What are the other Names of this Condition? (Also known as/Symptoms)

• Burkitt Lymphoma with Skin Involvement
• Cutaneous Involvement in Burkitt Lymphoma
• Skin Involvement in BL

What is Skin Involvement in Burkitt Lymphoma? (Definition/Background Information)

• Burkitt lymphoma (BL) is a very aggressive and fast-growing form of non-Hodgkin lymphoma. The lymphoma affects the B-cells of an individual’s immune system. There are 3 different kinds of Burkitt lymphoma and these include endemic, sporadic, and immunodeficiency-associated BL
• Skin Involvement in Burkitt Lymphoma is very rare and takes place secondary to systemic disease, meaning that the disease affects other body organs first, before affecting the skin. Primary cutaneous BL, where the skin is involved first before other body regions are affected, is generally not reported
• The signs and symptoms of Burkitt lymphoma are commonly dependent upon the site of involvement of the lymphoma. The condition frequently involves the bone marrow, liver, and gastrointestinal tract. Either a solitary lesion or widespread erosion of the skin may be observed, when skin is affected.  The manifestation may be in the form of plaques, nodules, or large-sized soft tissue masses
• The specific cause of Burkitt lymphoma is currently unknown; however, genes that likely play a role, have been identified. The most important gene involved is the c-MYC gene
• The gene involvement must be present, to make a valid diagnosis of Burkitt lymphoma. A diagnosis is typically made with the biopsy of affected lymph nodes or tumor tissue
• Burkitt lymphoma is generally treated with intensive chemotherapy supplemented with monoclonal antibody treatment (a drug that directly targets B-cells)
• As of now, the standard of care is intensive chemotherapy; but, a new clinical study has determined that low intensity chemotherapy may be effective in some cases. This provides the added benefit of less toxicity. Nevertheless, despite suitable treatment measures, the prognosis of mantle cell lymphoma is generally poor

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 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 Skin Involvement in Burkitt Lymphoma? (Age and Sex Distribution)

In general, Skin Involvement in Burkitt Lymphoma is an extremely rare occurrence.

• Children are more likely to develop endemic Burkitt lymphoma than adults; young boys around the ages of 5-8 years are especially susceptible to developing this disease
• Young adults are more often seen with sporadic Burkitt lymphoma
• Those with HIV/AIDS are also more likely to be affected by Burkitt lymphoma; individuals with AIDS and BL may present a lower incidence of skin involvement
• Around two-thirds of adults with the condition are males
• Individuals in equatorial Africa are much more likely be affected than the rest of the world

What are the Risk Factors for Skin Involvement in Burkitt Lymphoma? (Age and Sex Distribution)

The risk factors of Burkitt Lymphoma Involving Skin include:

• Young boys in the age group of 5-8 years and adult males
• Individuals belonging to the endemic regions of sub-Saharan Africa
• Individuals with weak immune systems, such as those having HIV/AIDS, organ transplant recipients who are on immunosuppressant drugs, etc.

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 Skin Involvement in Burkitt Lymphoma? (Etiology)

• The exact cause of Burkitt Lymphoma with Skin Involvement is unknown; though, gene mutations (involving the c-MYC gene) along-with chromosomal translocations have been reported
• In many cases, B-cells have a mutation in the proto-oncogene MYC
• However, it is known that Burkitt lymphoma is linked to Epstein-Barr virus (EBV), chronic malaria, and HIV. EBV-positivity is associated with endemic Burkitt lymphoma and a few sporadic cases of BL

What are the Signs and Symptoms of Skin Involvement in Burkitt Lymphoma?

The signs and symptoms of Burkitt lymphoma include:

• The main symptom is inflammation of the lymph nodes in the neck, groin, chest, abdomen, or armpit regions. However, the swelling is usually painless
• Enlarged lymph nodes in the chest and neck areas can result in swallowing difficulty, breathlessness, or sore throat
• The lymphoma may also cause fluid to collect in the individual’s abdomen (ascites). Due to this fluid collection, the gastrointestinal (GI) tract may also be affected, causing abdominal pain, diarrhea, and nausea

Burkitt Lymphoma with Skin Involvement may present the following:

