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• Cancer in individuals ≤19 yr of age is uncommon representing only about 1% of all new cancer cases in the USA

  
• Malignant neoplasms remain the second most common cause of all deaths (12.8%) among persons 1–14 yr of age in the USA
• Pediatric cancers


  • Differ markedly from adult malignancies in both prognosis and distribution by histology and tumor site
  • Common childhood tumors are lymphohematologic, embryonal, CNS tumors, soft tissue tumors
  • Unlike adults epithelial tumors are uncommon in children

  
• Tumor incidence is highest during early childhood and adolescence

  
• Percentage of different childhood tumors

  • Lymphohematopoietic cancers - 40%
  • Nervous system cancers - 30%
  • Soft tissue sarcomas - 10%
  • Embryonic tumors - 10%
  • Neuroblastoma - 6-7%
  • Wilms tumour - 6-7%
  • Retinoblastoma - 3%

  
• Embryonal tumors, acute leukemias, non-Hodgkin lymphomas, and gliomas

  • Peak in incidence from 2–5 yr of age

  
• As children age


  • Bone malignancies, Hodgkin disease, gonadal germ cell malignancies, and other carcinomas increase in incidence
• Oncogenes


  Genes implicated in the development of cancer
• Tumor suppressor genes


  Important regulators of cellular growth and programmed cell death or apoptosis
• Mechanisms by which proto-oncogenes can be activated to oncogenes

  1. Amplification

  2. Point mutation

  3. Translocation
• Tumor suppressor genes


  • Alteration in the regulation of tumor suppressor genes results in cancer
  • Mutations in P53 & Rb gene
• Knudson's "two-hit" model


  Inactivation of both alleles of a tumor suppressor gene is required for expression of a malignant phenotype

  
• Mechanism of cancer formation

  • Aberrant cellular growth
  • Signal transduction
  • Cell cycle control
  • DNA repair
  • Cellular growth and differentiation
  • Translational regulation
  • Senescence and apoptosis
  • Cancer stem cells

  
• Cell cycle


  All cells at some point enter the cell cycle, whether during embryonic development or normal body maintenance<|>Cell growth occurs via cell cycle
• Phases of the cell cycle

  • G0 - Cell is quiescent and withdraws from cell cycle
  • G1 - Genes actively direct synthesis of RNA and proteins
  • S - DNA replication
  • G2 - Final growth and activity before mitosis
  • M - The dividing phase of the cell cycle
• Cyclins


  Groups of proteins that control progress through each phase of the cell cycle (produced by proto-oncogenes)
• Cyclin inhibitors


  Proteins that inhibit the activity of cyclins, thereby inhibiting cell growth and cell division (produced by tumor suppressor genes)
• Cell cycle turnover


  • Rapidly dividing cells: epidermal, BM, epithelial lining of GIT, oropharynx
  • Slow dividing cells: fibroblasts, osteoblasts, osteoclasts
  • Non-dividing cells: striated muscle, nerve cells
• Cell cycle/growth stimulus


  • Internal signals: growth factors (tissue growth and differentiation, tissue injury)
  • External signals: infections
• Apoptosis


  A programmed physiologic process for normal cell turnover
• Aberrant cell division


  The primary characteristic of a cancer (malignant) cell, such a cell has lost the ability to control cell growth and the ability to undergo apoptosis

  
• Properties of cancer cells

  • Uncontrolled growth
  • Invasion
  • Metastasis
  • Angiogenesis
  • Immortality

  
• Genetic risk factors for childhood cancer

  • Neurofibromatosis
  • Down syndrome
  • Beckwith-Wiedemann syndrome
  • Ataxia-telangiectasia
  • Li-Fraumeni (P53) syndrome
  • Tuberous sclerosis
  • Xeroderma pigmentosum
  • Nevus basal cell carcinoma syndrome

  
• Viral risk factors for cancer

  • Epstein-Barr virus (EBV)
  • Hepatitis B virus
  • Hepatitis C virus
  • Human papillomavirus (HPV 16, 18)
  • Human herpes virus 8
• Unlike adult epithelial malignancies, the environmental risk of developing cancer is less common in children

  
• Childhood leukemia


  The most common malignant neoplasms in childhood, accounting for 41% of all malignancies in children <15 yr of age
• Types of childhood leukemia

  • Acute lymphoblastic leukemia (ALL) - 77%
  • Acute myelogenous leukemia (AML) - 11%
  • Chronic myelogenous leukemia (CML) - 2-3%
  • Juvenile chronic myelogenous leukemia (JCML) - 1-2%

  
• Pathogenesis of childhood leukemia

  • Genetic abnormalities in a hematopoietic cell
  • Unregulated clonal proliferation of cells
  • Growth advantage over normal cellular elements
  • Increased rate of proliferation
  • Decreased rate of spontaneous apoptosis
  • Disruption of normal marrow function and marrow failure
• Childhood leukemia


  • Peak incidence 2–6 yr of age
  • More common in boys than in girls
  • Chromosomal abnormalities associated with leukemia: Down syndrome, Bloom syndrome, ataxia-telangiectasia, Fanconi syndrome
• Environmental factors for childhood leukemia

  • Ionizing radiation
  • Drugs: Alkylating agents, Nitrosourea, Epipodophyllotoxin
  • Benzene exposure
  • Advanced maternal age
• In virtually all cases, the etiology of ALL is unknown
• Exposure to medical diagnostic radiation

  Increases the incidence of ALL
• 1. cell ALL


  Associated with Epstein-Barr viral infections
• In twins, if the first twin develops leukemia, the risk to the second twin is higher than in the general population
• Clinical features of childhood leukemia

  • Fever
  • Easy bruising
  • Epistaxis
  • Bleeding from any site
  • Bone pain
  • Joint swelling
  • Lymphadenopathy (50%)
  • Pallor
  • Weakness
  • Recurrent infections
  • Opportunistic infections
  • Purpuric and petechial skin lesions
  • Mucous membrane hemorrhage
  • Hepatosplenomegaly
  • Bone or joint tenderness or joint swelling and effusion
  • Testicular swelling

  
• Lab findings in childhood leukemia

  • Leukocyte count (median 33,000, 75% <20,000)
  • Thrombocytopenia (75% of patients)
  • Hepatosplenomegaly (30-40% of patients)
  • CNS symptoms (5% of patients)

  
• ALL classification


  Based on morphologic, immunologic, biochemical, and cytogenetic features<|>French-American-British (FAB) system: L1, L2, L3
• L1 ALL


  Lymphoblasts are small cells with scant cytoplasm
• Clinical features of ALL

  • Nonspecific fever, easy bruising, epistaxis, bleeding from any site, bone pain, joint swelling
  • Lymphadenopathy (50 percent)
  • Pallor, Weakness, recurrent infections
  • Opportunistic infections
• Clinical features of ALL

  • Pallor
  • Purpuric and petechial skin lesions
  • Mucous membrane hemorrhage
  • Lymphadenopathy, HSM
  • Bone or joint tenderness or joint swelling and effusion
  • Testicular swelling