Paraganglioma

Paraganglioma typically presents in adults aged 30-50 years, often with symptoms related to catecholamine secretion or mass effect; pathologically, it is a neuroendocrine tumor arising from extra-adrenal paraganglionic cells, and radiologically, it is characterised by a highly vascular mass, often located in the head, neck (carotid body, glomus jugulare), or abdomen (organ of Zuckerkandl).

Description

Paraganglioma is a rare neuroendocrine tumor derived from the paraganglia, a collection of cells that originate from the embryonic neural crest. These tumors can occur anywhere along the sympathetic and parasympathetic paraganglia, including the carotid body, vagal body, and along the spine.

Pathogenesis

Paragangliomas arise from paraganglionic cells, which are part of the autonomic nervous system. These cells have the capability to secrete catecholamines (adrenaline and noradrenaline), leading to various clinical symptoms. Some paragangliomas are associated with inherited genetic syndromes, including mutations in the SDH, VHL, and RET genes.

Subtypes

By Location

• Pheochromocytoma: An adrenal paraganglioma that secretes catecholamines.
• Head and Neck Paragangliomas: Often termed glomus tumours. Often non-secretory and located at carotid bodies, jugular glomus, tympanic glomus, and vagal bodies. Primarily arises from parasympathetic ganglia.
• Abdominal Paragangliomas: Commonly found in the organ of Zuckerkandl near the aorta. Primarily arises from sympathetic ganglia.

By Nervous System

• Nervous System
  • Parasympathetic
    Generally non-secretory
    • Intra-adrenal
      Arise within the adrenal medulla
      • Pheochromocytoma
        Most common
    • Extra-adrenal
      Arise outside the adrenal gland along the sympathetic chain
      • Abdomen
      • Organ of Zuckerkandl
      • Bladder base
      • Mediastinal paraganglioma
      • Aortosympathetic paraganglia
      • Great vessels of the chest – aortopulmonary paraganglia
      • Cardiac – along the epicardium, in the atrial cavity, the interatrial septum or the ventricles (rare)
  • Sympathetic
    • Carotid body paraganglioma (most common ~40-60%)
    • Jugulotympanic paraganglioma
    • Jugular paraganglioma
    • Tympanic paraganglioma
    • Vagal paraganglioma
    • Laryngeal paraganglioma

Epidemiology, Risk Factors & Associations

• Incidence peaks in 30-50-year age group.
• Equal distribution among males and females.
• Genetic predisposition in up to 30% of cases, especially in younger patients.

Hereditary paragangliomas are related to various mutations and part of several clinical syndromes:

• SDH Mutations: Common in head and neck paragangliomas (except SDHB mutation, which is linked to sympathetic paragangliomas).
• SDHB Mutation: Higher risk of malignancy.
• VHL Mutations: Associated with von Hippel-Lindau syndrome, typically linked to pheochromocytomas.
• RET Mutations: Linked to multiple endocrine neoplasia 2A.
• NF1 Mutations: Associated with neurofibromatosis type 1, more commonly linked to pheochromocytomas.
• Carney-Stratakis Syndrome / Carney Triad.

Clinical Features

• Hypertension, palpitations, headache, and sweating due to catecholamine secretion (in secreting tumours).
• Local mass effects such as dysphagia, hoarseness, or pulsatile neck masses (in head and neck paragangliomas).

Complications

• Hypertensive crises, especially during surgery or biopsy.
• Local invasion into surrounding structures.
• Metastasis, although relatively rare.

Pathological Features

Histopathology

• Macroscopic: Well-circumscribed, often encapsulated mass.
• Microscopic: Nest of cells (Zellballen pattern) surrounded by sustentacular cells.

Serology

• Elevated catecholamines and metanephrines (in functional tumours).

Biochemistry

• Chromogranin A elevation.

Radiological Features

General Features

• Highly vascular mass, with intense enhancement post-contrast and delayed washout due to rich capillary network
• Tumour spreads along the paths of least resistance.

CT

• Non-contrast: Homogeneous or slightly heterogeneous mass.
• C+ Arterial/Venous: Prominent and prolonged enhancement due to vascularity.

MRI

• Salt and pepper appearance due to small haemorrhages producing intrinsic T1 hyperintensity (salt) and hypointenese signal from vascular flow voids (pepper)
• T1: Isointense or hypointense to muscle. Foci of hyperintensity suggestive of haemorrhage.
• T2:
  • Hyperintense with serpinginous T2 vascular flow voids
  • Lightbulb bright hyperintensity in adrenal pheochromocytoma.
• T1 Gad+: Marked heterogenous prolonged enhancement

US

• B-mode: Can identify the mass and assess vascularity.
• Colour Doppler: Shows hypervascularity.

NM

• Ga-DOTATATE PET: Shows uptake due to overexpression of somatastatin receptors
• MIBG Scintigraphy: Specific for catecholamine-secreting paragangliomas.
• PET FDG: Non-specific. May show increased uptake.
• F-FDA and F-DOPA: Also specific for catecholamine production.

Grading and Staging

No standardized grading or staging system; assessment is based on tumor size, location, functional status, and metastatic spread.

Diagnosis

Based on clinical presentation, biochemical markers, and imaging findings. Genetic testing is recommended, especially in young patients or those with multiple tumors.

Differential Diagnosis

• Neuroblastoma: Common in children, different location and behavior.
• Carcinoid Tumor: Different histopathological and biochemical profile.
• Metastases: Different clinical and imaging features.

Management

• Surgical resection is the primary treatment.
• Pre-operative management of catecholamine secretion in functional tumors.
• Radiotherapy or chemotherapy for metastatic or unresectable disease.
• Long-term follow-up due to the risk of recurrence.