What is Parathyroid Carcinoma?

Parathyroid carcinoma is a rare malignant (cancerous) tumor of the parathyroid glands. It accounts for <1% of all cases of primary hyperparathyroidism. Unlike benign parathyroid adenomas, carcinomas are aggressive, invasive, and can metastasize (spread to other organs).

How Common is it?

• Very rare: <1 in 1 million people per year
• Accounts for <1% of primary hyperparathyroidism cases
• Equal incidence in men and women (unlike adenomas, which favor women)
• Typical age: 40-60 years (slightly younger than adenomas)

Causes and Risk Factors:

• Most cases are sporadic (no known cause)
• Genetic Syndromes: Hyperparathyroidism-Jaw Tumor (HPT-JT) syndrome (CDC73/HRPT2 gene mutation)
• Familial Isolated Hyperparathyroidism (FIHP)
• Multiple Endocrine Neoplasia (MEN1): Very rare association
• Prior Radiation to Neck: Possible risk factor

Symptoms:

Symptoms are due to severe hypercalcemia (much higher calcium levels than typical adenomas):

• Severe Bone Disease: Bone pain, fractures, "brown tumors" (osteitis fibrosa cystica)
• Kidney Stones: Recurrent nephrolithiasis
• Severe Fatigue, Weakness
• Gastrointestinal: Nausea, vomiting, constipation, abdominal pain, peptic ulcers, pancreatitis
• Neuropsychiatric: Confusion, depression, cognitive impairment, altered mental status
• Palpable Neck Mass: Unusual; benign adenomas are usually too small to feel
• Hoarseness: From recurrent laryngeal nerve involvement

Red Flags Suggesting Carcinoma (vs. Adenoma):

• Very High Calcium: Often >14 mg/dL (vs. 10.5-12 mg/dL in adenomas)
• Very High PTH: Markedly elevated (3-10x upper limit of normal)
• Palpable Neck Mass
• Hoarseness or Vocal Cord Paralysis
• Young Age with Severe Symptoms
• Family History of HPT-JT Syndrome

Diagnosis:

Labs:

• Serum Calcium: Markedly elevated (often >14 mg/dL)
• PTH: Very high (often >5x normal)
• Alkaline Phosphatase: Often very elevated (bone turnover)
• Phosphorus: Low

Imaging:

• Neck Ultrasound: Large, irregular mass; invasion into surrounding tissues
• Sestamibi Scan: Localizes tumor
• CT or MRI Neck: Assess for invasion into thyroid, trachea, esophagus, blood vessels
• Chest CT: Check for lung metastases
• Bone Scan or X-rays: Assess for bone metastases or skeletal involvement

Fine Needle Aspiration (FNA):

• Generally AVOIDED in suspected parathyroid lesions (risk of seeding tumor)

Definitive Diagnosis:

• Made at surgery or by pathology after tumor removal
• Histologic features: vascular invasion, capsular invasion, mitotic activity
• Sometimes difficult to distinguish from atypical adenoma

Treatment:

Surgery: En Bloc Resection (Only Potential Cure)

• Wide surgical excision of tumor with margins
• Remove affected parathyroid gland, ipsilateral thyroid lobe, and any involved structures
• Avoid tumor rupture during surgery (worsens prognosis)
• Remove involved lymph nodes if present
• Complete resection is critical—incomplete surgery leads to recurrence

Post-Operative Management:

• Severe Hungry Bone Syndrome: Expect profound hypocalcemia post-surgery; requires aggressive IV and oral calcium/Vitamin D replacement
• Monitor calcium, PTH closely

For Metastatic or Unresectable Disease:

• No curative options
• Goal: Control hypercalcemia and symptoms
• Medical Management:
  • Calcimimetics (Cinacalcet): Lower calcium by increasing sensitivity to calcium
  • Bisphosphonates (Zoledronic Acid): Reduce bone resorption
  • Denosumab: RANKL inhibitor; reduces calcium
  • Hydration, Loop Diuretics: Promote calcium excretion
• Radiation Therapy: Limited role; may be used for unresectable local disease or bone metastases
• Chemotherapy: Generally ineffective
• Repeat Surgery: For isolated, resectable recurrences or metastases

Prognosis:

• 5-Year Survival: 50-85% (varies by completeness of resection)
• 10-Year Survival: ~50%
• Recurrence Rate: 40-60% (even after complete resection)
• Metastases: Most commonly to lungs, bone, liver, lymph nodes
• Better Prognosis if: Complete initial resection with negative margins, no vascular invasion
• Worse Prognosis if: Metastatic disease, recurrence, incomplete resection

Long-Term Monitoring:

• Lifelong surveillance required (recurrence can occur decades later)
• Monitor: Calcium and PTH every 3-6 months for several years, then annually
• Imaging: Neck ultrasound, chest/abdominal CT periodically to detect recurrence or metastases