Paragangliomas

Definition

• Rare neuroendocrine tumors that arise from the extra-adrenal autonomic paraganglia organs derived from the embryonic neural crest
• Divided into:
  • Sympathetic paragangliomas
    • Usually secrete catecholamines (90%)
      • Closely related to Pheochromocytoma
      • Present in a similar fasion
    • Sympathetic paravertebral ganglia of thorax, abdomen, and pelvis.
  • Parasympathetic paragangliomas
    • More common
    • Most nonfunctional
    • Typically located along the glossopharyngeal and vagal nerves in the neck and at the base of the skull

Clinical

• Mostly asymptomatic
• Painless neck mass
• Symptomatic from excessive catecholamine secretion
  • Episodic hypertension, tachycardia, palpitations, sweating, pallor, headache, or nonspecific abdominal or flank pain

Epidemiology

• Rare

Aetiology

• ?Chronic hypoxia - increase incidence in people living in altitude
• 50% linked to inherited syndrome
• Genetic syndromes
  • Paraganglioma syndrome
  • Multiple endocrine neoplasia 2A and 2B
  • Neurofibromatosis Type 1
  • Von-Hippel-Lindau disease
  • Carney-Stratakis dyad
  • Carney triad

Location

• Parasympathetic
  • Most commonly arise in the carotid body (Carotid body tumour)
  • Less commonly from jugulotympanic and vagal paraganglia
  • Rarely from the laryngeal paraganglia
• Sympathetic
  • anywhere along the sympathetic chain
  • 75 percent of sympathetic paragangliomas arise in the abdomen
    • Most often at the junction of the vena cava and the left renal vein, or at the organ of Zuckerkandl, which resides at the aortic bifurcation near the take-off of the inferior mesenteric artery
  • 10 percent arise in the thorax
    • including pericardial locations
  • Sympathetic paragangliomas can also arise in the thyroid gland, adjacent to the thoracic spine, and at the level of the cauda equina.

Histology

• Epithelioid cells arranged in compact cell nests or trabecular patterns (the so-called Zellballen appearance)
• Spindle-shaped sustentacular or supporting cells are found peripheral to the chief cell nests
• Difficult to histologically tell if benign or malignant

Staging

• Carotid body tumour

  • Shamblin criteria

• Jugulotympanic paragangliomas

  • McCabe/Fletcher staging system outdated
  • New Fisch and Glasscock/Jackson

• AJCC 8th edition

  • Has a TNM for pheochromocytoma and paraganglioma

• Rule of 5’s

  • 50% have a genetic link NF-1, Carney stratakis, MEN 2A/Von hippel lindau
  • 5% metastasize
  • 5% produce catecholamines (MAJORITY NON FUNCTIONAL)

Investigations

• Urinary and/or plasma fractionated metanephrines and catecholamines
• CT/MRI
• Ultrasound is a good initial diagnostic study for patients with a suspected carotid body paraganglioma
• Genetic testing in all patients

Management