Burkitt Lymphoma.pptx for Guu

BURKITT
LYMPHOMA
DR(MRS) MILDRED OLUCHI IZUKA (MBBCh, FWACP, FMCPaed)
CONSULTANT PAEDIATRICIAN / Dep.HOD
DEPARTMENT OF PAEDIATRICS
FEDERAL MEDICAL CENTRE UMUAHIA / COLLEGE OF HEALTH SCIENCES GREGORY
UNIVERSITY UTURU
BURKITT LYMPHOMA
OUTLINE
• Introduction
• Epidemiology
• Pathophysiology
• Clinical features
• Staging
• Diagnosis
• Differential diagnosis
• Treatment
• Complications
• Prognosis
• conclusion
BURKITT LYMPHOMA
• First described by Denis Burkitt in Uganda 5 decades ago.
• The most common childhood malignancy, accounting for
more than half of all malignant tumors in tropical Africa.
• Has an incidence rate of 1:10,000 children.
• The ‘lymphoma’ belt extends b/w 10*N-15*S of the equator
with altitude not above 1500m, annual rainfall >50cm, with
ambient temperature not below 26.6*c.
• Age range at presentation is 4-14yrs with peak at 7yrs.
• M:F ratio is 2:1
• Commonest in people of low socioeconomic class.
• In Nigeria, it is common in the eastern and western regions
where humidity and temperatures are high.
• It is uncommon in the North
AETIOPATHOGENESIS
• BL is a neoplasm of B-cell xterized by the presence of

immunoglobulin and other B-cell markers on the cell surface.
• Current hypothesis on the aetiology of BL include:
 Early EBV infection
 Intense and chronic P. falciparum infestation.
 Chromosomal translocation; t(8;14), t(8;2) and t(8;22).
TYPES (CLINICAL VARIANT)
• Endemic (African Burkitt), seen in equitorial

Africa.
• Sporadic, seen in North America and Western
Europe.
• Immunodeficiency-associated BL, occurs
commonly in patients with HIV infection.
TYPES
characteristics Endemic BL Sporadic BL HIV associated BL
Epidemiology Median age 7yrs. Median age 30 yrs. Median age 10-
Equatorial region 19yrs.
HIV risk group
Associated with
malaria/climate
Clinical Facial (50%) Abdominal, ileo- Nodal and
presentation caecal (80%) extranodal mostly
abdomen
CNS (33%) Bone marrow (20%)
Other organs also Other organs also
affected affected
Geographic regions Equatorial Africa, N. America, N and E Endemic HIV areas
Papua New Guinea Europe and far East in Africa
EBV association 100% 30% 30-50%
PATHOPHYSIOLOGY
• The exact cause and pathophysiologic
mechanisms leading to the development of
Burkitt lymphoma are not known.
• However, Epstein-Barr virus (EBV) and malaria
infection as well as C-myc oncogene activation
are implicated
EBV:
• EBV is a member of the herpesvirus family that
has been strongly implicated in the endemic
form of Burkitt lymphoma (eBL).
PATHOPHYSIOLOGY
MALARIA:
• P. faciparum targets GC B cells via multiple pathways and
induces Activation-induced cytidine deaminase (AID).
• Deregulated expression of AID causes a c-myc translocation in
a cell latently infected with EBV.
PATHOPHYSIOLOGY
C-MYC ONCOGENE ACTIVATION
• The classic t(8;14)(q24;q32) reciprocal
translocation (85% of cases) results in the
transposition of the c-myc proto-oncogene on
chromosome 8 with one of the
immunoglobulin heavy chain genes on
chromosome 14, which results in activation of
the c-myc gene and is considered responsible
for tumor proliferation.
• Translocation t(8;14) is the most common,
present in 80% of Burkitt lymphoma cases.
PATHOPHYSIOLOGY
• In all the other cases, c-myc has been

