1. BURKITT’S LYMPHOMA
H.A MWAKYOMA, MD.

2. Burkitt's lymphoma
Burkitt lymphoma (or "Burkitt's tumor", or "Malignant lymphoma, Burkitt's type") is a cancer of the lymphatic system (in particular, B lymphocytes). It is named after Denis Parsons Burkitt, a surgeon who first described the disease in 1956 while working in equatorial Africa.

3. BURKITT’S LYMPHOMA
Burkitt’s lymphoma (or Burkitt Lymphoma) is an uncommon type of Non-Hodgkin Lymphoma (NHL).
Burkitt’s lymphoma commonly affects children.
It is a highly aggressive type of B-cell lymphoma that often starts and involves body parts other than lymph nodes

4. BURKITT’S LYMPHOMA
In spite of its fast-growing nature, Burkitt’s lymphoma is often curable with modern intensive therapies.

5. Classification
Currently Burkitt's lymphoma can be divided into three main clinical variants: the endemic, the sporadic and the immunodeficiency-associated variants.
The endemic variant occurs in equatorial Africa.
It is the most common malignancy of children in this area.
Children affected with the disease often also had chronic malaria which is believed to have reduced resistance to the Epstein-Barr virus and allowed it to take hold.

6. I: Endemic Burkitt’s lymphoma:
In equatorial Africa, about half of all childhood cancers are Burkitt’s lymphoma.
The disease involves children much more than adults, and is related to Epstein Barr Virus (EBV) infection in 95% cases
It characteristically has a high chance of involving the jawbone, a rather distinctive feature that is rare in sporadic Burkitt’s.
It also commonly involves the abdomen.

7. The endemic variant The disease characteristically involves the;
jaw or other facial bone,
distal ileum, cecum,
ovaries, kidney or
the breast

8. II: Sporadic Burkitt’s lymphoma :
The type of Burkitt’s lymphoma that affects the rest of the world, including Europe and the Americas is the sporadic type.
Here too, it's mainly a disease in children.
The link between Epstein Barr Virus (EBV) is not as strong as with the endemic variety, though direct evidence of EBV infection is present in one out of five patients.

9. Sporadic Burkitt’s lymphoma :
More than the involvement of lymph nodes, it is the abdomen that is notably affected in more than 90% of the children
Bone marrow involvement is more common than in the endemic variety.
Jaw involvement is extremely rare.

10. The sporadic type
Non-Hodgkins, which includes Burkitt's, accounts for 30-50% of childhood lymphoma. Jaw is less commonly involved, comparing with the endemic variant. Ileo-cecal region is the common site of involvement

11. III: Immunodeficiency-associated Burkitt lymphoma
Immunodeficiency-associated Burkitt lymphoma is usually associated with HIV infection or
occurs in the setting of post-transplant patients who are taking immunosuppressive drugs.
Actually, Burkitt lymphoma can be the initial manifestation of AIDS

12. Oncogenic Viruses
Burkitt's lymphoma is associated with oncogenic viruses—the Epstein-Barr virus (EBV) in endemic Burkitt's and human immunodeficiency virus (HIV) and rarely in the sporadic form.
EBV, or human herpesvirus 4, is the virus that causes infectious mononucleosis.

13. Oncogenic Viruses
The presence of EBV in patients with endemic Burkitt's has been interpreted as a side effect of the high rates of malaria in central Africa.
African children may have immune systems that cannot fight off infection with EBV because they have been weakened by malaria
The children's B-lymphocytes then reproduce at an unusually high rate

14. Lymphocytes and Oncogenes
Lymphocytes fall into two groups:
T cells, which regulate the immune system; and B cells, which produce antibodies.
Burkitt's lymphoma involves the B-cell lymphocytes.
In 1982, researchers discovered an oncogene (a gene that can release cells from growth constraints, possibly converting them into tumors) in 90% of patients with Burkitt's lymphoma.

15. Oncogenes
The gene was Called the C-myc oncogene, it is responsible for the uncontrolled production of B-lymphocytes
It results from a translocation, or exchange, of genetic material between the long arm of human chromosome 8 and the long arm of human chromosome 14
In a smaller number of patients with Burkitt's, the translocation involves chromosomes 2 and 22 or chromosomes 2 and 8

16. BL: Jaw swelling with ulceration

17. BL: disruption of teeth, partial airway obstruction

18. BL: Jaw swelling

19. microscopic appearance
By morphology (i.e. microscopic appearance) or
immunophenotype, it is almost impossible to differentiate these three clinical variants.
Immunodeficiency-associated Burkitt lymphoma may demonstrate more plasmacytic appearance or more pleomorphism, but these features are not specific

20. microscopic appearance
Consists of sheets of monotonous (i.e. similar in size and morphology) population of medium size lymphoid cells with high proliferative activity and apoptotic activity.
The "starry sky" appearance seen under low power is due to scattered tingible-bodies laden macrophages (macrophages containing dead body of apoptotic tumor cells).

