BURKITT

LYMPHOMA

MEDICAL STUDENTS
BATCH B
GROUP 1
PRESENTATION
1
A TYPICAL CLINICAL CASE
PRESENTATION
 In February 2020, an asymptomatic 5-year-old boy underwent a pediatric examination for a left
 submandibular swelling that gradually increased in size, with a hard-elastic consistency and was not
 painful on palpation. Blood tests, prescribed by the pediatrician and performed in a private medical
 center, were normal: the blood count with the leukocyte formula and the inflammation indexes such as
 ESR and PCR were not altered, LDH was normal and anti-CMV IgM were negative, anti-EBV VCA and
 anti-toxoplasma IgM. The child underwent an ultrasound of the neck which showed numerous lymph
 nodes increased in size in the left submandibular site; The pediatrician prescribed amoxicillin / clavulanic acid
 therapy for six days and despite taking antibiotics, the swelling had increased in size. In March the boy
 came to our hospital for further diagnostic information; he repeated the blood tests, which were normal,
 and underwent an ultrasound of the cervical, axillary and inguinal lymph nodes, testicles and complete
 abdomen. The ultrasound of the neck showed in the left submandibular seat a coarse lymph node of the
 size of 38x30 mm, with a markedly and unevenly hypoechoic echostructure and anarchic
 vascularization at the colour doppler.
TABLE OF CONTENT
 BACKGROUND
 INTRODUCTION
 EPIDEMIOLOGY
 PATHOGENESIS
 MALARIA ASSOCIATED AND AIDS ASSOCIATED LYMPHOMA
 INCIDENCE
 CCLINICAL FEATURES
 DIAGNOSIS
 STAGING
 DIFFERENTIAL DIAGNOSIS
 TREARMENT
 PROGNOSIS
 REFERENCES
Burkitt lymphoma

4
 Burkitt’s Lymphoma: Background
• Burkitt's lymphoma (BL) is a tumor which was
first described in 1958 by Denis Burkitt, a
surgeon working in Africa.
• It is a solid tumor of B lymphocytes which
form part of the white cell population in the
blood and lymph glands.
• It is one form of non-Hodgkin's lymphoma. The
type of cell affected in Burkitt's lymphoma is the
B lymphocyte which is normally involved in
fighting infection by producing antibodies.
 Endemic Burkitt lymphoma(BL) is the
most common childhood cancer in Africa
.

 The first description of Burkitt lymphoma

(BL) was probably that of Albert Cook,
the first missionary doctor in Uganda, who
founded Mengo Hospital and subsequently
Mulago Hospital, initially a centre for the
treatment of tuberculosis, which eventually
became the University Hospital of
Makerere University.
6
INTRODUCTION
 One of Cook’s patients was a child with a large
jaw tumour, and his illustration of the
appearance in his meticulous notes leaves little
doubt that this was a case of BL.

 In the first half of the 20th century, a number of

European pathologists working in equatorial
Africa noted the high frequency of jaw tumours or
of lymphomas in children (Smith & Elmes, 1934;
Davies, 1948; De Smet, 1956; Edington, 1956;
Thijs, 1957).
7
INTRODUCTION
 But it was Denis Burkitt who
provided the first detailed clinical
description of the tumour in 1958
while working at Mulago
Hospital (Burkitt, 1958).
 He recognized a number of
different clinical presentations of
tumours in children, including
jaw tumours and intra-
abdominal tumours, that could
occur either alone or together,
and it was this that led him to
believe that many, if not all
8
these
 Denis Parsons Burkitt
 Born 1911, Ireland; Died 1993
 Lost his right eye at the age of 11 in
an accident.
 Trained as a surgeon in Trinity
College, Dublin.
 Went to East Africa (Kenya,
Somaliland, then Uganda) in World
War II. Joined the colonial service in
Uganda in 1946 as GP in Lira, then
became a surgeon in Mulago
Hospital, Kampala.

 Saw his first case of jaw tumor in a

boy of 5 in the children’s ward in
1957, then a second a few weeks
later. Surgery not possible: both
children died soon after. 9
Recognition of Burkitt Lymphoma
1934-57:
1910: Descriptions of Jaw
Albert Cooke Tumors and High Frequency
Describes Jaw Tumor in of Lymphomas in African
Mengo Hospital. Children.
1958
Denis Burkitt
Describes a
Clinical Syndrome..

