Genetic analysis of a hereditary medullary thyroid carcinoma case with normal preoperative serum calcitonin levels

Pathol Res Pract. 2019 Oct;215(10):152529. doi: 10.1016/j.prp.2019.152529. Epub 2019 Jul 29.

Abstract

Context: Serum calcitonin is often elevated in medulla thyroid carcinoma (MTC) and thus serves as an indicator of primary and recurrent disease. However, there are MTC patients with normal Serum calcitonin and the underlying mechanisms are largely unknown.

Case description: A 48-year-old female patient presenting with a right anterior cervical mass was diagnosed with medullary carcinoma. She had elevated carcinoembryonic antigen (CEA) but normal Serum calcitonin levels. Next generation sequencing (NGS) of paired tumor and peripheral blood revealed a germline pathogenic RET mutation, indicating the hereditary nature of MTC in this patient. Two somatic loss-of-function mutations in DICER1 gene were also found, which we postulated to account for the normal calcitonin levels found in this patient. To our knowledge, this is the first report of a hereditary MTC case displaying a normal Serum calcitonin.

Conclusions: The case suggests NGS can be used in the diagnosis of hereditary MTC and exploring the reasons of normal Serum calcitonin in these patients.

Keywords: Calcitonin; DICER1; Hereditary medullary thyroid carcinoma; RET Oncogene.

Publication types

  • Case Reports

MeSH terms

  • Calcitonin / blood*
  • Carcinoembryonic Antigen / blood
  • Carcinoma, Medullary / blood
  • Carcinoma, Medullary / genetics*
  • Carcinoma, Medullary / pathology
  • Female
  • Germ-Line Mutation*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Middle Aged
  • Proto-Oncogene Proteins c-ret / genetics*
  • Thyroid Neoplasms / blood
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology

Substances

  • Carcinoembryonic Antigen
  • Calcitonin
  • Proto-Oncogene Proteins c-ret
  • RET protein, human