Neuroblastoma (metastatic)

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.