•Dependent on age (favorable if less than 18 months of age at diagnosis), stage (see Staging 10.11), and tumor location:

–Favorable prognosis in primary neuroblastoma include thorax, presacral, and cervical anatomic sites

–Involvement of lymph nodes is associated with poor prognosis

•Low-risk groups (see “Risk-Adapted Management” above) have more than 90% long-term survival

•Intermediate and high-risk groups:

–Response to initial treatment: children with complete remission (78% rate of response) or partial remission (60% rate of response)

–After consolidation therapy, including double high-dose chemotherapy with autologous stem cell support, event-free survival after 3 years is 40–60%

10.13.1 Futuristic Therapeutic Approaches

•New agents in evaluation: topotecan-irinotecan combination, temozolomide and I-131-MIGB. Controlled studies do not exist

•Immunotherapy with humanized antibodies linked to IL-2 showed improvement of survival

•Retinoids as inducer of apoptosis

•Targeted agents to the underlying pathogenic mechanism such as tyrokinase inhibitor, ALKase inhibitor (see above)

10.14Special Forms

10.14.1 Ganglioneuroblastoma

•Mostly in older children and adolescents

•Location: adrenal medulla and posterior mediastinum

•Can vary considerably in size

•Histologically contains typical neuroblastoma along with areas of differentiation intermixed with extensive fibrillar tissue

•Management as that for neuroblastoma

10.14.2 Ganglioneuroma

•Benign tumor

•Mainly in adolescents and young adults

•Often incidental diagnosis from a thoracic X-ray

•Urinary catecholamine levels are usually within normal range

•Macroscopically encapsulated tumor

•Histologically, ganglia cells and the presence of Nissl granules, bundles of neurofibrils, and myxomatous stroma

•Therapy: resection

•Postoperative sequelae after surgery of mediastinal ganglioneuroma: Horner syndrome may occur

10.14.3 Olfactory Neuroblastoma

•Older children and adults

•First peak at 11–20 years

•Second peak at 50–60 years

•Symptoms: unilateral nasal obstruction, epistaxis, anosmia, rhinorrhea, pain

•Metastatic spread in lymph nodes, lung, pleura, and/or bone (vertebrae) in about 25% of patients; brain involvement in 14% of patients

•Therapy: Radical tumor resection if possible, as well as radiotherapy

•Prognosis: About two-thirds of patients are cured

10.14.4Neuroblastoma Arising from Organ of Zuckerkandl (Location at the Bifurcation of the Aorta or Origin of the Inferior Mesenteric Artery)

•Tumor of the midline: behavior and procedure as described for other neuroblastomas

10.14.5 Pheochromocytoma

•Origin is chromaffin cells of the neural crest lineage

•Occurrence:

–Mostly in adrenal gland

–Twenty percent bilateral

–Occasionally multiple tumor locations

–Usually in children more than 10 years and in adults

•Symptoms: paroxysmal attacks of flushing, pallor, sweating, headache, palpitations, hypertension

•Weight loss

•Polydipsia

•Urinary catecholamine levels markedly increased

•Diagnostics: ultrasound, magnetic resonance imaging, scintigraphy but a definitive diagnosis can only be made pathologically

•Therapy: Before and during any diagnostic or therapeutic intervention, prophylaxis of hypertensive crises with alphaand beta-blockers and intensive care surveillance

•Primary treatment should be surgical resection

•For nonresectable disease: chemotherapy and octreotide approaches