Adrenal gland & paraganglia

Neuroblastic tumors

Ganglioneuroblastoma, intermixed and nodular



Last author update: 1 August 2014
Last staff update: 16 January 2024

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PubMed Search: Ganglioneuroblastoma

Carmen Perrino, M.D.
Debra L. Zynger, M.D.
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Cite this page: Perrino C, Zynger DL. Ganglioneuroblastoma, intermixed and nodular. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/adrenalganglioneuroblastoma.html. Accessed July 13th, 2024.
Definition / general
  • 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
  • Intermixed: composite tumor in the stroma rich category
    • Ganglioneuromatous tissue with interspersed, sharply defined, unencapsulated nests of variably differentiated neuroblastic cells
  • Nodular: composite tumor in the stroma rich category
Epidemiology
  • 4th most common tumor in childhood
  • 75 - 85% occur within first 4 years of life
  • M = F
Sites
  • Occur anywhere in anatomic distribution of sympathoadrenal neuroendocrine system
  • ~80% arise within abdomen or adrenal gland
  • ~20% within thoracic cavity
Etiology
  • Clonal proliferation of immature cells of neural crest origin
Clinical features
Diagnosis
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: hyperechoic mass

Spiral CT: hyperechoic mass

Prognostic factors
  • Multiple classification systems have been developed with the goal of stratifying patients into prognostic groups (see staging - neuroblastic tumors)
  • In Shimada Classification, intermixed type is favorable histology
  • Nodular subtype was initially categorized as unfavorable histology and in 2003, the INPC created 2 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)
    • 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
    • Differentiating neuroblastoma: MKI < 100, age 1.5 - 5 years
  • Unfavorable subset: composed of unfavorable nodule(s)
    • Any neuroblastoma, MKI > 200, any age
    • Any neuroblastoma, MKI 100 - 200, > 1.5 years
    • Undifferentiated neuroblastoma, any age
    • Poorly differentiated neuroblastoma, age > 1.5 years
    • Any neuroblastoma, age > 5 years
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
  • More homogeneous and mature appearance than neuroblastoma
  • Varies by subtype, from circumscribed ovoid mass to large multilobulated tumor
  • Stroma rich, nodular subtype: area(s) of stroma poor, immature tumor are usually hemorrhagic with well defined borders (J Natl Cancer Inst 1984;73:405)
  • Calcification (chalky white, yellow areas) and cystic degeneration may occur
  • If large, adrenal gland may be difficult to identify
Gross images

Contributed by Carmen Perrino, M.D. and Debra L. Zynger, M.D.
Stroma rich, intermixed type

Stroma rich, intermixed type

Focal undifferentiated component

Focal undifferentiated component

Stroma rich, nodular type Stroma rich, nodular type Stroma rich, nodular type

Stroma rich, nodular type

With treatment related changes

With treatment related changes

Microscopic (histologic) description
  • 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 = 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

Contributed by Carmen Perrino, M.D. and Debra L. Zynger, M.D.

Intermixed type
Composite types

Composite types

Intermixed type

Intermixed type

Ganglion cells

Ganglion cells

Fibrillary background

Fibrillary background

Aggregate of ganglion cells

Aggregate of ganglion cells


Lymphocyte aggregate

Lymphocyte aggregate

Area with Schwannian stroma

Area with Schwannian stroma

Maturing ganglion cells

Maturing ganglion cells

Stroma rich, intermixed type

Stroma rich, intermixed type


Nodular type
Stroma rich, nodular type

Stroma rich, nodular type

Neuroblast cell component

Neuroblast cell component

Homer Wright pseudorosettes

Homer Wright pseudorosettes

Vaguely formed Homer Wright pseudorosettes

Vaguely formed Homer Wright pseudorosettes

Hemorrhagic component

Hemorrhagic component

Cytology description
  • Ganglion cells: larger cells, abundant cytoplasm, fine chromatin, prominent nucleoli
  • Neuroblasts: uniform, small, blue cells with scant, eosinophilic, fibrillary cytoplasm; hyperchromatic to vesicular chromatin
    • May form Homer Wright pseudorosettes
Cytology images

Contributed by Carmen Perrino, M.D. and Debra L. Zynger, M.D.
Numerous ganglion cells

Numerous ganglion cells

Electron microscopy description
Molecular / cytogenetics description
  • Considered molecularly heterogeneous but much of genetic basis remains unexplained (Cancer 2003;98:2274)
  • ALK gene mutations have been implicated in some cases of ganglioneuroblastoma (Am J Pathol 2012;180:1223)
  • Ganglioneuroblastoma, stroma rich, nodular subtype, is considered a composite tumor consisting of separate clones (less aggressive stroma rich component; nodular component consisting of a favorable / unfavorable / both clones) (Cancer 2003;98:2274)
Molecular / cytogenetics images

Contributed by Leica Biosystems
<i>MYCN</i> (2p24) / <i>AFF3</i> (2q11)

MYCN (2p24) / AFF3 (2q11)

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