LIMFOMA MALIGNUM

LIMFOMA NON HODGKINS

 Limfoma are the third most common
malignancies in children and
adolescents
Most developing countries 10-13% newly
diagnosed
Developing countries: most common
malignancies
Heterogeneous disease, two main type:
1.Hodgkins disease (HD)
2.Non Hodgkins lymphoma (NHL)
Epidemiology
Non Hodgkins lymphoma: 1,5 times than HD
in children under 15 years
In the USA incidence rose by almost 30%
(1973-1991)
Male predominance, with a male to female
ratio of 3 : 1
Peaks incidence : 5-7 years
Patients at increased risk of NHL:
- Congenital immunodeficiency syndrome
- Acquired immunodeficiency syndrome
- Immunosuppressive theraphy
Epidemiology (cont)

Immunodeficiency states, the genetic

instability associated with chromosomal
abnormality contribute to the increase
of risk lymphoid malignancies.

Geographical state: NHL rare in Japan

and Burkitts lymphoma in Africa
 Histopathology, molecular biology
and immunophenotyping
Childhood lymphoma is mainly divided into three histological
and immunological subtypes:
1. B-Cell origin (small noncleaved, undifferentiated)
2. T-Cell origin ( majority of lymphoblastic
lymphomas express T-cell markers)
3. Large cell lymphomas ( B and T- Cell origin,also
Ki 1 positive cells in anaplastic large cell
lymphomas)
In Paediatric NHL can divided in three major categories,
according to the most widely accepted different classification
classification of childhood
NHL
Scheme LBL BCL LCL
Rapport Lymphoblastic Burkitts Histiocytic
lymphoma Non Burkitts lymphoma
Kiel Lymphoblastic Lymphoblastic, Imunoblastic
convoluted and Burkitts type centroblastic
unclassified and other B-
Cell
Working lymphoblastic Small,non Diffuse large
Formulation cleaved cell cell,
immunoblastic
REAL T lymphoblastic High grade B- Large cell
cell lymphoma Anaplastic
Burkitts large cell
B Cell lymphoma
Undifferentiated small non-cleaved lymphoma, B
cell lymphomas (Burkitts and non Burkitts
comprise 40-50% of childhood NHL
Small, non-cleaved cell lymphomas divided into:
Burkitts and non Burkitts lymphomas.
Small, non-cleaved cell lymphoma show B-cell
phenotype, express mostly IgM class
immunoglobulins ; and B cell antigen presented
by monoclonal antibodies CD 19 and CD 20;
HLA DR antigens and ALL antigen (CD 10)
Chromosome abnormality in 75% cases :
translocation of the distal end of the long arm of
chromosome 8 to the long arm of chromosome
14 t(8;14) (q24;q32).
Lymphoblastic lymphoma
Lymphoblastic lymphoma (convoluted and non
convoluted) comprise 30-40% of childhood NHL
More than 90% of lymphoblastic lymphoma are
derived from immature T cell and express thr
immunophenotypic markers of intrathymic T-
cell differentiation Early thymocyte (T10 and/or
T9), intermediate (T6;T10;T4;T8), immature
(T4;T8;T3)
T cell ALL and NHL show specific clinical feature,
Chromosome translocation are: t(1:14)
(p32;q11), t(10:14) (p24:q11); t (7:14) (q35:p11)
,t (8:14) (q24:q11)
Large cell lymphoma
Large cell lymphoma are two main type: large
cell, non-cleaved (B-cell origin) and cleaved
lymphomas(immunoblastic)
Large cell lymphoma 10% of childhood NHL are
immunoblastic lymphoma including K 1
positive or anaplastic large cell lymphoma
(ALCL).
Large cell, NHL is a heterogeneous group of
tumors: T-cell; B-cell or indeterminate
immunophenotype.
ALCL: express CD 30, translocation chromosom
t(2;5) ( p23:q25)
Molecular characterization of the t(2;5) has led
to the development of a reverse transcriptase
polymerase chain reaction (RT-PCR).
RT-PCR assay an important diagnostic tool.
Presentation and clinical features
Clinical presentation NHL is varied depend on
histological subtype; the extent of the disease
and primary site of tumor.
Typically have extranodal disease, often grows
rapidly and spreads by blood borne.
Two-third of patient with NHL have locally
advanced metastatic disease at the time of
diagnosis.
Spreads to the CNS have malignant pleocytosis
or cranial nerve palsies. Pancytopaenia suggests
bone marrow involvement
Primary site of disease is mostly correlated to
the histological subtype:
Burkitts lymphoma (small,non-cleaved cell
lymphoma):