translocated close to one of the
immunoglobulin light chain genes on
chromosome 2 (kappa light chain) [t(8;2)] or
22 (lambda light chain) [t(8;22)].
• Overproduction of the c-myc product may
change the lymphocytes into cancer cells, but
other gene mutations may be responsible for
the progression of Burkitt lymphoma.
CLINICAL FEATURES
• BL is the fastest growing tumor known in man with a potential
doubling time of 24hrs and cell loss rate of 70% of the cell
renewal rate.
• Interval b/w onset of symptoms and presentation is usually
short.
• 3 main sites commonly affected are abdomen, (mainly the
kidneys, ovaries and retroperitoneal structures), face, mainly
the jaw bones, and the spinal column.
• Occasional sites of involvement are thyroid gland, distal long
bones, skin, breasts, testes and parotid gland, vulva.
• Very rare areas are BM, L/Ns, lungs, mediastinum, liver, and
spleen.
CLINICAL FEATURES
 Facial tumors:
• Seen in younger age group, peak age 5yrs.
• Progressive painless swelling of jaw in one or more quadrants of the face.
• There is oral extension and soft tissue involvement of cheek and gum.
• Loose or malaligned teeth.
• Proptosis bcos maxillary tumors often spread upwards to involve the orbit.
 Abdominal tumor:
• Seen in older children, peak age 7yrs.
• Progressive abdominal swelling, pain.
• Sign include non tender , hard, craggy abdominal mass, ascites.
CLINICAL FEATURES
 CNS tumor:
• Common as a site of relapse.
• Peak age is 9yrs.
• Present with cranial nerve deficit e.g squints, blindness,
paraplegia/flaccid paralysis due to cord compression or
vascular compromise, bowel/bladder dysfunction, neck
stiffness, drowsiness, and coma.
• Testes and thyroid gland are tumor sanctuary sites.
CLINICAL STAGING
Zeigler & Magreth staging
STAGE TUMOUR 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 plus 1 or more extra-abdominal site
AR Intra-abdominal, more than 90% of tumor resected

CLINICAL STAGING
Ann Arbor system and St. Jude/Murphy staging
Stage I Single tumor (extranodal).

Single anatomic area (nodal).
Stage II Single tumor (extranodal) with regional node involvement.
Primary gastrointestinal tumor.
Lymphoma involving nodal areas on the same side of the
diaphragm.
Stage IIR Completely resected intra-abdominal disease.
Stage III Lymphoma involving sites on opposite sides of the diaphragm.

All primary intrathoracic tumors.
All paraspinal or epidural tumors.
Extensive intra-abdominal disease.
Stage IV Any of the above, with central nervous system (CNS) or bone
marrow involvement (< 25%) at presentation
INVESTIGATIONS
• Histology
• This is the hallmark of diagnosis
• An incision biopsy of tissue is taken and analyzed which reveals the
typical starry-sky appearance under low power.
• Cytology
• A. Air Dried Smear
• Ascitic fluid ,CSF or FNA can be used, stained with Romanowsky dye
which reveals the typical Burkitt cells.
TISSUE BIOPSY HISTOLOGY
TISSUE BIOPSY CYTOLOGY
• 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
INVESTIGATION
• B. Phase contrast microscopy i.e examination of tumor cells in living state:
• Cells appear as non coherent spherical and dark opaque , motile cells of 8-
12 microns in diameter.
• Radiological Investigations
• X-ray of the Jaw (lateral oblique view): shows loss of dental lamina dura,
dental malalignment and osteolytic lesion of bone.
• CSF Cytology
• Abdominal Ultrasound
• CT Scan
LAMINA DURA
LAMINA DURA
INVESTIGATION
• Gallium-67 scintigraphy, concentrates preferentially in tumor
sites. It is the most sensitive investigation.
• Others where necessary include
• CXR
• IVU
• Myelography in CNS involvement
INVESTIGATIONS
• FBC
• Serum electrolyte, urea, calcium, phosphate, creatinine and
uric acid
• Serum lactate dehydrogenase
• LFT
TREATMENT
• Chemotherapy:
• This is the main stay of treatment, Combination chemotherapy is
preferred . At least 6 cycles should be given.
• The modified Ziegler’s Regimen is commonly used which
employs CO(M/Cy)P.
• CNS Prophylaxis is with either intrathecal Methothrexate or
intrathecal Cytosine arabinoside.
• For CNS Burkitt : triple IT therapy using M, Cy and
Hydrocortisone
POST FIRST COURSE
TREATMENT
• Surgery
• Useful for debulking the tumour
• Radiation Therapy use of super fractionated radiotherapy

