What is the recommended approach for screening for parathyroid cancer?

Screening for Parathyroid Cancer

Parathyroid cancer should be screened for using a combination of biochemical testing (serum calcium and parathyroid hormone levels) and imaging studies (ultrasound and sestamibi scanning), with particular attention to clinical features suggesting malignancy such as severe hypercalcemia, large palpable neck mass, and elevated PTH ratio. 1, 2, 3

Biochemical Screening

The initial screening approach for parathyroid cancer includes:

• Serum calcium measurement (albumin-corrected) - values >3 mmol/L (>12 mg/dL) raise suspicion for malignancy 3
• Parathyroid hormone (PTH) level - markedly elevated levels suggest possible malignancy
• Third-generation to second-generation PTH assay ratio - ratio >1 is highly suspicious for parathyroid carcinoma 3, 4
• 25-OH Vitamin D levels to exclude hypovitaminosis D as a secondary cause of hyperparathyroidism 1

Imaging Studies

When biochemical testing suggests hyperparathyroidism with features concerning for malignancy:

• Neck ultrasound - first-line imaging to evaluate for parathyroid lesions and suspicious features (size >3 cm, irregular borders, local invasion) 1, 3
• Sestamibi dual-phase scan with SPECT or SPECT/CT - provides functional information about parathyroid tissue 1
• CT neck without and with IV contrast (4D-CT) - helpful for precise localization and evaluation of local invasion 1

High-Risk Clinical Features

Pay particular attention to these red flags for parathyroid cancer:

• Severe hypercalcemia (albumin-corrected calcium >3 mmol/L)
• Palpable neck mass >3 cm
• Third/second generation PTH assay ratio >1
• Intraoperative findings suggesting local invasion or metastasis 3

Important Caveats

• Fine needle aspiration (FNA) is contraindicated in suspected parathyroid cancer due to risk of tumor seeding and difficulty differentiating benign from malignant disease on cytology 2
• Genetic testing for CDC73/HRPT2 mutations should be considered, as 15-20% of seemingly sporadic parathyroid carcinomas have underlying germline mutations 3
• In patients with multiple endocrine neoplasia (MEN) syndromes, regular screening for hyperparathyroidism should begin at age 11 for high-risk RET allele carriers and age 16 for moderate-risk carriers 1

Diagnostic Confirmation

Definitive diagnosis of parathyroid cancer requires one of the following pathological features:

1. Vascular invasion
2. Perineural invasion
3. Gross invasion into adjacent structures
4. Metastasis 3

Management Approach

If parathyroid cancer is suspected preoperatively:

1. Refer to an experienced endocrine surgeon
2. Plan for en bloc resection with negative margins
3. Avoid rupture of the tumor capsule during surgery
4. Consider adjuvant radiation therapy for high-risk features (positive margins, angioinvasion) 2, 5

Regular postoperative surveillance with calcium and PTH measurements is essential, as recurrence occurs in more than 50% of patients with parathyroid carcinoma 2.