• Skin patches with involvement of the subcutaneous tissues may be observed initially
• Sometimes, the overlying skin may be unaffected but subcutaneous nodules may be present
• The skin involvement may manifest through the presence of solitary tumors, or widespread dissemination may take place
• The reddish skin lesions may be in the form of nodules or plaques; the size may vary from 3-15 cm
• In severe cases, multiple rapidly-growing soft tissue tumors with eroding skin surfaces can be noted
• The skin may be also affected or ulcerated due to underlying bone invasion into the subcutaneous tissues and dermis
• The sites of presentation may include the legs (thighs), groin and abdomen, chest, armpits, back, scalp, and other sites
• Cutaneous lesions are also reported in BL that shows recurrence

Other general symptoms may include:

• Fever, night sweats, and fatigue
• Loss of appetite, weight loss
• If the cancer has reached the bone marrow, individuals may display anemia (low red blood cell count) and thrombocytopenia (low platelet count)
• Burkitt lymphoma can also affect the central nervous system. If the cancer has spread to these regions, then the individual may have headaches, confusion, an inability to focus, and seizures
• Some symptoms are specific to the two types of Burkitt lymphoma - namely the endemic type and sporadic type
• Endemic type involves swelling of the jaw, while the sporadic form typically does not involve the same
• Abdominal symptoms are more commonly found in the sporadic form, than the endemic form

How is Skin Involvement in Burkitt Lymphoma Diagnosed?

A diagnosis of Skin Involvement in Burkitt Lymphoma may involve:

• A physical examination and evaluation of medical history
• Additional testing may be done to aid in the diagnosis, which may include:
• Blood tests
• Lymphangiogram (LAG)
• Biopsy from the affected area (lymph nodes):
  • 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 affected region
  • Ultrasound scan of the affected region
  • Computerized tomography (CT) scan of the affected region
  • Vascular radiological studies
  • Whole body bone scan
  • Whole body CT-PET scans to determine how far the lymphoma has spread, by checking the size and metabolic rate (a reflection of uncontrolled growth) of lymph nodes, throughout the body. This can also help determine, if the cancer has spread to other organ systems
  • Brain MRIs are used if neurological symptoms are present, which can help determine if the cancer has spread to the brain, or to tissues that cover the brain
• Bone marrow aspiration and biopsy is performed and sent to a laboratory for a pathological examination, to determine if the bone marrow is involved. Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, histochemical stains, molecular testing, and very rarely electron microscopic studies. However, a bone marrow biopsy is not needed in the early stages of the condition
• Flow cytometry to identify cells as they flow through an instrument, called a flow cytometer. Flow cytometry measures the number and percentage of cells in a blood sample, and cell characteristics such as size, shape, and the presence of biomarkers on the cell surface. This method helps to sub-classify the condition and also to detect residual levels of disease after treatment. This tool can help in diagnosing relapse and restart treatment as needed
• Fluorescence in situ hybridization (FISH): It is a test performed on the blood or bone marrow cells to detect chromosome changes (cytogenetic analysis) in blood cancer cells. The test helps in identifying genetic abnormalities that may not be evident with an examination of cells under a microscope
• Immunophenotyping to identify a specific type of cell in a sample, which can help determine the best treatment course to be followed
• Polymerase chain reaction (PCR): It is used to measure the presence of certain biomarkers in blood or bone marrow cells. The test is ultrasensitive and detects extremely low amounts of biomarkers remaining in blood, which can be missed by cytogenetic methods, such as FISH, karyotype, or flow cytometry. PCR allows a more sensitive follow-up of patients in remission and can help determine whether additional treatment is necessary
• GI endoscopy: It may be performed to assess the extent of tumor spread
• 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
• 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

There are 4 possible stages of Burkitt lymphoma:

• Stage I - only one group of lymph nodes has cancer
• Stage II - two groups of lymph nodes are cancerous. However, the two groups are either in the chest area (above the diaphragm) or in the abdomen region (below the diaphragm)
• Stage III - multiple groups of lymph nodes are affected, and the cancer is present above and below the diaphragm
• Stage IV - the lymphoma has reached the bone marrow or organs, not in the lymphatic system

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 Skin Involvement in Burkitt Lymphoma?

