What are the treatment options for parathyroid tumors based on the WHO 2022 classification?

Treatment Options for Parathyroid Tumors Based on WHO 2022 Classification

Treatment for parathyroid tumors should be determined by their histopathological classification according to the 2022 WHO guidelines, with surgical resection being the primary treatment modality for most parathyroid neoplasms. 1

Key Changes in WHO 2022 Classification of Parathyroid Tumors

• The 2022 WHO classification has replaced the term "atypical parathyroid adenoma" with "atypical parathyroid tumor" to reflect parathyroid neoplasms of uncertain malignant potential 1
• The term "parathyroid hyperplasia" is now primarily used for secondary hyperplasia (often caused by chronic renal failure) rather than for primary hyperparathyroidism 1
• Primary hyperparathyroidism-related multiglandular disease is now classified as "multiglandular multiple parathyroid adenomas" reflecting its nature as germline susceptibility-driven multiglandular parathyroid neoplasia 1
• The concept of "parafibromin deficient parathyroid neoplasm" has been introduced for tumors showing complete absence of nuclear parafibromin immunoreactivity 1

Treatment Options by Tumor Type

Parathyroid Adenoma

• Complete surgical resection is the recommended primary treatment 2
• Two surgical approaches are available:
  • Bilateral neck exploration (BNE) - traditional approach examining all parathyroid glands 2
  • Minimally invasive parathyroidectomy (MIP) - targeted removal of affected gland with shorter operating times and faster recovery 2
• Preoperative localization with imaging is essential for MIP approach 2

Atypical Parathyroid Tumor

• Complete surgical resection with negative margins is recommended 1, 3
• More extensive follow-up is required compared to benign adenomas due to uncertain malignant potential 1
• Complete submission of specimens for microscopic examination with multiple levels and ancillary biomarkers is crucial for accurate diagnosis 1

Parathyroid Carcinoma

• En bloc surgical resection with microscopically negative margins offers the best chance of cure 3, 4
• Diagnosis requires one of the following: angioinvasion, lymphatic invasion, perineural invasion, local malignant invasion, or documented metastatic disease 1
• Documentation of mitotic activity and Ki67 labeling index is recommended 1
• For persistent or recurrent disease (occurs in >50% of cases), surgical resection remains the primary treatment modality 3
• Medical management with cinacalcet and bisphosphonates can help control hypercalcemia in inoperable cases 5, 4
• Chemotherapy and external beam radiation have generally been ineffective 3

CDC73-Related (Hyperparathyroid-Jaw Tumor) Syndrome

• Surgical management with parathyroidectomy is the primary treatment 2
• Surveillance for carriers of pathogenic germline variants in CDC73 should begin at age 5-10 years 2
• Surveillance should include:
  • Annual biochemical screening for hyperparathyroidism (total calcium, corrected for serum albumin) 2
  • Dental panoramic films every 5 years 2
  • Renal ultrasound every 5 years 2
• Biopsy of suspicious neck lesions is discouraged due to risk of seeding carcinomatous cells 2

Special Considerations

• Parafibromin immunohistochemistry is valuable for diagnosis, as loss of nuclear parafibromin staining should prompt consideration of germline analysis of CDC73 2, 1
• Approximately 25% of patients with apparently sporadic parathyroid cancer carry germline HRPT2/CDC73 mutation, making genetic testing important 4
• For persistent or recurrent disease, reoperation is rarely curative but can offer significant palliation for metabolic derangements 3
• In inoperable cases, calcimimetics like cinacalcet can effectively control hypercalcemia 5, 4

Monitoring and Follow-up

• For parathyroid carcinoma, close monitoring is essential as persistent or recurrent disease occurs in more than 50% of patients 3
• For CDC73-related syndrome, women of reproductive age should undergo routine gynecologic assessment with uterine ultrasound as clinically indicated 2
• Patients with hypercalcemia should be evaluated for primary hyperparathyroidism and managed in consultation with an endocrinologist 2
• Consideration should be given to referral to a high-volume parathyroid surgeon for optimal outcomes 2