BURKITT’S LYMPHOMA TA OGUNLESI (FWACP).

Presentation on theme: "BURKITT’S LYMPHOMA TA OGUNLESI (FWACP)."— Presentation transcript:

1 BURKITT’S LYMPHOMA TA OGUNLESI (FWACP)

2 Burkitt’s Lymphoma (BL) is a B-cell lymphoma.
BL was discovered by Dennis Burkitt, a British Surgeon who was working in Uganda. It is the commonest childhood malignancy in Africa. Also found in South America, Papua New Guinea and very rarely in UK & US. That is contrary to the pattern in the developed world where Leukaemias are the commonest childhood cancers. TA OGUNLESI (FWACP)

3 EPIDEMIOLOGY OF BL Sex: Commoner among males. M:F = 2:1
Age: 4 to 8 years but peaks at 7 years (Hardly seen < 2yrs) There are 2 types: Endemic & Sporadic Endemic type occurs in a defined part of Africa & SE Asia: 10O-16O North & South of the Equator; Temperature > 16OC & Rainfall > 75cm TA OGUNLESI (FWACP)

4 EPIDEMIOLOGY OF BL This area corresponds with an area of “malaria holoendemicity” in Africa. In Nigeria, BL is prevalent in the West & East where humidity & temperature are high but NOT in the North. Sporadic type occurs in the western world. TA OGUNLESI (FWACP)

5 AETIOLOGY OF BL BL is a neoplasm of B lymphocytes.
3 issues involved in the current concept of African BL: Early Epstein Barr Virus Infection Intense and chronic plasmodium falciparum infestation Chromosomal translocation TA OGUNLESI (FWACP)

6 AETIOLOGY OF BL Early EBV infection causes massive proliferation of B-cells because these cells have C3-d –like receptors for the virus. Anti-EBV antibodies are commonly elevated in pre-BL children. P. falciparum promotes further enhancement of B-cell proliferation by suppressing T-cells. T-cells are needed to eliminate EBV-infected cells. TA OGUNLESI (FWACP)

7 AETIOLOGY OF BL Chromosome 8 contains C-myc gene, an oncogene which regulates cellular proliferation. When the C-myc gene is translocated to Chromosomes 2, 14 or 22, it loses its capacity to regulate cellular proliferation. The final result is uncontrolled excessive proliferation of B-cells. TA OGUNLESI (FWACP)

8 CLINICAL PRESENTATION
GENERAL SYMPTOMATOLOGY Weight loss Anorexia Recurrent Fever Malaise TA OGUNLESI (FWACP)

9 CLINICAL PRESENTATION
Incidence of BL in Africa is 1/10,000 The incidence in Nigeria used to be 55% at UCH, Ibadan Cancer Registry but more recent reports suggest a decline in incidence to 19%. The incidence of the other childhood tumors may be on the increase but BL remains the commonest. TA OGUNLESI (FWACP)

10 CLINICAL PRESENTATION
It is the fastest growing tumor known in man. Doubling rate is ≈ 24 hours (cell loss rate = 70% of cell renewal rate) The interval between onset of symptoms & presentation is usually short: Facial tumor presents within an average of 4 weeks while abdominal tumor takes longer. TA OGUNLESI (FWACP)

11 CLINICAL PRESENTATION
BL commonly affects the face, abdomen and CNS. In the endemic form of BL, facial bones (Maxilla, mandible and orbits) are mostly affected. BL of jaw bone is more common in the younger age group (with the peak at 5 yrs). The abdomen is mostly affected in the sporadic form of BL. It is also commoner in the relatively older population (with the peak at 7 yrs) TA OGUNLESI (FWACP)

12 CLINICAL PRESENTATION
Kidneys & ovaries are the commonest abdominal viscera affected by BL. Liver, spleen and lymph nodes are very rarely involved. CNS involvement may occur either as primary lesion or as relapses. Facial involvement may be associated with tumors at other sites especially abdomen TA OGUNLESI (FWACP)

13 CLINICAL PRESENTATION
FACIAL (50% of cases in Ibadan) Swelling of the affected jaw Loosening of the teeth Proptosis Bleeding & ulceration from the oral cavity Rapidly growing and painless cervical/submandicular lymph nodes TA OGUNLESI (FWACP)

14 JAW BL TA OGUNLESI (FWACP)

15 CLINICAL PRESENTATION
ABDOMINAL (75% of cases in Ibadan) Abdominal distension Palpable, craggy, non-tender masses over the affected areas Ascites Pressure symptoms like intestinal obstruction May present with acute renal failure TA OGUNLESI (FWACP)

16 CLINICAL PRESENTATION
CNS (15% of cases in Ibadan) Peak age is 9 years Single or Multiple Cranial nerve deficits: squints, blindness Paraplegia (spastic or flaccid) Bladder & Bowel dysfunction Neck Stiffness, drowsiness & coma TA OGUNLESI (FWACP)

17 CLINICAL PRESENTATION
No tissue is exempt from tumor involvement BL does not metastasize but may be multifocal in origin Involvement of the Reticulo-endothelial system (peripheral lymph nodes and bone marrow) is commoner in the Sporadic Type but very rare in the Endemic type. It may take the form of: Reactive lymphopoiesis with peripheral lymphocytosis Leukaemia TA OGUNLESI (FWACP)

18 INVESTIGATIONS HISTOLOGY: That is the hallmark of diagnosis
Histology must be done before chemotherapy Finding: Closely packed hyperchromatic monomorphic lymphoid cells interspersed with phagocytic histiocytes. This is described as STARRY SKY appearance (STARS: Histiocytes; SKY: TUMOR CELLS TA OGUNLESI (FWACP)

