II. Epidemiology

  1. Incidence Childhood Cancer in developed nations: 105-150 cases per million children

III. Risk Factors

  1. Childhood Cancer Survivors (Alkylating Agents, radiotherapy, Stem Cell Transplant)
    1. Acute Myelogenous Leukemia
    2. CNS Tumor
    3. Non-Hodgkin Lymphoma
    4. Myelodysplastia
  2. DNA damage repair defects (Ataxia-telangiectasia, Bloom Syndrome, Fanconi Anemia)
    1. Leukemia
    2. Lymphoma
    3. Myelodysplasia
    4. Wilms Tumor
    5. Hepatocellular Carcinoma
    6. Stomach Cancer
    7. Colon Cancer
    8. Breast Cancer
  3. Denys-Drash Syndrome
    1. Wilms Tumor
  4. Down Syndrome
    1. Acute Lymphoblastic Leukemia
    2. Acute Myelogenous Leukemia
  5. Family History of Retinoblastoma (first degree relative)
    1. Retinoblastoma
    2. Osteosarcoma
  6. Gastrointestinal Syndrome (Familial adenomatous polyposis, Gardner Syndrome)
    1. Colon Cancer
    2. Hepatoblastoma
    3. Medulloblastoma
    4. Miscellaneous gastrointestinal cancers
  7. Hemihypertrophy Syndrome (Beckwith-Wiedemann syndrome)
    1. Hepatoblastoma
    2. Wilms Tumor
  8. Immunodeficiency Disorder (Wiskott-Aldrich Syndrome, Common and Severe Combined Immunodeficiency)
    1. Leukemia
    2. Non-hodgkin Lymphoma
  9. Li-Fraumeni Syndrome (autosomal dominant p53 germline mutation)
    1. Adrenal Tumor
    2. Brain Tumor
    3. Soft Tissue Sarcoma
    4. Bone Sarcoma
  10. Neurocutaneous Syndrome (Neurofibromatosis, Tuberous Sclerosis, von Hippel-Lindau Disease)
    1. Optic glioma
    2. CNS Tumor
    3. Neurofibrosarcoma
    4. Peripheral nerve sheath tumor
    5. Leukemia
    6. Wilms Tumor
  11. Turner Syndrome
    1. Gonadoblastoma
  12. WAGR Syndrome
    1. Wilms Tumor
  13. Xeroderma Pigmentosum
    1. Melanoma (and other skin cancer)

IV. Causes: Hematologic

  1. Shared symptoms among Hematologic Cancers
    1. Pallor and Fatigue
    2. Persistent fever or recurrent without source
    3. Anorexia
    4. Bone pain
    5. Lymphadenopathy and hepatosplenomegaly
    6. Petechiae, Purpura or Gingival Bleeding
  2. Specific Hematologic Cancers
    1. Leukemia (34% of Pediatric Cancers, Acute Lymphoblastic Leukemia, Acute Myelogenous Leukemia)
      1. Persistent or recurrent infections
    2. Lymphoma (11% of Pediatric Cancers, Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma)
      1. B-Symptoms (Night Sweats, fever and weight loss)
      2. Abdominal Pain, abdominal mass, Vomiting, Constipation
    3. Histiocytosis (<0.5% of Pediatric Cancers)
      1. Rashes (masquerades as refractory Eczema)
      2. Chronic Otorrhea
      3. Proptosis
      4. Diabetes Insipidus

V. Causes: Head and Neck (and neurologic)

  1. Central nervous system tumors (22% of Pediatric Cancers)
    1. Persistent Headache (especially morning or causing night awakening)
    2. Vomiting
    3. Ataxia
    4. Squiniting, Proptosis or Diplopia
    5. Cranial Nerve deficit
    6. Seizure
    7. Developmental delay or regression (e.g. school performance or personality sudden change)
    8. Torticollis
    9. Increasing Head Circumference or bulging Fontanelle (Increased Intracranial Pressure)
  2. Neuroblastoma (7% of Pediatric Cancers)
    1. Abdominal Mass or neck mass
    2. Failure to Thrive, anorexia, pallor
    3. Eye changes (periorbital Ecchymosis, Proptosis, horner syndrome, iris heterochromia, squinting, rapid-chaotic eye movements)
    4. Oposoclonus-Myoclonus syndrome (dancing eyes, dancing feet)
    5. Neurologic deficits (e.g. leg weakness)
    6. Bowel or Bladder obstruction
    7. Bone pain or back pain
    8. Subcutaneous Nodules and Lymphadenopathy
    9. Bursts of cathecholamine hypersecretion (attacks of sweating, Flushing, Hypertension, pallor and Palpitations)
  3. Nasopharyngeal carcinoma (<0.5% of Pediatric Cancers)
    1. Cervical Lymphadenopathy
    2. Nasal obstruction or Epistaxis
    3. Dysphagia
    4. Trismus
    5. Headache
    6. Persistent or Recurrent Fever
    7. Cranial Nerve deficit
  4. Retinoblastoma (2% of Pediatric Cancers)
    1. Leukoria (white reflex in place of typical Red Reflex - Cat's Eye Reflex)
    2. Squinting or Vision Loss

