Burkitt's lymphoma is a highly aggressive B-cell lymphoma characterized by a translocation of the c-myc gene. It typically presents as a rapidly growing abdominal or facial tumor in children. Treatment involves intensive short-duration chemotherapy, which can cure over 80% of cases of the endemic form. Prognosis is generally good if the cancer is localized and responds well to chemotherapy, but patients presenting with widespread or refractory disease have a worse outcome.

1. Burkitt’s lymphoma
Abegunde O.V

2. OUTLINE
• Introduction
• Epidemiology
• Aetiopathogenesis
• Classification
• Clinical features
• Differential diagnosis
• Investigations
• Staging , treatment and outcome
• Complications
• Conclusion
• References

3. Introduction
• Lymphomas are solid tumours of lymphocytes which are malignant
• They present as solid tumours of lymph node or other lymphoid
organ or tissue resulting in their enlargement.
• 2 broad classifications:
– Hodgkin’s Lymphoma
– Non-Hodgkin’s lymphoma
• Non-Hodgkin’s Lymphoma two subtypes:
– B-cell lymphoma
– T-cell and natural killer (NK) cell lymphoma

4. Working formulation developed by national
cancer institute of USA( 1981)
• Classified non-hodgkins lymphoma into
• Low grade
• Intermediate grade
• High grade
Based on morphology
Low-grade
• Small lymphocytic
• Follicular small cleaved
• Follicular mixed small/large cell

5. • Intermediate grade
• Follicular large cell
• Diffuse small-cleaved cell
• Diffuse mixed small and large cell
• Diffuse large cell
High-grade
• Immunoblastic large cell
• Lymphoblastic cell
• Diffuse small non-cleaved (Burkitt's) or non burkitt

6. • WHO/REAL Classification divided B-cell NHL into 3 clinical categories
– Indolent Lymphoma
– Aggressive Lymphoma
– Highly Aggressive Lymphoma

7. • Indolent Lymphoma
• Small Lymphocytic Cell Lymphoma
• Follicular Lymphoma (Grade 1-2)
• Lymphoplasmacytic Lymphoma
• Splenic/Nodal Marginal Zone Lymphoma
Aggressive Lymphoma
• Diffuse Large B-cell Lymphoma
• Follicular Lymphoma (Grade 3)
• Mantle Cell Lymphoma

8. • Highly Aggressive Lymphoma
• Burkitt’s Lymphoma
• Lymphoblastic Lymphoma

9. Introduction
• Burkitt’s lymphoma is a form of non –hodgkin’s lymphoma
• highly aggressive childhood B- Cell neoplasm characterized by the
translocation and deregulation of the c-myc gene on chromosome 8
• first described by Dennis Burkitt, a British surgeon practising in
Uganda in 1956
• fastest growing tumour known to man
• doubling time of ≈ 24 hours.

10. Epidemiology
• Commonest childhood malignancy in Nigeria with relative frequency
55% of all paediatric tumour
• Most affected age grp: 4 - 9 years
Rare < 2 years and > 15 years
• Males >> females (M:F = 2:1)

11. Epidemiology cont’d
• Tropical rain forest of Africa, Latitudes 10-10º North and South of the
Equator and other parts of the world with similar climatic conditions
such as Papua New Guinea.
• Common in equatorial Africa and regions ( Temp ≥ 16°C & Rainfall ≥
50cm)
• Common in children from low socioeconomic clan.
• Uncommon in children from high socio-economic class, living in
endemic areas.

12. Types of burkitt’s lymphoma
• Three distinct clinical forms are recognized
Endemic , Sporadic and Immunodeficiency- Associated.
• Although histologically identical and with similar clinical behaviour,
these different forms differ in epidemiology, clinical presentation and
genetic features

13. Endemic burkitt’s lymphoma
• Endemic BL (African)refers to those cases occurring in African children
• usually 2–16 years old,mean age of 7yrs(rare below 2yrs of age)
• male : female ratio of 2:1
• Maxilla is involved more commonly than the mandible
• Posterior segments more affected
• Sometimes all four quadrants show tumor involvement
• Occurs in region where malaria in holoendemic.

14. Sporadic BL
• Sporadic Burkitt’s lymphoma also known as ” non –African” occurs
worldwide.
• it includes those cases occurring with no specific geographic or
climatic association.
• It accounts for 1%–2% of lymphoma in adults and up to 40% of
lymphoma in children in the U.S. and western Europe.
• Most often present as abdominal tumours with bone marrow
involvement
• Mean age of occurrence is 11 years.

