(Pediatr Clin N Am 2008;55:97; Principles and Practice of Pediatric Oncology. 6th ed. Philadelphia, PA: LWW; 2011;886–922)
Definition: Solid neoplasm of the sympathetic nervous system
Epidemiology
• 650 new cases in the United States per year
• Accounts for 8–10% of childhood cancer and 15% of cancer deaths in children
• Most common non-CNS solid tumor of childhood
• Incidence peaks at 0–4 yrs of age; median age 23 mo
Clinical Presentation
• Depends on location, disease extent, and presence of paraneoplastic syndromes
• Can arise anywhere along sympathetic nervous system; 65% abdomen (½ from adrenal)
• Dz dissemination occurs through lymphatic and hematogenous spread
• Bone marrow, bone, and liver most common sites of metastasis
• Periorbital region spread → periorbital swelling and “raccoon eyes” at presentation
• Many well-documented paraneoplastic syndromes
• Horner syndrome: Unilateral ptosis, miosis, and anhidrosis assoc w/ thoracic or cervical
primary tumor (sx not resolved w/ tumor resection)
• Pepper syndrome: Massive involvement of liver w/ metastatic dz +/− resp distress
• Opsoclonus myoclonus ataxia syndrome (1–3% of NB cases)
• Myoclonic jerking and random eye movement with or without ataxia
• Often assoc w/ favorable and differentiated tumor; may not resolve w/ resection
Diagnostic Testing
• Definitive tissue bx and pathologic diagnosis is required for diagnosis, or positive bone marrow with elevated vanillylmandelic acid (VMA)/homovanillic acid (HVA)
• Urinary testing w/ ↑ HVA or VMA
• Initial dx testing should include CT or MRI; assess tumor site/extent & for metastasis
• Brain imaging only if clinically indicated
• Bilateral bone marrow biopsies to evaluate for bone marrow involvement
• Bone scan and/or MIBG to assess for bone metastasis
Staging
• Stage 1: Localized tumor w/ complete resection; neg lymph nodes (LNs)
• Stage 2A: Localized tumor with incomplete resection; negative LNs
• Stage 2B: Local tumor +/− gross total resxn; + ipsilateral LNs; neg contralateral LNs
• Stage 3: (a) unresectable unilateral tumor infiltrating across midline +/− LN involvement; (b) local unilateral tumor w/ contralateral + LN involvement; (c) midline unresectable tumor w/ bilateral extension or bilateral LN involvement
• Stage 4: Any 1° tumor w/ dissem/extension to LN, bone, BM, liver, skin, other organ
• Stage 4S: Local 1° tumor w/ dissemination to skin, liver, BM (only for infants <1 yo)
Prognostic Features
• Age >1–2 at dx assoc w/ worse prognosis than infants
• N-myc amplified or diploid DNA content assoc w/ worse prognosis
• Pathologic characteristics differentiate into “favorable” and “unfavorable” prognoses
• Treatment based on risk stratification
Treatment/Outcomes
• Low risk (Low stage [stage 1, 2A, or 2B], favorable N-myc, ploidy, and histology)
• Excellent prognosis w/ surgery alone for stage 1 disease
• 2-yr event-free survival for all low-risk disease 85–100%
• No chemo w/ incomplete resection for favorable stage 2A/2B dz (survival >95%)
• If life-/organ-threatening disease at diagnosis or disease progress, chemo effective adjuvant Rx for stage 2A and 2B
• Stage 4S w/o n-MYC amplification spont regresses w/o Rx or need for resection unless clinical indications to rx (respiratory failure, DIC)
• Intermediate-risk dz (age <1 yo w/ stage 3 dz (regardless of MYCN status or histology), age >1 yo w/ favorable histologic features, infants w/ stage 4 dz, and a subset of infants w/ 4S dz w/ diploid tumors or unfavorable histology, and no MYCN amplification)
• Surgical resection and multiagent chemo (cisplatin/carboplatin, doxorubicin, etoposide, cyclophosphamide) are backbone of treatment
• Survival greater than 95% if favorable histologic and biologic characteristics
• Long-term survival >90%
• High-risk disease (age >1 yr, disseminated dz, or localized dz w/ unfavorable markers such as MYCN amplification)
• Chemoresponsive but poor long-term prognosis; 40–50% long-term survival
• Std Rx w/ induction, local control, consolidation, & Rx of min dz w/ biologic agents
• Great correlation between tumor response at induction and survival
• Induction includes multiagent chemotherapy
• Local control w/ aggressive surg resection & external beam XRT to 1° tumor site
• NB one of most radiosensitive tumors of childhood
• Consolidation therapy includes myeloablative chemotherapy w/ stem cell rescue
• Biologic Rx includes cis-retinoic acid & immunorx (monoclonal ab, GM-CSF, IL-2)