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Dr.

Alex Osei-Akoto DCH-CHS, KNUST

Outline
Introduction Epidemiology Aetiology Incidence Clinical features Clinical presentation & Staging Investigation and Diagnosis Treatment & Prognosis Complications

Introduction
Burkitt lymphoma (BL)- a highly aggressive B-cell

neoplasm characterized: translocation and deregulation of the c-myc gene on chromosome 8. Clinical forms: endemic, sporadic, and immunodeficiency-associated. histologically identical and have similar clinical behaviour, differences in epidemiology, clinical presentation, and genetic features

Introduction
Endemic (African) form: jaw or facial bone tumor that

spreads to extranodal sites including the mesentery, ovary, testis, kidney, breast, bone marrow and meninges Nonendemic (Sporadic): usually abdominal presentation, involving the distal ileum, stomach , cecum and/or mesentery, kidney, testis, ovary, breast, bone marrow, or central nervous system. Immunodeficiency-related: more often involve lymph nodes

Introduction
Denis Burkitt -1958

Malignancy of B lymphoctes
Commonest childhood malignancy in

tropical Africa More than half of all tumours in African children Multiple primary foci Can present in a variety of ways

Epidemiology
Burkitts lymphoma belt

10-15 north & south of equator Altitude <1500m Temperature >26.6 C Annual rainfall >50cm Coincides with malaria endemic areas Original Hypothesis Anthropod-borne (possible Mosquito) Virus

Aetiology
Exact cause & mechanisms unknown
Epstein-Barr Virus (EBV): >80% Chn under 5 infected

Immortalized B cell
B cell proliferation Activated c-myc oncogene (Chromosome 8)

Falciparum Malaria

Oncogenes

Chromosomal abnormalities

t(8:14) -80%, t(8:22) -15%, t(2:8) -5%

?Immune deficiency Malnutrition/Poverty

Incidence
Commonest childhood malignancy in Africa

Accounts >55% of all Paediatric tumours Over 90% b/n ages 4 9yrs, peak 4-7(5)yrs 13/100,000 children in Uganda 15/100,000 children(5-9yr) in Nigeria 0-7.6/100,000 pop. in lymphoma. Belt Commoner in rural areas

Cancer cases seen in Kumasi in 2008


NUMBER M F

Burkitts lymphoma
Nephroblastoma ( Wilms) Leukaemia (ALL) Retinoblastoma

78 (40 abd,30 jaw, 8 abd+ jaw)


10 7 3

50
3 5 2

28
7 2 1

Non-Hodgkins lymphoma (NHL)


Total

2
100

1
61

1
39

Cancer Cases seen in Kumasi-2009


NUMBER
Burkitts lymphoma Nephroblastoma (Wilms) Neuroblastoma Leukaemia (ALL) Hodgkin's Lymphoma Retinoblastoma Non-Hodgkins lymphoma (NHL) 57 14 5 5 4 3 2

M
31 10 2 4 3 2 2 2 1

F
26 4 3 1 1 1 0 0 0

Rhabdomyosarcoma 2 Burkitts leukaemia 1

Cancer cases seen in Kumasi in 2010


Diagnosis Total No. Remission On Treatment Defaulters Deaths Burkitts Lymphoma Nephroblastoma (Wilms) Rhabdomyosarcoma Hodgkins Lymphoma ALL Neuroblastomas Non-Hodgkins TOTAL

72 12 3 2

11 2 -

46 9 3 2

3 -

12 1 -

3
4 2 98

2
15

Maintenance
2 2 64

1
2 16

Clinical features
Short Hx b/n S/S onset & presentation

Fastest growing tumour

Doubling time of 24 hrs 2-16 years Peak 4-7 years

Uncommon < 1 yr Rare below 2yrs (1%) & > 20yrs <10% of cases are >15years

Male : Female = 2:1

Clinical features
80 70 60 50 40 30 20 10 0 1 4 7 10 13 16 19 22 25 Age distribution in 480 BL patients upto 25yrs (Uganda)

Age distribution of Burkitts cases 2000-2007


Overall Age Distribution of Patients
20 15

Percent

10

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Age (years)

Age and Gender distribution


*

Sites of Burkitts Tumour


Usually multifocal, involvement of 1 of the

following sites Facial Abdominal viscera CNS Thyroid, Distal long bones, Skin, Breast, Kidney, Testes/Ovaries, Parotid glands Rarely: Bone Marrow, Lymph nodes, lungs, Mediastenum, Liver, Spleen

Common sites of primary tumour Kumasi 2000-2007

Sites of Burkitts cases in Kumasi 2009


Site Abdominal Jaw Combined Abdominal +Jaw Testes Armpit Number 25 21 5 2 2

Neck
Leg Total

1
1 57

Site of primary tumour and Gender

Clinical Features
Burkitt classically

described: Large extranodal tumours affecting

jaw bones (maxilla & mandible) and abd. viscera

Clinical Presentation
Often in good general health

until disease is well advanced Weight loss Anorexia Fever Malaise

Jaw swelling (75%) Abdominal swelling (60%) CNS involvement (30%)

Clinical presentation
Facial Tumours

Younger, peak 5yr Progressive Painless jaw swelling ( 1) Maxilla > Mandible Proptosis 2 orbital involvement(Maxilla)

Clinical presentation
Facial Tumour Oral extension Loose teeth Misaligned teeth

Maxillary Tumour with Orbital extension-Proptosis


Before Treatment

After Treatment

Maxillary Tumour with orbital extension


Before Treatment

After Treatment

Clinical presentation
Abd. Tumours Older children Peak age -7yr Progressive abd. swelling Non-tender, hard, craggy abd. Mass

