Adrenal gland and paraganglia
Neuroblastic tumors
Ganglioneuroblastoma-other, Nodular variant

Author: Carmen Perrino, M.D. (see Authors page)
Editor: Debra Zynger, M.D.

Revised: 22 January 2016, last major update October 2014

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Ganglioneuroblastoma [title] nodular,

See also: Intermixed variant

Cite this page: Ganglioneuroblastoma, Nodular variant. PathologyOutlines.com website. http://pathologyoutlines.com/topic/adrenalganglioneuroblastomaother.html. Accessed June 24th, 2017.
Definition / general
  • Ganglioneuroblastoma: neoplasm of neuroectodermal origin comprised of mixture of neuroblasts and ganglion cells in varying proportions
    • Divided into stroma-rich (well-differentiated, intermixed, nodular) and stroma-poor categories depending on amount of Schwannian, spindle cell stroma
  • Nodular variant: composite tumor in the "stroma-rich" category

See also: Intermixed variant
Epidemiology
  • 4th most common tumor in childhood
  • 75-85% occur within first 4 years of life
  • M=F
Sites
  • Occurs anywhere in anatomic distribution of sympathoadrenal neuroendocrine system
  • ~80% arise in abdomen or adrenal gland, ~20% arise in thoracic cavity
Etiology
  • Clonal proliferation of immature cells of neural crest origin
Clinical features
Diagnosis
  • Must have at least 1 grossly identifiable nodule
  • Microscopically, admixture of neuroblasts and ganglion cells
Laboratory
  • Increased urine catecholamine metabolites (homovanillic acid, vanillylmandelic acid)
  • Increased urine/serum dopamine as adjunct laboratory test
Radiology description
  • MRI: hypointensity on T1-weighted image with rapid enhancement and hyperintensity on T2-weighted image (Intern Med 1995;34:1168)
Radiology images
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Spiral CT shows well circumscribed
hyperechoic mass in right adrenal gland

Prognostic factors
  • International Neuroblastoma Staging System (INSS), see Neuroblastic tumors - ganglioneuroblastoma
  • Shimada Classification, see Neuroblastic tumors - ganglioneuroblastoma
  • International Neuroblastoma Pathology Classification System (INPC), see Neuroblastic tumors - ganglioneuroblastoma
    • Ganglioneuroblastoma, nodular subtype was initially categorized as unfavorable histology
    • In 2003, the INPC created two prognostically different subsets within this subtype (Cancer 2003;98:2274, Cancer 2000;89:1150)
      • Favorable subset: composed of Schwannian-rich, stroma-dominant component favorable nodule(s) (definition below)
        1. Poorly differentiated or differentiating neuroblastoma: mitosis-karyorrhexis index (MKI) (count of cells undergoing mitosis or karryhorexis, based on 5,000 cell count from random fields) ≤200, age < 1.5 years
        2. Differentiating neuroblastoma: MKI <100, age 1.5-5 years
      • Unfavorable subset: composed of unfavorable nodule(s) (definition below)
        1. Any neuroblastoma, MKI >200, any age
        2. Any neuroblastoma, MKI 100-200, > 1.5 years
        3. Undifferentiated neuroblastoma, any age
        4. Poorly differentiated neuroblastoma, age > 1.5 years
        5. Any neuroblastoma, age > 5 years
  • Additional prognostic factors, see Neuroblastic tumors - ganglioneuroblastoma
Case reports
Treatment
  • Depends on prognostic stage (Pediatr Blood Cancer 2009;53:563, UpToDate - Treatment and prognosis of neuroblastoma)
    • Low risk
      • Surgical resection alone is mainstay
      • Chemotherapy only if tumor is unresectable or symptoms of spinal cord/respiratory/bowel compromise
      • Expectant observation in some infants with small adrenal masses, localized neuroblastoma, or asymptomatic stage 4S disease
    • Intermediate risk
      • Surgical resection
      • Moderate chemotherapy
      • Radiation only if disease progresses despite surgery/chemotherapy
    • High risk
      • Induction: intensive chemotherapy
      • Local control: surgical resection, radiation
      • Consolidation: chemotherapy, myeloablative therapy, autologous stem cell transplant
      • Maintenance: cis-retinoic acid or immunotherapy
Gross description
  • By definition, at least 1 macroscopic nodule must be present
  • Grossly identifiable separate areas of mature (Schwannian, spindle cell stroma-rich) and immature (neuroblasts, stroma-poor) areas
  • Area(s) of stroma-poor, immature tumor are usually hemorrhagic with well-defined borders (J Natl Cancer Inst 1984;73:405)
Gross images
PathOut Flickr Images:
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With treatment-related changes

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Stroma-rich, nodular type

Microscopic (histologic) description
  • Histology correlates with gross findings, with separate mature areas (stroma-rich) and immature areas (comprised of neuroblasts, stroma-poor)
  • Architecture: lobular, diffuse/solid, organoid
  • Neuroblasts
    • Homer Wright pseudorosettes: circular, ovoid, angular zones of pale-staining neuritic cell processes surrounded by tumor cell nuclei; may rarely palisade
    • Minimal cytoplasm, may have cytoplasmic tail
    • Round to ovoid nuclei with stippled salt and pepper chromatin, inconspicuous nucleoli
  • Ganglion cells
    • Abundant granular eosinophilic cytoplasm (Nissl substance is rough endoplasmic reticulum)
    • Distinct cell borders
    • Nuclear enlargement, eccentric nuclei, prominent nucleoli
  • May see neuromelanin pigment (brown, finely granular; rarely present), cystic degeneration, hemorrhage, dystrophic calcification
Microscopic (histologic) images
PathOut Flickr Images:
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Stroma-rich, nodular type

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Neuroblast cell component

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Homer Wright pseudorosettes

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Vaguely formed Homer Wright pseudorosettes

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Hemorrhagic component

Cytology description
  • Ganglion cells: larger cells, abundant cytoplasm, fine chromatin, prominent nucleoli
  • Neuroblasts: uniform, small, blue cells with hyperchromatic to vesicular chromatin and scant, eosinophilic, fibrillary cytoplasm
    • May form Homer Wright pseudorosettes
Positive stains
Negative stains
Electron microscopy description
Molecular / cytogenetics description
  • Genetic basis of ganglioneuroblastoma, stroma-rich, nodular subtype is unclear
  • Some propose that separate histologic areas (stroma-rich versus neuroblastoma/stroma-poor areas) consist of distinct clones (Cancer 2003;98:2274)
  • More recently, one study examined the distinct histologic areas separately and determined they do not definitively arise from separate clones (Mod Pathol 2014 Aug 1 [Epub ahead of print])
    • In situ hybridization for MYCN showed gains in neuroblasts in 100% (8/8) of cases, ganglion cells in 50% (4/8) of cases, and Schwann cells in 0% (0/8) of cases
    • SNP arrays showed that overall there were fewer genetic alterations in the ganglioneuromatous component than the neuroblastoma component, but there were not a remarkable number of alterations which were exclusive to one histologic area