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Thymoma in multiple endocrine neoplasia type 1: a case report and systematic review

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Abstract

Background

Multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome that combines endocrine and non-endocrine tumors. Thymic neuroendocrine tumors are uncommon components that predict poor prognosis in patients with MEN1. We aimed to summarize the clinical characteristics of thymoma in MEN1 by reviewing the current reports from the literature.

Methods

A patient with multiple endocrine neoplasia type 1 (parathyroid hyperplasia, pituitary adenoma, and insulinoma) was found to have a 2 × 1.5 cm thymic mass during long-term follow-up. Thoracoscope surgery was performed, and a histopathology examination revealed WHO Type B3 thymoma. A pathogenic mutation of c.783 + 1G > A in the MEN1 gene was identified. We further searched PubMed and EMBASE for thymoma in association with MEN1.

Results

A comprehensive overview of the literature concerning characteristics of MEN1-related thymoma was summarized. Clinical characteristics and differences between thymoma and thymic carcinoid are highlighted.

Conclusions

Besides carcinoid, other tumors, including thymoma, need to be identified for thymic space-occupying lesions in MEN1 patients. The impact of thymoma on the long-term prognosis of MEN1 patients needs further investigation.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

MEN1:

multiple endocrine neoplasia type 1

CT:

computed tomography

PA:

pituitary adenoma

MG:

myasthenia gravis

PHPT:

primary hyperparathyroidism

EPT:

nteropancreatic endocrine tumors

AT:

adrenocortical tumor

surg:

surgery

radio:

radiotherapy.

References

  1. R.V. Thakker, P.J. Newey, G.V. Walls, J. Bilezikian, H. Dralle, P.R. Ebeling, S. Melmed, A. Sakurai, F. Tonelli, M.L. Brandi et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J. Clin. Endocrinol. Metab. 97(9), 2990–3011 (2012)

    Article  CAS  PubMed  Google Scholar 

  2. S.K. Agarwal, The future: genetics advances in MEN1 therapeutic approaches and management strategies. Endocr. Relat. Cancer 24(10), T119–T134 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. S.G. Waguespack, Beyond the “3 Ps”: a critical appraisal of the non-endocrine manifestations of multiple endocrine neoplasia type 1. Front. Endocrinol. 13, 1029041 (2022)

    Article  Google Scholar 

  4. J.M. de Laat, C.R. Pieterman, M.F. van den Broek, J.W. Twisk, A.R. Hermus, O.M. Dekkers, W.W. de Herder, A.N. van der Horst-Schrivers, M.L. Drent, P.H. Bisschop et al. Natural course and survival of neuroendocrine tumors of thymus and lung in MEN1 patients. J. Clin. Endocrinol. Metab. 99(9), 3325–3333 (2014)

    Article  PubMed  Google Scholar 

  5. N. Singh Ospina, G.B. Thompson, F.R.C. Nichols, S.D. Cassivi, W.F. Young Jr, Thymic and bronchial carcinoid tumors in multiple endocrine neoplasia type 1: the Mayo Clinic experience from 1977 to 2013. Horm. Cancer 6(5–6), 247–253 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. I. Christakis, W. Qiu, A.M. Silva Figueroa, S. Hyde, G.J. Cote, N.L. Busaidy, M. Williams, E. Grubbs, J.E. Lee, N.D. Perrier, Clinical features, treatments, and outcomes of patients with thymic carcinoids and multiple endocrine neoplasia type 1 syndrome at MD Anderson Cancer Center. Horm. Cancer 7(4), 279–287 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. L. Ye, W. Wang, N.S. Ospina, L. Jiang, I. Christakis, J. Lu, Y. Zhou, W. Zhu, Y. Cao, S. Wang et al. Clinical features and prognosis of thymic neuroendocrine tumors associated with multiple endocrine neoplasia type 1: a single-center study, systematic review, and meta-analysis. Clin. Endocrinol. 87(6), 706–716 (2017)

    Article  CAS  Google Scholar 

  8. F.J. Palmer, T.M. Sawyers, Hyperparathyroidism, chemodectoma, thymoma, and myasthenia gravis. Arch. Intern. Med. 138(9), 1402–1403 (1978)

