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Diagnosis and management of parathyroid cancer

Nature Reviews Endocrinology volume 8, pages 612–622 (2012)Cite this article

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Abstract

Parathyroid cancer is rare, but often fatal, as preoperative identification of malignancy against the backdrop of benign parathyroid disease is challenging. Advanced genetic, laboratory and imaging techniques can help to identify parathyroid cancer. In patients with clinically suspected parathyroid cancer, malignancy of any individual lesion is established by three criteria: demonstration of metastasis, specific ultrasonographic features, and a ratio >1 for the results of third-generation:second-generation parathyroid hormone assays. Positive findings for all three criteria dictate an oncological surgical approach, as appropriate radical surgery can achieve a cure. Mutation screening pinpoints associated conditions and asymptomatic carriers. Molecular profiling of tumour cells can identify high-risk features, such as differential expression of specific micro-RNAs and proteins, and germ line mutations in CDC73, but is unsuitable for preoperative assessment owing to the potential risks associated with biopsy. A validated, histopathology-based prognostic classification can identify patients in need of close follow-up and adjuvant therapy, and should prove valuable to stratify clinical trial cohorts: low-risk patients rarely die from parathyroid cancer, even on long-term follow-up, whereas 5-year mortality in high-risk patients is around 50%. This insight has improved the approach to parathyroid cancer by enabling risk-adapted surgery and follow-up.

Key Points

  • Parathyroid lesions <3 cm in patients with serum calcium levels <3 mmol/l are rarely malignant if other features suggestive of cancer are absent, but only <5% of patients have such lesions

  • Family history, assessment of specific ultrasonographic criteria and specific parathyroid hormone assay findings can help to confirm a preoperative diagnosis or suspicion of cancer

  • Preoperative molecular profiling can reveal high-risk features, but requires biopsy, which is currently not recommended

  • Germ line or somatic mutations of CDC73, and rarely MEN1, occur in 15–100% of patients with parathyroid cancer; they indicate increased risk, but cannot establish a diagnosis of malignancy

  • Vascular invasion predicts distant recurrence, whereas invasion of vital organs and lymph node metastases predict locoregional recurrence; the presence of both criteria confers a highly adverse outcome

  • Local excision is associated with poor outcomes; consequently, surgery with curative intent requires complete resection using en bloc or oncological techniques

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Figure 1: Algorithm for assessment of parathyroid lesions.
Figure 2: Scatter plot of albumin-corrected calcium levels versus tumour size for benign and malignant parathyroid lesions.
Figure 3: The stages of parathyroid cancer.
Figure 4: Algorithm for surgical treatment of patients with suspected parathyroid cancer.

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Acknowledgements

K.-M. Schulte and N. Talat gratefully acknowledge the contribution of Salvador Diaz-Cano, MD, PhD, FRCPath (Department of Histopathology, King's College Hospital, King's Health Partners, London, UK) for providing us with the histopathology images in Figure 3.

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  1. Department of Endocrine Surgery, King's Health Partners, Denmark Hill, London, SE5 9RS, UK

    Klaus-Martin Schulte & Nadia Talat

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  1. Klaus-Martin Schulte
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K.-M. Schulte wrote the manuscript and contributed to discussions of its content. K.-M. Schulte and N. Talat both researched the data for the article and participated in review and/or editing of the manuscript before submission.

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Correspondence to Klaus-Martin Schulte.

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Supplementary information

Supplementary Table 1

Comparison of clinical features in patients with parathyroid cancer or adenoma (DOC 43 kb)

Supplementary Table 2

Novel PTH assays identify parathyroid cancer by ratios rather than total values (DOC 41 kb)

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Schulte, KM., Talat, N. Diagnosis and management of parathyroid cancer. Nat Rev Endocrinol 8, 612–622 (2012). https://doi.org/10.1038/nrendo.2012.102

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