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.
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
6.
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
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
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
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
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