Present with abdominal tumor, with or without

ascites. Pain, swelling, nausea, and vomiting
resulting from intestinal obstruction cause by
direct compression of the bowel lumen or
intussuception. Patient with abdominal mass,
mostly ascites are at risk for tumor lysis
syndrome especially when chemotherapy is start

Presentation with a right iliac fassa mass is

common and can be confused with appendicitis.
Jaw involvement particularly in young children
under 5 years.
Bone marrow involvement is more common in
Lymphoblastic lymphoma:
LBL most commonly presents as a mediastinal
tumor, often with associated pleural effusion.
Respiratory distress from airway compression,
or swelling of neck, face and arm from
obstruction of superior vena cava.
Liver and spleen may also be involved.
The CNS including cranial nerve involvement Is
rare involved at diagnosis, and in the prsence of
widespread (> 25%) bone marrow
involvement,leukemia is usually diagnosed.
Patient with large-cell lymphoma can present
with an anterior mediastinal mass and
symptomas similar to those of lymphoblastic
disease, or with abdominal disease causeing
intestinal abstruction.
DIAGNOSIS,STAGING AND
PROGNOSIS
NHL grows very rapidly in children; therefore,
expeditious diagnosis is essential.
Diagnosis mostly established by examining
tumor tissue obtain by open biopsy, which
should be sufficient to permit morphological;
immunophenotypic; cytogenetic and molecular
studies.
If the patients clinical condition is unstable
(large abdominal or mediastinal mass) less
invasive procedure
Determination of histological; immunopheno-
typing and cytogenetic is imortant to decide
treatment.
Serum studies is not aid the specific diagnosis
of lymphoma, but may help to exclude non
lymphoid tumor.
Initial Staging studies for diagnosis
of histological subtypes of NHL
Complete blood count (with differential)
Test for Human Immunodeeficiency Virus (HIV)
and Epstein Barr Virus (EBV)
Blood chemistry: electrolyte; uric acid;
calcium;phosphorus; lactic dehydrogenase;
BUN ;creatinine
Examination of cerebrospinal fluid
Bone marrow aspiration and biopsi
Bilateral chest X-ray
Abdominal ultrasonography
CT scan
MRI
St. Judes staging for childhood NHL
Stage I: A single tumor (extranodal) or single anatomical
area (nodal) with the exclusion of the mediastinum or
abdomen
Stage II: A single tumor (extranodal) with regional node
involvement.
Two or more nodal areas on the same side of
diaphragm
Two single (extranodal) tumor with or wthout regional
node involvement in the same side of diaphragm.
Stage III: Two single tumor (extranodal) on opposite
sides of diaphragm
Two or more nodal areas above the diaphragm
All the primary intrathoracic tumor
All extensive primary intra abdominal mass ,unresectable
Paraspinal or epidural tumor,regardless of other tumor
Stage IV: Any of the above with initial CNS and/or BM
involvement.
Treatment

Principles of therapy and pretreatment

considerations:

1. Surgery and radiation therapy were

effective in patients with stage I and II
disease, but more than two-third of the
patients relapse.
2. Chemotherapy is now the main
treatment modality for all histologies
and stage of childhood NHL.