Child hood tumor

Teshe 2008 E.C

02/20/24 1
 Paediatric Oncology
Kids are not “little adults”
Most common adult
cancers
Prostate
Breast
Lung
Most common pediatric
cancers
Leukemia
Brain tumors
Lymphoma
Pediatric Epidemiology
Solid tumors (excluding CNS tumors) are much less
common
Extent of disease and age are prognostic factors but
for very different reasons than adults
Pediatric Epidemiology
Incidence increasing
Genetics rarely
important
Rare prior risk factors
Mortality has
decreased dramatically
over the last 30 years
Potential exists for uniform
curability
Predisposing Factors
Genetic
 Syndromes ( Trisomy 21), bone marrow failure
syndrome
Hereditary
 Wilms tumor, Retinoblastoma
Environmental
 Radiation, toxins
Unique aspects
Overall prognosis is good
Usually otherwise healthy children
May have specific sensitivity for treatment
 CNS sensitivity
 Growth issues
Long term aspects
 Secondary malignancies
 Developmental and CNS toxicity
 Cardiac, renal and pulmonary toxicity
 Reproductive function
General Principle of Cancer
Treatment
Biopsy/ Definitive diagnosis prior to initiation of
chemotherapy
Staging
Local therapy
 Surgery
 Radiation
 Chemotherapy
Systemic therapy
 Chemotherapy
 Biologic agents
 Bone marrow transplantation
02/20/24 8
02/20/24 9
THE LEUKEMIAS
The leukemias are the most common malignant neoplasms in
childhood.
CLASSIFICATION: on the bases of leukemic cell morphology
and natural history.
a) Acute lymphoblastic leukemia ( ALL ) accounts for about 77% of
cases of childhood leukemia.
b) Acute myelogenous leukemia ( AML ) =11% .
c) Chronic myelogenous leukemia ( CML ) = 2–3% .
d) Juvenile chronic myelogenous leukemia ( JCML ) = 1–2%.
e) Others = 7– 9% .

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Acute leukemias
 Untreated , rapidly fatal with in weeks to a few months of the
diagnosis.
 With treatment, often are curable.
 The malignant cells (very immature in appearance and
function ) = blasts.
Lymphoblasts=ALL
Myeloblasts=AML

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Chronic Leukemias

Even with out treatment, patients survive for many

months to years.
Unfortunately , the chronic Leukemias evolve in to
forms of acute leukemia( the blast crises).
All chronic Leukemias in children are of
nonlymphocytic lineage.
The leukemic cells are more mature and functional
than the blasts of acute Leukemias.

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Acute Lymphoblastic Leukemia(ALL)
The first disseminated cancer shown to be curable .
 A heterogeneous group of malignancies : varying clinical
behaviors and responses to therapy.
 Characterized by large numbers of lymphoblasts in the bone
marrow and on peripheral smear.

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ALL: Epidemiology/ Etiology/Risk factors.
Striking peak incidence between 2–6 yr of age.
 Slightly more frequent in boys than in girls; more
prevalent in whites than black children.
The etiology of ALL is unknown, several factors are
associated with childhood leukemia.
Genetic conditions: more common in children with
certain chromosomal abnormalities .
Examples: Down syndrome, Bloom syndrome, ataxia-
telangiectasia, Fanconi syndrome, and others.

02/20/24 14
ALL: Epidemiology/ Etiology/Risk factors.

Identical twins= risk to the second twin if one develops

leukemia is greater than that in the general population.
-(As high as 100% if the first twin is diagnosed during the
first year of life and the twins shared the same
(monochorionic placenta).
- If the first twin develops ALL by 5–7 yr of age, the risk to
the second twin is at least twice that in the general
population, regardless of zygosity.
Environmental factors:
Examples: Ionizing radiation, benzene exposure, Drugs,
infections ( EBV-B-cell ALL), etc.
02/20/24 15
Classification-ALL
Depends on the morphology, phenotypic characteristics as
measured by cell membrane markers, and cytogenetic and
molecular genetic features.
1. Morphologic : the French-American-British (FAB) classification.
a) L1 lymphoblasts: small, scant cytoplasm, absent or inconspicuous
nucleoli. By far the most common type.
b) L2 lymphoblasts: larger, more abundant cytoplasm and one or more
prominent nucleoli. Sometimes mistaken for myeloblasts.
c) L3 lymphoblasts: large, deeply basophilic and vacuolated cytoplasm
and prominent nucleoli. Evidence of a mature B-cell leukemia
(Burkitt leukemia);rare.

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Classification-ALL
2. Immunophenotypic: (surface markers) :
a) About 85% of cases of ALL are derived from progenitors of B
cells( Non –T, non-B ALL)
b) About 15% are derived from T cells, and
c) About 1% are derived from B cells.
d) A small percentage of children surface markers of both
lymphoid and myeloid derivation.

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ALL- Presentation.
Initial presentation = usually nonspecific; many have
had signs or symptoms for less than 4 weeks.
 Anorexia, fatigue, and irritability , an intermittent,
low-grade fever.
 Bone or joint pain, particularly in the lower
extremities, may be present.
Signs and symptoms of bone marrow failure (pallor,
fatigue, bruising, or epistaxis, as well as fever, which
may be caused by infection).

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ALL- Presentation.
On physical examination:
Pallor , purpuric and petechial skin lesions, or mucous
membrane hemorrhage.
Lymphadenopathy, splenomegaly, or, less commonly,
hepatomegaly.
 Rarely, signs of increased intracranial pressure
( papilledema, retinal hemorrhages, and cranial nerve
palsies.)
 Respiratory distress is usually related to anemia but may
occur owing to a large mediastinal mass of
lymphoblasts(typically in adolescent boys with T-cell
ALL).

