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RAS Mutation-Positive Follicular Variant of Papillary Thyroid Carcinoma Arising in a Struma Ovarii

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Abstract

Struma ovarii is an ovarian mature teratoma composed exclusively or predominantly of thyroid tissue. Malignant transformation of struma ovarii is rare and poorly understood, although this process is thought to be similar to carcinogenesis in malignant tumors of differentiated thyroid tissue originating in the thyroid gland. Genetic alterations in the mitogen-activated protein kinase pathway, including mutations of BRAF, RAS, and RET genes, have been implicated in the development of differentiated thyroid carcinoma arising in the thyroid gland. We report here a case with RAS mutation detected in a malignant struma ovarii. The patient is a 38-year-old female who had a 2.4 cm ovarian cyst noted incidentally on a first trimester ultrasound. She proceeded to ovarian cystectomy post-delivery, with pathologic examination detecting a papillary thyroid carcinoma, follicular variant, arising in a cystic teratoma. The tumor was tested for BRAF, RAS, and RET/PTC mutations. HRAS codon 61 mutation was identified. This is the first report of RAS mutation detected in the follicular variant of papillary carcinoma arising in a struma ovarii. It provides evidence that tumors developing in this setting involve molecular mechanisms similar to those implicated in tumors developing in the thyroid gland.

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References

  1. Makani S, Kim W, Gaba A. Struma ovarii with a focus of papillary thyroid cancer: a case report and review of the literature. Gynecol Oncol 94:835–9, 2004.

    Article  PubMed  Google Scholar 

  2. Logani S et al. Cystic ovarian metastasis from papillary thyroid carcinoma: a case report. Thyroid 11(11):1073–5, 2001.

    Article  CAS  PubMed  Google Scholar 

  3. Young R, Jackson A, Wells, M. Ovarian metastasis from thyroid carcinoma 12 years after partial thyroidectomy mimicking struma ovarii: report of a case. Int J Gynecol Pathol 13(2):181–5, 1994.

    Article  CAS  PubMed  Google Scholar 

  4. Flavin R et al. BRAF T1799A Mutation occurring in a case of malignant struma ovarii. Int J Surg Pathol 15(2):116–20, 2007.

    Article  CAS  PubMed  Google Scholar 

  5. Kimura ET et al. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res 63:1454–7, 2003.

    CAS  PubMed  Google Scholar 

  6. Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res 63:1454–7, 2003.

    CAS  PubMed  Google Scholar 

  7. Soares P, Trovisco V, Rocha AS, Lima J, Castro P, Preto A, Maximo V, Botelho T, Seruca R, Sobrinho-Simoes M. BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC. Oncogene 22:4578–80, 2003.

    Article  CAS  PubMed  Google Scholar 

  8. Frattini M, Ferrario C, Bressan P, Balestra D, De Cecco L, Mondellini P, Bongarzone I, Collini P, Gariboldi M, Pilotti S, Pierotti MA, Greco A. Alternative mutations of BRAF, RET and NTRK1 are associated with similar but distinct gene expression patterns in papillary thyroid cancer. Oncogene, 23(44):7436–40, 2004.

    Article  CAS  PubMed  Google Scholar 

  9. Cohen Y, Xing M, Mambo E, Guo Z, Wu G, Trink B, Beller U, Westra WH, Ladenson PW, Sidransky D. BRAF mutation in papillary thyroid carcinoma. J Natl Cancer Inst 95:625–7, 2003.

    CAS  PubMed  Google Scholar 

  10. Grieco M, Santoro M, Berlingieri MT, Melillo RM, Donghi R, Bongarzone I, Pierotti MA, Della Porta G, Fusco A, Vecchio G. PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas. Cell 60:557–63, 1990.

    Article  CAS  PubMed  Google Scholar 

  11. Bongarzone I, Butti MG, Coronelli S, Borrello MG, Santoro M, Mondellini P, Pilotti S, Fusco A, Della Porta G, Pierotti MA. Frequent activation of ret protooncogene by fusion with a new activating gene in papillary thyroid carcinomas. Cancer Res 54:2979–85, 1994.