Ascites, variable Any abdominal organ

Abdominal Burkitts
Before Treatment

After Treatment

Clinical presentation

Multiple SitesJaw + Abdomen

Clinical presentation
CNS Site of initial involvement/relapse Peak age 9yrs Cranial nerve palsy Paraplegia(-paresis) Sphincter dysfunction Pseudo-meningitis/coma CSF pleocytosis

Clinical presentation
Other sites Testes /Ovaries Thyroid

Subcutaneous tumour

Cardiac
Breast Long bones BM; LN; liver; Spleen

Investigation 1
Histology starry sky-immature lymphocytes + macrophage Cytology Radiology X-ray (jaw, CXR, others); USG; CT; Radioisotope Blood FBC:- may be normal, or Hb; WBC; Plt Renal function Uric acid, LDH Na; K; Cl; PO4; Ca

Investigation 2
Bone marrow aspiration and biopsy R/O

unexpected bone marrow involvement Lumbar puncture is necessary for evaluation of CNS involvement. Abd. Paracentesis or thoracentesis for cytogenetic studies if ascites or pleural effusion is present

Diagnosis & Investigations


Clinical Presentation Histology (Hallmark of Diagnosis) Incisional biopsy Starry Sky appearance (*Not pathognomic) Cytology Quicker and easier FNA, Ascitic fluid, CSF Radiological investigations Loss of lamina dura/ Osteolysis/ Malalignment Blood investigations

Starry-sky appearance
Sheets of uniform monotonous cells

-with round to oval nuclei with multiple nucleoli (2-5) -abundant division figures (frequent mitotic figures) - cytoplasm is moderate and basophilic, with small vacuoles (monomorphic, medium-sized cells with round nuclei, multiple nucleoli, and basophilic cytoplasm) Diffuse scattering of phagocytic macrophages with retracted cytoplasm among the tumour cells

Clinical Staging (Ziegler & Magrath 1974)

Stage

Criteria

A Solitary extra abdominal site AR Resected ( 90%) intra-abd. tumour B Multiple extra-abdominal sites C Intra-abd. tumour facial tumour D Intra-abd. tumour with sites other than facial

Clinical Staging (NCI)


Stage Definition I Dx limited to one anatomical area II a. Dx limited to two contiguous areas - b. Dx in 2 or more non-adjacent areas, but on same side of diaphragm III a. Dx involves structures on both sides of diaphragm b. Dx involves structures on both sides of diaphragm + spread of cells to BM or blood stream IV - Dx involves CNS

Differential Diagnosis
BL is greater imitator of other pathology Jaw swelling Rhabdomyosarcoma Dental abscess Dentiginous cyst Ossifying fibroma Osteomyelitis Osteogenic sarcoma Maxilla tumour Fibrous dysplasia

Differential Diagnosis

Orbital involvement Retinoblastoma / Neuroblastoma ALL / Rhabdomyosarcoma Abdominal swelling Nephroblastoma Neuroblastoma Abdominal MTB Non Burkitt, Non Hodgkins Lymphoma

Treatment
Supportive treatment (very important)

Treat/ Prevent Tumour Lysis Syndrome Blood and blood products Treat infection vigorously Symptomatic Nutritional support Psychological support

Treatment
Chemotherapy Mainstay of treatment (CTX; VCR; MTX; Pred) Surgery Excision biopsy; tumour debulking; laminectomy Radiation therapy (Not very useful) Radiosensitive, but rapid growth b/n therapy Superfractional therapy (days dose 3 @ q4h Toxicity with BM aplasia Used as last resort e.g. CNS relapse not responsive to drugs Immunoaugmentation therapy

Treatment
High relapse rate with single agent (CTX) COMP
Cyclophosphamide + vincristine (Oncovin) +

Methotrexate + Prednisone CHOP Cyclophosphamide + vincristine (Oncovin) + Doxorubicin + Prednisone CHOP plus methotrexate Cyclophosphamide + vincristine (Oncovin) + Doxorubicin + Prednisone + Methotrexate

Prognosis
Good Prognosis
Isolated jaw mass (i.e. stage A) 90% resected abdominal tumour (i.e. stage AR)

Poor Prognosis
CNS involvement
Male sex (sanctuary site testis) Bone Marrow involvement

Intra-abd.
Prognosis depends on extent & tumour size at

presentation

Prognosis
90% response with chemotherapy
80% complete response
10% partial response

50% relapse
Early relapse (<3mths) do poorly Relapse >3mths respond well, on initial chemo.

Up to 30% of CNS cases can be salvaged


Prophylactic IT MTX to prevent CNS relapse

Complications
Acute Tumour Lysis Syndrome Spinal Cord Compression Complication of cytotoxic therapy Nausea, anorexia and vomiting Alopecia, reversible Bone marrow suppression Neutropenic fever / sepsis Haemorrhagic cystitis 2 Cyclophosphamide Azoospermia, testicular atrophy, amennorrhea Extravasation e.g. 2 Vincristine Mucositis

Summary
Commonest childhood malignancy in Ghana Rapid onset (Fast growing tumour)

24hr tumour Doubling time Multiple primary foci Facial / Abdominal / CNS etc Diagnosis Histology or Cytology Chemotherapy main therapy Combination therapy with CTX Treat / Prevent Tumour Lysis Syndrome

Thank you