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Diagnosis-ALL
ALL is strongly suggested by peripheral blood findings indicative of bone
marrow failure.
Anemia and thrombocytopenia = in most patients.
Leukemic cells are often not observed in the peripheral blood in routine
laboratory examinations.
Total leukocyte counts( WBC): NORMAL, DECREASED OR INCREASED.
Most patients with ALL present with total leukocyte counts of less than
10,000/Μl.
ALL is diagnosed by a bone marrow evaluation that demonstrates more
than 25% of the bone marrow cells as a homogeneous population of
lymphoblasts.
CSF(staging lumbar puncture): for leukemic cells, performed in
conjuction with the first intrathecal chemotherapy.
CXR: for mediastinal mass.

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 ALL-TREATMENT
 Childhood ALL was the first disseminated cancer shown to be curable
and as such has represented the model malignancy for the principles of
cancer diagnosis, prognosis, and treatment.
 The single most important prognostic factor in ALL is the treatment:
without effective therapy the disease is fatal.
 The choice of treatment of ALL is based on the estimated clinical risk of
relapse in the patient, which varies widely among the subtypes of ALL.
(RISK STRATIFICATION)
Three of the most important predictive factors are :
A) The age of the patient at the time of diagnosis,
B) The initial leukocyte count, and
C) The speed of response to treatment (i.e., how rapidly the
blast cells can be cleared from the marrow or peripheral blood).

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 ALL-TREATMENT
Average risk: but a patient between 1–10 yr of age and
with a leukocyte count of less than 50,000/μL.
Higher risk: are children who are older than 10 yr of age
or who have an initial leukocyte count of more than
50,000/ μL.
Recent trials have shown that the outcome for patients at
higher risk can be improved by administration of more
intensive therapy despite the greater toxicity of such
therapy.
Most children with ALL are treated on clinical trials
conducted by national or international cooperative groups.

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ALL-TREATMENT
1.Remission induction: the initial therapy designed to eradicate the
leukemic cells from the bone marrow.
Therapy is usually given for 4 wk and consists of vincristine
weekly, a corticosteroid such as dexamethasone or prednisone, and
either repeated doses of native l-asparaginase or a single dose of a
long-acting asparaginase preparation.
 Intrathecal cytarabine or methotrexate, or both, may also be given.
Patients at higher risk also receive daunomycin at weekly intervals.
With this approach, 98% of patients are in remission.
Remission: defined by less than 5% blasts in the marrow and a
return of neutrophil and platelet counts to near-normal levels after
4–5 wk of treatment.
Intrathecal chemotherapy is usually given at the time of diagnosis
and once more during induction.
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ALL-TREATMENT
2. CONSOLIDATION THERAPY(14-28 WEEKS): continued systemic
chemotherapy , which may be more intense in higher risk groups and CNS
PROPHYLAXIS.
 The second phase of treatment focuses on CNS therapy in an effort to prevent
later CNS relapses.
 Intrathecal chemotherapy is given repeatedly by lumbar puncture in
conjunction with intensive systemic chemotherapy.
 The likelihood of later CNS relapse is thereby reduced to less than 5%.
 A small proportion of patients with features that predict a high risk of CNS
relapse receive irradiation to the brain and spinal cord.
 This includes those patients who have lymphoblasts in the CSF and an elevated
CSF leukocyte count at the time of diagnosis

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ALL-TREATMENT
3. Maintenance phase: (lasts 2-3 years)
Patients are given daily mercaptopurine and weekly
methotrexate, usually with intermittent doses of
vincristine and a corticosteroid.
A small number of patients with particularly poor
prognostic features, principally those with the t(9;22)
translocation known as the Philadelphia chromosome,
may undergo bone marrow transplantation during the
first remission.
NB. In ALL, this chromosome is similar but not identical
to the Philadelphia chromosome of chronic
myelogenous leukemia (CML).
02/20/24 25
Complications/ Follow up
The major impediment to a successful outcome is relapse of the
disease.
Relapse occurs in the bone marrow in 15–20% of patients with
ALL and carries the most serious implications, especially if it
occurs during or shortly after completion of therapy.
 Intensive chemotherapy with agents not previously used in the
patient followed by allogeneic stem cell transplantation can
result in long-term survival for a few patients with bone
marrow relapse .
OTHER SITES OF RELAPSE:
CNS: which was the most common site of relapse before prior to
CNS prophylaxis.
Usually present with signs and symptoms of increased
intracranial pressure and may present with isolated cranial
nerve palsies

02/20/24 26
Definition of relapse
More than 50% lymphoblasts in a single bone marrow
aspirate
More than 25% lymphoblasts in the bone marrow and
2% or more circulating lymphoblasts
Relapse occur in bone marrow in 15-20% of patients
Complications/ Follow up
TESTES (1-2%): becoming the most common site of extramedullary relapse.
(painless swelling of one or both testes).
Treatment includes systemic chemotherapy and local irradiation.
 Tumor lysis syndrome: Hyperuricemia, Hyperkalemia,
Hyperphosphatemia.

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SUPPORTIVE CARE.
 Treatment of complications:
Myelosupression:
Transfusional support: RBCS/ PLATLETS.
Treatment of infections: high index of suspicion and aggressive empirical
antimicrobial therapy for sepsis in febrile children with neutropenia.
 Patients need to receive prophylactic treatment of Pneumocystis carinii
pneumonia during chemotherapy and for several months after completing
treatment.
Metabolic support:( tumorlysis syndrome).
Treatment of hyper viscosity/Compressive symptoms.

