Pediatric Malignancies

Dr/Rasha Teleb
Leukemia
• They account for 41% of pediatric malignancies.
• Types of leukemias
 Acute lymphoblastic leukemia (ALL): represents about 75% of all leukemias.
 Acute myeloid leukemia (AML): accounts for 20% of leukemias.
 Chronic myeloid leukemia (CML): most of the remaining 5% of leukemias.
Acute lymphoblastic leukemia (ALL)
• The peak incidence is between 2-6 yr of age
• boys are slightly more frequently affected than girls.
• The disease is more common in children with certain chromosomal abnormalities
e.g. Down syndrome, and Fanconi syndrome.
 ALL: Classification
• Morphologic subtypes:
L1: predominantly small cells with little cytoplasm.
L2: Larger, pleomorphic cells with increased cytoplasm, irregular nuclear shape, and
prominent nucleoli.
L3: Cells have finely stippled and homogeneous nuclear chromatin, prominent
nucleoli, and deep blue cytoplasm with prominent vacuolization.
• Immunological subtypes:
T- cell ALL (14%)
B- cell ALL (0.6)
Pre B- ALL (18 %) and early pre B- ALL (67 %).
 Clinical Manifestations
• Symptoms
 Non specific symptoms: e.g. anorexia, irritability, lethargy and loss of weight. 
Fever: intermittent low grade fever
 Bone pain due to expansion of subperiosteal infilteration by leukemic cells and
arthralgia due to joint infiltration.
 Symptoms of progressive bone marrow failure: e.g. pallor, purpura, bruising,
epistaxis and repeated infections.
 Symptoms of increased intracranial tension that indicate leukemic involvement of
the C.N.S e.g. headache, vomiting and blurring of vision.
• Signs
 Fever: pyrexia at presentation can be due to the disease process itself or viral
respiratory infection, otitis media and other infections.
 Pallor: it is due to defective erythropoieses from infiltration of bone marrow and
blood loss from bleeding.
 Petechiae, bruising and mucous membrane bleeding.
 Generalized lymphadenopathy, splenomegaly or less commonly hepatomegaly.
 Signs of mediastinal compression: respiratory distress is related to large
mediastinal mass, This problem is most typically seen in adolescent boys with T- cell
ALL.
 Signs of increased intracranial pressure e.g. papilledema, retinal hemorrhages, and
cranial nerve palsies.
 Laboratory diagnosis
1- Hemogram shows:
 Anemia and thrombocytopenia.
 Total leucocytic count (WBCs): < 10,000/mm3 in most patients, >50,000/ mm3 in 20%. Blast
cells in peripheral hemogram are suggestive of diagnosis of leukemia.
2- Bone marrow examination: demonstrates more than 25% of the bone marrow cells as a
homogeneous population of lymphoblasts. Bone marrow biopsy may be needed
3- Lumbar puncture: to examine the CSF for malignant cells. If overt CNS leukemia is present,
a worse stage is implied.
4- Serum uric acid, liver function tests and renal function before onset of treatment.
5- Cytogenetic studies: to detect chromosomal abnormalities that may influence the prognosis
and the choice of therapy.
6- Immumophenotyping
7- Chwst X-ray: for mediastinal lymph nodes in Tcell leukemia
• Differential diagnosis
1- Acute myelogenous leukemia.
2- Tumors that infiltrate the bone marrow e.g. neuroblastoma, lymphomas, and
retinoblastoma.
3- Diseases of bone marrow failure: such as aplastic anemia.
5- Infectious mononucleosis: with purpura and anemia, it presents with fever,
lymphadenopathy and hepatosplenomegaly. Hemogram shows atypical
lymphocytes, Paul Bunnell test is positive.
• Treatment of standard risk ALL
 The single most important prognostic factor in ALL is the treatment.
The important prognostic factors are the age (1-10 years) of the patient, the initial
leukocytic count and the speed of response to treatment.
• Drug therapy Treatment includes 3 phases + intrathecal therapy
1- Induction of remission (4 weeks)
 Vincristine: weekly.
 Dexamethazone or prednisone.
 Repeated doses of L-asparaginase or a single dose of a long-acting asparaginase.
 Intrathecal cytarabine or methotrexate or both.
 Cases with a high risk ALL also receive daunomycin at weekly intervals.
Remission is defined as less than 5% blasts in the marrow and a return of
neutrophil and platelet counts to near-normal levels after 4-5 week of treatment.
2- Consolidation intensification phase: using multiagent chemotherapy lasts from 14-
28 weeks
3- Maintenance therapy: lasts for 2-3 yr and includes:
Mercaptopurine: daily.
