Malignant struma ovarii: next-generation sequencing of six cases revealed Nras, Braf, and Jak3 mutations

Abstract

Purpose

Struma ovarii (SO) is a highly specialized ovarian teratoma, consisting of thyroid tissue. Rarely, carcinomas histologically identical to their thyroid counterparts may occur, and are comprehensively defined as malignant struma ovarii (MSO). Their optimal management is controversial, and the molecular profile of the malignant counterpart in the ovary is incompletely known. In this study, the clinicopathological and molecular features of six MSO from different Italian Institutions were analysed, to explore genetic profiles of potential therapeutic interest.

Methods

The histopathological features and immunoprofile (according to the known markers Galectin-3, HBME1, cytokeratin 19 and CD56) were reviewed. In addition, all cases underwent genetic analysis with a next-generation sequencing (NGS) hot spot cancer panel detecting mutations in 50 genes involved in cancerogenesis. RET/PTC rearrangements and TERT promoter alterations were also evaluated.

Results

Papillary carcinoma in all similar to its thyroid counterpart was found in five of six cases, including classical (two tumors) and follicular variant (three tumors) types. The last case was a poorly differentiated carcinoma. An activating gene mutation, was detected in five of six cases, including two NRAS, two BRAF, and one JAK3 oncogene mutations. No alterations were found in the other panel genes, nor in TERT promoter, or in RET chromosomal regions.

Conclusions

MSO is a rare condition. Papillary carcinoma is the predominant malignant type, sharing both histomorphological and molecular features of its thyroid counterpart. Interestingly, the single case of poorly differentiated carcinoma displayed a JAK3 mutation. The presence of such driving mutation could be of potential interest in guiding postoperative treatment.

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Acknowledgements

Dr. Stefano Rosso and Dr. Roberto Zanetti of CPO and the Piedmont Cancer Registry, Turin, are acknowledged for providing some follow-up information. The authors would also like to thank Dr. Roberto Jura, former Head of Biella Hospital Gynaecology Department for his helpful collaboration.

Funding

This study was supported by Fondazione Cassa di Risparmio di Torino (CRT), grant no. 2016.2726, to the Molecular Oncology laboratory of « Edo ed Elvo Tempia » Foundation. It was also partially supported by a grant from the Associazione Italiana Ricerca sul Cancro (AIRC, Milan, No. IG 20100 to MP and MV).

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Correspondence to Poli Roberta.

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Roberta, P., Maria, S., Enrico, G. et al. Malignant struma ovarii: next-generation sequencing of six cases revealed Nras, Braf, and Jak3 mutations. Endocrine (2020). https://doi.org/10.1007/s12020-020-02438-7

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Keywords

  • Struma ovarii
  • RAS mutation
  • BRAF mutation
  • JAK3
  • Thyroid cancer
  • Next-generation sequencing