Burkitt lymphoma is an aggressive form of non-Hodgkin lymphoma that was first described in Africa. It exists in both endemic and sporadic forms. Endemic Burkitt lymphoma is associated with malaria and EBV infection, presenting commonly as jaw tumors in young children. Sporadic Burkitt lymphoma presents more often as abdominal tumors and affects older individuals. Diagnosis involves biopsy and imaging. Treatment requires intensive chemotherapy which is usually very effective, though prognosis is poorer with CNS involvement or large tumor burden. Complications can include tumor lysis syndrome requiring supportive care.

1. BURKITT`S LYMPHOMA
BY
Dr OLATUNYA OS
DEPT OF PAEDIATRICS
College of Medicine
Ekiti State University

2. •INTRODUCTION
•EPIDEMIOLOGY
•PATHOGENESIS
•CLINICAL FEATURES
•INVESTIGATION
•DIFFERENTIAL DIAGNOSIS
•TREATMENT
•COMPLICATIONS
•PROGNOSIS
•CONCLUSION
OUTLINE

3. Burkitt lymphoma is the fastest growing malignancy
in humans, was first described by an Dr. Dennis
Burkitt, an Irish surgeon working in Kampala,
Uganda. In 1958 he described 28 cases of sarcoma
of the jaw which he reported as round cell sarcoma
that seemed to occur with extraordinary frequency
in the jaws of children in tropical east Africa.
INTRODUCTION

4. Two types -Endemic (African Burkitt)
-Sporadic (Non Endemic) Burkitt -U.S.A
-Europe
-Israel
ENDEMIC TYPE
• Incidence rate is 10: 100, 000 children
• Geographical belt
• Sex ratio M: F is 2: 1
• Peak age range is 4 – 8 years
 100 – 150 north and south of the equator
 Annual rainfall >75cm all year round
 Temperature does not fall < 16C
 Altitude < 1500m
 The geographical belt coincides with malaria
holoendemic areas – tropical Africa (Lymphoma belt)
EPIDEMIOLOGY

5.  Epstein-Bar Virus transforms B cells and immortlizes them
 Environmental factor –Holoendemic malaria promotes
polyclonal proliferation of B cells
 Chromosomal translocation – cytogenetic error emerges and
endows the cell with survival advantage
√ undernutrition and low socioeconomic class.
3 stage pathogenetic step required for development of endemic
Burkitt lymphoma
PATHOGENESIS

7. ENDEMIC SPORADIC
Incidence 10/100,000 0.2/100,000
Occurrence Climatically determined Not climatically determined
95% of tumor carrying EBV
genome in their cell
20% of tumors carry EBV genome
in their cells
By 3yrs almost entire
population is infected
EBV infection tends to be late in
adolescence or early childhood
Associated with low
socioeconomic status
Commonest
Presentation
Jaw mass Abdominal mass
Chromosomal
break point
75% upper arm of C-MYC More often within C-MYC

8.  JAW TUMORS
 ABDOMINAL TUMORS
 CNS INVOLVEMENT
 PERIPHERAL NODE
ENDEMIC
75%
60%
30%
Rare
 ABDOMINAL TUMORS
 PERIPHERAL NODE
 JAW TUMORS
 CNS INVOLVEMENT
NON-ENDEMIC
90%
20%
10%
5%
CLINICAL FEATURES

9.  Rapidly growing jaw swelling, painless, maxilla is 2X
more affected than mandible
 Malaligned teeth
 Loosening of teeth, tooth loss
 Oral extension and soft tissue swelling
 o/e hard firm jaw swelling that does not transilluminate,
JAW SWELLING
Doubling time 24hours
Growth fraction 100%
CLINICAL FEATURES
A very rapidly growing tumour

10. JAW MASS DENTAL ANARCHY WITH LOSS OF TOOTH

11.  Painless diffuse abdominal mass which is progressive
 Affects older age group
 Has a predilection for paired organs (ovaries, kidneys
mesentery) except the spleen and liver
 Examination will show a diffuse abdominal mass. If
intraperitoneal will moves with respiration.
Extraperitoneal doesn’t move with respiration
 Ascites may be present
CLINICAL FEATURES
ABDOMINAL BURKITT

12.  Due to spinal cord compression from an extradural
tumor
 CNS is a common site of relapse
 Flaccid bilateral symmetric paralysis of the
lower limb
 Spinal root pain
 Bowel dysfunction (constipation) and bladder
dysfunction (incontinence)
 Sensory loss
CNS BURKITT MAY PRESENT
WITH PARAPLEGIA & OTHERS
CLINICAL FEATURES

