Lymphomas are tumors of the lymphatic system, ie they originate from cells (lymphocytes), present in the lymph nodes (or lymphatic glands), in the spleen and bone marrow, which form the immune system that defends the body from infections.
Lymphoma can develop in any organ where lymphocytes are present and are distinct into Hodgkin's lymphoma And non-Hodgkin's lymphoma on the basis of the type of cells that constitute them. Lymphomas can appear as indolent, that is, with a low degree of malignancy, and aggressive, that is, with a high degree of malignancy.
Burkitt's lymphoma, also called "diffuse, non-separated small cell lymphoma”Is a type of aggressive non-Hodgkin's lymphoma that grows and spreads very quickly, forming a tumor mass. Burkitt's lymphoma originates from lymphocytes B, a subpopulation of white blood cells that protects the body from bacteria and viruses by producing antibodies.
There are three main types of Burkitt's lymphoma:
- sporadic form, in some cases associated with Epstein-Barr virus infection, can occur at any age but usually develops in children and young adults
- form associated with immunodeficiency, in people who have human immunodeficiency virus (HIV) or are immunosuppressed, for example due to an organ transplant
- endemic form, more common in the presence of malaria and papillomavirus (HPV) and more frequent in the equatorial areas
The tumor mass can form in different areas of the body, such as:
- facial bones
- other organs
and can spread to the brain and spinal cord through blood or lymphatic vessels. Burkitt's lymphoma accounts for approximately 1-5% of all non-Hodgkin's lymphomas and is more common in Caucasians than in people of African or Asian descent. Burkitt's lymphoma most commonly affects children and young adults and is more widespread in males compared to females, with a ratio of 3-4 to 1, respectively.
With intensive chemotherapy, life expectancy is excellent in children, much less in adults.Symptoms
Usually, the endemic form of Burkitt's lymphoma is linked to the Epstein Barr virus (EBV) and occurs in the form of a maxillary tumor with an increase in the volume of the jaw or facial bones. In adolescents, the endemic form often appears in the abdominal area.
There sporadic form it is not related to EBV and is most frequently located in the abdomen, where it can cause intestinal obstruction. However, other organs may be involved, such as the ear, nose, throat and, more rarely, the eye sockets, kidneys and bones.
In adults, the tumor mass can reach large dimensions with possible involvement of the liver, spleen and bone marrow.
Burkitt's lymphoma is characterized by very rapid growth. It originates from the digestive tract, mainly from the intestine, extending to the peritoneum and, sometimes, also to the liver, pancreas, spleen, kidneys or ovaries. In about 35% of cases it invades the bone marrow and in 15% of cases the central nervous system.
Burkitt's lymphoma signs and symptoms can include:
- swollen, painless lymph nodes in the neck, armpits or groin
- abdominal pain or swelling, nausea
- chest pain, cough or difficulty in breathing
- persistent fatigue, alteration of the general state
- night sweats
- unexplained weight loss
Non-Hodgkin's lymphomas are cancers that arise from B lymphocytes. Sometimes their appearance is linked to a weakened immune system but, in most cases, the cause is unknown.
Normally, the life cycle of lymphocytes requires older cells to die and the body to produce new ones to replace them. In non-Hodgkin's lymphomas, however, aging lymphocytes do not die but continue to grow and divide.
Excess lymphocytes accumulate in the lymph nodes, causing them to increase in volume.
Burkitt's lymphoma is associated with Epstein Barr virus (EBV), human immunodeficiency virus (HIV) and some specific shifts in pieces of chromosomes (chromosomal translocations) that cause excessive activity (overexpression) of the gene called c -MYC. The shift of the c-MYC gene from chromosome 8 to chromosome 14 is the hallmark of Burkitt's lymphoma and occurs in approximately 95% of cases. Following chromosomal translocation, the c-MYC gene causes increased proliferation of B lymphocytes.
Recently the World Health Organization (WHO) has inserted further specifications related to the presence of translocations of the BCL2 and BCL6 genes, including them in the group of “high-grade lymphomas”.
Clinically, the WHO classifies Burkitt's lymphoma into three groups: endemic, sporadic and related to immunodeficiency.