19 TA OGUNLESI (FWACP)

20 INVESTIGATIONS Starry Sky appearance is NOT pathognomonic of BL.
May also occur in: Lymphocytic lymphoma Hodgkins paragranuloma Stem cell lymphoma TA OGUNLESI (FWACP)

21 INVESTIGATIONS CYTOLOGY
Done on CSF, Ascitic fluid & Fine Needle Tumor Aspirate using any of these method: Phase Contrast Microscopy (examination of tumor cells in the living state) Air Dried Smear (examination of dead & fixed cells) Tumor cells are ROUND CELLS with SCANTY intensely BASOPHILIC CYTOPLASM with large VACUOLES and PROMINENT NUCLEI & NUCLEOLI. TA OGUNLESI (FWACP)

22 TA OGUNLESI (FWACP)

23 INVESTIGATIONS RADIOLOGY
Early bone features include osteolytic lesions manifesting as LOSS OF DENTAL LAMINA DURA (affecting both erupted & unerupted teeth) These are seen even in the absence of clinically obvious jaw mass Abdominal Ultrasonographic Scan Computerized Tomographic Scan Gallium-67 Scintigraphy TA OGUNLESI (FWACP)

24 INVESTIGATIONS Others as necessary include:
CSF analysis: Lymphocytosis and ↓Glucose Serum Electrolytes, Urea & Creatinine Serum Uric acid, Calcium & Phosphate Serum Lactate Dehydrogenase (LDH) – used as a tumor marker to monitor response to treatment & relapse TA OGUNLESI (FWACP)

25 CLINICAL STAGING Several staging methods but most popular is the Ziegler & Magrath (1974) A: Solitary extra-abdominal site B: Multiple extra-abdominal site C: Intra-abdominal ± Facial tumor D: Intra-abdominal ± other sites apart from facial AR: Resected (90%) intra-abdominal tumor TA OGUNLESI (FWACP)

26 DIFFERENTIAL DIAGNOSIS
Abdominal Mass Neuroblastoma Nephroblastoma Abdominal Tuberculosis Orbital Mass Retinoblastoma Acute Lymphoblastic Leukaemia TA OGUNLESI (FWACP)

27 DIFFERENTIAL DIAGNOSIS
Jaw Mass Cellulitis Rhabdomyosarcoma Dental abscess Dentigenous cyst Mandibular osteomyelitis Ossifying Fibroma Ameloblastoma TA OGUNLESI (FWACP)

28 TREATMENT CHEMOTHERAPY Drugs: IV Cyclophosphamide 1000mg/m2 DAY 1
IV Vincristine 1.5mg/m2 DAY 1 IV Methotrexate 37.5mg/m2 DAY 1 Oral Prednisolone 40mg/m2 DAYS 1 to 5 CNS PROPHYLAXIS IT Methotrexate 12.5mg/m2 DAYS 1 & 5 OR Cytosine Arabinoside 30mg/m2 DAYS 1 & 5 TA OGUNLESI (FWACP)

29 TREATMENT The drugs are given in a course.
The courses are repeated every 2 weeks Between 4 and 6 courses are adequate. Combination therapy increases the long-term survival rate from 20% to 50% TA OGUNLESI (FWACP)

30 TREATMENT SURGERY – Only useful in advanced BL.
Mortality can be reduced significantly if surgical resection of at least 80 – 90% tumor bulk is done before chemotherapy RADIATION – Less useful because of toxicity. IMMUNOAUGMENTATION - New BONE MARROW TRANSPLANTATION – New, innovative & experimental TA OGUNLESI (FWACP)

31 PROGNOSIS Good Isolated jaw mass Completely resectable mass Bad
Male sex Intra-abdominal mass Relapse CNS involvement Bone marrow involvement TA OGUNLESI (FWACP)

32 ACUTE TUMOR LYSIS SYNDROME
Acute metabolic emergency in childhood cancers It occurs in rapidly growing solid tumors and leukaemias. It is caused by massive destruction of cancer cells either: Spontaneously due to inadequate blood supply to the tumor Following massive cellular destruction by drugs TA OGUNLESI (FWACP)

33 ACUTE TUMOR LYSIS SYNDROME
The cellular metabolites, particularly, uric acid are released into the circulation The renal excretory system may be overwhelmed by the load of uric acid. This causes renal tubular damage resulting in renal failure and several systemic complications TA OGUNLESI (FWACP)

34 CARDINAL FEATURES OF ATLS
Hyperuricaemia Hyperphosphataemia Hyperkalaemia Hypocalcaemia Metabolic acidosis Hypoglycaemia TA OGUNLESI (FWACP)

35 PRESENTATION OF ATLS Tetany Positive Chvostek’s sign
Cardiac arrhythmias Diaphoresis Seizures Hyperventilation ECG changes (peaked P wave, elevated ST segment) Anuria Fluid retention (Hypertension, CCF) TA OGUNLESI (FWACP)

36 PREVENTION OF ATLS Pre-chemotherapy allopurinol (a Xanthine Oxidase inhibitor) 10mg/kg/day for 48 – 72 hours before commencement of cytotoxics Hyperhydration (3Litres/m2 of 5% Dextrose Saline infusion per day) Diuretics (IV Frusemide 2mg/kg) TA OGUNLESI (FWACP)

37 PREVENTION OF ATLS Uricaise (500 – 1000i.u daily) if serum uric acid remains elevated despite allopurinol use. Alkanization of urine with Sodium Bicarbonate infusion. Specific treatment of electrolyte derangements Dialysis is best used when ATLS is established TA OGUNLESI (FWACP)