Adrenal gland and paraganglia
Neuroblastic tumors
General

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

Revised: 20 January 2016, last major update March 2015

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

PubMed Search: Neuroblastic tumor [title]

General
  • Neoplasms of neuroectodermal origin comprised of neuroblasts or ganglion cells
  • On a spectrum, from least → most differentiated: neuroblastoma → ganglioneuroblastoma → ganglioneuroma
Terminology
  • Neuroblastoma: composed only of immature neuroblasts; Schwannian stroma-poor
  • Ganglioneuroblastoma: composed of mixture of immature neuroblasts and ganglion cells; Schwannian stroma-rich
  • Ganglioneuroma: composed only of ganglion cells; Schwannian stroma-dominant
Epidemiology
  • Neuroblastoma and ganglioneuroblastoma are 4th most common malignant tumors in childhood after leukemia (ALL), CNS tumors, lymphoma
  • 85% of cases occur in first 4 years of life
  • M = F
Sites
  • Occur anywhere in anatomic distribution of sympathoadrenal neuroendocrine system
  • Most commonly occur in abdomen, especially adrenal gland
Etiology
  • Clonal proliferation of immature cells of neural crest origin
Clinical Features
  • Asymptomatic or palpable mass with variable watery diarrhea syndrome (due to secretion of vasoactive intestinal peptide), opsoclonus/myoclonus
Diagnosis
  • Spectrum of tumors, composition ranges from pure neuroblasts (neuroblastoma) → mixture of neuroblasts and ganglion cells (ganglioneuroblastoma) → pure ganglion cells (ganglioneuroma)
Laboratory
  • Increased urine catecholamine metabolites (homovanillic acid, vanillylmandelic acid)
  • Increased urine / serum dopamine
Radiology Description
Prognostic Factors
  • Staging system for neuroblastoma and ganglioneuroblastoma:
    • International Neuroblastoma Staging System (INSS) (J Clin Oncol 1993;11:1466)
      • I: localized, complete gross excision with/without microscopic residual disease, negative lymph nodes
      • IIA: localized, incomplete gross excision, negative lymph nodes
      • IIB: localized, with/without complete gross excision, positive ipsilateral lymph nodes, negative contralateral lymph nodes
      • III:
        • Unilateral, unresectable, crosses midline, with/without positive regional lymph nodes
        • Localized, positive contralateral regional lymph nodes
        • Midline, bilateral extension or lymph node involvement
      • IV: positive distant lymph nodes, bone, bone marrow, liver, and/or other organs (except those in IV-S)
      • IV-S: localized (stage I or II) with dissemination to liver, skin, and/or bone marrow
  • Ganglioneuroblastoma and neuroblastoma stratified into prognostic groups based on followed classification schemes:
  • Ganglioneuroma has a favorable prognosis
Case Reports
Treatment
  • Ganglioneuroblastoma, neuroblastoma: depends on prognostic stage (Pediatr Blood Cancer 2009;53:563)
    • Low risk: surgical resection (and chemotherapy if unresectable or symptomatic)
      • Expectant observation in some with small adrenal masses, localized neuroblastoma, or asymptomatic stage 4S disease
    • Intermediate risk: surgical resection, moderate chemotherapy (and radiation if disease progresses)
    • High risk: induction chemotherapy, surgical resection, radiation, consolidation chemotherapy / possible stem cell transplant, maintenance chemo/immunotherapy
  • Ganglioneuroma: complete resection with adrenalectomy (J Med Case Rep 2014;8:131)
Gross Description
  • Considerable variation in size
  • Circumscribed mass to multilobular
  • Usually solitary, white-tan
  • Varying amounts of hemorrhage, necrosis, cystic degeneration, calcification
Gross Images
Ganglioneuroblastoma, Flickr images contributed by Dr. Carmen Perrino and Dr. Debra Zynger:
Missing Image

Stroma-rich, intermixed type

Missing Image

Focal undifferentiated component

Missing Image Missing Image Missing Image

Stroma-rich, nodular type

Missing Image

With treatment-related changes


Images hosted on other servers:
Missing Image Missing Image Missing Image

Adrenal ganglioneuroma

Missing Image

Ganglio-neuroblastoma

Missing Image

Composite ganglioneuroma
and pheochromocytoma

Micro Description
  • Neuroblastoma: immature neuroblasts
  • Ganglioneuroblastoma: immature neuroblasts + ganglion cells
  • Ganglioneuroma: ganglion cells
  • Tumors are on a spectrum, contain some/all of the following cell types:
    • Neuroblasts
      • Homer Wright pseudorosettes = circular, ovoid, angular zones of pale staining neuritic cell processes surrounded by tumor cell nuclei; may rarely palisade
      • Round to ovoid nuclei with stippled salt and pepper chromatin, inconspicuous nucleoli
      • Minimal cytoplasm, may have cytoplasmic tail
    • Ganglion cells
      • Nuclear enlargement, eccentric nuclei, prominent nucleoli
      • Abundant granular eosinophilic cytoplasm (Nissl substance = rough endoplasmic reticulum)
      • Distinct cell borders
  • May see neuromelanin pigment (brown, finely granular; rarely present), cystic degeneration, hemorrhage, dystrophic calcification
Micro Images
Ganglioneuroblastoma, Flickr images contributed by Dr. Carmen Perrino and Dr. Debra Zynger:
Missing Image

Neuroblast cell component

Missing Image Missing Image

Numerous ganglion cells

Missing Image

Homer Wright pseudorosettes

Missing Image

Vaguely formed Homer Wright pseudorosettes

Missing Image

Hemorrhagic component

Missing Image

Stroma-rich, nodular type

Missing Image

Focal undifferentiated component and calcification


Images hosted on other servers:
Missing Image Missing Image

Adrenal neuroblastoma

Missing Image Missing Image

Ganglioneuroma: vimentin+, synaptophysin+, S100+

Missing Image Missing Image Missing Image

Composite tumor, ganglioneuroma and pheochromocytoma

Virtual Slides
Hosted on other servers, all from adrenal gland:
Missing Image Missing Image

Neuroblastoma

Missing Image

Neuroblastoma, cystic

Missing Image Missing Image

Neuroblastoma metastatic to skull (left), neck (right)

Missing Image Missing Image

Ganglioneuroblastoma, right is therapy-associated

Missing Image

Adrenal and retroperitoneal ganglioneuro-
blastoma

Missing Image Missing Image

Adrenal gland ganglioneuroma

Missing Image

Adrenal gland pheochromocy-
toma, focus of ganglioneuroma

Cytology Description
  • Tumors are on a spectrum, contain some / all of the following cell types:
    • 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 pseudorosette
Cytology Images
Images hosted on other servers:
Missing Image Missing Image

Ganglioneuroma of the neck, Schwann cells and ganglion cells

Positive Stains
Molecular / Cytogenetics Description
  • Ganglioneuroma: usually not associated with genetic abnormalities (Clin Endocrinol (Oxf) 2014;80:342)
  • Ganglioneuroblastoma: considered molecularly heterogeneous, but much of genetic basis remains unexplained (Cancer 2003;98:2274)
  • Neuroblastoma: extensive molecular heterogeneity, but some known aberrations include MYCN amplification, chromosome 1p deletion, gain of chromosome 17q (Annu Rev Med 2015;66:49)