Cause: Malignancy arising from cells of neural crest that form sympathetic ganglia and adrenal medulla

Epidem: Most common malignant tumor of infancy (J Pediatr 1975;86:254). Accounts for 6-8% of all childhood malignancies; > 90% cases diagnosed in children < 5 yr (J Nucl Med 2004;45:1172). Most common primary site is the retroperitoneum. About 60% of pts have mets to cortical bone, bone marrow, lymph nodes, and liver at time of dx (J Pediatr Hematol Oncol 1999;21:181). Chromosome 1p36 deletions common in neuroblastoma cells, but recent studies favor chromosome 16p12-13 as a more likely predisposition locus (Med Pediatr Oncol 2001;36:37; Cancer Res 2002;62:6651). Most common genetic abnormality in primary neuroblastoma is gain of 17q genetic material (J Clin Oncol 1999;17:2264).

Pathophys: Histopath: One of the small round cell tumors of childhood; cells may clump and form rosettes. Located anywhere along sympathetic chain; > 50% are in abdomen, and 2/3 of these arise in adrenal gland. Other locations include posterior mediastinum (20%), pelvis (< 5%), and neck (< 5%).

Staging: International Neuroblastoma Staging System

Stage 1: Localized tumor with complete gross excision, with/without microscopic residual disease; representative regional
nodes neg for disease (nodes attached to and removed with primary tumor may be pos)

Stage 2A: Localized tumor with incomplete gross excision; identifiable ipsilateral and contralateral lymph nodes negative microscopically

Stage 2B: Localized tumor with complete or incomplete gross excision; ipsilateral regional lymph nodes pos for tumor, contralateral lymph nodes neg microscopically

Stage 3: Unresectable tumor infiltrating across midline with or without regional lymph node involvement or localized tumor with contralateral regional lymph node involvement; or midline tumor with bilateral extension by infiltration (unresectable) or by lymph node involvement

Stage 4: Any primary tumor with dissemination to distant lymph nodes, cortical bone, bone marrow, liver, or other organs (except as defined in stage 4S)

Stage 4S: Localized primary tumor as defined for stage 1 or 2 with dissemination limited to liver, skin, or bone marrow. Only applies to infants < 1 yr of age (J Clin Oncol 1993; 11:1466).

Sx: Bone pain, irritability

Si: HT, abdominal mass, fever, generalized malaise, anorexia, weight loss, pallor, subcutaneous nodes, periorbital mets common, intractable diarrhea secondary to vasoactive intestinal peptide (VIP) production, acute myoclonic encephalopathy, signs of catecholamine secretion, syndrome mimicking erythroblastosis

Crs: Associated with neurofibromatosis and Hirschsprung’s disease (Cancer 1999;86:364) Diff Dx: Wilms’ tumor

Lab: CBC: usually nl, with mets anemia and thrombocytopenia, ESR usually elevated with mets. Bone marrow aspiration: pos in up to 70% (Am J Dis Child 1970;119:49). Urinary catecholamine: 95%
have increased levels of VMA, HVA, or both; 24- hr urine quantification most accurate.

Xray: Chest Xray to r/o pulmonary mets, thoracic tumor, tumor extension into posterior mediastinum; KUB may demonstrate mass with stippled calcifications. CT scan helps distinguish neuroblastoma from Wilms’ tumor. Bone scan to r/o bony mets. Metaiodobenzylguanidine (MIBG) has a high sens and specif for identifying mets to cortical bone, bone marrow, and lymph nodes (Pediatr Radiol 1990;20:157).

Rx: Low-risk disease—surgery usually sufficient—includes stages 1, 2a, and 2b without N-myc amplification. Those with N-myc amplification and favorable histology are low risk. Infants with stage 2 regardless of N-myc amplification are low risk. Intermediate-risk disease: stage 3 without N-myc amplification, infants with stage 4 without N-myc amplification. Intermediate-risk group has 80-90% survival after 9- mo course of chemotherapy using cisplatin, etoposide, cyclophosphamide, and doxorubicin (Pediatr Drugs 2004;6:107). High risk includes stage 2a or 2b with N-myc amplification and unfavorable histology, stage 3, 4, or 4S with N-myc amplification, and older pts with N-myc amplification and stage 2, 3, or 4 tumors. Rx often involves increased dose intensity during induction chemotherapy, high-dose myeloablative therapy with allogeneic or autologous bone marrow or peripheral blood stem cell transplant, surgery, radiation therapy in some cases, and maintenance or biologic therapy to eradicate minimal residual disease (Curr Opin Oncol 2004;17:19).