    Article  CAS  PubMed  Google Scholar 

  9. L.J. Vroegindeweij-Claessens, C.C. Tijssen, G.J. Creemers, J.H. Lockefeer, J.L. Teepen, Myasthenia gravis and thymoma in multiple endocrine neoplasias (MEN-1) syndrome. J. Neurol. Neurosurg. Psychiatry 53(7), 624–625 (1990)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. G. De Toma, M. Plocco, V. Nicolanti, S. Brozzetti, C. Letizia, A. Cavallaro, Type B1 thymoma in multiple endocrine neoplasia type 1 (MEN-1) syndrome. Tumori 87(4), 266–268 (2001)

    Article  PubMed  Google Scholar 

  11. Y. Kojima, H. Ito, S. Hasegawa, T. Sasaki, K. Inui, Resected invasive thymoma with multiple endocrine neoplasia type 1. Jpn J. Thorac. Cardiovasc. Surg. 54(4), 171–173 (2006)

    PubMed  Google Scholar 

  12. B.S. Miller, R.Y. Rusinko, L. Fowler, Synchronous thymoma and thymic carcinoid in a woman with multiple endocrine neoplasia type 1: a case report and review. Endocr. Pr. 14(6), 713–716 (2008)

    Article  Google Scholar 

  13. M.J. Hall, J. Innocent, C. Rybak, C. Veloski, W.J. Scott, H. Wu, J.A. Ridge, J.P. Hoffman, H. Borghaei, A. Turaka, M.B. Daly, Bilateral granulosa cell tumors: a novel malignant manifestation of multiple endocrine neoplasia 1 syndrome found in a patient with a rare menin in-frame deletion. Appl. Clin. Genet. 8, 69–73 (2015)

    PubMed  PubMed Central  Google Scholar 

  14. M. Tomita, N. Ichiki, T. Ayabe, H. Tanaka, H. Kataoka, K. Nakamura, Thymoma (World Health Organization type B3) with neuroendocrine differentiation in multiple endocrine neoplasia type 1. J. Surg. Case Rep. 2017(4), rjx071 (2017)

    Article  PubMed  PubMed Central  Google Scholar 

  15. Z. Fan, L. Wang, J. Wang, C. Gu, Thymoma (World Health Organization Type AB) in multiple endocrine neoplasia type 1: a case report. J. Surg. Case Rep. 2022(7), rjac290 (2022)

    Article  PubMed  PubMed Central  Google Scholar 

  16. Expert Committee on Neuroendocrine Neoplasms CSoCO, [Chinese expert consensus on lung and thymus neuroendocrine neoplasms]. Zhonghua Zhong Liu Za Zhi 43(10), 989–1000 (2021)

    Google Scholar 

  17. J. Rosai, E. Higa, J. Davie, Mediastinal endocrine neoplasm in patients with multiple endocrine adenomatoses. A previously unrecognized association. Cancer 29(4), 1075–1083 (1972)

    Article  CAS  PubMed  Google Scholar 

  18. A. Sakurai, S. Suzuki, S. Kosugi, T. Okamoto, S. Uchino, A. Miya, T. Imai, H. Kaji, I. Komoto, D. Miura et al. Multiple endocrine neoplasia type 1 in Japan: establishment and analysis of a multicentre database. Clin. Endocrinol. 76(4), 533–539 (2012)

    Article  Google Scholar 

  19. G. Effraimidis, U. Knigge, M. Rossing, P. Oturai, A.K. Rasmussen, U. Feldt-Rasmussen, Multiple endocrine neoplasia type 1 (MEN-1) and neuroendocrine neoplasms (NENs). Semin. Cancer Biol. 79, 141–162 (2022)

    Article  CAS  PubMed  Google Scholar 

  20. A.G. Knudson Jr, Mutation and cancer: statistical study of retinoblastoma. Proc. Natl. Acad. Sci. USA 68(4), 820–823 (1971)

    Article  PubMed  PubMed Central  Google Scholar 

  21. C. Larsson, B. Skogseid, K. Oberg, Y. Nakamura, M. Nordenskjold, Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature 332(6159), 85–87 (1988)

