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

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Abstract

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.

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Acknowledgements

The authors thank Filipa Areia for her skilful help with the histological procedures. We are also grateful to Dr. Alexandra Mayer for her assistance with the statistical analysis. Many thanks to Sandra Gonçalves for her kind support with the paper figure. Associação de Endocrinologia Oncológica (AEO) and iNOVA4Health (UIDB/04462/2020), which is funded by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, are also acknowledged.

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Authors and Affiliations

  1. Unidade de Investigação em Patobiologia Molecular (UIPM), Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023, Lisboa, Portugal

    M. M. Moura, B. M. Cavaco & V. Leite

  2. Serviço de Anatomia Patológica, Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 , Lisboa, Portugal

    R. A. Cabrera

  3. Unidade de Investigação Clínica (UIC), Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 , Lisboa, Portugal

    S. Esteves

  4. i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal

    P. Soares

  5. IPATIMUP - Instituto de Patologia e Imunologia, Universidade do Porto, Rua Júlio Amaral de Carvalho 45, 4200-135, Porto, Portugal

    P. Soares

  6. Departamento de Patologia, Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-135, Porto, Portugal

    P. Soares

  7. Serviço de Endocrinologia, Instituto Português de Oncologia de Lisboa Francisco Gentil E.P.E., Rua Prof. Lima Basto, 1099-023 , Lisboa, Portugal

    V. Leite

  8. NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo dos Mártires da Pátria 130, 1169-056, Lisboa, Portugal

    V. Leite

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  1. M. M. Moura
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  2. R. A. Cabrera
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  4. B. M. Cavaco
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Correspondence to M. M. Moura.

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This study was conducted with approval from the Institutional Ethics Committee of IPOLFG.

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Moura, M.M., Cabrera, R.A., Esteves, S. et al. Correlation of molecular data with histopathological and clinical features in a series of 66 patients with medullary thyroid carcinoma. J Endocrinol Invest 44, 1837–1846 (2021). https://doi.org/10.1007/s40618-020-01456-6

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