21. BL: microscopic appearance

22. BL
Pathology
Benign equivalent is replicating small noncleaved cell of germinal center:
Diffuse infiltration of lymph node
Very high mitotic rate, lot of ineffective proliferation;
Attracts macrophages to phagocytize> starry sky pattern at low power
Cytology: round nucleus, smaller than that of reactive macrophage
Vesicular chromatin and 2-5 nucleoli
Immunophenotype:
Positive: Monoclonal light chain, CD19, CD10
Negative: CD5

23. BL: Touch preparation, Wright stain

24. BL: Touch preparation,

25. Malignant B cell characteristics
Normal B cells possess rearranged immunoglobulin heavy (IgH) and light chain genes,
unlike most T-cells and other cells of the body in which the genes are germline.
Each isolated B-cell possesses a unique IgH gene rearrangement, reminiscent of the fingerprint of a person.

26. Malignant B cell characteristics
Since Burkitt lymphoma and other B-cell lymphomas are a clonal proliferative process, all tumor cells from one patient are supposed to possess identical IgH genes
When the DNA of tumor cells is analyzed using electrophoresis, a clonal band can be demonstrated since identical IgH genes will move to the same position.

27. Malignant B cell characteristics
On the contrary, when a normal or reactive lymph node is analyzed using the same technique, a smear rather than a distinct band will be seen.
This technique is useful since sometimes benign reactive processes (e.g. infectious mononucleosis) and malignant lymphoma can be difficult to distinguish.

28. Malignant B cell characteristics
Burkitt's lymphoma is a solid tumor of B lymphocytes, the lymphocytes that the immune system uses to make antibodies.
The genes for making antibodies are located on chromosomes 14 (the heavy [H] chains), 2 (kappa light chains), and 2 (lambda light chains).
These genes are expressed only in B lymphocytes because only B cells have the necessary transcription factors for the promoters and enhancers needed to turn these antibody genes "on".

29. Malignant B cell characteristics
In most (approximately 90%) of the cases of Burkitt's lymphoma, a reciprocal translocation has moved the proto-oncogene c-myc from its normal position on chromosome 8 to a location close to the enhancers of the antibody heavy chain genes on chromosome 14

30. Malignant B cell characteristics

32. Malignant B cell characteristics
In all the other cases, c-myc has been translocated close to the antibody genes on chromosome 2 or 22.
In every case, c-myc now finds itself in a region of vigorous gene transcription, and it may simply be the overproduction of the c-myc product (a transcription factor essential for mitosis of mammalian cells) that turns the lymphocyte cancerous.

33. Malignant B cell characteristics
Uncontrolled mitosis of this cell results in a clone of cancer cells, Burkitt's lymphoma.
Many other human cancers involve chromosome aberrations, such as translocations, at the loci of known proto-oncogenes.
The heavy chain gene locus on chromosome 14 is a dangerous place.
Several other proto-oncogenes produce cancerous B cells — leukemias, lymphomas, and multiple myelomas — when translocated into this locus.

34. Malignant B cell characteristics
The risk of translocations involving the heavy chain gene locus is probably especially high because breaks in its DNA occur naturally during the synthesis of antibodies

35. CYTOGENETICS
Most BL cell lines show a specific translocation involving chromosome 8 (breakpoint at 8q24) and either 2, 14 or 22.
The type of immunoglobulins produced by this B-cell tumor correlates with the type of translocation:
those with the 8;2 translocation produce predominantly kappa light chains;
those with the 8;22 translocation produce lambda light chains;
those with the 8;14 translocation produce immunoglobulins with both types of light chains

36. In summary: cytogenetics
Almost by definition, Burkitt lymphoma are associated with c-myc gene translocation. The most common variant is t(8;14)(q24;q32) while rarer variants include t(2;8)(p12;q24) and t(8;22)(q24;q11).
A three-way translocation, t(8;14;18), has also been identified.
It is curable.

37. Treatment
Effect of the chemotherapy, as with all cancers, depends on the time of diagnosis. With faster growing cancers, such as this one, the cancer actually responds faster than with slower growing cancers. .
This rapid response to chemotherapy can be hazardous to patient as a phenomenon called "tumor lysis syndrome" could occur. Close monitoring of patient and adequate hydration is essential during the process.

38. Chemotherapy
Cyclophosphamide
Doxorubicin
Vincristine
Methotrexate etc