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BURKITT’S LYMPHOMA
H.A MWAKYOMA, MD.
Burkitt's lymphoma
• Burkitt lymphoma (or "Burkitt's tumor", or
"Malignant lymphoma, Burkitt's type") is a
cancer of the lymphatic system (in
particular, B lymphocytes). It is named
after Denis Parsons Burkitt, a surgeon
who first described the disease in 1956
while working in equatorial Africa.
BURKITT’S LYMPHOMA
• Burkitt’s lymphoma (or Burkitt Lymphoma)
is an uncommon type of Non-Hodgkin
Lymphoma (NHL).
• Burkitt’s lymphoma commonly affects
children.
• It is a highly aggressive type of B-cell
lymphoma that often starts and involves
body parts other than lymph nodes
BURKITT’S LYMPHOMA
• In spite of its fast-growing nature,
Burkitt’s lymphoma is often curable with
modern intensive therapies.
Classification
Currently Burkitt's lymphoma can be divided into
three main clinical variants: the endemic, the
sporadic and the immunodeficiency-associated
variants.
• The endemic variant occurs in equatorial Africa.
 It is the most common malignancy of children in this
area.
 Children affected with the disease often also had
chronic malaria which is believed to have reduced
resistance to the Epstein-Barr virus and allowed it
to take hold.
I: Endemic Burkitt’s lymphoma:
• In equatorial Africa, about half of all childhood
cancers are Burkitt’s lymphoma.
• The disease involves children much more than
adults, and is related to Epstein Barr Virus
(EBV) infection in 95% cases
• It characteristically has a high chance of
involving the jawbone, a rather distinctive
feature that is rare in sporadic Burkitt’s.
• It also commonly involves the abdomen.
The endemic variant
 The disease characteristically involves the;
jaw or other facial bone,
 distal ileum, cecum,
 ovaries, kidney or
 the breast
II: Sporadic Burkitt’s lymphoma :
• The type of Burkitt’s lymphoma that affects
the rest of the world, including Europe
and the Americas is the sporadic type.
• Here too, it's mainly a disease in
children.
• The link between Epstein Barr Virus (EBV)
is not as strong as with the endemic
variety, though direct evidence of EBV
infection is present in one out of five
patients.
Sporadic Burkitt’s lymphoma :
• More than the involvement of lymph
nodes, it is the abdomen that is notably
affected in more than 90% of the
children
• Bone marrow involvement is more
common than in the endemic variety.
• Jaw involvement is extremely rare.
The sporadic type
• Non-Hodgkins, which includes Burkitt's,
accounts for 30-50% of childhood
lymphoma. Jaw is less commonly
involved, comparing with the endemic
variant. Ileo-cecal region is the common
site of involvement
III: Immunodeficiency-associated
Burkitt lymphoma
• Immunodeficiency-associated Burkitt
lymphoma is usually associated with HIV
infection or
• occurs in the setting of post-transplant
patients who are taking
immunosuppressive drugs.
• Actually, Burkitt lymphoma can be the initial
manifestation of AIDS
Oncogenic Viruses
• Burkitt's lymphoma is associated with
oncogenic viruses—the Epstein-Barr virus
(EBV) in endemic Burkitt's and human
immunodeficiency virus (HIV) and rarely in
the sporadic form.
• EBV, or human herpesvirus 4, is the virus
that causes infectious mononucleosis.
Oncogenic Viruses
• The presence of EBV in patients with endemic
Burkitt's has been interpreted as a side effect of
the high rates of malaria in central Africa.
• African children may have immune systems that
cannot fight off infection with EBV because they
have been weakened by malaria
• The children's B-lymphocytes then reproduce at
an unusually high rate
Lymphocytes and Oncogenes
Lymphocytes fall into two groups:
• T cells, which regulate the immune system; and
B cells, which produce antibodies.
• Burkitt's lymphoma involves the B-cell
lymphocytes.
• In 1982, researchers discovered an oncogene
(a gene that can release cells from growth
constraints, possibly converting them into
tumors) in 90% of patients with Burkitt's
lymphoma.
Oncogenes
• The gene was Called the C-myc oncogene, it is
responsible for the uncontrolled production of Blymphocytes
• It results from a translocation, or exchange, of
genetic material between the long arm of human
chromosome 8 and the long arm of human
chromosome 14
• In a smaller number of patients with Burkitt's, the
translocation involves chromosomes 2 and 22 or
chromosomes 2 and 8
BL: Jaw swelling with ulceration
BL: disruption of teeth, partial
airway obstruction
BL: Jaw swelling
microscopic appearance
• By morphology (i.e. microscopic
appearance) or
• immunophenotype, it is almost impossible
to differentiate these three clinical variants.
