What is the initial management and treatment approach for a patient diagnosed with paraganglioma?

Initial Management and Treatment of Paraganglioma

The initial management of paraganglioma should involve a multidisciplinary approach with observation as first-line for asymptomatic head and neck paragangliomas, while functional or symptomatic paragangliomas require surgical resection following appropriate preoperative preparation. 1

Diagnostic Evaluation

• Initial biochemical testing should include measurements of plasma free or urinary fractionated metanephrines to identify functional tumors 2
• Imaging evaluation should include:
  • Somatostatin receptor (SSTR) PET/CT using gallium-68 radiolabeled somatostatin analogs as the preferred functional imaging modality (sensitivity approaching 100% for head and neck paragangliomas) 1
  • Whole-body MRI as an alternative imaging option to reduce radiation exposure 1
  • 18F-FDOPA PET is a good alternative if SSTR PET is unavailable 1
• Genetic testing should be considered in all patients with paraganglioma, particularly those with SDHx mutations, which are present in up to 50% of cases 3, 2

Treatment Algorithm Based on Tumor Location and Functionality

Head and Neck Paragangliomas (HNPGLs)

• For asymptomatic HNPGLs without compelling indications for treatment:

  • Initial observation trial is recommended to characterize tumor behavior 1
  • Follow-up imaging at 3-6 months and at 1 year following diagnosis 1
  • Median growth rates may be as low as 1.0 mm/year with median doubling time of 4.2-5.7 years 1

• Indications for intervention in HNPGLs:

  • Sustained growth or compression of vital head and neck structures 1
  • Progression after radiation 1
  • Severe or progressive symptoms from cranial neuropathy 1
  • Brainstem compression, severe pain, bleeding, or brain ischemia 1

• Special considerations for specific HNPGLs:

  • Vagal paragangliomas: rarely consider for resection due to high risk of vocal cord paralysis 1
  • Tympanic paragangliomas: often safe for resection with low complication rates 1
  • Jugular and carotid paragangliomas: consider preoperative angiography with embolization 1

Functional Paragangliomas (Catecholamine-Secreting)

• Preoperative management:

  • Alpha-adrenergic blockade is essential to prevent perioperative complications 1, 2
  • Add beta-blockers only after adequate alpha blockade to treat tachycardia 1
  • High-sodium diet and administration of 1-2 liters of saline 24 hours prior to surgery 1
  • Use of compressive stockings to reduce orthostatic hypotension 1

• Surgical approach:

  • Complete surgical extirpation (R0 resection) is the mainstay of potentially curative approaches 1
  • Functional paragangliomas (predominantly retroperitoneal) should be resected as an initial priority in patients with multifocal disease 1
  • Minimally invasive approaches when feasible 2

Management of Metastatic Disease

• For asymptomatic or stable metastatic disease:

  • Active surveillance for patients with stable/very slow-growing metastatic lesions (stable >12 months), particularly with low tumor burden 1

• For symptomatic or progressive metastatic disease:

  • Local therapies (surgery, radiation, interventional procedures) for symptomatic oligometastatic disease 1
  • Targeted radionuclide therapy (131I-MIBG) as first-line systemic therapy for SSTR- or MIBG-positive metastatic tumors with moderate-to-high tumor burden 1
  • Chemotherapy (cyclophosphamide, dacarbazine, vincristine) for rapidly progressive disease or high visceral tumor burden 1
  • Tyrosine kinase inhibitors (sunitinib) or temozolomide for progressing tumors not eligible for radionuclide therapy 1

Follow-up Recommendations

• For non-metastatic disease after treatment:

  • Measurement of plasma or urine metanephrines by 8 weeks post-treatment for functional tumors 1
  • Imaging at 3-6 months post-treatment 1
  • Annual blood pressure measurements, clinical assessment, and biochemical measurements 1
  • Whole-body MRI at least every 2-3 years to detect new paragangliomas, metastases, or progression 1, 4

• For metastatic disease:

  • SSTR PET/CT to evaluate disease progression 1
  • More frequent imaging initially, with interval determined by disease behavior 1

Important Considerations and Pitfalls

• Paragangliomas in patients with SDHD mutations have a high incidence of multifocality, requiring thorough preoperative evaluation 1
• Elective surgical resection of HNPGLs should be avoided in elderly and debilitated patients, and those unable to tolerate specific cranial neuropathies 1
• For patients with bilateral or multifocal HNPGLs, a staged approach is recommended to avoid bilateral cranial nerve palsies 1
• Thorough cranial nerve examination and laryngoscopy before and after surgical intervention or radiotherapy for HNPGLs is essential 1
• Lifelong follow-up is recommended due to the risk of recurrence, metastasis, or progression, especially in patients with SDHD mutations 1, 4