Origin and impact of multifocal growth in sporadic vs. hereditary medullary thyroid cancer

Eur J Surg Oncol. 2024 Nov;50(11):108625. doi: 10.1016/j.ejso.2024.108625. Epub 2024 Aug 29.

Abstract

Multifocal growth is characteristic of hereditary medullary thyroid cancer (MTC), whereas origin and impact of multifocal growth is enigmatic for sporadic MTC. To address this, 460 RET-negative patients with sporadic MTC, stratified by 1 (93.3 %), 2 (5.7 %) and 3 (1.1 %) thyroid tumor foci, were compared with 219 RET-positive patients with hereditary MTC, stratified by 1 (38.4 %), 2 (45.7 %), 3 (6.4 %), 4 (6.8 %) and ≥5 (2.7 %) thyroid tumor foci. For sporadic MTC, significant associations were identified with bilateral thyroid lobe involvement, microscopic lymphatic invasion, extrathyroid extension, node and distant metastases, number of node metastases, preoperative basal calcitonin level, and decreasing biochemical cure. For hereditary MTC, significant associations were limited to bilateral thyroid lobe involvement, largest thyroid tumor diameter, and preoperative basal calcitonin level. In sporadic MTC, multifocal growth is due to lymphatic invasion with frequent node metastases, whereas in hereditary MTC, it reflects malignant progression from C-cell hyperplasia to cancer.

Keywords: Lymph node metastases; Malignant progression; Medullary thyroid carcinoma; Microscopic lymphatic invasion; RET proto-oncogene; Tumor multifocality.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Calcitonin* / blood
  • Carcinoma, Medullary / congenital
  • Carcinoma, Medullary / genetics
  • Carcinoma, Medullary / pathology
  • Carcinoma, Neuroendocrine / genetics
  • Carcinoma, Neuroendocrine / pathology
  • Disease Progression
  • Female
  • Humans
  • Lymphatic Metastasis*
  • Male
  • Middle Aged
  • Multiple Endocrine Neoplasia Type 2a / genetics
  • Multiple Endocrine Neoplasia Type 2a / pathology
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins c-ret* / genetics
  • Thyroid Neoplasms* / genetics
  • Thyroid Neoplasms* / pathology
  • Thyroidectomy
  • Young Adult

Substances

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

Supplementary concepts

  • Familial medullary thyroid carcinoma
  • Thyroid cancer, medullary