13.  Cranial nerve deficits
 Signs of raised intracranial pressure
 INTRA-CRANIAL TUMOR
CENTRAL NERVOUS SYSTEM
CLINICAL FEATURES

14.  Lungs, pleura (usually)
 Testes
 Thyroid gland
 Skin
 Bone marrow involvement
OTHER SITES
 Proptosis
OCULAR MASS
CLINICAL FEATURES CONTD

15. STAGE TUMOR SITE
A Solitary extra – abdominal site e.g. solitary facial
tumor
B Multiple extra – abdominal site e.g. facial tumor in >1
quadrant of the face
C Intra – abdominal tumor + facial tumor
D Intra – abdominal tumor + site other than facial (CNS,
Testis)
AR Resectable 90% intra – abdominal tumor
CLINICAL STAGING

16.  Burkitt cells are homogenous in size and
shape.
 10 – 25 um in diameter
 Contain round or oval nuclei with 2 - 5
nucleoli.
 They are small round cells with intensely
basophilic
cytoplasm which stain intensely with methyl
green
pyronine because of high RNA content.
 Cytoplasm contains lipid vacuoles
INVESTIGATIONS
Cytology =

17.  Starry sky appearance seen under low power.
 Numerous small round cells with
macrophages interspaced in between them.
 The macrophages contain nuclear debris
probably ingested from tumor cells that have
undergone apoptosis.
INVESTIGATIONS CONT
Tissue biopsy
Histology =

18. The starry- sky appearance
NB:
1. The stars are due to vacuolated macrophages washed off
during preparation and containing debris derived from
the rapid cell turnover seen in Burkiit
2. The sky constitute the Burkiitt cells in the background
CSF CYTOLOGY: looking for Burkitt cells

19.  INTRAVENOUS UROGRAM
 ABDOMINAL CT SCAN
Lateral oblique view shows loss of
lamina dura (not
pathognomonic) in both erupted and
unerupted teeth
Dental malalignment
 ABDOMINAL ULTRASONOGRAPHY
 X-RAY OF THE JAW
RADIOLOGICAL/IMAGING STUDIES
INVESTIGATIONS CONTD

20.  POSITRON EMISSION TOMOGRAPHY
 GALLIUM 67 SCINTIGRAPHY
 MYELOGRAPHY
 CRANIAL CT SCAN
RADIOLOGICAL/IMAGING STUDIES

21.  Osteosarcoma
 MALIGNANT TUMOR
 OSTEOMYELITIS OF THE JAW BONE
 TRAUMA
 Dentigerous cyst
 Ameloblastoma
 Fibrous dysplasia
 Ossifying fibroma
 BENIGN TUMORS
JAW SWELLING
DIFFERENTIAL DIAGNOSIS

22.  TB spine
 Neuroblastoma
PARAPLEGIA
 Retinoblastoma
 Rhabdomyosarcoma
 Neuroblastoma
OCULAR MASS
 Neuroblastoma
 Nephroblastoma
 Non Hodgkins Non Burkitts lymphoma
 Ovarian tumors
 Abdominal TB
ABDOMINAL MASS
DIFFERENTIAL DIAGNOSIS CONTD

23.  Useful as marker of tumor burden
 Used to monitor response to treatment,
tumor regression and relapse
 Liver function test
 Serum lactate dehydrogenase
 Phosphates and uric acid may be increased due to
high turnover rates of cells in the tumor
 Used for monitoring treatment and complication
 Serum electrolyte and urea, calcium, phosphate, creatinine,
uric acid.
 May be normal
 May show anemia, leucopenia or
thrombocytopenia
 Full blood count
Blood investigations are done as baseline investigations
before chemotherapy and are also done weekly for
possible detection of Tumor Lysis Syndrome
BLOOD INVESTIGATIONS

24.  Alkalinization of urine
 Hydration
URIC ACID
XANTHINE
HYPOXANTHINE
XANTHINE
OXIDASE
PURINE
DNA, RNA
 Allopurinol – inhibits xanthine oxidase
Very important due to possible tumor lysis syndrome
 SUPPORTIVE
Goal of treatment is to achieve complete cure
TREATMENT

25.  Radiotherapy
 Surgery
 Chemotherapy
 DEFINITIVE
 Psychological support
 Monitor full blood count and platelet count weekly
 Folinic acid
 SUPPORTIVE
TREATMENT CONTD

