DEFINITION AND PATHOGENESIS

  • Derived from the primordial neural crest cells migrated from the developing spinal cord to the sympathetic ganglia and adrenal medulla
  • Two mutation theory: 1st in the germ cell, 2nd in the somatic cell

IMPORTANCE

  • Third most common childhood malignancy (after leukemia and brain tumors)(most common extracranial solid tumor in children)

CLINICAL FEATURES

  • Younger age than rhabdomyosarcoma and Ewing’s sarcoma (90% diagnosed by age 5)
  • M:F = 1.25:1
  • Original tumor found in the para-midline area from the base of the skull to pelvis (and adrenal and organ of Zuckerkandl) including dorsal root ganglia (63% retroperitoneal, 16% mediastinal, 3% sacral, 2% cervical)
  • Rarely familial (AD with variable penetrance)
  • Chronically ill, fever, weight loss, GI symptoms, anemia, joint pain
  • 1/5 have hypertension, "blueberry muffin baby", "myoclonus-opsoclonus" syndrome
  • 80-90% have elevated urinary catecholamines/metabolites (nor- and epinephrine/VMA, HVA, MHPG)
  • "Opsoclonus-hypoclonus-ataxia syndrome )paraneoplastic syndrome)

RADIOLOGIC FEATURES

  • Metastases commonly occur in bones, esp. skull, femur, and humerus (may be symmetrical)

GROSS PATHOLOGY

  • White to yellowish soft, hemorrhagic lesions

HISTOLOGIC FEATURES

  • Shimado histopathology
  • Chromosomal abnormalities in 80% (deletion/rearrangements of short arm of chromosome 1)
  • E rosette inhibition due to serum ferritin synthesized by the tumor coating T lymphocytes
  • Sheets of small lymphocyte-like cells.
  • Rosettes can be found only rarely in metastases
  • Taillike eosinophilic cell extension is virtually diagnostic
  • EM: neurosecretory granules (except in undifferentiated tumors)

DIFFERENTIAL CLINICOPATHOLOGIC DIAGNOSIS

  • If taken out of context can be mistaken for Ewing’s sarcoma or lymphoma

DISEASE COURSE AND TREATMENT

  • VMA/HVA ratio ?1.5 with ? prognosis
  • ? prognosis with presence of serum neuron specific enolase
  • ? prognosis with MYCN oncogene amplification
  • 5 year survival is 15% (? prognosis if <1 year of age)
  • XRT + chemotherapy

REFERENCES

Brodeur GM, Azar C, Brother M, : Neuroblastoma: effect of genetic factors on prognosis and treatment. Cancer 70:1685-1992.


DuBois SG, Kalika Y, Lukens JN, : Metastatic sites in stage IV and IVS neuroblastoma correlate with age, tumor biology and survival. J Pediatr Hematol Oncol 21:181-9,1999.


Evans AE: Staging and treatment of neuroblastoma. Cancer 45:1799-1802,1980.


Mirra JM: Neurogenous tumors. In Bone Tumors, Clinical, radiologic, and pathologic correlations. JM Mirra (Ed), Lea & Febiger, Philadelphia, 1989., pp 801-867.


Shimada H, Chatten J, Newton WA, : Histopathologic prognostic factors in neuroblastic tumors: definition of subtypes of ganglioneuroblastoma and age-linked classification of neuroblastoma. J Natl Cancer Inst 73:405-16,1984.