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Prognosis
 Most children with ALL can now be expected to have long-term survival,
with the survival rate >80% at 5 yr from
 Characteristics generally believed to adversely affect outcome include
• Age <1 yr or >10 yr at diagnosis
• A leukocyte count of >50,000/?L at diagnosis
• T-cell immunophenotype
• A slow response to initial therapy
• Hyperdiploidy
• The Philadelphia chromosome
• Testicular disease at diagnosis
• CNS 3 at diagnosis
 More-favorable characteristics include
• A rapid response to therapy
• Hyperdiploidy
• Trisomy of specific chromosomes
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Acute Myeloid Leukemia (AML)
AML is a clonal proliferation of myeloid precursors with a
reduced capacity to differentiate into more mature cellular
elements
AML accounts for 11% of the cases of childhood leukemia in
industrial countries but less relatively more common in Africa,
with the ratio of AML to ALL is roughly 1:1
Male and female distributions are nearly equal at all ages
In the first year of life, AML accounts for nearly one third of all
newly diagnosed leukemias.
 For the rest of the first decade of life, ALL is more common
than acute myeloid leukemia by a ratio of 4:1. The incidence of
these diseases is roughly equal during adolescence
Classification
The new WHO classification
1. AML with recurrent genetic abnormalities — 11 percent
2. AML with myelodysplasia-related features — 6 percent
3. Therapy-related AML and MDS — 2 percent
4. AML, not otherwise specified — 81 percent
5. Myeloid sarcoma
6. Myeloid proliferations related to Down syndrome
• Transient abnormal myelopoiesis
• Myeloid leukemia associated with Down syndrome
7. Blastic plasmacytoid dendritic cell neoplasm
Clinical Manifestation
Symptoms of acute myeloid leukemia can be divided
into those caused by:-
1. A deficiency of normally functioning cells,
2. Those due to the proliferation and infiltration of the
abnormal leukemic cell population, and
3. Constitutional symptoms.
AML Work Up/ Pre Rx investigations
Pancytopenia is usually expected but WBC could be elevated
even more than 1X 109/L
Serum uric acid and lactic dehydrogenase levels are frequently
elevated
Serum muramidase (lysozyme) levels are usually increased in
patients with monocytic leukemias.
Other signs of tumor lysis, including hyperkalemia,
hypocalcemia, and lactic acidosis, may be present.
Blood and urine cultures should always be obtained in a child
with fever and leukemia.
Coagulation tests should also be performed during initial
diagnosis to look for evidence of DIC that might suggest APL.
Cont…
Routine chest radiography
If the patient has abdominal pain and distention,
abdominal images often depict free air suggestive of a
perforation.
Radiographic examination of the extremities may
reveal findings such as metaphyseal bands at the
distal femurs (most commonly observed in young
children with ALL), periosteal new bone formation,
focal lytic lesions, or pathologic fractures.
Echocardiography
CT scan with any indications
Cont…
Diagnostic bone marrow aspiration or biopsy
Flow cytometry and special stains assist in identifying
myeloperoxidase-containing cells
CSF samples should be obtained before any therapy is
begun
Treatment
Management of AML involves multiagent
chemotherapy in addition to supportive care
Depending on the chromosomal abnormalities
retinoic acid can be used as well as biologic agents
Intensive supportive care is mandatory
Remission induction may involve stem cell
transplantation
 Childhood lymphoma

02/20/24 38
 B. Lymphoma
The term lymphoma refers to cancers that originate
in the body's lymphatic tissues.
 Lymphatic tissues include the lymph nodes( thymus,
spleen, tonsils, adenoids, and bone marrow, as well as
the channels (called lymphatics
Lymphomas are divided into two broad categories
Non-Hodgkin lymphoma is somewhat less
common than Hodgkin disease
In Developed countries, the childhood rate is lower
than the young-adult rate
In developing countries Highest incidences among
young children
02/20/24 39
Hodgkin Disease
Defined by specific malignant cells, called
Reed-Sternberg cells,
Epidemiologic feature of HL is its bimodal
age
 In industrialized countries, the early peak
occurs in the middle to late 20s, with a
second peak after 55 yr of age.
 In developing countries, the early peak
occurs before adolescence
02/20/24 40
Risk factors
Infection:
Epv, human herpesvirus 6, CMV
Genetic:
Increased association of HD with specific HLA antigens
in families
The risk is 100-fold for an unaffected monozygotic twin of
an affected twin
Immunodeficiency:
Congenital(e.g ataxia-telangiectasia) or
acquired, such as HIV infection,
02/20/24 41
Clinical presentation
Painless, non-tender, firm, rubbery,
lymphadenopathy
Cervical in 70-80%
Axillary in 25%.
Other sites are supraclavicular, inguinal, and, less
often, epithrochlear or popliteal.
A mediastinal mass(50%) may cause superior vena
cava obstruction, respiratory symptoms, or both.
 Splenomegaly, hepatomegaly, or both.

