Table of contents
Parathyroid carcinoma
What's new
Added 2024 ESMO, 2023 ES, and 2016 ES guidelines for the diagnosis and management of parathyroid carcinoma.
Background
Overview
Definition
Parathyroid carcinoma is a rare malignant tumor originating from the parathyroid glands, characterized by excessive production of PTH, which results in severe hypercalcemia and associated complications.
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Pathophysiology
Parathyroid carcinoma is generally sporadic but can also develop as part of specific syndromes, such as hyperparathyroidism-jaw tumor syndrome and MEN1 or multiple endocrine neoplasia 2A. Common mutations identified in patients with parathyroid carcinoma include HRPT2/CDC73 and CCND1. Mutation in the HRPT2/CDC73 gene leads to reduced expression of parafibromin and the calcium-sensing receptor.
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Epidemiology
The incidence of parathyroid carcinoma in the US is estimated at 0.36 per 1,000,000 person-year and accounts for less than 1% of all primary hyperparathyroidism cases.
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Risk factors
Risk factors include environmental exposures and prior head and neck radiotherapy.
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Disease course
Functioning parathyroid carcinoma presents with primary hyperparathyroidism and symptoms and signs related to hypercalcemia. Nonfunctioning parathyroid carcinoma usually presents with a palpable solid neck mass, dysphagia, and change in voice due to laryngeal nerve palsy. Parathyroid carcinoma is often detected postoperatively and is associated with a high rate of recurrence.
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Prognosis and risk of recurrence
The prognosis of parathyroid carcinoma is generally poor, with a high rate of recurrence and a significant number of patients developing multiple disease recurrences. The reported overall survival rates are 78-91% at 5 years and 60-72% at 10 years.
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Guidelines
Key sources
The following summarized guidelines for the evaluation and management of parathyroid carcinoma are prepared by our editorial team based on guidelines from the European Society of Medical Oncology (ESMO 2024), the Endocrine Society (ES 2023), and the American Association of Endocrine Surgeons (AAES 2016).
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Screening and diagnosis
Classification and risk stratification
Staging: as per ESMO 2024 guidelines, use the AJCC TNM 8th edition system for parathyroid carcinoma staging.
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TNM classification for parathyroid carcinoma (AJCC)
Tumor classification
Tx: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Atypical parathyroid neoplasm (neoplasm of uncertain malignant potential)
T1: Localized to the parathyroid gland with extension limited to soft tissue
T2: Direct invasion into the thyroid gland
T3: Direct invasion into the recurrent laryngeal nerve, esophagus, trachea, skeletal muscle, adjacent lymph nodes, or thymus
T4: Direct invasion into major blood vessels or spine
Lymph node classification
Nx: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1a: Metastasis to level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes) or superior mediastinal lymph nodes (level VII)
N1b: Metastasis to unilateral, bilateral, or contralateral cervical (level I, II, III, IV, or V) or retropharyngeal nodes
Metastasis classification
M0: No distant metastasis
M1: Distant metastasis present
The AJCC does not provide anatomic stage and prognostic groups for parathyroid carcinoma due to insufficient data.
Diagnostic investigations
Diagnostic imaging
As per ESMO 2024 guidelines:
Obtain neck ultrasound to assess lesions suspicious of parathyroid carcinoma.
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Consider obtaining 99mTc-sestamibi SPECT for the diagnosis of parathyroid carcinoma, recognizing that it cannot differentiate parathyroid carcinoma from adenoma.
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Imaging for staging
Genetic testing
Diagnostic procedures
FNA: as per ESMO 2024 guidelines, consider obtaining fine-needle aspiration cytology and washout PTH measurements to differentiate parathyroid carcinoma from other neck or thyroid nodules, but recognizing that these methods cannot differentiate it from adenoma.
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Histopathology
Medical management
Management of local/locoregional disease, surgical resection
As per ESMO 2024 guidelines:
Perform upfront surgery with en bloc removal of the parathyroid lesion avoiding capsule rupture and local seeding, along with homolateral thyroid lobo-isthmectomy and central node dissection when a preoperative diagnosis of parathyroid carcinoma is made.
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Discuss reoperation with ipsilateral thyroid lobo-isthmectomy and central node dissection within 1 month of initial surgery in cases of pathological diagnosis of parathyroid carcinoma after parathyroidectomy.
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Management of local/locoregional disease (adjuvant radiotherapy)
Management of advanced/metastatic disease
Management of hypercalcemia
Follow-up and surveillance
Follow-up
As per ESMO 2024 guidelines:
Obtain lifelong laboratory follow-up, including measurement of calcium and PTH, every 3-4 months during the first 2 years, every 6 months during the subsequent 3 years, and annually thereafter.
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Obtain neck ultrasound and CT of the neck, chest, and abdomen, along with neck MRI, in cases of calcium and/or PTH elevation.
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Consider obtaining FDG-PET to complete the workup, especially in rapidly progressing cases. B