    CAS  PubMed  Google Scholar 

  12. Santoro M, Dathan NA, Berlingieri MT, Bongarzone I, Paulin C, Grieco M, Pierotti MA, Vecchio G, Fusco A. Molecular characterization of RET/PTC3; a novel rearranged version of the retproto-oncogene in a human thyroid papillary carcinoma. Oncogene 9:509–16, 1994.

    CAS  PubMed  Google Scholar 

  13. Nikiforov YE. RET/PTC rearrangement in thyroid tumors. Endocr Pathol 13:3–16, 2002.

    Article  CAS  PubMed  Google Scholar 

  14. Namba H, Rubin SA, Fagin JA. Point mutations of ras oncogenes are an early event in thyroid tumorigenesis. Mol Endocrinol 4:1474–9, 1990.

    Article  CAS  PubMed  Google Scholar 

  15. Ezzat S, Zheng L, Kolenda J, Safarian A, Freeman JL, Asa SL. Prevalence of activating ras mutations in morphologically characterized thyroid nodules. Thyroid 6:409–16, 1996.

    Article  CAS  PubMed  Google Scholar 

  16. Zhu Z, Gandhi M, Nikiforova MN, Fischer AH, Nikiforov YE. Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations. Am J Clin Pathol 120:71–7, 2003.

    Article  CAS  PubMed  Google Scholar 

  17. Adeniran AJ, Zhu Z, Gandhi M, Steward DL, Fidler JP, Giordano TJ, Biddinger PW, Nikiforov YE. Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. Am J Surg Pathol 30:216–22, 2006.

    Article  PubMed  Google Scholar 

  18. Nikiforov YE. Thyroid carcinoma: molecular pathways and therapeutic targets. Mod Path 21:537–43, 2008.

    Article  CAS  Google Scholar 

  19. Golbert L. H-RAS gene expression in human multinodular goiter. Histol Histopathol 22:409–16, 2007.

    CAS  PubMed  Google Scholar 

  20. Davis, KP et al. Primary ovarian carcinoid tumors. Gynecol Oncol 61: 259–65, 1996.

    Article  CAS  PubMed  Google Scholar 

  21. Cyniak-Magierska A et al. Prevalence of RAS point mutations in papillary thyroid carcinoma: a novel mutation at codon 31 of K-RAS. Exp Clin Endocrinol Diabetes 115:594–9, 2007.

    Article  CAS  PubMed  Google Scholar 

  22. Hara H et al. N-ras mutation: an independent prognostic factor for aggressiveness of papillary thyroid carcinoma. Surgery 116(6):1010–6, 1994.

    CAS  PubMed  Google Scholar 

  23. Roth L, Talerman A. The Enigma of Struma Ovarii. Pathology 39(1):139–46, 2007.

    Article  PubMed  Google Scholar 

  24. Cicarelli A et al. Thyrotoxic adenoma followed by atypical hyperthyroidism due to struma ovarii: clinical and genetic studies. Eur J Endocrinol 150:431–7, 2004.

    Article  Google Scholar 

  25. Suarez, HG. Genetic alterations in human epithelial thyroid tumours. Clin Endocrinol 48:531–46, 1998.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Dept of Endocrinology, UPMC, Suite 3B, Falk Medical Bldg, 3601 5th Ave, Pittsburgh, PA, 15213, USA

    Christopher Coyne

  2. Dept of Pathology, UPMC, Suite 3B, Falk Medical Bldg, 3601 5th Ave, Pittsburgh, PA, 15213, USA

    Yuri E. Nikiforov

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  1. Christopher Coyne
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  2. Yuri E. Nikiforov
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Correspondence to Christopher Coyne.

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Coyne, C., Nikiforov, Y.E. RAS Mutation-Positive Follicular Variant of Papillary Thyroid Carcinoma Arising in a Struma Ovarii. Endocr Pathol 21, 144–147 (2010). https://doi.org/10.1007/s12022-009-9097-8

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