02/20/24 42
Clinical presentation
Systemic symptoms :Unexplained fever,
night sweats, and weight loss are also
common.
Several immune-mediated paraneoplastic
syndromes, such as ITP and autoimmune
hemolytic anemia
Other nonspecific symptoms, including
fatigue, poor appetite, itching, or hives
02/20/24 43
 PATHOLOGICAL & CLINICAL FEATURES OF HL (Western Data)
HISTOLOGY (%) AGE PATHOLOGY CHARACTERISTICS &
SUBTYPE GRO STAGES AT PRESENTATION
UP
Lymphocyte- 5 20- L&H cells, difficult Males more affected,
Predominant 40 pathologic Dx, stage I-IIA, late relapses
Nodular form is a & transformation to
NON-CLASSIC HL NHL-HA

Nodular sclerosis 65-80 15-40 Lacunar cells, Females more affected,

birefrigent fibrotic mediastinal, hilar &
bands supraclavicular LAP,
stage I-IIIA/B

Mixed Cellularity 20-35 30-50 RS cells frequent, Retroperitoneal disease

necrosis, partial frequent, often
nodal involvement symptomatic stage II-
& heterogenous IVA/B

Lymphocyte - <5 40- RS cells numerous & Febrile, wasting

Depleted 80 bizare/diffuse syndrome, liver & BM
fibrosis involvement common
02/20/24 stage II-IVB 44
 Ann Arbor Staging Classification
STAGE I :
 Involvement of a single lymph node (1) or of a single
extralymphatic organ or site (IE)
Stage II:
 Involvement of two or more lymph node regions on
the same side of the diaphragm (II) or
 Localized involvement of an extralymphatic organ or
site and one or more lymph node regions on the same
side of the diaphragm (IIE)

02/20/24 45
…..
Stage III
 Involvement of lymph node regions on both sides of the
diaphragm (III), which may be accompanied by
involvement of the spleen (IIIS).
 By localized involvement of an extralymphatic organ or
site (IIIE) or both (IIISE).
Stage IV
 Diffuse or disseminated involvement of one or more
extralymphatic organs or tissues with or without
associated lymph node involvement.

02/20/24 46
…..
B -sypmtoms : at least one of the following
symptoms:
Drenching night sweats,
Unexplained fevers > 38°C,
> 10% loss of body weight in the past 6 months.
A -involves the absence of symptoms described
above.
E - contiguous involvement of extranodal sites

02/20/24 47
 Classification of ALL
Lymphocyte predominance( LpHL ) 10–15%
 M>F, younger patients, localized disease
 Is common with HIV infected patient
 Non classical HL
Mixed cellularity (Ms)30% s :
 May have interstitial fibrosis, but fibrous bands are not observed. common children
≤10 yr of age, presents as advanced disease with extranodal extension.
Nodular sclerosis:
 Is notable for fibrous bands that result in a nodular pattern
 NS is the most common subtype, affecting
 40% of younger patients and 70% of adolescents with HD.
Lymphocyte depletion
 This class has large numbers of HRS cells with sarcomatous variants a hypocellular
background because of fibrosis and necrosis.
 This type is also extremely rare.

02/20/24 48
NEW WHO/REAL CLASSIFICATION
 Nodular lymphocyte predominance
 Classical Hodgkin lymphoma
• Lymphocyte rich
• Mixed cellularity
• Nodular sclerosis
• Lymphocyte depletion
 Anaplastic large cell lymphoma Hodgkin-like
HD appears to arise in lymphoid tissue and spreads to
adjacent lymph node areas in a relatively orderly fashion.
Hematogenous spread also occurs, leading to involvement
of the liver, spleen, bone, bone marrow, or brain, and
usually is associated with systemic symptoms

02/20/24 49
 Diagnosis
The CBC count may reveal the following:
Anemia:
Hemolytic anemia (Coombs positive),
chronic disease,
Bone marrow involvement
Lymphopenia,
Thrombocytopenia

02/20/24 50
 Diagnosis
Lymph node biopsy

Reed-Sternberg cell.
Reed-Sternberg cells are large, abnormal lymphocytes that may
contain more than one nucleus 51
Immunophenotyping
FNAC: is not recommended because of lack of stromal
tissue and the difficulty of classfication
Bone marrow biopsy: is if BM involvement suspected and
in those with stage III, or IV disease or B symptoms
Lactate dehydrogenase levels (LDH), which reflects bulk
of disease;
Alkaline phosphatase, which indicates bony metastasis;
Urinalysis may reveal proteinuria.( Nephrotic syndrome)
associated Hodgkin lymphoma)
Liver function and renal function test
Electrolyte and uric acid

02/20/24 52
 Imaging
Chest radiography: to see mediastinal mass.
CT or MRI of neck, chest, abdomen, and/or pelvis
U/s of the abdominal and pelvic
Bone scan is if alkaline phosphatase level
increased or bone pain
Gallium-67 scan is helpful in identifying areas of
increased uptake, which can then be re-evaluated
at the end of treatment, to see response
Positron emission tomography (PET)
Lymph angiograms, rarely are used today

02/20/24 53
Treatment
Radiation therapy:
Chemotherapy
COPP (Cyclophosphamide, vincristine [Oncovin],
Procarbazine, and prednisone)
 ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine,
and dacarbazine),
 The MOPP regimen (mechlorethamine [nitrogen mustard],
vincristine, Procarbazine, and prednisone)
“Risk-adapted” protocols are based on staging criteria as
well as rapidity of response to initial chemotherapy.
Surgical Care
Staging laparotomy and splenectomy are no longer
routinely performed in patients with Hodgkin lymphoma.