15. Immunodeficency- associated BL
• This variant of Burkitt’s lymphoma accounts for 30%–40% of non-
Hodgkin’s lymphoma in HIV+/AIDS patients.
• It can also occur in people with congenital conditions that cause
immune deficiency and in organ transplant patients on
immunosuppressive drugs.
• Present as cases usually with nodal involvement with frequent bone
marrow involvement
• Involves distal ileum ,ceacum and mesentry

16. Compared to the endemic type ,the incidence of Epstein-barr infection
is considerably lower in the other two types of burkitt lymphoma .
In the sporadic type Epstein- barr occurs in 20% of the patients
In the immunodeficiency –associated type it occurs in 30-40% of
patients.

18. Burkitt’s lymphoma

19. Aetiopathogenesis
• The exact etiology and pathophysiologic mechanisms to the
development of Burkitt lymphoma are not known.
• However several theories exist.
• Chromosomal aberration
• Role of microbial and parasitic infection
• Herbal exposure
• Low socioeconomic factors

20. Aetiopathogenesis
• Chromosomal abberation
• Chromosome 8 carries the C-myc gene, which regulates
lymphomagenesis.
• As a result of an alteration in VDJ-recombinase (enzyme responsible
for gene re-arrangement)
1. C-myc gene is translocated from Chromosome 8
2. In exchange for antibody coding genes on Chromosome 2, 14 or 22.
3. The ability to control / regulate cellular proliferation is lost by the
gene in its new position.
4. Resulting in immortalization of the B-Lymphocytes

21. • Three alterations have been described
• Translocation resulting in the transposition of the C-myc proto-
oncogene on chromosome 8 with one of the immunoglobulin heavy
chain (IgH) genes on chromosome 14. [t(8;14)(q24;q32) ].
• This occurs in 60-70% of cases.

22. • c-myc on chromosome 8 translocated close to the λ-light-chain gene
on chromosome 22 [t(8;22)(q24;q11)]. 10-15% of cases.
• c-myc on chromosome 8 translocated close to the ƙ-light-chain gene
on chromosome 2 [t(8;2)(p12;q24)]. 2-5% of cases.
• These result in overexpression of the c-myc gene and is considered
responsible for tumor proliferation.

23. Translocation of c-myc gene

24. Aetiopathogenesis
Role of Epstein barr virus and malaria
• Epstein Barr virus infection is implicated especially African BL.
• Chronic exposure of infants to malaria results in immunosuppression
which permits the proliferation of EBV- transformed cell.
• The lymphocytes have receptors(C 3d-like) for EBV and are its
specific target.
• The genetic instability of the EBV+, aberrantly regulated B cells leads
to a greater risk of c-myc rearrangement, and then to lymphoma.

25. Role of EBV

26. • Herbal exposure
• The sap of the milk bush (Euphorbia tirucalli ) and other
Euphorbiaceae species are possible environmental risk factors for BL
due to their ability to activate the viral replication cycle in the latent
phase of EBV-infected cells.
• These plants are used traditionally in many cultural activities in
tropical Africa such as religious (wedding and birth of twin
ceremonies), human (to treat sore throat, headache, diarrhoea and
wounds),

27. Euphorbia tirucalli

28. • Low socioeconomic factors may be associated with a poor defense
response toward environmental exposures due to poor nutrition
and/or poor hygienic conditions
• Other environmental factors to be considered in its etiology include
schistosomiasis and exposure to pesticides

29. Clinical features
• Rapidly growing tumor with a doubling time of about 24hrs
• Rapidly progressive painless facial swelling of the jaw in 1 or more
quadrants.
• presentation within 2-6 weeks of illness.
• Intraoral extension of swelling to involve the cheek or gingivae
• Proptosis in children may occur in association with maxillary lesions
• Pain and paresthesia associated with jaw lesions
• Loosening of teeth

30. Burkitt’s lymphoma with severe orbital
involvement

31. Clinical features cont’d
• Premature exfoliation of deciduous teeth
• Overlying mucosa may be hemorrhagic or ulcerated.
• Non tender rapidly enlarging submandibular or cervical lymph nodes
• Progressive, painful abdominal swelling
• Bowel obstruction secondary to growth of the abdominal mass
mimicking acute appendicitis

32. Other symptoms
• Weight loss > 10% body weight in 6mths
• Anorexia
• Fatigue
• Unexplained Fever (on & off) (Fever > 38.0)
• Malaise
• Night sweats

33. investigations
• Haematology
Full Blood Count
• Blood chemistry
Electrolyte, urea, creatinine, calcium, uric acid, phosphates, LDH
Liver function test
• Retroviral screening

34. investigations
• Radiographic
• -Lateral Oblique Plain Radiographs:
Chest (lung metastasis and Mediastinal
involvement)
Jaw (PAR, upper and lower occlusal, PA skull)
• CT scan
• MRI
• Abdominal USS

35. • Lesion appears hypodense on computed tomography scan and
hypoechoic on ultrasound scan.