may be the last resort e.g in CNS relapse unresponsive to drugs
.
• Immune-augumentatation Therapy uses monoclonal
antibodies as adjuvant to chemotherapy and surgery
COMPLICATION
TUMOUR LYSIS SYNDROME
 Metabolic triad
- Hyperuricaemia
- Hyperkalaemia
- Hyperphosphataemia
 Secondary complication
- Renal failure
- Hypocalcaemia
PROGNOSIS
• Prognosis is good for stage A and AR
• For intra-abdominal tumors prognosis depends on the extent
and size of the tumor at presentation.
• Prognosis is poor in CNS and bone-marrow involvement
• Presentation above 13 yrs of age confers poor prognosis
• Male sex confers poorer prognosis
• Relapse rate is up to 50%
• Relapse shortly after remission has a poorer prognosis
SIDE EFFECT OF SOME AGENTS
• Cyclophosphamide, sterility, hemorrhagic cystitis, emesis, reversible alopecia BM
suppression, increased risk of acute non lymphocytic leukemia
• Adriamycin, severe local tissue necrosis, mucositis, cardiac toxicity and
cardiomyopathy
• Vincristine, peripheral and autonomic neuropathy, motor weakness
• Procarbazine, hypersensitivity rash, disulfiram-like effect
• Etoposide, alopecia, myelosuppression, nausea and vomiting
• Bleomycin, increased pigmentation of skin and subcut sclerotic plaques, mucositis,
progressive pulmonary fibrosis and respiratory failure during anesthesia, fever, chills
• Prednisolone, wt gain gastritis, fluid retention, striae, hypertension, cushingoid
features
PREVENTION
General health Hand washing, use of ITN, clean environment
promotion
Specific protection
Early diagnosis and Prompt diagnosis through FNAC, Histology, CSF cytology, USS
prompt treatment and commencement of appropriate treatment
(Chemotherapy)
Limitation of Prevention of Tumour lysis syndrome – Rasburicase,

disability Allopurinol and hyperhydration
Rehabilitation limb prostheses; physiotherapy , psychotherapy; Support

groups, Renal replacement therapy
THANK YOU!!!
SUGGESTED READINGS
Nelson textbook of Paediatrics, 19TH & 20TH edition.
Paediatrics and child health in a tropical region, 3rd edition
Paediatric Heamatology and Oncology (Oxford Specialist
Handbooks in Paediatrics)
https://emedicine.medscape.com/
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BURKITT

• BL is a neoplasm of B-cell xterized by the presence of

• Endemic (African Burkitt), seen in equitorial

• In all the other cases, c-myc has been

STAGE TUMOUR SITE

B Multiple extra-abdominal site, e.g. facial tumor in > 1

D Intra-abdominal plus 1 or more extra-abdominal site

AR Intra-abdominal, more than 90% of tumor resected

Stage I Single tumor (extranodal).

Stage III Lymphoma involving sites on opposite sides of the diaphragm.

• They are small round cells with intensely basophilic

• Radiation Therapy use of super fractionated radiotherapy

Limitation of Prevention of Tumour lysis syndrome – Rasburicase,

Rehabilitation limb prostheses; physiotherapy , psychotherapy; Support

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