02/20/24 54
Prognosis
The stage of the cancer, size of the tumor and how
quickly it shrinks after initial treatment or relapse
"In children with NHL, 5-year survival is about 90% for
those with Stage I or Stage II at the time of diagnosis,
Close to 70% for those with more advanced Stage III or
IV disease." 1
Lymphocytic predominant HD: present with early
disease and have an excellent prognosis.
Anaplastic large cell lymphoma Hodgkin-like has a
poor response to conventional HD
02/20/24 55
Prognosis
FAVORABLE:
 <10, F, favorable subtypes (LP and NS) and
 Stage I non-bulky disease
UNFAVORABLE:
 Persistently elevated ESR
 LD histopathology
 Bulky disease--largest dimension >10cm
 B symptoms
 Long-term complications
Are related to radiation or chemotherapy;
Secondary malignancy (e.g., acute myelogenous
leukemia, breast, lung, thyroid, non-Hodgkin
lymphoma),
Sepsis (e.g., splenectomy or splenic irradiation), sterility,
Short stature,
Hypothyroidism,
Subclinical pulmonary dysfunction, and ischemic heart
disease

02/20/24 57
…..
Patients with favorable prognostic factors and early-
stage disease have an event-free survival (EFS) of 85–
90% and an overall survival (OS) at 5 yr of 95%
Prognosis after relapse depends on the time from
completion of treatment to recurrence, site of relapse
(nodal vs. extranodal), and presence of B symptoms at
relapse.
Patients who relapse >12 mo after chemotherapy
alone or combined modality therapy have the best
prognosis and usually respond to additional standard
therapy, resulting in a long-term survival of 60–70%.

02/20/24 58
Non Hodkins lymphoma
NHL accounts for approximately 60% of all
lymphomas in children and adolescents.
 It represents 8–10% of all malignancies in children
between 5–19 yr of age
Children Vs Adult
- In children is high grade ,extranodal and poor
prognosis ,
- Approximately 70% present with advanced disease of
stages III or IV
Depend primarily on subtype and sites .
02/20/24 59
Etiology
Most NHL present with de novo disease,
Immune deficiencies :inherited or acquired
Viral etiologies (e.g., HIV, EBV HIV-I, HTLV-I,
hepatitis C, Borrelia burgdorferi, hepatitis B virus) or
Genetic syndromes (e.g. Bloom syndrome).
Pesticide exposure
Radiation therapy,

02/20/24 60
The four major pathological subtypes
1. Burkitt lymphoma (BL)( 40% )
Immunophenotypic :B cell origin cytogenetic
markers t(8;14) (90%),a t(2;8) or t(8;22)10%)
commonly (sporadic type) head and neck (endemic
type) disease with involvement of the bone marrow or
CNS
2. Lymphoblastic lymphoma (LL),( 30%);
Immunophenotypic 80% T cell and 20% B cell;
Cf: intrathoracic or mediastinal supradiaphragmatic
mass, also has a predilection BM and CNS
02/20/24 61
02/20/24 62
NHKL
ENDEMIC SPORADIC
10/100,000 0.9/100,000
EBV ASS >95% <20%
JAW(58%),ABD(58) JAW(7%), ABD(91%)
CNS(19), CNS(14)
MARROW(7%) BM(20%),
ORBIT(11) ORBIT(1%)

02/20/24 63
3 Diffuse large B-cell lymphoma (DLBCL)
( 20%)
B cell origin Either an abdominal
or mediastinal rarely BM or
CNS
4 . Anaplastic large cell lymphoma
(ALCL)( 10%).
Mostly T -cell .Either with a primary
cutaneous (10%) or systemic disease
(fever, weight loss) liver, spleen, lung,
mediastinum, rarely BM or CNS
02/20/24 64
Clinical manifestation
Lymph glandular system
lymphadenopathy in any of the lymphnodes
Chest:
Mediastinal lymph nodes can compress the nearby trachea.
Superior venacava obstraction:
It can cause swelling in the face and arms and a bluish-red
coloration of the head, arms, and upper chest.
Pleural effusion is sometimes observed
Esophageal compression may lead to dysphagia
Abdomen: If the lymphoma grows inside the abdomen,
peritoneal fluid.
The pressure or blockage can also cause vomiting, constipation.
GUT: obstructive uropathy symptoms
02/20/24 65
Diagnosis
Fine needle aspiration (FNA) biopsy
Bone marrow aspiration and biopsy
Lumbar puncture (spinal tap):
Pleural or peritoneal fluid sampling
Immunohistochemistry
Fluorescent in situ hybridization (FISH):
Polymerase chain reaction (PCR):
A chest x-ray may be done to look for enlarged lymph nodes
inside the chest.
Computed tomography (CT or CAT) scan
 Biopsy, bone marrow, CSF, or pleural/paracentesis fluid)
should be tested by flow cytometry for immunophenotypic
origin (T, B, or null) and cytogenetics (karyotype).