36. Radiographic findings
• ill-defined radiolucency
• Loss of lamina dura and developmental crypt(s) around erupted and
unerupted teeth
• Uniform widening of periodontal membrane space(garrington’s sign)
• Teeth may be displaced, causing malocclusion and/or
exfoliation.(Dental Anarchy)
• Root truncation

37. • Histopathologic examination
Bone Marrow Aspiration (BMA)/Biopsy
Lumbar puncture for CSF cytology
• Cytogenetic studies
• Flow cytometry – in determining a clonal cell population and in
differentiating between B-cell and T-cell antigen

39. Differential diagnosis
• Clinical differential diagnosis
• Other jaw malignancies of childhood
• Ewing’s sarcoma
• Osteosarcoma
• Ameloblastoma
• Dentigerous cyst
• Embryonal Rhabdomyosarcoma
• Acute infection / Dentoalveolar Abscess

40. Differential diagnosis
Differential Diagnosis of burkitt’s lymphoma(histologic)
• Neuroblastoma
• Nephroblastoma
• Retinoblastoma
• Lymphoblastic lymphoma
• Blastic mantle cell lymphoma
• Diffuse large B-cell lymphoma
• Embryonal Rhabdomyosarcoma

41. Histology
Histologic examination:
homogenous sheets of lymphoblasts, with round to oval nuclei,
slightly coarse chromatin, multiple nucleoli, and intensely basophilic
vacuolated cytoplasm that contains neutral fat.
The homogenous appearance is interspersed with scattered
macrophages, containing necrotic debris, giving a starry- sky
appearance

42. Thus they tend to stand out as “stars” set against the “night sky”
of the hyperchromatic neoplastic lymphoid cells, giving it the
so-called starry sky appearance.
Mitotic figures are numerous

44. • ‘starry sky’ appearance is not pathognomonic of BL and is also seen in
• Hodgkin’s Paragranuloma
• Stem cell and Lymphocytic lymphomas

45. Fine Needle Aspiration Cytology
Leishmann’s Stain shows
large monomorphic lymphoblasts containing distinct nucleoli,
abundant deeply basophilic and vacuolated cytoplasm.

46. Leishmann’s Stain

47. SHOWING A POSITIVE REACTION IN NEARLY ALL TUMOUR
CELLS
STAINING FOR Ki-67

48. Immunophenotype
• BL cells express surface IgM and B-cell associated antigens {CD 19,
CD 20, CD 22, CD 79a,} as well as CD 10 HLA-DR, and CD 43.
• They also show nuclear staining for BCL-6 protein.
• Expression of CD 21, the Epstein-Barr virus receptor is dependent on
the EBV status of the tumour
• Virtually all the cells in Burkitt’s lymphomas are proliferating, shown
by expression of Ki-67.
• These tumors are negative for T-cell antigens CD2, CD 7, CD 8 and
Bcl-2.

49. DIAGNOSIS
• WHO classification requires that for a diagnosis to be made, there
must be
1. High growth factor
2. Ki67 staining of over 99%
3. Evidence of c-MYC rearrangement

50. Staging, treatment and outcome
• The staging of BL is important as it helps the clinician in choosing a
treatment protocol and also eventual prognosis and outcome.
• Different types of staging have been used in BL
• Ann Arbor staging
• St Jude / Murphy staging system
• Ziegler and Magrath

51. Ann Arbor method
• Patient are staged on I-IV Based on site and extent of their tumour .
• Also A and B
• A –without systemic symptoms
• B –systemic symptoms ;fever >38 ⁰c
• weightloss >10% body weight in past 6mths
• night sweats

52. Ann arbor method
I. Lymph node involvement in one anatomical region
II. Involvement of 2 or more lymph node regions on the same side
of the diaghragm either above or below
III. Involvement of lymph node regions on both sides of the
diaphragm.
IV. Disseminated (Multifocal) involvement of 1 or more
extralymphatic organs.