VI. Causes: Musculoskeletal

  1. Rhabdomyosarcoma (6% of Pediatric Cancers, as well as other less common, soft tissue Sarcomas)
    1. Findings specific to location and to mass effect
  2. Osteosarcoma (2% of Pediatric Cancers)
    1. Localized bone pain
    2. Palpable mass
    3. Localized swelling or deformity
    4. Pathologic Fracture
  3. Ewing Sarcoma (2% of Pediatric Cancers)
    1. Localized bone pain
    2. Palpable mass
    3. Persistent Fever Without Source
    4. Fatigue and weight loss

VII. Causes: Genitourinary and Abdominal

  1. Wilms Tumor (5% of Pediatric Cancers, as well as other, less common renal tumors)
    1. Abdominal mass or Abdominal Pain
    2. Hematuria
    3. Vomiting
    4. Constipation
    5. Persistent Fever
    6. Hypertension
  2. Germ Cell Tumors (3% of cancers)
    1. Palpable Scrotal Mass or abdominal mass
    2. Vaginal Bleeding or Amenorrhea
    3. Precocious Puberty
    4. Constipation
    5. Enuresis
  3. Hepatic Tumors (1% of Pediatric Cancers)
    1. Hepatomegaly or other abdominal distention

VIII. Symptoms: Constitutional

  1. Pallor, Fatigue, malaise
    1. Leukemia
    2. Lymphoma
    3. Neuroblastoma
    4. Ewing Sarcoma
    5. Histiocytosis
  2. Fever (persistent or recurrent, especially if >2 weeks, without source)
    1. Leukemia
    2. Lymphoma
    3. Neuroblastoma
    4. Ewing Sarcoma
    5. Histiocytosis
    6. Wilms Tumor
    7. Nasopharyngeal cancer
  3. Anorexia with weight loss
    1. Leukemia
    2. Lymphoma
    3. CNS Tumor
    4. Abdominal Mass

IX. Symptoms: Neurologic

  1. Headache (especially new, different that is persistent, morning or causing night awakening, occipital, supine)
    1. CNS Tumor
    2. Neuroblastoma
    3. Leukemia
    4. Lymphoma
    5. Nasopharyngeal cancer
  2. School performance deterioration or sudden personality change
    1. CNS Tumor
  3. Suddenly non-ambulatory
    1. See musculoskeletal symptoms - bone pain or joint pain (below)
    2. CNS Tumor

X. Symptoms: Gastrointestinal

  1. Abdominal mass
    1. Neuroblastoma
    2. Nephroblastoma
    3. Lymphoma
    4. Hepatic tumor
    5. Ovarian Tumor
  2. Hepatosplenomegaly
    1. Leukemia
    2. Lymphoma
    3. Hepatic Mass
  3. Vomiting
    1. CNS Tumor
    2. Neuroblastoma (abdominal)
    3. Wilms Tumor
    4. Lymphoma (abdominal)
    5. Hepatoblastoma
  4. Intractable watery Diarrhea
    1. Neuroblastoma (Vasoactive Intestinal Peptide secretion)

XI. Symptoms: Genitourinary

  1. Urinary Retention or Enuresis
    1. Neuroblastoma
    2. Spinal cord tumor
    3. Pelvic mass (e.g. Ovarian Mass, soft tissue Sarcoma)
  2. Scrotal swelling or Scrotal Mass
    1. Germ cell tumor
    2. Leukemia
    3. Soft tissue Sarcoma
  3. Isolated right-sided Varicocele
    1. Renal tumor
    2. Lymphoma
    3. Sarcoma

XII. Symptoms: Musculoskeletal

  1. Bone pain, joint pain, limp
    1. Osteosarcoma
    2. Ewing Sarcoma
    3. Leukemia
    4. Neuroblastoma
    5. Histiocytosis
  2. Back pain, Torticollis, kyphoscoliosis or lordosis
    1. CNS Tumor or spinal tumor
    2. Neuroblastoma
    3. Leukemia
  3. Osteoporosis
    1. Hepatoblastoma

XIII. Symptoms Dermatologic

  1. Refractory Eczematous Dermatitis
    1. Histiocytosis
  2. Palpable subcutanoeus masses
    1. Soft tissue Sarcoma
    2. Neuroblastoma
    3. Leukemia
    4. Histiocytosis

XIV. Symptoms: Hematologic

  1. Lymphadenopathy (refractory to treatment, persistent >4-6 weeks, >2 cm firm, non-tender nodes)
    1. Lymphoma
    2. Leukemia
    3. Rhabdomyosarcoma
    4. Nasopharyngeal cancer
    5. Neuroblastoma
  2. Hemorrhagic changes (Petechiae, Gingival Bleeding, Petechiae, Ecchymosis, Epistaxis)
    1. Leukemia
    2. Lymphoma
    3. Neuroblastoma
    4. Ewing Sarcoma

XV. Associated Conditions

  1. Refractory infections
    1. Leukemia
    2. Lymphoma
    3. Neuroblastoma
    4. Ewing Sarcoma
  2. Cushing Syndrome
    1. Wilms Tumor
  3. Hypercalcemia
    1. Leukemia
    2. Wilms Tumor
  4. Diabetes Insipidus
    1. Craniopharyngioma
    2. Germinoma
    3. Histiocyctosis
    4. Supasellar tumor involving Pituitary Gland
  5. Growth arrest
    1. Craniopharyngioma
    2. Germinoma
    3. Pituitary tumor (suprasellar)
  6. Precocious Puberty
    1. Adrenal tumor
    2. CNS tumor
    3. HCG-secreting germ cell tumor
    4. Rhabdomyosarcoma
  7. Pubertal Delay
    1. Pituitary tumor

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