L., Chen, J., Rao, H. L., Guo, Y., Huang, H. Q., Zhang, L., ... & Hu, L. Y. (2015). Hepatitis B virus reactivation and hepatitis in diffuse large B-cell lymphoma patients with resolved hepatitis B receiving rituximab-containing chemotherapy: risk factors and survival. Chinese journal of cancer, 34(3), 1.
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Bajpayee, G., Kutner, M., Preeshagul, I., Burger, A., D'Souza, L. S., & Kasmin, F. (2014, April). ACUTE LIVER FAILURE AS INITIAL MANIFESTATION OF DIFFUSE LARGE B CELL LYMPHOMA. In JOURNAL OF GENERAL INTERNAL MEDICINE (Vol. 29, pp. S297-S297). 233 SPRING ST, NEW YORK, NY 10013 USA: SPRINGER.
Sanii, S., Kosari, F., & Khodadad, K. (2011). Primary Hepatic Diffuse Large B-Cell Lymphoma in a Patient with Scleroderma. Iranian Journal of Pathology, 6(1), 46-50.
Olszewski, A. J., Winer, E. S., & Castillo, J. J. (2014). Improved survival with rituximab-based chemoimmunotherapy in older patients with extranodal diffuse large B-cell lymphoma. Leukemia research, 38(8), 866-873.
Ueno, S., Yamaguchi, M., Kimura, M., Odagiri, H., Shiraki, K., Uemoto, S., ... & Kobayashi, T. (2005). Expression of CD29 on lymphoma cells and/or CD36 on microvascular endothels correlates with high serum LDH level in diffuse large B-cell lymphomas (DLBCLs) and is frequent in de novo CD5-positive DLBCLs. International journal of oncology, 27(5), 1241-1246.