• Also called schwannian stroma-poor neuroblastic tumor
  
• #4 most common malignancy (solid or not) in children after leukemia, medulloblastoma / PNET and astrocytoma
  
• 500 new cases/year in US
  
• Most common tumor before age 1 year; 80% are under age 4 years, median age at diagnosis is 21 months; rare in adults
  
• 25% occur in adrenal medulla, also along sympathetic chain (neck, posterior mediastinum, paravertebral, retroperitoneum)
  
• Associated with Beckwith-Wiedemann syndrome, Hirschsprung disease, neurofibromatosis type 1, fetal hydantoin syndrome, opsoclonus / myoclonus, heterochromia iridis and Cushing syndrome
  
• Older children may present with bone pain, respiratory or GI complaints due to metastatic disease
  
• Young children present with large abdominal masses that may fill abdomen or thorax, fever and weight loss
  
• Usually increased levels of catecholamines, but without symptoms
  

• Derived from neural crest cells capable of multilineage differentiation
  
• For children less than age 1, neuroblastomas don't make trophic factor for Schwann cells, causing apoptosis
  
• For children age 1+, some neuroblastomas make trophic factor for Schwann cells, leading to inward migration of Schwann cells, leading to TrkA expression then leading to tumor cell differentiation
  

• Spreads to adjacent tissue including kidney, spine (dumbbell extension)
  
• Metastases are usually early and widespread to bone marrow, bones (skull or orbit; multiple, often symmetrical), lymph nodes, meninges, liver (Pepper syndrome), ovary or paratesticular region; lung and brain uncommon
  
• Maturation: 30% regress or mature to ganglioneuroma; maturation associated with high numbers of Schwann cells that migrate into tumor, express high levels of NGF receptors p140 TrkA and p75 NGFR, induce differentiation
  
• Causes 15% of childhood cancer deaths
  
• Screening programs detect more tumors, but don’t reduce mortality (Int J Cancer 2003;103:538)
  

5 year survival:

• age < 1 year old and stage I/II: 95-98%
• < 1 year old and stage IV-S: 80%
  
• < 1 year old and stage IV: > 50%
• > 1 year old and stage III/IV is 10%
  
• 3 year overall survival is 30%
  

• 8 day old baby with adrenal morphologic features associated with anencephaly (Arch Pathol Lab Med 1979;103:119)
  
• 18 year old presenting with primary ovarian tumor and abdominal metastases (Am J Surg Pathol 1982;6:283)
  
• Metastatic disease with pheochromocytoma differentiation after surgery and chemoradiotherapy (Am J Surg Pathol 2004;28:548)
  

• Surgery, chemotherapy and bone marrow transplantation
  

• Varies from in situ lesions (minute nodules) to 1 kg
  
• Usually well circumscribed but may be infiltrative
  
• Composed of soft, gray-pink, brain-like tissue
  
• Well differentiated tumors are yellow-tan and resemble ganglioneuroma
  
• Large tumors have hemorrhage, necrosis, calcification and cysts
  
• 90% unilateral; may be locally invasive to liver or pancreas
  

Right sided neuroblastoma   Encapsulated tumor displacing liver

• Vaguely nodular due to incomplete fibrous encapsulation
  
• Small blue cell tumor (minimal cytoplasm, hyperchromatic round nuclei) with poorly defined cytoplasmic borders
  
• 25-35% have Homer-Wright pseudorosettes (tumor cells surround central space filled with fibrillar extensions [neurites] of cells without a central lumen)
  
• May have neuropil (fine fibrillary matrix) between tumor cells; may have alveolar, pseudovascular or Schiller-Duvall body appearance due to hemorrhage
  
• May have prominent calcification; necrosis common; rarely has “zellballen” appearance or bizarre tumor giant cells
  
  INPC classification of neuroblastoma:
  
  • Classic (undifferentiated) neuroblastoma: also called grade III/IV or stroma-poor; small / medium cells with thin rim of cytoplasm, indistinct cell borders, round / oval nuclei with salt and pepper (coarsely granular) chromatin and indistinct nucleoli; no neuropil, although coagulative necrosis may resemble neuropil; 5% or less of tumor has features of differentiation towards ganglion cells with vesicular nuclei and prominent nucleoli; no / minimal ganglioneuromatous stroma
    
  • Poorly differentiated neuroblastoma: classic pattern but with neuropil
    
  • Differentiating neuroblastoma: 6-49% of tumor cells show ganglionic differentiation (abundant eosinophilic or amphophilic cytoplasm, large eccentric nuclei with vesicular chromatin and single prominent nucleoli), often at periphery of tumor; if 50% or more, call ganglioneuroblastoma, intermixed; usually abundant neuropil
  
  
• Note: diagnosis of “neuroblastic tumor unclassifiable” may be appropriate for small biopsies; “neuroblastoma, NOS” may be appropriate if poor histologic sections, hemorrhage, necrosis, crush, cystic degeneration or marked calcification
  

Undifferentiated neuroblastoma    Low power

Neuroblastoma

• Chromogranin, synaptophysin, vimentin, neurofilament, neuron-specific enolase (monoclonal antibody is more specific), nerve growth factor receptors and ALK
  

• p53, CD99, FLI1, desmin, myogenin, keratin, CD45, variable EMA and variable WT1
  

• 1p36.33 deletion, N-myc amplification, 14p deletion, 17q gain, diploid or hyperdiploid and TrKA gene expression abnormalities
  

• Neurosecretory granules, synaptic endings, neurites forming complex interdigitating meshwork in center of Homer-Wright pseudorosettes and neuropil representing mass of unmyelinated axons
  

Neurosecretory granules

• Desmoplastic small round cell tumor
  
• Ewing/PNET : usually does not present with metastatic disease, older children, no neuropil, CD99+, chromogranin-
  
• Lymphoma
  
• Monophasic Wilm’s tumor: no differentiation towards immature ganglion cells
  
• Rhabdomyosarcoma: strap cells, rhabdomyoblasts and muscle marker+
  
  

• Usually incidental finding at autopsy in 0.4 to 2.5% of infants less than 3 months
  
• May not be neoplastic or may mature into ganglioneuroma
  

• Clusters of immature neuroblasts, from 0.7 to 9.5 mm, with frequent cystic change
  
  

• Cannot grade tumors as favorable or unfavorable
  

• Extensive fibrosis and calcification may obscure margin involvement
  
• Also necrosis and chronic inflammation
  

This information is intended for physicians and related personnel, who understand that medical information is often imperfect, and must be interpreted in the context of a patient's clinical data using reasonable medical judgment. This website should not be used as a substitute for the advice of a licensed physician.

All information on this website is protected by copyright of PathologyOutlines.com, Inc. Information from third parties may also be protected by copyright. Please contact us at copyrightPathOut@gmail.com with any questions (click here for other contact information).