O’Connor 1960- Burkitt 1962:

61: Lymphoma. 10 Climatic
Milestones in endemic burkitt lymphoma
[bl] research

Endemic Burkitt's lymphoma: a polymicrobial disease?

Rosemary Rochford, Martin J. Cannon & Ann M. Moormann
Nature Reviews Microbiology 3, 182-187 (February 2005)
Epidemiology and Pathogenesis
of Burkitt Lymphoma

12
Epidemiology: clues to the pathogenesis of Burkitt
lymphoma
 The two major epidemiological clues to the
pathogenesis of Burkitt lymphoma (BL) are:
 1. the geographical association with malaria –
BL incidence relates to the malaria
transmission rate – and:
 2. early infection by Epstein–Barr virus
(EBV).
 Both agents cause B cell hyperplasia, which is
almost certainly an essential component of
lymphomagenesis in BL.
 Epidemiology: clues to the pathogenesis of Burkitt
lymphoma [contd.]

 The critical event in lymphomagenesis is the creation of a

MYC translocation, bringing the MYC gene into
juxtaposition with immunoglobulin genes and causing its
ectopic expression, thereby driving the proliferation of BL
cells.
 It is highly likely that such translocations are mediated by the
activation-induced cytidine deaminase (AID) gene, which is
responsible for hypervariable region mutations as well as
class switching. Stimulation of the Toll-like receptor 9 by
malaria-associated agonists induces AID, providing a
mechanism whereby malaria could directly influence BL
pathogenesis.
 Epidemiology: clues to the pathogenesis of
Burkitt lymphoma [contd.]

 EBV-containing cells must reach the memory cell compartment

in order to survive throughout the life of the individual, which
probably requires traversal of the germinal centre. Normally,
cells that do not produce high affinity antibodies do not survive
this passage, and are induced to undergo apoptosis.
 EBV, however, prevents this, and in doing so may also enhance
the likelihood of survival of rare translocation-containing cells.
 In 1964, the Epstein-Barr virus [EBV] was
recognized in electron micrographs of BL-cells.
 This led to the finding that BL-patients had high
antibody titres to EBV antigens.
 Apart from this, it was shown that over 80% of
tumors contain multiple copies of EBV-DNA
genome.
 It is also established that over 80% of African
children under 5 years of age were infected with
EBV whilst studies in Ugandan children
demonstrated that those who had high EBV
antibodies subsequently developed BL.
 All this evidence pointed to EBV as a possible
caustive agent. 16
Endemic BL & endemic malaria
Malaria Association with BL
 1964: Dalldorf suggests climatic distribution could
relate to holoendemic malaria.
 Geographic distribution of malaria and BL very
similar (NB. Zanzibar – formerly free of both).
 BL has higher incidence in regions of intense
malarial infection (some exceptions).
 De Thé: chloroquine prophylaxis in Mara Masai
region: decrease (?) in incidence of BL
 Sickle cell trait protects against malaria trend to
protection against BL, but insufficient data.

18
Malaria Association with BL [contd.]
 The so-called lymphoma
belt (black) extending across
equatorial Africa.
 It extends approximately 100
–150 north and south of the
equator with a prolongation
to the south on the east coast.
 Altitude is usually not above
1500 meters.
 Annual rainfall is not less
than 50cm.
 Ambient temperatures not
below 26.6 0C.
19
Malaria Association with BL
[contd.]

Chloroquine prophylaxis was

given in the middle period.

20
Malaria: Possible Pathogenetic Mechanisms
 Malariahas also been postulated as a co-factor, by
priming the lymphatic system for a causative agent.

 Malariacould promote BL in various ways, but

probably acts primarily through its ability to
increase the fraction of cells infected by EBV. It
could also alter the cell types infected by EBV – e.g.,
permit infection of immature cells

 Themalarial attack is said to activate polyclonal

B-cells.Polyclonal not monoclonal

21
 Malaria: Possible Pathogenetic
Mechanisms [contd.]
 Advances in cytogenics have thrown more light on the
pathogenesis of BL.
 C-MYC, an oncogene located on the long arm of
chromosome 8, has been observed to be translocated to
the genetic loci on chromosome 14, 2 or 22 that code for
immunoglobulins.
 Uncontrolled proliferation of B-lymphocytes results,
probably representing the critical step in the oncogenesis
of BL.
 The fact that the tumour can arise wherever B-
lymphocytes are found in the body probably explains
that varied presenting sites and clinical features.