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St. Jude Staging System for Childhood
NHL
STAGE I
• A single tumor (extranodal) or single anatomic area (nodal),
with the exclusion of mediastinum or abdomen
STAGE II A
•
s
, with or without involvem ingle tumor (extranodal) with
regional node involvement
• Two or more nodal areas on the same side of the diaphragm
• Two single (extranodal) tumors with or without regional node
involvement on the same side of the diaphragm
• A primary gastrointestinal tract tumor, usually in the ileocecal
areaent of associated mesenteric nodes only, which must be
grossly (>90%) resected
67
…..
Stage III
ሿ Two single tumors (extranodal) on opposite sides of the
diaphragm
ሿ Two or more nodal areas above and below the diaphragm
ሿ Any primary intrathoracic tumor (mediastinal, pleural, or
thymic)
ሿ Any extensive primary intra-abdominal disease

Stage IV
 Any of the above, with initial involvement of central
nervous system or bone marrow at time of diagnosis

02/20/24 68
General symptoms
B symptoms
Fever and chills
Sweating (particularly at night)
Unexplained weight loss
The presence of B symptoms is often related to the
presence of more rapidly growing lymphoma cells.
Since NHLs most frequently disseminate
hematogenously, this staging system has proven to be
much less useful than for HL, which disseminates
principally by contiguous lymphatic extension

02/20/24 69
 Treatment
Multiagent systemic chemotherapy and intrathecal
chemotherapy.
 COPAD (Cyclophosphamide, vincristine, prednisone and
doxorubicin),
 COMP (Cyclophosphamide, vincristine, methotrexate, 6-
mercaptopurine and prednisone).
 Advanced disease usually is treated by 4–6 moths
Radiation therapy
 Is rarely, if ever, used, except in special circumstances such as
CNS involvement in LL or occasionally BL, acute SVC, and acute
paraplegias.
Surgery
 Is used mainly for diagnostic and/or biologic specimens and
staging but rarely is used for debulking large masses
 TLS hyperuricemia hyperkalemia, hyperphosphatemia, hypocalcemia, oliguria, and
renal failure a, require vigorous hydration and either a Xanthines oxidase inhibitor
(allopurinol,) or, more often, recombinant urate oxidase
70
 DIFFERENTIAL DIAGNOSIS
Head and neck lymphadenopathy should be differentiated from
infectious nodal etiologies;
Mediastinal masses from HD and germ cell tumors; abdominal
involvement from other abdominal malignant masses such as
Wilms tumor, neuroblastoma, and rhabdomyosarcoma;
Bone marrow involvement from precursor B (Pre-B) acute
lymphoblastic leukemia and T-cell acute lymphoblastic leukemia
 The distinction between non-Hodgkin lymphoma and acute
leukemia is arbitrary.
In most treatment protocols, acute leukemia is now defined on the
basis of marrow involvement above than some threshold (typically
a blast count of >25%) irrespective of the presence of bulky

02/20/24 71
SUPPORTIVE CARE
Some patients require G-CSF prophylaxis to prevent
fever and neutropenia following myelosuppressive
chemotherapy
Prophylactic antibiotics to prevent infections.

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COMPLICATIONS
Chemotherapy for advanced disease are at acute risk
for serious mucositis, infections, cytopenias
Electrolyte imbalance(TLS), and poor nutrition.
 Long-term complications may include growth
retardation, cardiac toxicity, gonadal toxicity with
infertility, and secondary malignancies.

02/20/24 73
PROGNOSIS.
The prognosis is excellent for most forms of
childhood and adolescent NHL.
Localized disease have a 90–100% chance of survival,
 Advanced disease have a 60–95% chance of survival.
The variation in survival depends on pathological
subtype, tumor burden at diagnosis (LDH level), +/-
CNS disease, and specific sites of metastatic spread.

02/20/24 74
02/20/24 75
ETIOLOGY.
2ND Most common neoplasm next to leukemia
Etiology is not well defined.
Familial and hereditary syndromes associated
E.g Neurofibromatosis type 1 and 2
 Ionizing radiation

02/20/24 76
PATHOGENESIS.
Among the >100 histologic categories
5 categories constitute 80% of all pediatric brain
tumors:
 Juvenile pilocytic astrocytoma
 Medulloblastoma/primitive neuroectodermal tumor
(PNET)
 Diffuse astrocytoma
 Ependymoma
 Craniopharyngioma

02/20/24 77
CLINICAL MANIFESTATIONS
Depend on
• Location
• Type
• Rate of growth

02/20/24 78
…..
 The first year of life, supratentorial tumors predominate
 From 1–10 yr of age, Infratentorial tumors predominate.
 After 10 yr of age, supratentorial tumors again
predominate,
• Infratentorial tumor location (43.2%),
• Supratentorial location (40.9%),
• Spinal cord (4.9%),
• Multiple sites (11%).

02/20/24 79
 Glioma

Pineal region umor

Chiasmal glioma
Craniopharigoma Brain stem
tumor gliaoma
Meduloblastoma
Ependymoma
Cerebellar
strocytoma
02/20/24 80
Infratentorial Tumors
 Presents with increased ICP
 The classic triad of headache, vomiting, and
papilledema
 Disorders of equilibrium, gait, and coordination
 Torticolis may result in cerebellar tonsil herniation
 Blurred vision, diplopia, and nystagmus
 CRANIAL Nerve PALSIES
 Focal neurologic deficit

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Supratentorial tumors
 OLDER CHILDREN
 VISUAL SYMPTOMS
 SEIZURES
 FOCAL NEUROLOGIC DEFICIT
 SCHOOL FAILURE
 PERSONALITY CHANGES
 Speech disruption
Suprasellar region and third ventricular
region:may present with neuroendocrine deficits such as diabetes
insipidus, galactorrhea, precocious puberty, delayed puberty, and
hypothyroidism.
Spinal cord tumors :and spinal cord dissemination of brain tumors
manifest as long nerve tract motor and/or sensory deficits, bowel and
bladder deficits, and back or radicular pain.

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DIAGNOSIS.
History, P/E including ophthalmologic examination
 MRI , CT

Neuroendocrine dysfunction hormonal assay

Both serum and CSF β-human chorionic

gonadotropin and α-fetoprotein can assist in the
diagnosis of germ cell tumors.