 Methotrexate: weekly.
 Intermittent doses of vincristine and corticosteroid.
Intrathecal therapy: methotrexate, hydrocortisone, ara-c (cytarabine).
 It is given repeatedly by lumber puncture to avoid CNS relapse.
Patients who have lymphoblasts in the CSF and an elevated CSF leucocyte count at
the time of diagnosis receive irradiation to the brain and spinal cord.
Bone marrow transplantation
Supportive therapy: blood or blood product transfusions growth factor, treatment of
infection, and management of metabolic disturbances.
• Types of relapse
1- Bone marrow relapse: is the most common and the most serious. Bone marrow
transplantation following intensive chemotherapy is ideal for patients with bone
marrow relapse.
2- CNS relapse: manifests by increased intracranial tension, convulsions and cranial
nerve paralysis. The diagnosis is confirmed by the presence of leukemic cells in the
CSF. The treatment includes intrathecal medication, craniospinal irradiation and
systemic chemotherapy.
3- Testicular relapse: painless swelling of one or both testes. The diagnosis is
confirmed by biopsy. Treatment includes systemic chemotherapy and local
irradiation.
Lymphomas
• Lymphomas are the 3rd most common cancer in children
• They include non-Hodgkin lymphomas and Hodgkin disease.
Non-Hodgkin lymphoma (NHL)
Malignant clonal proliferation of primarily T or B-lymphocytes with increased
frequency in children with immunodeficiency diseases.
Pathological primary subtypes
 Small non-cleaved cell lymphoma (Burkitt and non-Burkitt subtypes, B-cell
origin).
 Lymphoblastic lymphoma: T- cell type
 Large cell NHL: T- cell, B- cell or indeterminate cell origin.
• Clinical manifestations:
1- Presentation is determined by the disease site:
 Abdominal lymphoma: presents by abdominal mass or distention, nausea,
vomiting or change in bowel habits.
 Mediastinal lymphoma: presents by mediastinal mass, pleural effusions or
respiratory distress.
 Head and neck regions: painless, firm lymph nodes. 2- Involvement of other
systems:
 Bone marrow: anemia or pancytopenia.
 CNS: manifestations of increased intracranial pressure and cranial nerve paralysis.
• Diagnosis
1- Complete and differential blood count.
2- Bone marrow and CSF study for malignant cells.
3- Tissue diagnosis by:
 Lymph node biopsy, either excisional or fine needle aspirate.
 Thoracotomy or mediastinoscopy for biopsy of mediastinal mass.
 Thoracocentesis for detection of malignant cell in pleural effusion.
 Open abdominal biopsy for abdominal mass.
4- Imaging study: chest x-ray and CT and MRI of chest, abdomen, bone and brain.
Treatment:
• combination of chemotherapy Regimen of ALL for those with lymphoblastic
lymphoma for 1.5 years.
• Surgery for completely resectable masses.
Hodgkin lymphoma
• Incidence: it is not common in children. It occurs in late childhood to adolescence,
males are more affected than females.
• Pathologic classification
1- Nodular sclerosing type.
2- Mixed cellularity type.
3- Lymphocytic predominant type.
4- Lymphocytic depletion type: the least common and least favorable.
The cardinal cell is the Reed-Sternberg cell (mirror cell with 2 nuclei each with
prominent nucleolus and distinct membrane).
• Clinical manifestations
 General symptoms and signs: lethargy, anorexia, unexplained fever, night sweating
and weight loss.
 Painless enlargement of lymph nodes. The nodes are firm, non-tender and usually
discrete.
 Mediastinal syndrome is a common presentation.
 Extra-nodal involvement e.g. intrathoracic leading to tachypnea and pulmonary
insufficiency.
• Investigations
1- Blood count: neutrophilic leukocytosis, lymphopenia, sometimes eosinophilia and
monocytosis.
2- Lymph node biopsy: confirms the diagnosis.
3- Bone marrow biopsies should be done in all patients with advanced disease.
4- Liver function tests.
5- Imaging study: X- ray chest, CT chest and abdomen, and bone scan.
Treatment: chemotherapy, radiotherapy or combined modality therapy.
 Wilms tumor (nephroblastoma)
 Wilms tumor is an embryonal tumor of the kidney.
 It may arise in one or both kidneys.
 It is the most common genitourinary malignancy-affecting children, it accounts for
about 6%of childhood malignancies, so ranks fourth in incidence among solid tumors
of childhood.
 It occurs in equal frequency in boys and girls most commonly between 2-5 years,
the mean age of diagnosis is 4 years.
 The majority of Wilms tumors are of sporadic occurrence however in a few
children it occurs in setting of associated malformation or syndrome.