• Immunodeficiency-associated Burkitt
lymphoma may demonstrate more
plasmacytic appearance or more
pleomorphism, but these features are not
specific
microscopic appearance
• Consists of sheets of monotonous (i.e.
similar in size and morphology) population
of medium size lymphoid cells with high
proliferative activity and apoptotic activity.
• The "starry sky" appearance seen under
low power is due to scattered tingiblebodies laden macrophages (macrophages
containing dead body of apoptotic tumor
cells).
BL: microscopic appearance
BL
•
Pathology
– Benign equivalent is replicating
small noncleaved cell of
germinal center:
– Diffuse infiltration of lymph
node
– Very high mitotic rate, lot of
ineffective proliferation;
– Attracts macrophages to
phagocytize> starry sky
pattern at low power
– Cytology: round nucleus, smaller
than that of reactive macrophage
– Vesicular chromatin and 2-5
nucleoli
– Immunophenotype:
• Positive: Monoclonal light
chain, CD19, CD10
• Negative: CD5
BL: Touch preparation, Wright stain
BL: Touch preparation,
Malignant B cell characteristics
• Normal B cells possess rearranged
immunoglobulin heavy (IgH) and light
chain genes,
• unlike most T-cells and other cells of the
body in which the genes are germline.
• Each isolated B-cell possesses a unique
IgH gene rearrangement, reminiscent of
the fingerprint of a person.
Malignant B cell characteristics
• Since Burkitt lymphoma and other B-cell
lymphomas are a clonal proliferative
process, all tumor cells from one patient
are supposed to possess identical IgH
genes
• When the DNA of tumor cells is analyzed
using electrophoresis, a clonal band can
be demonstrated since identical IgH genes
will move to the same position.
Malignant B cell characteristics
• On the contrary, when a normal or reactive
lymph node is analyzed using the same
technique, a smear rather than a distinct
band will be seen.
• This technique is useful since sometimes
benign reactive processes (e.g. infectious
mononucleosis) and malignant lymphoma
can be difficult to distinguish.
Malignant B cell characteristics
• Burkitt's lymphoma is a solid tumor of B
lymphocytes, the lymphocytes that the immune
system uses to make antibodies.
• The genes for making antibodies are located on
chromosomes 14 (the heavy [H] chains), 2
(kappa light chains), and 2 (lambda light chains).
• These genes are expressed only in B
lymphocytes because only B cells have the
necessary transcription factors for the promoters
and enhancers needed to turn these antibody
genes "on".
Malignant B cell characteristics
• In most (approximately 90%) of the cases
of Burkitt's lymphoma, a reciprocal
translocation has moved the protooncogene c-myc from its normal position
on chromosome 8 to a location close to
the enhancers of the antibody heavy chain
genes on chromosome 14
Malignant B cell characteristics
Malignant B cell characteristics
• In all the other cases, c-myc has been
translocated close to the antibody genes
on chromosome 2 or 22.
• In every case, c-myc now finds itself in a
region of vigorous gene transcription, and
it may simply be the overproduction of the
c-myc product (a transcription factor
essential for mitosis of mammalian cells)
that turns the lymphocyte cancerous.
Malignant B cell characteristics
• Uncontrolled mitosis of this cell results in a clone
of cancer cells, Burkitt's lymphoma.
• Many other human cancers involve
chromosome aberrations, such as
translocations, at the loci of known protooncogenes.
• The heavy chain gene locus on chromosome 14
is a dangerous place.
• Several other proto-oncogenes produce
cancerous B cells — leukemias, lymphomas,
and multiple myelomas — when translocated
into this locus.
Malignant B cell characteristics
• The risk of translocations involving the
heavy chain gene locus is probably
especially high because breaks in its DNA
occur naturally during the synthesis of
antibodies
CYTOGENETICS
• Most BL cell lines show a specific translocation involving
chromosome 8 (breakpoint at 8q24) and either 2, 14 or
22.
• The type of immunoglobulins produced by this B-cell
tumor correlates with the type of translocation:
 those with the 8;2 translocation produce predominantly
kappa light chains;
 those with the 8;22 translocation produce lambda light
chains;
 those with the 8;14 translocation produce
immunoglobulins with both types of light chains
In summary: cytogenetics
• Almost by definition, Burkitt lymphoma are
associated with c-myc gene translocation.
The most common variant is
t(8;14)(q24;q32) while rarer variants
include t(2;8)(p12;q24) and
t(8;22)(q24;q11).
• A three-way translocation, t(8;14;18), has
also been identified.
• It is curable.
Treatment
• Effect of the chemotherapy, as with all cancers,
depends on the time of diagnosis. With faster
growing cancers, such as this one, the cancer
actually responds faster than with slower
growing cancers. .
• This rapid response to chemotherapy can be
hazardous to patient as a phenomenon called
"tumor lysis syndrome" could occur. Close
monitoring of patient and adequate hydration is
essential during the process.
Chemotherapy
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Cyclophosphamide
Doxorubicin
Vincristine
Methotrexate etc