26.  Give total of 6 courses (2 weekly)
 CNS prophylaxis - IT methotrexate 15mg/m2 days 1 and 4
 NB: IV folinic acid 0.25mg/kg/day, day 2 to 4 may be
given to obviate some cytotoxicity
 IV cyclophosphamide 1000mg/m2 day 1
 IV oncovin (vincristine) 1.4 mg/m2 day 1
 IV methotrexate 15mg/m2 day 1
±Tabs prednisolone 40mg/m2 daily for 5 days
± Cytosine Arabinoside
 COMP
 Chemotherapy – systemic chemotherapy is the
treatment of
choice as tumor is highly chemosensitive
 DEFINITIVE
TREATMENT CONTD

27.  IV cyclophosphamide 30 – 40mg/kg day 1
 IV oncovin (vincristine) 1.4 mg/m2 day 1
 PO methotrexate 15mg/m2 days 1, 2 and 3
CNS involvement
IT Arac C 30mg/m2 day 1, 2 and 3
IT Methotrexate 15mg/m2 day 4
Cycles repeated 2 weekly for 6 cycles
 COM
OTHER REGIMEN

28.  Immunoaugumentation
 Radiation therapy
 Surgery
 CHOP + Methotrexate
 Cyclophosphamide
 Doxorubicin
 Oncovin
 Prednisolone
 CHOP
OTHER TREATMENT MODALITIES

29. This is due to rapid release of intracellular content in blood stream in
- Large tumor burden
- Rapid cell turnover
- Rapid turnover response to chemotherapy
Constellation of metabolic disturbances that may be seen after
initiation of cancer treatment. It usually occurs in patient with bulky
rapidly proliferating and treatment responsive tumors
It is due to release of intracellular ions and metabolic by-products
into the systemic circulation.
 TUMOR LYSIS SYNDROME
COMPLICATIONS

30.  Metabolic triad
- Hyperuricaemia
- Hyperkalaemia
- Hyperphosphataemia
 Secondary complication
- Renal failure
- Hypocalcaemia
 TUMOR LYSIS SYNDROME COMPONENTS

31. Hyperkalemia Severe: >6 mEq/L
and rapid rise or
ECG changes
ECG and cardiac
monitoring
Remove potassium
from all IV fluids
Administer sodium
polystyrene resin
(Kayexalate): 1-2
g/kg mixed with 3
mL sorbitol/g resin
PO q6h
Give loop diuretic:
Furosemide 0.5-2
mg/kg IV q6-24h
Sodium polystyrene
resin contains sulfa
and induces allergic
reaction in sensitive
individuals
Severity Intervention Notes
 TUMOR LYSIS SYNDROME

32. Hyperkalemia Severe: >6 mEq/L
and rapid rise or
ECG changes
Insulin and
dextrose: 0.1 U/kg
regular insulin IV
with 2 mL/kg 25%
dextrose q30-60min
Sodium
bicarbonate: 1-2
mEq/kg IV infused
over 5-10 min
If ECG changes:
Calcium gluconate
10%: 100
mg/kg/dose IV
infused over 3-5
min; may repeat in
10 min
Dialysis may be
required
Calcium gluconate
not compatible
with sodium
bicarbonate; must
separate infusions
by thoroughly
flushing the access
line
Severity Intervention Notes

33. Hyperphosph
atemia
Moderate to
severe
Aluminum hydroxide:
50-150 mg/kg/d PO
divided q4-6h
Normal saline IV bolus
and mannitol 0.25-1 g/kg
IV bolus
Consider dialysis if >10
mg/dL or poor renal
function
Compensatory
hypocalcemia may
coexist
Severity Intervention Notes

34. Elevated uric
acid level
Mild to
severe
Recombinant urate
oxidase (Rasburicase)
0.2 mg/kg IV q12-24h
Continue
hyperhydration
Continue maintenance
fluid; increased 2- to 4-
fold
Continue allopurinol:
300 mg/m2/d
Alkalinize urine with
sodium bicarbonate
Start dialysis if level
>10 mg/dL or if renal
failure occurs
Best management is
prophylaxis;
recombinant urate
oxidase is a new,
effective therapy for
severe hyperuricemia
and may obviate
dialysis
Severity Intervention Notes

35.  Relapse rate is up to 50%
 Overall response to chemotherapy is 90%
 Isolated jaw mass (Stage A)
 Completely resected abdominal tumor (Stage AR)
 GOOD PROGNOSIS
 CNS involvement
 Presentation after 13 years of age (adults respond to treatment more
poorly than children)
 Bone marrow involvement
 Tumor burden (large)
 POOR PROGNOSIS
PROGNOSIS

36. THANK YOU