Pathology: Triphasic appearance, with varying proportions of three cell types
(blastemal, stromal, epithelial).
• Clinical features
 Asymptomatic abdominal mass usually discovered accidentally by parents or
routine abdominal examination. The mass is firm and smooth and does not cross the
midline.
 Associated symptoms include abdominal pain, fever, and hematuria.
 Hypertension may occur in 25% of cases of Wilms tumor
 Bilateral Wilms tumor may occur.
• Investigations
1- Plain abdominal x-ray: shows soft tissue mass displaced bowel.
2- Abdominal ultrasound: define the mass and enable assessment of contra lateral
kidney.
3- CT and MR scanning enable more precise definition of tumor spread.
4- A plain chest radiograph and/or chest CT scanning should be obtained to
determine the presence of pulmonary metastasis.
5- Biopsy from the tumour.
• Differential diagnosis:
Hydronephrosis, polycystic diseases of the kidney and other malignancy such as
neuroblastoma, lymphoma.
• Treatment
Preoperative chemotherapy: this is a four-week course of vincristine and
actinomycin D for nonmetastatic disease.
Surgery is done at 5th week followed by postoperative chemotherapy at week 7.
Radiotherapy is required for incompletely resected diseases and in cases with lung
metastasis.
Prognosis Prognosis is good: survival for localized disease is 90% and for
metastatic disease is 70%
 Neuroblastoma
 Neuroblastoma is an embryonal tumor derived from neural crest cells that form the
adrenal medulla and the sympathetic nervous system.
 It is the third most common solid tumour of childhood.
 The age incidence: 90% are less than 5 years.
Etiology: is unknown,
- It may be attributed to environmental and genetic factors
- exposure to phenytoin in utero may confer a higher risk for neuroblastoma
development.
- Familial neuroblastoma is found in 1-2% of cases.
Pathology It ranges from undifferentiated small round cells (neuroblastoma) to
tumours containing mature ganglion cells (ganlioneuroblastoma or ganglioneuroma)
• Clinical manifestations
 The commonest primary sites are adrenal gland. Other sites: abdomen, chest,
pelvis and neck, sympathetic ganglia.
Neuroblastoma has several diverse presentations because of different site of
origin:
- Abdominal mass: it is the commonest presentation, it is hard, irregular and non
tender mass located in right or left upper quadrant, it commonly crosses the
midline.
- Posterior mediastinal mass: the tumor may be a symptomatic or it may present
with, mediastinal syndrome, progressive dyspnea, dysphagia and stridor.
- Proptosis: proptosis may be unilateral or bilateral.
- Multiple skin nodules in infancy: these nodules are firm and purple in color, they
mainly occur in infants under the age of 6 months.
- Spinal cord compression: may cause paralysis and bowel or bladder dysfunction
- Pancytopenia, arthritis and bone pain: may be the presentation of neuroblastoma
due to wide spread bone metastasis.
- Cervical neuroblastoma: presented with neck mass, Horner syndrome (unilateral
ptosis, myosis, and anhydrosis).
- Paraneoplastic syndromes including secretory diarrhea, profuse sweating and
hypertension.
• Investigations
- Plain x ray: may show calcification in abdominal neuroblastoma or mixed lytic
and sclerotic areas in the long bones and skull
- Ultrasound scan, CT or MRI: define primary tumour extent
- Bone marrow: multiple site aspirates are necessary to exclude infiltration of bone
marrow.
- Urinary catecholamines urinary catecholamines (vanillylmandelic acid and
homovanillic acid) are elevated in at least 90% of patients at diagnosis.
- Biopsy: in addition to routine histology and immunocytochemistry, molecular/
genetic study is required.
Differential diagnosis:
- Wilms tumor: abdominal ultrasound or CT examination is able to differentiate the
tumors.
- Leukemia: it presents by fever, pallor, purpura, hepatosplenomegaly and
lymphadenopathy it is diagnosed by blood picture and bone marrow examination
• Treatment:
- Complete surgical excision is the initial treatment of choice for patients with localized
neuroblastoma.
- In patients with advanced diseases: combination chemotherapy usually is given after
confirmation of the diagnosis. Delayed resection of primary tumor is undertaken after
numerous courses of chemotherapy.
- The most common chemotherapeutic agents are vincristine, cyclophosphamide,
doxorubcin, cisplatin and etoposide.
- Radiation therapy often given to primary tumor bed and area of metastatic disease.
• Prognosis: the prognosis is affected by:
- Age of the patient at presentation of the disease.
- Stage of the disease.
- The primary site.
- The presence or absence of metastasis.
- Cytogenetics and histopathology.