53. Ziegler and Magrath
A. Solitary extra-abdominal site
AR. Resectable (90%) intra-abdominal tumour
B. Multiple extra-abdominal site
C. Intra-abdominal tumour ± facial tumour
D. Intra-abdominal tumour + site other than facial e.g (testis)

54. Management
Management is multidisciplinary involving
• Oncologist
• Hematologist
• Pediatrician
• Dental surgeon

55. Management
• HISTORY
• EXAMINATION
• INVESTIGATION
• TREATMENT

56. Treatment
• Systemic chemotherapy is the treatment of choice, and Burkitt’s
lymphomas respond well.
• Short duration, high intensity combination chemotherapy is used.
• However, sporadic and immunodeficiency-associated BL do not have as
much sensitivity seen in endemic BL.
• Cyclophosphamide therapy alone has been curative for 80% of children
with early stage endemic type , however combination chemotherapy is the
choice for extensive disease

57. Pre-chemotherapy medications:
• Fluid preload to ensure high urinary output
• Correction of any metabolic imbalance or hematologic abnormality
• Allopurinol – to offset hyperuricaemia occuring from high cell loss rate
• Start 24-48hrs before chemotherapy
• Dose 200-500mg, usually 100mg t.d.s
• Persistent ↑ uric acid despite allopurinol use
give uricaise 500 – 1000i.u

58. Treatment regimen
• Treatment options for patients with limited stage disease include the
following:
• COMP – Cyclophosphamide + vincristine (Oncovin) + Methotrexate +
Prednisone
• CHOP – Same as above with Hydroxydaunorubicinhydrochloride
replacing Methotrexate
• CHOP plus Methotrexate

59. • RCHOP-Rituximab, a monoclonal anti-CD20 antibody, may improve
outcome
• Intrathecal Methotrexate and Cytosine arabinoside – CNS prophylaxis
• The course is repeated every 2weeks in 6 courses

60. Supportive therapy cont’d
• Hydration : @ least 2L/m2 of fluid/day, to promote uric acid excretion
and prevent uric acid nephropathy.
• Alkalinization of Urine to PH 7 – 8
• Blood and blood products
• Antibiotics
• Psychological support
• Surgical Laminectomy
• Dialysis

61. • Surgery is only indicated for patients with small, completely
resectable abdominal tumours or patients with obstruction who
cannot begin chemotherapy immediately.
• Is also indicated for debulking prior to chemotherapy(Greatly
improves prognosis)

62. • Follow-up
• To evaluate patient response
• Observe for relapse
• For documentation

63. Outcome
• Adverse Outcome , among children and adult patients can be
predicted on presentation with the following ;
• -Male sex
• - older age
• - advanced stage
• - poor performance status
• - bulky disease / intra- abdominal tumour

64. • - CNS or marrow involvement
• -failure to achieve complete remission
• In paediatric patients a poorer prognostic outcome is expected in
patients ;
• -↑ 15yrs of age

65. complications
• Facial disfigurement
• Deranged occlusion
• Obstructive symptoms
• Tumour lysis syndrome
1. Hypocalcaemia
2. Hyperphosphatemia
3. Hyperuricaemia
4. Hyperkalemia
5. Metabolic acidosis
• Leukaemia
• CNS symptoms

66. • Complications of cytotoxic therapy
• Nausea, vomitting,haemorrhagic cystitis, alopecia, marrow
suppression e.t.c

67. Conclusion
• Burkitt’s lymphoma is a unique neoplasm as :
• It is the first human tumor to be causally associated with a virus
(EBV).
• The c-myc of Burkitt’s lymphoma is the first oncogene to be described
in a lymphoma .
• It is the first type of non- Hodgkin’s lymphoma to be described in
association with HIV infection.
• Among human neoplasms, it has the shortest doubling time with its
unequalled proliferation rate creating special challenges for diagnosis
and treatment.

68. References
• Oral and maxillofacial pathology fourth edition Neville.
• Burkitt lymphoma ;diagnosis,prognosis,symptoms and treatment
webMD
• National update course 2019 lecture .The role of immunochemistry
in diagnosis of lymphoreticular disorders. Dr Ajayi
• Non hodgkins lymphoma update lecture west Africa Dr Adeyemi
• Pathology class notes .

69. N
• Thank you for listening….