Complications of Burkitt Lymphoma with Skin Involvement are generally the result of chemotherapy, or due to cancer spread. These may include:

• The lymphoma generally spreads to the abdomen, blood, bone marrow, or the central nervous systems. The treatment may be adjusted by the oncologist, to deal with spread of the cancer
• Chemotherapy weakens the immune system, and so an infection may be a possible complication. Chemotherapy may also cause the following:
  • Anemia
  • Thrombocytopenia
  • Ulcers in the mouth
  • Nausea, fatigue
  • Hair loss
  • Peripheral neuropathy (abnormal changes in sensation/feeling in one’s hands and feet)
• Another major complication of the condition is tumor lysis syndrome. The death and breakdown of cancer cells can cause the kidneys to be overloaded. In order to prevent this complication, physicians usually prescribe rasburicase. However, if left untreated, tumor lysis syndrome can result in the need for dialysis

How is Skin Involvement in Burkitt Lymphoma Treated?

The most common form of treatment of Burkitt lymphoma is intensive chemotherapy. The treatment usually lasts at least a month, but may also last up to 8-months. An inpatient treatment is provided, since some of the drugs need to be given quite frequently, or need to be continually administered.

• Chemotherapy drugs that may be used include: Cyclophosphamide, vincristine, ifosfamide, doxorubicin, methotrexate, cytarabine, and etoposide
• The drugs are usually given intravenously, either through a central line (catheter placed in a vein near the chest/heart) or through a PICC line (peripherally inserted central catheter) in the arm
• Also, chemotherapy may be given intrathecally, to deliver the drugs directly to the cerebrospinal fluid, in order to prevent the spread of the cancer to the fluid, or to treat the condition if cancer has spread to the cerebrospinal fluid
• Rituximab may be used in combination with the chemotherapy. Rituximab is a monoclonal antibody that targets a protein called CD20. This protein is found on the surface of cancerous B-cells. The antibody works by recognizing and attaching to cells with CD20. The antibody then directs the immune system, to destroy the particular cell
• Other drugs, such as rasburicase, antibiotics, and growth factors, may be used to address potential complications of chemotherapy

Skin-directed therapies are used (and often in combination) when Skin Involvement in Burkitt Lymphoma is mostly confined to the skin presenting associated signs and symptoms. This may include the following treatment measures:

• Sunlight therapy (or exposure to ultraviolet light)
• Use of topical steroids and chemotherapy
• Systemic chemotherapy
• Radiation therapy to affected (local) skin area
• Other systemic treatment measures, such as the use of interferons, retinoids, etc.
• Biological therapy

In some cases, stem cell transplants may be considered. This may be performed so that the individuals can undergo more intensive chemotherapy. In this form of treatment, very high doses of chemotherapy drugs are used, which results in a destruction of the bone marrow and stem cells along with the cancer cells. The individual is then usually given donor stem cells, or the individuals own stem cells, which were collected before the treatment.

How can Skin Involvement in Burkitt Lymphoma be Prevented?

Currently, there are no specific methods or guidelines to prevent the formation of Burkitt Lymphoma with Skin Involvement.

What is the Prognosis of Skin Involvement in Burkitt Lymphoma? (Outcomes/Resolutions)

• The prognosis of Burkitt lymphoma is usually guarded. The overall 5-year survival rate is around 44%. About 60% of adults treated with intensive chemotherapy are cured of the lymphoma
• Children and adolescents are more likely to have better outcomes than adults, especially if the adults are over the age of 40 years
• The prognostic values are not known to be affected by Burkitt Lymphoma with Skin Involvement. Although, when skin involvement is observed in AIDS-infected patients, the prognosis is extremely poor and a short survival period is noted
• 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 
• An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment
• Individuals with the cancer, which has involved sites outside of the lymphatic system, may have a poorer outcome. If the lymphoma reappears after the treatment (comes back after initially responding to treatment), the prognosis is generally poor
• Progression to bone marrow failure is usually associated with short survival
• 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

Additional and Relevant Useful Information for Skin Involvement in Burkitt Lymphoma:

A recent clinical trial found that low-intensity chemotherapy is every effective and much less cytotoxic. However, since this only a recent finding and more research needs to be done for this type of treatment, the current standard of care is still intensive chemotherapy.