Skip to main content
Top
Published in: BMC Cancer 1/2012

Open Access 01-12-2012 | Case report

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

Authors: Boban Stanojevic, Radan Dzodic, Vladimir Saenko, Zorka Milovanovic, Vesna Krstevski, Petar Radlovic, Marko Buta, Bozidar Rulic, Lidija Todorovic, Bogomir Dimitrijevic, Shunichi Yamashita

Published in: BMC Cancer | Issue 1/2012

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
1.
go back to reference 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. 10.1016/j.ygyno.2004.06.003.CrossRefPubMed 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. 10.1016/j.ygyno.2004.06.003.CrossRefPubMed
2.
go back to reference 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. 10.1097/00004347-199310000-00008.CrossRefPubMed 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. 10.1097/00004347-199310000-00008.CrossRefPubMed
3.
go back to reference Tavassoli F, Devilee P: World Health Organization classification of tumours. Pathology and genetics of tumours of the breast and female genital organs. 2003, IARC Press, Lyon Tavassoli F, Devilee P: World Health Organization classification of tumours. Pathology and genetics of tumours of the breast and female genital organs. 2003, IARC Press, Lyon
4.
go back to reference Matsuda K, Maehama T, Kanazawa K: Malignant struma ovarii with thyrotoxicosis. Gynecol Oncol. 2001, 82: 575-577. 10.1006/gyno.2001.6315.CrossRefPubMed Matsuda K, Maehama T, Kanazawa K: Malignant struma ovarii with thyrotoxicosis. Gynecol Oncol. 2001, 82: 575-577. 10.1006/gyno.2001.6315.CrossRefPubMed
5.
go back to reference Nikiforov YE: Thyroid carcinoma: molecular pathways and therapeutic targets. Mod Path. 2008, 21: 537-643.CrossRef Nikiforov YE: Thyroid carcinoma: molecular pathways and therapeutic targets. Mod Path. 2008, 21: 537-643.CrossRef
6.
go back to reference Coyne C, Nikiforov YE: RAS mutation-positive follicular variant of papillary thyroid carcinoma arising in a struma ovarii. Endocr Pathol. 2010, 21: 144-147. 10.1007/s12022-009-9097-8.CrossRefPubMed Coyne C, Nikiforov YE: RAS mutation-positive follicular variant of papillary thyroid carcinoma arising in a struma ovarii. Endocr Pathol. 2010, 21: 144-147. 10.1007/s12022-009-9097-8.CrossRefPubMed
7.
go back to reference 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.PubMed 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.PubMed
8.
go back to reference Xing M: BRAF mutation in thyroid cancer. Endocr Relat Cancer. 2005, 12: 245-262. 10.1677/erc.1.0978.CrossRefPubMed Xing M: BRAF mutation in thyroid cancer. Endocr Relat Cancer. 2005, 12: 245-262. 10.1677/erc.1.0978.CrossRefPubMed
9.
go back to reference 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
10.
go back to reference Nikiforov YE, Biddinger PW, Thompson LD, FASCP, FCAP: Diagnostic Pathology and Molecular Genetics of the Thyroid, A Comprehensive Guide for Practicing Thyroid Pathology. 2009, Wolters—Kluwer, , 177- Nikiforov YE, Biddinger PW, Thompson LD, FASCP, FCAP: Diagnostic Pathology and Molecular Genetics of the Thyroid, A Comprehensive Guide for Practicing Thyroid Pathology. 2009, Wolters—Kluwer, , 177-
11.
go back to reference 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. 10.1097/PAS.0b013e3180309e6a.CrossRefPubMed 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. 10.1097/PAS.0b013e3180309e6a.CrossRefPubMed
12.
go back to reference DeLellis RA, Lioyd RU, Heitz PU, Eng C: World Health Organization classification of tumours. Pathology and genetics of tumours of endocrine organs. 2004, IARC Press, Lyon DeLellis RA, Lioyd RU, Heitz PU, Eng C: World Health Organization classification of tumours. Pathology and genetics of tumours of endocrine organs. 2004, IARC Press, Lyon
13.
go back to reference 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. 10.1507/endocrj.K11E-054.CrossRefPubMed 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. 10.1507/endocrj.K11E-054.CrossRefPubMed
14.
go back to reference 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. 10.1007/s00268-005-0298-0.CrossRefPubMed 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. 10.1007/s00268-005-0298-0.CrossRefPubMed
15.
go back to reference 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. 10.1177/1066896906299131.CrossRefPubMed 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. 10.1177/1066896906299131.CrossRefPubMed
16.
go back to reference 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. 10.1097/PAS.0b013e31802f5404.CrossRefPubMed 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. 10.1097/PAS.0b013e31802f5404.CrossRefPubMed
17.
go back to reference 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. 10.1089/thy.2005.15.1355.CrossRefPubMed 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. 10.1089/thy.2005.15.1355.CrossRefPubMed
18.
go back to reference 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. 10.1111/j.1365-2559.2009.03401.x.CrossRefPubMed 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. 10.1111/j.1365-2559.2009.03401.x.CrossRefPubMed
19.
go back to reference 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. 10.1210/jc.2002-021186.CrossRefPubMed 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. 10.1210/jc.2002-021186.CrossRefPubMed
20.
go back to reference 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. 10.1309/ND8D9LAJTRCTG6QD.CrossRefPubMed 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. 10.1309/ND8D9LAJTRCTG6QD.CrossRefPubMed
21.
go back to reference 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. 10.1046/j.1365-2265.1999.00704.x.CrossRef 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. 10.1046/j.1365-2265.1999.00704.x.CrossRef
23.
go back to reference 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. 10.1002/cncy.20063.CrossRefPubMed 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. 10.1002/cncy.20063.CrossRefPubMed
24.
go back to reference 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. 10.1200/JCO.2003.10.130.CrossRefPubMed 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. 10.1200/JCO.2003.10.130.CrossRefPubMed
25.
go back to reference Cerottini JP, Caplin S, Saraga E: The type of K-ras mutation determines prognosis in colorectal cancer. Am J Surg. 1998, 175: 198-202. 10.1016/S0002-9610(97)00283-3.CrossRefPubMed Cerottini JP, Caplin S, Saraga E: The type of K-ras mutation determines prognosis in colorectal cancer. Am J Surg. 1998, 175: 198-202. 10.1016/S0002-9610(97)00283-3.CrossRefPubMed
26.
go back to reference 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. 10.1210/jc.86.7.3211.PubMed 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. 10.1210/jc.86.7.3211.PubMed
Metadata
Title
Unilateral follicular variant of papillary thyroid carcinoma with unique KRAS mutation in struma ovarii in bilateral ovarian teratoma: a rare case report
Authors
Boban Stanojevic
Radan Dzodic
Vladimir Saenko
Zorka Milovanovic
Vesna Krstevski
Petar Radlovic
Marko Buta
Bozidar Rulic
Lidija Todorovic
Bogomir Dimitrijevic
Shunichi Yamashita
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2012
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-12-224

Other articles of this Issue 1/2012

BMC Cancer 1/2012 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine