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paragangliomas

Thursday 20 November 2003

extra-adrenal pheochromocytomas, phaeochromocytomas

Digital cases

- Case 153 (HPC:153) : Juxtarenal paraganglioma.
- Case 331 (HPC:153) : Peritoneum (adrenal) malignant paraganglioma with lymph node metastases.

Definition: Paragangliomas arise in specialized neural crest cells associated with segmental or collateral autonomic ganglia throughout the body.

Extra-adrenal paragangliomas occur most commonly in the head and neck region, usually involving the carotid bodies or glomus jugulare, and are observed less frequently in the mediastinum, retroperitoneum, lungs, duodenum, orbit, larynx, urinary bladder, and spinal cord paragangliomas.

Extra-adrenal phaeochromocytomas occur and may be referred to as paragangliomas, although this term is also used to describe vascular head and neck tumours, which most commonly develop at the carotid bifurcation. Pheochromocytomas are neoplasias of neural crest origin arising from the adrenal medulla.

Localization

- adrenal paraganglioma (pheochromocytoma)
- extra-adrenal paraganglioma

  • carotid body paraganglioma
  • jugulotympanic paraganglioma (glomus jugulare tumor)
  • vagal paraganglioma (vagal body tumor)
  • mediastinal paraganglioma (aortic body tumor, mediastinal aorticosympathetic paraganglioma)
  • retroperitoneal paraganglioma - juxtarenal paraganglioma
  • vesical paraganglioma
  • cephalic paraganglioma and cervical araganglioma (hean and neck paraganglioma)
  • gangliocytic paraganglioma (duodenal, bronchial)
  • cauda equina paraganglioma
  • nasopharyngeal paraganglioma
  • laryngeal paraganglioma
  • orbital paraganglioma
  • cardiac paraganglioma
  • pulmonary paraganglioma (#15166677#)
  • thyroid paraganglioma

Microscopic synopsis

- architectural pattern

  • zellballen pattern
  • anastomosing trabecular pattern
  • mixed pattern
  • diffuse pattern (solid pattern)
  • arcuate vascular network
  • confluent tumor necrosis

- cytological pattern

  • argyrophilic cells
  • pleomorphic paraganglioma (pleomorphic cells)
  • gangliocytic paraganglioma (duodenal)

- +/- hyaline globules
- mitosis
- +/- extensive local invasion
- +/- extensive vascular invasion

Variants

- pigmented paraganglioma (#8491482#)
- oncocytic pheochromocytoma (#11075859#)
- gangliocytic paraganglioma (#15492999#)
- immature paraganlioma
- paraganglioma with extensive gangliocytic differentiation (mixed pheochromocytoma and ganglioneuroma) (#3181953#, #10839612#)

Functional classification

- secreting paragngliomas (chromaffin-positive paragangliomas)
- non-secreting paragngliomas (chromaffin-negative paragangliomas)

Immunochemistry

- NSE + (100%)
- chromogranin-A +
- CD56+
- synaptophysin+
- neurofilament+
- Leu-enkephalin + (76%)
- Met-enkephalin + (75%)
- somatostatin + (67%)
- pancreatic polypetide + (51%)
- VIP + (43%)
- substance P + (31%)
- adrenocorticotropic hormon + (28%)
- calcitonin + (23%)
- bombesin + (15%)
- neurotensin + (12%)
- CK- (cytokeratins -)

Ultrastructure

- abundant dense core granules with an eccentric halo ("norepinephrine-type" granules)

Susceptibility syndromes

- germline mutations may be detected in approximately 25% of unselected cases
- von Hippel-Lindau disease (VHL)
- multiple endocrine neoplasia type 2 (MEN 2)
- phaeochromocytoma-paraganglioma syndrome
- neurofibromatosis type 1

- familial paraganglioma-GIST syndrome (#15383933#, #11857563#)
- Carney triad (paraganglioma, gastrointestinal stromal tumor (GIST), pulmonary chondroma)

- SDH mutations

  • Germline mutations in three of the succinate dehydrogenase (SDH, mitochondrial complex II) subunits (SDHD, SDHB and SDHC) cause susceptibility to head and neck paragangliomas, and may be found in approximately 20% of unselected patients.
  • In addition, germline SDHD and SDHB mutations may cause phaeochromocytoma susceptibility with or without associated head and neck paragangliomas.
  • Recent studies suggest that germline SDHD and SDHB mutations are an important cause of familial and isolated phaeochromocytoma. (dysregulation of hypoxia-responsive genes and impairment of mitochondria-mediated apoptosis)

References

- Baysal BE. On the association of succinate dehydrogenase mutations with hereditary paraganglioma. Trends Endocrinol Metab. 2003 Dec;14(10):453-9. PMID: #14643060

- Lack EE, Lloyd RV, Carney JA, Woodruff JM; Association of Directors of Anatomic and Surgical Pathology. Recommendations for reporting of extra-adrenal paragangliomas. Mod Pathol. 2003 Aug;16(8):833-5. PMID: #12920230#

- Lack EE, Lloyd RV, Carney JA, Woodruff JW; Association of Directors of Anatomic and Surgical Pathology. Recommendations for the reporting of extra-adrenal paragangliomas. The Association of Directors of Anatomic and Surgical Pathology. Hum Pathol. 2003 Feb;34(2):112-3. PMID: #12612877#

- Maher ER, Eng C. The pressure rises: update on the genetics of phaeochromocytoma. Hum Mol Genet. 2002 Oct 1;11(20):2347-54. PMID: #12351569#

Portfolio

  • Immature paraganglioma of the vesical region
  • Adrenal pheochromocytoma (Adrenal paraganglioma)
  • Adrenal pheochromocytoma (Adrenal paraganglioma)