Correlation of molecular data with histopathological and clinical features in a series of 66 patients with medullary thyroid carcinoma

M. M. Moura, R. A. Cabrera, S. Esteves, B. M. Cavaco, P. Soares, V. Leite

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Purpose: Medullary thyroid carcinoma (MTC) displays a wide variety of histopathological features, and several histological variants have been described. In follicular cell-derived thyroid carcinomas, there is a good correlation between genotype and phenotype. In this study, we investigated whether such a correlation is also present in MTC. Methods: The histopathological features were evaluated in a series of 66 molecularly characterised tumours and correlated with the clinical characteristics. Results: Most MTC exhibited the classical variant (83.3%). Other variants included spindle cell (6.1%), pseudopapillary (4.5%), paraganglioma-like (3.0%), angiosarcoma-like (1.5%), and oncocytic follicular (1.5%). Tumours were classified into four groups: group 1, with somatic p.Met918Thr and p.Ala883Phe RET mutations; group 2, with other RET mutations; group 3, with RAS mutations; and group 4, without RET or RAS mutations. Tumours from groups 1 and 4 were typically associated with the classical variant, with abundant fibrosis, lymphovascular invasion, extrathyroidal extension, and more advanced stages of disease, whereas group 2 included histological variants other than the classical variant (namely, pseudopapillary and paraganglioma-like), with tumours that were highly cellular, less invasive, and with a better overall prognosis. In tumours from group 4, amyloid deposition was characteristically absent or low. The spindle cell variant appeared only in tumours from group 3, which had high cellularity and a degree of invasion and prognosis intermediate between groups 1 and 2, but better than group 4. The grade of fibrosis correlated directly with the clinical outcome. Conclusion: Our results support the idea that a genotype–phenotype correlation does, indeed, exist in MTC. However, further studies are warranted to confirm these findings in a larger sample size.

Original languageEnglish
Pages (from-to)1837 - 1846
JournalJournal of Endocrinological Investigation
Issue number9
Early online dateFeb 2021
Publication statusPublished - Sep 2021


  • Genotype–phenotype correlation
  • Histopathological features
  • Medullary thyroid carcinoma
  • Prognosis
  • Tumour fibrosis


Dive into the research topics of 'Correlation of molecular data with histopathological and clinical features in a series of 66 patients with medullary thyroid carcinoma'. Together they form a unique fingerprint.

Cite this