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Treatment
Surgery
Radiation therapy
Chemotherapy
Specific treatment

02/20/24 84
 Neuroblastoma

02/20/24 85
EPIDEMIOLOGY
 Cancer which arise from primitive sympathetic ganglion
cells.
Third most common pediatric cancer, 8% of childhood
malignancies.
 NB is the most commonly diagnosed neoplasm in infants.
 The median age at diagnosis is 2 yr, and 90% of cases are
diagnosed by 5 yr of age.
Slightly higher in boys and in whites
Risk factor includes
• Maternal factors(opium consumption, folate def
• Genetic factors(NF1,turner syndrome)
• Familial neuroblastoma (1-2% of cases)
02/20/24 86
Clinical presentation
Abdominal mass(2/3rd), a firm, nodular that is
palpable in the flank or midline is causing abdominal
discomfort
Mediastinal tumors : tracheal or narrowing with
resultant stridor breathing difficulty, may cause the
superior vena cava syndrome .
Horner syndrome (ptosis, miosis, and Anhydrosis)
Involvement of the cervical paravertebral sympathetic
chain and inferior cervical (stellate) ganglion can result

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….
Tumor infiltration of the
periorbital bones, typically
unilateral, can cause the
characteristic periorbital
ecchymosis ("raccoon eyes"),
ptosis, and proptosis
Metastatic spread to the skin
manifests as papules or
subcutaneous nodules that
can be distributed over the
entire body. (as firm, bluish-
red, and nontender )

02/20/24 88
….
The most common sites of metastasis are the long
bones and skull, BM, liver, LD, and skin. Lung
metastases are rare,
Paravertebral tumors —
The subsequent epidural spinal cord compression,
can cause pain, motor or sensory deficits, or loss of
bowel and/or bladder control.

02/20/24 89
….
Opsoclonus-myoclonus-ataxia (OMA) are rapid, dancing
eye movements, rhythmic jerking, and/or ataxia.
this paraneoplastic syndrome includes the presence of
serum autoantibodies
Catecholamine secretion by tumor may give rise to
symptoms (eg, hypertension,)
Secretion of VIP ( vasoactive intestinal peptide)
- abdominal distension and intractable secretory diarrhea
These symptoms usually resolve after removal of the
tumor

02/20/24 90
Staging
Stage 1: Localized tumor confined to the area of origin.
Stage 2A: Unilateral tumor with incomplete gross resection;
identifiable ipsilateral and contralateral lymph node negative for
tumor.
Stage 2B: Unilateral tumor with complete or incomplete gross
resection; with ipsilateral lymph node positive for tumor;
identifiable contralateral lymph node negative for tumor.
Stage 3: Tumor infiltrating across midline with or without regional
lymph node involvement; or unilateral tumor with contralateral
lymph node involvement; or midline tumor with bilateral lymph
node involvement
Stage 4: Dissemination of tumor to distant lymph nodes, bone
marrow, bone, liver, or other organs except as defined by Stage 4S.
Stage 4S: Age <1 year old with localized primary tumor as defined in
Stage 1 or 2, with dissemination limited to liver, skin, or bone
marrow (less than 10 percent of nucleated bone marrow cells are
tumors
02/20/24 91
PATHOLOGY
Spectrum of tumors with variable degrees of neural
differentiation, ranging from undifferentiated small
round cells (neuroblastoma) to tumors containing
mature ganglion cells (ganglioneuroblastoma or
ganglioneuroma).
NB is small round blue cell tumors, as
rhabdomyosarcoma, Ewing sarcoma, and non-Hodgkin
lymphoma,retinoblastoma,primitive neuro ectodermal
tumor

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DIAGNOSTIC
 History and physical examination.
 Blood counts,
 Liver and kidney function.
 In addition, ferritin and lactate dehydrogenase (LDH) they may be
elevated initially and can be expected to return to normal during
adequate treatment.
 Abdominal u/s by CT or MRI scan .
 Chest radiograph ( [AP] and lateral);
 Chest CT or MRI are necessary only if the chest radiograph is positive
 A radionuclide bone scan - spread to cortical bone
 Biobsy
 In about 90% of cases elevated levels of catecholamines or its
metabolites are found in the urine or blood.
 This metabolites include dopamine, homovanillic acid (HVA), and/or
vanillylmandelic acid (VMA).
02/20/24 93
Treatment
SURGERY

CHEMOTHERAPY

RADION THERAPY

Stage 4S disease spontaneusly regress

02/20/24 94
4. Wilms tumor
• Is the most common renal malignancy in children
the fourth most common childhood cancer
F:M is 1.1 to 1 for unilateral tumor
is 1.7 for bilateral involvement
8 cases per million children <15 yr of age.
 It usually occurs b/n 2–5 yr of age,
 6% of pediatric cancers
 Is the second most common malignant abdominal
tumor in childhood
02/20/24 95
Associated congenital syndromes
WAGR
 (Wilms tumor, aniridia, GU anomalies, and mental
retardation )
deletion of the WT1 gene located at 11p13
Denys-Drash,
 is a triad of progressive renal disease, male
pseudohermaphroditism, and Wilms tumor.
Beckwith-Wiedemann syndromes.
 macrosomia, macroglossia, omphalocele,, and
hemihypertrophy

02/20/24 96
PATHOLOGY
 Most Wilms tumors are solitary lesions.
7% of patients have bilateral.
 The gross appearance of Wilms tumor is typically
gray or tan.
Favorable :
blastema, epithelia, and stromal
Unfavorable: Clear cell sarcoma,anaplsia,rhabdoid

