Unilateral follicular variant of papillary thyroid carcinoma with unique KRAS mutation in struma ovarii in bilateral ovarian teratoma: a rare case report

BMC Cancer

Shunichi Yamashita³  Bogomir Dimitrijevic²  Lidija Todorovic²  Bozidar Rulic¹  Marko Buta¹  Petar Radlovic¹  Vesna Krstevski⁵  Zorka Milovanovic⁴  Vladimir Saenko³  Radan Dzodic¹  Boban Stanojevic² 

[1]Institute of Oncology and Radiology of Serbia, Surgical Oncology Clinic, Pasterova 14, 11000, Belgrade, Serbia

[2]Laboratory for Radiobiology and Molecular Genetics “Vinca”, Institute of Nuclear Sciences, University of Belgrade, Mike Petrovica Alasa12-14, P.O. Box 522, 11000, Belgrade, Serbia

[3]Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852-8523, Japan

[4]Department of Pathology, Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000, Belgrade, Serbia

[5]Department of Pathology, Medical Center Valjevo, 14000, Valjevo, Serbia

关键词: KRAS mutation;    Follicular variant of papillary thyroid carcinoma;    Struma ovarii;   

Others  :  1080383
DOI  :  10.1186/1471-2407-12-224

 received in 2012-01-18, accepted in 2012-06-08,  发布年份 2012

【 摘 要 】

Background

Struma ovarii (SO) is a rare form of ovarian mature teratoma in which thyroid tissue is the predominant element. Because of its rarity, the differential diagnosis between benign and malignant SO has not been clearly defined. It is believed that malignant transformation of SO has similar molecular features with and its prognosis corresponds to that of malignant tumors originating in the thyroid.

Case presentation

We report 35-year-old woman with bilateral ovarian cysts incidentally detected by ultrasound during the first trimester of pregnancy. Four months after delivery of a healthy child without complication she was admitted to the hospital for acute abdominal pain. Laparoscopic left adnexectomy was performed initially in a regional hospital; right cystectomy was done later in a specialized clinic. Intraoperative frozen section and a final pathology revealed that the cyst from the left ovary was composed of mature teratomatous elements, normal thyroid tissue (>50%) and a non-encapsulated focus of follicular variant of papillary thyroid carcinoma (PTC).

Normal and cancerous thyroid tissues were tested for BRAF and RAS mutations by direct sequencing, and for RET/PTC rearrangements by RT-PCR/Southern blotting. A KRAS codon 12 mutation, the GGT → GTT transversion, corresponding to the Gly → Val amino acid change was identified in the absence of other genetic alterations commonly found in PTC.

Conclusion

To the best of our knowledge, this is the first time this mutation is described in a papillary thyroid carcinoma arising in struma in the ovarii. This finding provides further evidence that even rare mutations specific for PTC may occur in such tumors. Molecular testing may be a useful adjunct to common differential diagnostic methods of thyroid malignancy in SO.