- endemic form, is linked to malaria and EBV. The distribution of endemic cases of Burkitt's lymphoma in Africa and Papua New Guinea corresponds to the areas where malaria and Epstein Barr virus prevail. In children under the age of 18, the frequency of cancer is about 3-6 cases per 100,000 children per year. The average age at assessment (diagnosis) is 6 years
- sporadic form, is localized in North America and Europe with an "average age at diagnosis of 45 years. Sporadic Burkitt's lymphoma has an estimated annual frequency of 4 per 1 million children under the age of 16 and 2.5 per 1 million adults. In children, the mean age at diagnosis is 3 to 12 years
- variant related to "immunodeficiency, it is associated with HIV and, to a lesser extent, with organ transplantation. People with HIV in whom antiviral treatment is ineffective are particularly susceptible to Burkitt's lymphoma. The variant associated with immunodeficiency has a frequency of 22 per 100,000 people in United States
To ascertain (diagnose) non-Hodgkin's lymphoma, doctors collect information about the person's and their family's present and past health and proceed with:
- medical examination, the doctor checks the presence of enlarged lymph nodes by palpating the regions of the neck, armpits and groin, as well as enlargement of the spleen or liver
- blood and urine tests, to rule out an "infection or" other disease
- image surveys, include X-rays, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)
- lymph node biopsy, The laboratory analysis of a small piece of tissue coming from the lymph nodes can reveal the presence of a lymphoma and allow to ascertain its type
- bone marrow harvest, the aspiration of the bone marrow, through the insertion of a needle into the iliac bone, allows to identify the characteristic cells of non-Hodgkin's lymphomas
For the diagnosis of Burkitt's lymphoma it is essential that the tissue taken from the lymph nodes is adequate. Fine needle aspiration may not provide enough tissue to diagnose the disease, therefore, an excisional biopsy, ie the removal of an entire lymph node, is preferable.
The methods used to analyze the biopsy are:
- microscopic analysis
- flow cytometry
In case of suspected Burkitt lymphoma, confirmation is carried out through investigations:
If lymphoma is diagnosed, it is necessary to perform bone marrow aspiration, as well as evaluation of the cerebrospinal fluid (CSF) to assess the extent of involvement and rule out the possible presence of distant spread of tumor cells. An important support to the diagnosis also derives from imaging investigations using positron emission tomography, combined with computed tomography (PET / CT). In areas with limited resources, ultrasound may also be used.
Laboratory tests required for the diagnosis of Burkitt's lymphoma include:
- complete blood count with differential white blood cell count (leukocyte formula)
- erythrocyte sedimentation rate (ESR)
- complete metabolic panel (CMP)
- prothrombin time (PT)
- partial thrombloplastin time (PTT)
- serum lactate dehydrogenase
- uric acid
- analysis for l’'hepatitis B
- pregnancy test in women
- test for human immunodeficiency virus (HIV)
The diagnosis, evaluation, management and treatment of Burkitt's lymphoma requires a team of specialists consisting of a pathologist, a hematologist, an oncologist, a pharmacologist and a radiologist.Therapy
Although the choice depends on the stage, age and general condition of the patient, standard therapy involves a few months of intensive chemotherapy. It is important that treatment is started as soon as possible, at the latest within 48 hours of diagnosis.
Burkitt's lymphoma responds well to multi-drug, short-rotation, and specifically designed chemotherapy.
Chemotherapy is a treatment that uses different drugs to stop the growth of cancer cells, killing them or preventing them from dividing and can be:
- systemic, is taken orally, intravenously or intramuscularly. The drugs enter the blood and can reach cancer cells throughout the body
- intrathecal, the therapy is injected directly into the cerebrospinal fluid
- regional, is injected directly into an organ or body cavity such as the abdomen. The drugs primarily affect cancer cells in that area
Treatment of Burkitt's lymphoma can include the following:
- combination chemotherapy, it is a treatment that uses two or more anticancer drugs, with or without monoclonal antibodies. Steroid drugs can be added to the treatment to reduce inflammation and lower the immune response
- monoclonal antibody therapy (for example, Rituximab), is given by infusion using identical antibodies produced in the laboratory from a single type of immune system cell (cell clone). These antibodies are able to bind specifically to antigens present on the tumor, helping to kill cancer cells, blocking their growth or preventing them from spreading. Monoclonal antibodies can be used alone or to transport drugs, toxins or radioactive material directly to cancer cells
- central nervous system prophylaxis with intrathecal chemotherapy, chemotherapy is given into the cerebrospinal fluid as a preventive measure to reduce the chance of lymphoma cells spreading to the brain and spinal cord
Burkitt's lymphoma is an emergency. The key to treating the disease is the combination of appropriate, rapid and personalized treatment, with the resolution of the frequent metabolic problems that occur at the start of treatment. Although the treatment of Burkitt's lymphoma already has a good success rate, research is continuing its activity focusing on targeted drugs, the so-called “targeted therapy”, which are increasingly effective and with fewer unwanted effects.
Management must be performed in centers specialized in oncology and hematology.Bibliography
Graham BS, Lynch DT. Burkitt Lymphoma. StatPearls [Internet]. 2021; August 11
National Institutes of Health (NIH). National Cancer Institute. Adult Non-Hodgkin Lymphoma Treatment (PDQ®) - Patient Version (English)