02/20/24 97
CLINICAL PRESENTATION
 Mostly present with an asymptomatic abdominal mass.
Usually parent to notice it while bathing the infant.
Symptoms can include abdominal pain (30 %), hematuria
(12- 25 %), and hypertension (25%).
A subset of patients with subcapsular hemorrhage can
present with rapid abdominal enlargement, anemia,
hypertension
P/E, nontender, smooth mass that rarely crosses the
midline and generally does not move with respiration.
Vigorous palpation may rupture the renal capsule,
resulting in tumor spillage, which increases the tumor
stage and the need for more intensive therapy

02/20/24 98
….
Abdominal ultrasonography
Doppler ultrasonography should be performed to detect
tumor infiltration of the renal vein and inferior vena cava,
CT is recommended to further evaluate the nature and
extent of the mass
Imaging of the chest
CT scanning provides confirmation of the intrarenal origin
of the mass
It also may provide information on the extent of tumor,
growth into the inferior vena cava, and integrity of the
contralateral kidney
Occasionally, angiography may be requested to plan the
surgical procedure.
Bone scans are obtained for clear cell sarcoma of the kidney
and MRI or CT of the brain in a malignant rhabdoid tumor.
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Pathogenesis
Favorable Unfavorable

Contain epithelia, stroma, blastema Cells with large hyperchromatic nuclei,

Devoid of anaplasia with multipolar mitotic figures
Common with good prognosis Focal/ diffuse areas of anaplasia
High rate of tumor relapse and death
Subtypes: clear cell sarcoma, rhabdoid
tumor
Poor prognosis

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Staging
Stage
I Confined to kidney, intact capslar surface, completely excisable

II Confined to kidney, but capsule is penetrated and regional extension,

vessel infiltration and local spillage into flank area, completely
excisable
III Post surgical residual, but no hematogenous spread, confined to
abdomen, may involve perirenal bed, draining lymph nodes and
surrounding tissue and organ by contiguity. Not completely
removable due to infiltration of vital structure

IV Hematogenous metastasis to lungs and liver

V Bilateral renal involvement at diagnosis

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DIFFERENTIAL DIAGNOSIS
 The differential diagnosis of Wilms tumor includes
neuroblastoma and other renal tumors.
Imaging studies and tissue histology differentiate Wilms
tumor from these other disorders.
Neuroblastoma can be differentiated from Wilms tumor by
contrast-enhanced CT or ultrasonography, which
distinguishes renal and nonrenal tissue.
Final diagnostic confirmation is based upon tissue
Clear cell sarcoma of the kidney — Clear cell sarcoma is the
second most common pediatric renal tumor.
Rhabdoid tumor of the kidney — Rhabdoid tumor of the
kidney is a highly malignant renal tumor, which occurs
most frequently in children less than two years of age and
almost never in those older than five years of age

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Laboratory
Complete blood count
Renal function
Urinalysis,
Liver function,
Serum calcium, a, and coagulation studies
Coagulation studies should be considered because
acquired von Willebrand's disease occur in approximately
8 percent of patients with Wilms tumors at diagnosis .
This abnormality appears to have minimal clinical
significance, although some experts suggest that the
coagulopathy should be corrected perioperative

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Treatmentt
SURGERY
CHEMOTHERAPY
RADIATION
Bilateral Wilms’ tumor
bilateral partial nephrectomy
chemotherapy
radiation
survival rate=60-85%

02/20/24 104
Prognosis
Based on histologic type, stage, size
Generally,>60% at any stage
>90% survive from stage I-III.

02/20/24 105
5. Rhabdomyosarcoma
 Most common of the soft tissue sarcomas
≈ 5- 8% of cancers in children
Occurs in any anatomic site
Head and neck 40 %
Genitourinary tract 20%
Trunk 10%
Retroperitoneal 10%
Increased frequency of occurrence in patients
with Neurofibromatosis
Pathogenesis
Arise from embrogonic mesenchyme of striated
skeletal muscle
Belongs to group of small round cell tumors
Four histologic subtypes
1. Embryonal type (60% ):-Intermediate Px
2. Botryoid type – Embryonal variant 6% :-Mostly found
in bladder, nasopharynx, Vagina, middle ear.
3. Alveolar tumors( 15% ):- Carries the poorest Px
4. Pleomorphic type ( Adult form) ≈1%:-Undifferentiated
sarcoma
Clinical manifestation
Symptoms are mainly due to mass effects
Mass /Lung – superficial
Nasopharynx – Nasal congestion, epistaxis, mouth
breathing and difficulty of swallowing
CNS extension – Cranial N palsy, increase ICP
Middle ear – Pain, Otorrhea, hearing loss, mass in the ear
canal
Laryngeal tumor – croupy cough, progressive stridor
GU- hematuria, obstruction and mass
Diagnosis
Histology :- small round blue cell
Differentiated by the use of biopsy with immuno
histochemical staining
CT, MRI – Localize, dissemination
Radionuclide bone scanning – Metastasis
CBC, OFT
Treatment Group III Tumors
Group I tumors Gross residual tumor
Complete local excision Multiagent
Chemotherapy chemotherapy +
Group II tumors Radiotherapy
Microscopic residual after surgery Group IV Tumor
Local radiation ----- Metastatic Tumor
Multiagent chemotherapy Systemic
chemotherapy +
irradiation
Prognosis
Poor in disseminated diseases
Resectable – diseases free survival is 80-90%
Incompletely resected disease free survival is apprx.
70%