22
Evidence for Importance of Deregulated Myc
 Myc not expressed in normal germinal follicle
cells
 Multiple types of translocation (8;14, 2;8 and
8;22 as well as (rarely) non-Ig translocations
are associated with major structural changes or
mutations (regulatory region or coding region)
in Myc.
 Myc translocations also present in B cell
neoplasms in mice and rats.

23
 Burkitt’s Lymphoma -
Karyotype:

* Here is an actual karyotype (courtesy of Janet Finan and C. M.

Croce) of a cell from the tumor of a patient with Burkitt's
lymphoma. The long (q) arm of the resulting chromosome 8 is
shorter (8q-) than its normal homologue; the long arm of
Burkitt’s Lymphoma -
* In most (approximately
90%) of the cases of
Burkitt's lymphoma, a
reciprocal
translocation has
moved the proto-
oncogene c-myc from
its normal position on
chromosome 8 to a
location close to the
enhancers of the
antibody heavy chain
genes on chromosome
AIDS-associated Burkitt lymphoma
 Ziegler et al (1984) described the increased incidence of
NHLs in homosexual males and subsequently, the
association of BL with HIV seropositivity was reported
(Wiggill et al, 2011).
 Since then, the relationship between NHL and HIV
infection has been confirmed in many parts of the world,
including, for example, South Africa.
 It remains uncertain, however, how much HIV infection
predisposes to BL in equatorial Africa. In fact, the
relationship is tenuous at best, at least in children as,
although a few percent of children with BL are HIV
positive, this is similar to the frequency of HIV infection in
children in the normal population.
26
 AIDS-associated Burkitt lymphoma
[contd.]
 Similarly, although HIV infection is more prevalent in adults, the
degree to which it predisposes to adult BL in equatorial Africa is
uncertain (Parkin et al, 2000; Mutalima et al, 2010).
 HIV is known to alter the immune response to malaria, resulting
in increased prevalence and severity of clinical malaria (Flateau et
al, 2011), and this could, in turn, result in an increased
predisposition to BL. HIV infection also causes B-cell
hyperplasia, and, like malaria, increases the proportion of
circulating EBV-containing cells, resulting from the reactivation
of EBV infection, thus increasing the EBV load in HIV-infected
individuals (Bonnet et al, 2006; Richard et al, 2010). However,
the memory B cell population is reduced in HIV infection, and
other B cells may become the primary EBV reservoir (Richard et
al, 2010).

27
AIDS-associated Burkitt lymphoma
[contd.]
 Thus, even though HIV+ individuals have a higher
EBV load than HIV) persons, the lack of an obvious
connection between HIV infection and predisposition
to BL, at least in children, may be indicative of
differences in the pathogenesis of HIV+ and HIV) BL
in Africa that have yet to be determined.

28
 Burkitt’s Lymphoma: Incidence
 The incidence of Burkitt's lymphoma [BL] shows
great geographical variation.

 It is the most common childhood tumor in

equatorial Africa but is very rare in children in
Western countries.
 BL accounts for over half of all malignant
tumours in tropical Africa.
 Over 90% of patients present between the ages of
4 and 9 years.
 Peak age being 5 years.
 Age distribution of Burkitt lymphoma in
Africa (a) and the United States (b).

Jaw and orbital tumours are particularly common in young

children in African Burkitt lymphoma (fraction of patients with
jaw tumours is indicated by the red column in (a)) but not in
30
Burkitt lymphoma in the United States.
 Burkitt’s Lymphoma: Incidence [contd.]
 No cases have been reported under one year of
age.

 Rarely cases have been reported above 20 years.

 Males are twice more likely to suffer from this

disorder as opposed to females.
 MALES
 Recently Burkitt's lymphoma has been diagnosed
in around 2% of AIDS patients.
Clinical Features of Burkitt
Lymphoma

32
 Clinical Features of Burkitt Lymphoma
1. The jaw * is the
part of the body
most affected,
often presenting as
a swelling in 75 %
of patients, with
the maxilla being
more affected than
the mandible.
Clinical Features of Burkitt Lymphoma
[contd].
Note:
* In African [endemic] Burkitt's lymphoma the
jaw is the commonest site where it causes
visible swelling of the cheek and loosening of
the teeth.

