Case Presentation - Summer, 2008

Burkitt's Lymphoma
ThinPrep® non-gyn cytology, Cellient cell block

NOTE: The diagnosis and analysis for this case study were provided by an independent physician. All conclusions and opinions are those of the physician and not Hologic, Inc.

History: 37 year old male

Specimen type: Left Lateral Neck, Lymph node FNA

Case provided by: Park Ridge Hospital, Fletcher, North Carolina

Burkitt's lymphoma is an uncommon type of Non-Hodgkin's lymphoma. While Burkitt's lymphoma can occur in adults, it more commonly affects children. It affects males more than females both during childhood and as an adult. This form of lymphoma is of B cell origin and is highly aggressive. Burkitt's lymphoma typically originates in and involves areas of the body other than the lymph nodes. Although this form of lymphoma is very aggressive it is often curable with modern intensive therapies. Burkitt's lymphoma is 1000 more times more common in persons with AIDS and 2% of AIDS patients will develop this disease.

Burkitt's lymphoma has three clinical variants: the endemic, the sporadic and the immunodeficiency-associated variants.

The endemic variant is also known as the "African" variant occurring in equatorial Africa and is the most common malignancy in children of this geographical area. In 95% of the cases this variant is linked to infection with Epstein Barr Virus (EBV). It commonly arises in the jaw bone and abdomen of children. Peak incidence of this variant occurs between ages 4-7.

The sporadic or "Non-African" variant is a form of Burkitt's lymphoma that occurs outside of Africa. In this variant the link with the EBV is not as strong however the presence of the virus can be identified in one out of five patients. It rarely affects the jaw and in 90% of the cases affects the abdomen. Bone marrow involvement frequently occurs with this variant. It typically occurs in young adults with 1-2% of all lymphomas occurring at median age of 30.

The immunodeficiency-associated variant primarily occurs in patients with HIV and the presence of EBV can be identified in 25-40% of the cases.

In all of the clinical variants of Burkitt's lymphoma patients have a risk of having central nervous system involvement, and the translocation of the Myc protein is a constant genetic feature.

A diagnosis of Burkitt's lymphoma is made based on morphology of a biopsy specimen, immunohistochemistry, flowcytometry and genetics. Cytologically, Burkitt's lymphoma can have different morphologic looks. In some cases, more commonly in children and immunodeficiency states there is plasmacytoid differention. In Burkitt's lymphoma the cells are medium in size despite its classification as a small non cleaved lymphoma. Nuclei are round to oval and occasionally multiple. Nucleoli are small but multiple. The nuclear membrane is typically smooth but can be notched or indented. The blastic chromatin pattern is a characteristic feature and appears finely stippled but not as powdery as lymphoblastic lymphoma. Cytoplasm is moderate in amount and stains deep blue with tiny lipid vacuoles. Tingible body macrophages are typically present in the background giving the specimen the characteristic "starry sky" appearance.

In adults, the most commonly used staging system for Burkitt's lymphoma and other Non Hodgkin's lymphomas is the Ann Arbor system. There are four designated stages with this system:
  • Stage I: The lymphoma is either limited to one group of lymph nodes either above or below the diaphragm, or is in an organ or part of the body other than the lymph nodes, but has not spread to other organs or lymph nodes.
  • Stage II: The lymphoma is either in two or more lymph node groups on the same side of the diaphragm, or is in only one organ or site other than the lymph nodes but has spread to the lymph nodes near that organ or site.
  • Stage III: The lymphoma is present in groups of lymph nodes on both sides of the diaphragm. It may involve an organ or site outside the lymph nodes, the spleen, or both.
  • Stage IV: The lymphoma is spread throughout one or more organs outside the lymph nodes. There may or may not be involvement of lymph nodes that are remote from the affected organs.
The patients' condition can be described in more detail by using letters to denote specific general symptoms and/or the body parts that have been affected.

For children, the most common staging system is that of the St Jude's Children Research Hospital. This system separates the early stages of the disease (Stage I&II) from the more advanced stages (Stage III&IV).

It is important to start treatment for this lymphoma as soon as possible due to its aggressive nature. There are different courses of treatment for children and adults.

Children with this type of lymphoma are typically treated with radiation therapy and chemotherapy. Children with endemic Burkitt's lymphoma are most commonly treated with cyclophosphamide (Cytoxan). Cyclophosphamide works by suppressing the immune system. It can be administered either orally or intravenously. If the tumor involves the jaw and area around the eyes, radiation is the therapy of choice. For children with sporadic Burkitt's a short course of high dose chemotherapy is administered. The patients head and spine may be treated with radiation therapy and intrathecal methotrexate to help keep the tumor from spreading to the central nervous system.

Adults diagnosed with sporadic Burkitt's lymphoma undergo a combination of radiation therapy and chemotherapy. A newer high dose chemotherapy regimen called CODOX-M/IVAC is a combination of chemotherapy drugs that has shown good results. In patients with AIDS, a low dose chemotherapy regimen is given. This is due to the fact that their immune systems are already compromised. Patients with HIV infection don't respond as well to treatment as those patients without the infection.

Newer treatment options are available and these include bone marrow or stem cell transplantation and monoclonal antibodies.

The prognosis for children with Burkitt's lymphoma is good. In the United States, approximately 80% of children treated for early stage Burkitt's remain free from relapse three years after treatment. With the treatment of the newer CODOX-M/IVAC combination chemotherapy the cure rate for children and adults is above 90%.

In adults with Burkitt's the prognosis depends on several factors. The International Prognosis Index (IPI) is used to predict the patients' chance of recurrence and survival rate by assigning a "1" to the following five factors:
  • age over 60 years
  • the lymphoma is classified as Stage III or Stage IV
  • the lymphoma has spread to more than one site outside the lymph nodes
  • high levels of lactate dehydrogenase (an enzyme used to measure tumor burden)
  • poor general health
An IPI rating of 0 or 1 is associated with a 70% of disease free survival at the end of five years and 73% overall survival after five years. A rating of 5 is associated with a five-year rate of 40% disease free survival and 26% overall survival.

In patients with HIV, the factors that affect the prognosis are as follows: the CD4 lymphocyte count: the presence of opportunistic infection; involvement of the bone marrow; the spread of lymphoma beyond the lymph nodes; age and patients overall strength. For patients that are HIV positive the average length of survival is six months.

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  5. Demay, Richard M: The Art and Sciences of Cytopathology. 1996:810-811.