    Article  CAS  PubMed  Google Scholar 

  22. R.V. Thakker, P. Bouloux, C. Wooding, K. Chotai, P.M. Broad, N.K. Spurr, G.M. Besser, J.L. O'Riordan, Association of parathyroid tumors in multiple endocrine neoplasia type 1 with loss of alleles on chromosome 11. N. Engl. J. Med 321(4), 218–224 (1989)

    Article  CAS  PubMed  Google Scholar 

  23. A.A. Pannett, R.V. Thakker, Somatic mutations in MEN type 1 tumor, consistent with the Knudson “two-hit” hypothesis. J. Clin. Endocrinol. Metab. 86(9), 4371–4374 (2001)

    CAS  PubMed  Google Scholar 

  24. D.C. Strollo, M.L. Rosado de Christenson, J.R. Jett, Primary mediastinal tumors. Part 1: tumors of the anterior mediastinum. Chest 112(2), 511–522 (1997)

    Article  CAS  PubMed  Google Scholar 

  25. R. Dixit, N.S. Shah, M. Goyal, C.B. Patil, M. Panjabi, R.C. Gupta, N. Gupta, S.V. Harish, Diagnostic evaluation of mediastinal lesions: analysis of 144 cases. Lung India 34(4), 341–348 (2017)

    Article  PubMed  PubMed Central  Google Scholar 

  26. A. Mandl, J.M. Welch, G. Kapoor, V.I. Parekh, D.S. Schrump, R.T. Ripley, M.F. Walter, J. Del Rivero, S. Jha, W.F. Simonds et al. Two distinct classes of thymic tumors in patients with MEN1 show LOH at the MEN1 locus. Endocr. Relat. Cancer 28(11), L15–L19 (2021)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. P. Goudet, A. Murat, C. Cardot-Bauters, P. Emy, E. Baudin, H. du Boullay Choplin, Y. Chapuis, J.L. Kraimps, J.L. Sadoul, A. Tabarin et al. Thymic neuroendocrine tumors in multiple endocrine neoplasia type 1: a comparative study on 21 cases among a series of 761 MEN1 from the GTE (Groupe des Tumeurs Endocrines). World J. Surg. 33(6), 1197–1207 (2009)

    Article  PubMed  Google Scholar 

  28. P. Ferolla, A. Falchetti, P. Filosso, P. Tomassetti, G. Tamburrano, N. Avenia, G. Daddi, F. Puma, R. Ribacchi, F. Santeusanio et al. Thymic neuroendocrine carcinoma (carcinoid) in multiple endocrine neoplasia type 1 syndrome: the Italian series. J. Clin. Endocrinol. Metab. 90(5), 2603–2609 (2005)

    Article  CAS  PubMed  Google Scholar 

  29. N. Singh Ospina, S. Maraka, V. Montori, G.B. Thompson, W.F. Young Jr, When and how should patients with multiple endocrine neoplasia type 1 be screened for thymic and bronchial carcinoid tumors? Clin. Endocrinol. 84(1), 13–16 (2016)

    Article  Google Scholar 

  30. A. Lagarde, G. Mougel, L. Coppin, M. Haissaguerre, L. Le Collen, A. Mohamed, M. Klein, M.F. Odou, A. Tabarin, H. Brixi, T. Cuny, B. Delemer, A. Barlier, P. Romanet, Systematic detection of mosaicism by using digital NGS reveals three new MEN1 mosaicisms. Endocr. Connect 11(11), e220093 (2022)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Our patients acknowledge that they cannot be identified via the paper and have been fully anonymized.

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Authors and Affiliations

  1. Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, 100730, Beijing, China

    Yuting Gao, Ran Li, Lingge Wu, Hongbo Yang, Jiangfeng Mao & Weigang Zhao

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  1. Yuting Gao
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Contributions

Y.G. and W.Z. prepared the manuscript; Y.G., L.W., R.L., and J.M. collected clinical data collection; Y.G. and R.L. searched the database and identified the included studies; H.Y. and W.Z. revised and oversaw the work. All authors participated in the discussions about the manuscript and approved the final version.

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Correspondence to Weigang Zhao.

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Gao, Y., Li, R., Wu, L. et al. Thymoma in multiple endocrine neoplasia type 1: a case report and systematic review. Endocrine 82, 442–449 (2023). https://doi.org/10.1007/s12020-023-03440-5

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  • DOI: https://doi.org/10.1007/s12020-023-03440-5

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