* In non-African Burkitt’s lymphoma the

tumor commonly arises in the abdomen
where it causes swelling and discomfort.
 Clinical Features of Burkitt Lymphoma
[contd].

2. The maxillary
tumor often
spreads to
involve the orbit,
causing
exophthalmos.
The swelling is
often painless.
 Clinical Features of Burkitt Lymphoma
[contd].
 3. Early in the
course of the
illness, looseness
of the teeth may
occur, with
gingival swelling
[which on a
radiograph of the
jaw may show
loss of lamina
dura].-peri apical
luscency
 Clinical Features of Burkitt Lymphoma
[contd].
 4. Abdominal
masses involving
the ovaries,
kidneys,
mesenteric nodes
and peritoneum
are also
encountered.
 Clinical Features of Burkitt Lymphoma
[contd].
 5. Patients may also present with paraplegia,
which indicates involvement of the CNS,
secondary to damage to the vertebral body.

 6. BL is one of the commonest causes of

paraplegia in the African child.Tryto r/o Tb
spine

 7. Abnormal CSF cytology or cranial nerve

palsy may be the only evidence of CNS
involvement.
 Clinical Features of Burkitt Lymphoma
[contd].
 8. Other organs occasionally involved include
the breast, thyroid and testis.
 Clinical Features of Burkitt Lymphoma
[contd].
 9. An unusual feature of BL is presentation as
leukemia.
 This is considered a pre-terminal event and is
seen in patients with extensive tumour burden
and in cases of relapse.
 Bone marrow infiltration can occur in 15-20% of
patients.
Diagnosis of Burkitt Lymphoma

41
 Burkitt’s Lymphoma –
Diagnosis
 *A rapidly growing tumor of the jaws or
abdomen should raise the suspicion of a BL.
* Loose teeth and involvement of other organs
should strengthen this suspicion.
• The rate of growth of the tumour is so rapid that

the patient can present within one or two

weeks of the onset.
• A longer history makes the suspicion less.
 Burkitt’s Lymphoma –
Diagnosis
 * Burkitt's lymphoma is diagnosed from a biopsy sample
of the tumor. A small piece of the tumor is removed by
surgery and the sample, stained by specific dyes, is
examined under the microscope by a pathologist.

 * Burkitt's lymphoma can be differentiated from other

tumors by the distinctive pattern of tumor cells which is
known as a “starry-sky” pattern.

 * It is possible to use specialized laboratory techniques to

determine the presence of EBV in the tumor cells.
Burkitt’s Lymphoma –
Diagnosis … cont’d
* Biopsies of
Burkitt’s
Lymphoma
patients show
a ‘starry sky’
pattern like the
one seen to the
left.
The tumor cells

 A diagnosis can be confirmed by biopsy and

histology.

 Histologically, BL in the African child is the

same as in the sporadic cases elsewhere.

 BL [high-grade, small non-cleaved cell

lyphoma as per the Working Formulation]
being a malignancy of B-cell origin,
characteristically bears surface
immunoglobulin.
 The description of the tumor cells
 The tumour consists of sheets of
fairly uniform rather monotonous
cells of about 10-25 um in
diameter.

 The nuclei are round to oval, and

contain multiple [2-5] prominent
nucleoli.

 The cytoplasm is moderate, lightly

basophilic or amphophilic, and is
intensely pyrinophilic; i.e., it
stains intensely with methly green
pyronine.
“starry sky” appearance
 Scattered diffusely
amongst the tumour
cells are benign
phagocytic
macrophages with
retracted cytoplasm,
thereby creating empty
spaces between the
cells and the adjacent
tissue.
 This striking feature
creates the
About the “starry sky” appearance.....

 This “starry sky” appearance is not

pathognomonic for BL, as it is seen in other
rapidly dividing lymphoreticular malignancies.
 Burkitt’s Lymphoma – Diagnosis [contd.]
 Other investigations include:
 Plain radiographs of affected bones.

 Intravenous urograms [IVU].

 Intra- or extra-medullary tumours of the spinal column

can be diagnosed with myelograms.

 CT scans can be of immense help in CNS involvement.