【 授权许可】

   
2012 Stanojevic et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Makani S, Kim W, Gaba AR: Struma ovarii with a focus of papillary thyroid cancer: a case report and review of the literature. Gynecol Oncol 2004, 94:835-839.
• [2]Devaney K, Synder R, Norris H, Tavassoli F: Proliferative and histologically malignant struma ovarii: a clinicopathological study of 54 cases. Int J Gynecol Pathol 1993, 12:333-343.
• [3]Tavassoli F, Devilee P: World Health Organization classification of tumours. Pathology and genetics of tumours of the breast and female genital organs. IARC Press, Lyon; 2003.
• [4]Matsuda K, Maehama T, Kanazawa K: Malignant struma ovarii with thyrotoxicosis. Gynecol Oncol 2001, 82:575-577.
• [5]Nikiforov YE: Thyroid carcinoma: molecular pathways and therapeutic targets. Mod Path 2008, 21:537-643.
• [6]Coyne C, Nikiforov YE: RAS mutation-positive follicular variant of papillary thyroid carcinoma arising in a struma ovarii. Endocr Pathol 2010, 21:144-147.
• [7]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 2003, 63:1454-1457.
• [8]Xing M: BRAF mutation in thyroid cancer. Endocr Relat Cancer 2005, 12:245-262.
• [9]Melillo RM, Castellone MD, Guarino V, De Falco V, Cirafici AM, Salvatore G, Caiazzo F, Basolo F, Giannini R, Kruhoffer M, Orntoft T, Fusco A, Santoro M: The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells. J Clin Invest 2005, 115:1068-1081.
• [10]Nikiforov YE, Biddinger PW, Thompson LD, FASCP, FCAP: Diagnostic Pathology and Molecular Genetics of the Thyroid, A Comprehensive Guide for Practicing Thyroid Pathology. Wolters—Kluwer, ; 2009:177.
• [11]Volante M, Collini P, Nikiforov YE, Sakamoto A, Kakudo K, Katoh R, Lloyd RV, LiVolsi VA, Papotti M, Sobrinho-Simoes M, Bussolati G, Rosai J: Poorly differentiated thyroid carcinoma: the Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach. Am J Surg Pathol 2007, 31:1256-64.
• [12]DeLellis RA, Lioyd RU, Heitz PU, Eng C: World Health Organization classification of tumours. Pathology and genetics of tumours of endocrine organs. IARC Press, Lyon; 2004.
• [13]Stanojevic B, Dzodic R, Saenko V, Milovanovic Z, Pupic G, Zivkovic O, Markovic I, Djurisic I, Buta M, Dimitrijevic B, Rogounovitch T, Mitsutake N, Mine M, Shibata Y, Nakashima M, Yamashita S: Mutational and clinico-pathological analysis of papillary thyroid carcinoma in Serbia. Endocr J 2011, 58:381-393.
• [14]Dzodic R, Markovic I, Inic M, Jokic N, Djurisic I, Zegarac M, Pupic G, Milovanovic Z, Jovic V, Jovanovic N: Sentinel lymph node biopsy may be used to support the decision to perform modified radical neck dissection in differentiated thyroid carcinoma. World J Surg 2006, 30:841-6.
• [15]Flavin R, Smyth P, Crotty P, Finn S, Cahill S, Denning K, Li J, O’Regan E, O’Leary J, Sheils O: BRAF T1799A mutation occurring in a case of malignant struma ovarii. Int J Surg Pathol 2007, 15:116-120.
• [16]Schmidt J, Derr V, Heinrich M, Crum C, Fletcher J, Corless C, Nose V: BRAF in papillary thyroid carcinoma of ovary (struma ovarii). Am J Surg Pathol 2007, 31:1337-1343.
• [17]Elisei R, Romei C, Castagna MG: RET / PTC3 rearrangement and thyroid differentiation gene analysis in a struma ovarii fortuitously revealed by elevated serum thyroglobulin concentration. Thyroid 2005, 15:1355-1361.
• [18]Celestino R, Magalhães J, Castro P, Triller M, Vinagre J, Soares P, Sobrinho-Simões M: A follicular variant of papillary thyroid carcinoma in struma ovarii. Case report with unique molecular alterations. Histopathology 2009, 55:482-487.
• [19]Vasko V, Ferrand M, Di Cristofaro J, Carayon P, Henry JF, de Micco C: Specific pattern of RAS oncogene mutations in follicular thyroid tumors. J Clin Endocrinol Metab 2003, 88:2745-2752.
• [20]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 2003, 120:71-7.
• [21]Esapa CT, Johnson SJ, Kendall-Taylor P, Lennard TWJ, Harris PE: Prevalence of ras mutations in thyroid neoplasia. Clin Endocrinol (Oxf) 1999, 50:529-535.
• [22]Kim S, Zhu X: Lessons from mouse models of thyroid cancer. Thyroid 2009, 19:1317-1331.
• [23]Ohori NP, Nikiforova MN, Schoedel KE, LeBeau SO, Hodak SP, Seethala RR, Carty SE, Ogilvie JB, Yip L, Nikiforov YE: Contribution of molecular testing to thyroid fine-needle aspiration cytology of “follicular lesion of undetermined significance/atypia of undetermined significance. Cancer Cytopathol 2010, 118:17-23.
• [24]Garcia-Rostan G, Zhao H, Camp RL, Pollan M, Herrero A, Pardo J, Wu R, Carcangiu ML, Costa J, Tallini G: Ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer. J Clin Oncol 2003, 21:3226-3235.
• [25]Cerottini JP, Caplin S, Saraga E: The type of K-ras mutation determines prognosis in colorectal cancer. Am J Surg 1998, 175:198-202.
• [26]Elisei R, Romei C, Vorontsova T, Cosci B, Veremeychik V, Kuchinskaya E, Basolo F, Demidchik EP, Miccoli P, Pinchera A, Pacini F: RET/PTC rearrangements in thyroid nodules: studies in irradiated and not irradiated, malignant and benign thyroid lesions in children and adults. J Clin Endocrinol Metab 2001, 86:3211-3216.