 Bone marrow infiltration can occur in 15-20% of patients

and makes bone marrow aspiration with histology and

peripheral blood smears necessary.
 CSF cytology at 1st visit [since > 50% of patients may

have CNS involvement at some time in the course of the

disease].
 Staging of Burkitt Lymphoma

 Staging: This is a description of the extent of tumor

spread in the body and is useful in determining the
form of treatment and outcome.
 It should therefore be carried out as early as
possible.
 Two methods can be used. 50
Staging of Burkitt Lymphoma: [method 1]
Stage Definition
I. Disease limited to one anatomical area
II. a. Disease limited to two contiguous areas
b. Disease present in two or more non-adjacent areas,
but on the same side of the diaphragm.
III. a. Disease involves structures on both sides of the
diaphragm
b. Disease involves structures on both sides of the
diaphragm, but also with presence of tumour cells
in the bone marrow or blood stream.
IV. Disease involves the CNS
Staging of Burkitt Lymphoma: [method 2]

 Method 2: For a simple evaluation, patients can be divided into

two groups:

 Those with small tumour burdens [stages A,B,AR].

 Those with large tumour burden [stages C and D].

Staging of Burkitt Lymphoma: [method 2]
Stage Definition
A. A single Extra-abdominal tumour site
B. Multiple Extra-abdominal tumour site
AR. Completely [> 90%] resected Intra-abdominal
tumour
C. Intra-abdominal tumour without involvement of
other sites
D. Intra-abdominal and Extra-abdominal tumour sites.
Differential Diagnosis of Burkitt
Lymphoma

54
Differential Diagnosis of Burkitt Lymphoma
 A. [In cases of jaw swelling]: dental cysts;
osteomyelitis of the jaw bones.
 B. [In orbital swelling]: advanced
retinoblastoma; metastatic neuroblastoma;
rhabdomyosarcoma.
 C. [In ovarian tumours]: neuro-abdominal
swelling.
 D. Tuberculosis of the spine [Potts’s disease]
should always be borne in mind when the
patient presents with paraplegia.
Treatment of Burkitt Lymphoma

56
 Burkitt’s Lymphoma –
Treatment
• Although Burkitt's lymphoma is a very rapidly growing
tumor it responds well to aggressive treatment.
• In African children the drug cyclophosphamide is the
treatment of choice. This drug is so effective that one
dose may be enough to cause the tumor to disappear.
However, it is very important to complete the course of
treatment in order to prevent the tumor recurring.
 * In AIDS patients treatment is less successful because of
the underlying HIV infection. In addition to drugs, these
patients are usually given X-rays which cause the tumor to
shrink.
 Burkitt’s Lymphoma –
Treatment [contd.]
• The drugs that have been found to be effective are
cyclophosphamide, methotrexate, cytosine
arabinoside, vincristine and melphalan. ;
[+prednisolone].

• A single large dose of drugs is preferred to smaller

doses of a larger amount over a longer period.

• The disease stage is more important than the size of

the tumour.
 Burkitt’s Lymphoma – Treatment
[contd.]
• Cyclophosphamide: 30-40mg/kg, repeated at 2-3
weekly intervals.
• Vincristine: 1.4mg/m2 iv on the first day of a four
day schedule.
• Methotrexate: 15mg.m2, and
• Cytosine arabinoside 250mg/m2 are given in a
daily infusion for 3 days.
• [Methotrexate and cytosine arabinoside are available
for intra-thecal administration and many centers use
them prophylactically, with beneficial results,
especially against relapse.
 Burkitt’s Lymphoma – Treatment
[contd.]
• It is necessary to follow the blood parameters with
a weekly full blood count.

• A satisfactory urinary output before the onset of

chemotherapy should be ensured with adequate
fluid intake.

• In anticipation of the hyperuricemia that usually

follows chemotherapy, allopurinol [100mg thrice
daily], is usually given.
• Fungating or ulcerating tumours of the jaw can be
treated with chlorhexidine [0.5%] in water as a
mouth wash or spray.

• Radiotherapy is not very effective, probable

because of the rapid growth of the tumour.
Treatment Results

Complete
Remission

62
Treatment Results [contd.]
Nigerian girl [after
Nigerian girl [before treatment] treatment]
Need to Improve Access to Care for More Children

3.5
weeks

Total cost
of chemo
~ $200

INCTR African BL Treatment

Project
64
 Burkitt’s Lymphoma – Prognosis
• Factors considered important for prognosis include:
 The extent of the tumour burden;
 Bone marrow involvement;
 Peripheral manifestation;
 CNS involvement
 Presentation above the age of 13 years.
• Although the overall response of BL to
chemotherapy is about 90%, the relapse rate is up to
50%.
• Relapse shortly after remission has a poorer prognosis,
but younger patients survive better.
 List of Sources
 1. Ian McGrath: http://www.google.com.ng/url?
sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CCAQFjAA&url=http%3A%2F
%2Finctr.ctisinc.com%3A9000%2Fsites%2FInCTR%2FOERC%2FPowerPoint
%2520Presentations%2FLeukemia%2520and%2520Lymphoma%2FBurkitt
%2520Lymphoma%2520Overview.ppt&ei=C0_wU4vjLq-
w7Abh9YD4DA&usg=AFQjCNFbOEprQUqWcG2-
up4jYKGzMCETpA&bvm=bv.73231344,d.ZGU.
 I Magrath, 2009. Denis Burkitt and the African lymphoma
[http://ecancer.org/journal/3/full/159-denis-burkitt-and-the-african-lymphoma.php].
  2. Catherine Hanson, Richard Hildreth, David Duke, Kelly Lewis, Ray Lewis:
https://www.google.com.ng/search?q=burkitt%27s+lypmhoma%2C+ppt&ie=utf-8&oe=utf-
8&aq=t&rls=org.mozilla:en-US:official&client=firefox-
a&channel=sb&gfe_rd=cr&ei=C0_wU5nwA8ao8wftkoKwDg.
 3. Michele Bernasconi:
http://www.google.com.ng/url?
sa=t&rct=j&q=&esrc=s&source=web&cd=14&ved=0CGgQFjAN&url=http%3A%2F
%2Fwww.eicr.uzh.ch%2Fresearch%2FInfektiologie%2FHUMBIO
%2FBIO430MB.ppt&ei=gFPwU7n0LsPF7AbhnYCQDg&usg=AFQjCNGGqbOB28vy
wcET6lK63B3dn-3kTw&bvm=bv.73231344,d.ZGU.
List of Sources [contd.]
 4. Deeter Neumann:
http://www.google.com.ng/url?
sa=t&rct=j&q=&esrc=s&source=web&cd=13&ved=0CGMQFjAM&url=http%3A
%2F%2Fgenetics564.weebly.com%2Fuploads
%2F8%2F6%2F5%2F7%2F865764%2Fdeeter_neumann.ppt&ei=gFPwU7n0LsPF7
AbhnYCQDg&usg=AFQjCNEI8vrnGyFdIL-
3QX5EckQUKRCmCg&bvm=bv.73231344,d.ZGU.
 5. Wilson F P , and Berns J S [2012] .CJASN ;7:1730-1739.[The pathway to the
formation of uric acid]: http://cjasn.asnjournals.org/content/7/10/1730.full.
 6. Jessica Hochberg and Mitchell S. Cairo . Tumor lysis syndrome: current
perspective. haematologica | 2008; 93(1).
 7. https://www.globalgiving.org/projects/cure-250-children-with-burkitt-lymphoma-
in-africa/photos/?pageNo=3
 8. Endemic Burkitt's lymphoma: a polymicrobial disease? Rosemary Rochford,
Martin J. Cannon & Ann M. Moormann. Nature Reviews Microbiology 3, 182-187
(February 2005).
  9. INCTR African BL Treatment Project [Multi-Center Study of the Treatment
and Characterization of Burkitt Lymphoma in Africa …A collaborative protocol of
INCTR’s African Burkitt Lymphoma Strategy Group].
List of Sources [contd..]
 10. Tiu, R.V., Mountantonakis, S.E., Dunbar, A.J., Schreiber, Jr.,
M.J.N[2007]. Tumor Lysis Syndrome. Seminars in Thrombosis and
Hemostasis, vol. 33, number 4, 2007. 397-407.
 11. Ejeckam, G.C., Adimorah, G.I., Asindi, A.A.., (1999). Ch 57.
Childhood Tumours. In Paediatrics and Child Health in a Tropical
Region , Azubuike, J.C., Nkanginieme, K.E.O. [Eds.], 1st Edition,
African Educational Services, Owerri, Nigeria. 474 – 484.
 12. Hochberg,J. , and Cairo, M.S. (2008). Purine catabolism
pathway. Haematologica 2008;93:9-13.
Thank you

 Dr. Denis Burkitt [1911 –

1993]
69