Cribriform-morular variant of papillary thyroid carcinoma (CMVPTC) usually occurs in the setting of familial adenomatous polyposis (FAP) although it can rarely arise sporadically. Poorly differentiated thyroid carcinoma (PDTC) is a follicular cell-derived neoplasm with more aggressive behavior than well-differentiated carcinomas such as CMVPTC. We report the case of a 35-year-old woman without FAP history who presented a left neck mass and complained of back pain. Imagiological examinations revealed a nodule in the left lobe of thyroid and multiple nodular lesions in the bone and lungs suggestive of metastases. The patient was submitted to total thyroidectomy and radioactive iodine. The tumor was composed of CMVPTC and PDTC components that shared the same somatic APC gene mutation (p.Cys520Tyr_fsX534). Besides this mutation, no CTNNB1, BRAF, N-RAS, and H-RAS gene mutations were detected in any of the 2 components. To the best of our knowledge, this is the first report of a sporadic CMVPTC with transformation into PDTC. Although the majority of CMVPTCs carry an indolent clinical outcome, the coexistence of poorly differentiated areas may justify the aggressiveness of the CMVPTC reported here.

1. LiVolsi, VA, Albores-Saavedra, J, Asa, SL. Papillary carcinoma. In: DeLellis, RA, Lloyd, RV, Heitz, PU, Eng, C, eds. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Endocrine Organs. Lyon, France: IARC Press; 2004:57-66.
Google Scholar
2. Nosé, V . Familial thyroid cancer: a review. Mod Pathol. 2011;24(suppl 2):S19-S33.
Google Scholar | Crossref | Medline | ISI
3. Harach, HR, Williams, GT, Williams, ED. Familial adenomatous polyposis associated thyroid carcinoma: a distinct type of follicular cell neoplasm. Histopathology. 1994;25:549-561.
Google Scholar | Crossref | Medline | ISI
4. Tomoda, C, Miyauchi, A, Uruno, T. Cribriform-morular variant of papillary thyroid carcinoma: clue to early detection of familial adenomatous polyposis-associated colon cancer. World J Surg. 2004;28:886-889.
Google Scholar | Crossref | Medline | ISI
5. Cameselle-Teijeiro, J, Chan, JK. Cribriform-morular variant of papillary thyroid carcinoma: a distinct variant representing the sporadic counterpart of familial adenomatous polyposis-associated thyroid carcinoma? Mod Pathol. 1999;12:400-411.
Google Scholar | Medline | ISI
6. Cetta, F, Montalto, G, Gori, M, Curia, MC, Cama, C, Olschwang, S. Germline mutation of the APC gene in patients with familial adenomatous polyposis-associated thyroid carcinoma: a result from a European cooperative study. J Clin Endocrinol Metab. 2000;85:286-292.
Google Scholar | Medline | ISI
7. Cameselle-Teijeiro, J, Ruiz-Ponte, C, Loidi, L, Suarez-Penaranda, J, Baltar, J, Sobrinho-Simoes, M. Somatic but not germline mutation of the APC gene in a case of cribriform-morular variant of papillary thyroid carcinoma. Am J Clin Pathol. 2001;115:486-493.
Google Scholar | Crossref | Medline | ISI
8. Xu, B, Yoshimoto, K, Miyauchi, A. Cribriform-morular variant of papillary thyroid carcinoma: a pathological and molecular genetic study with evidence of frequent somatic mutations in exon 3 of the beta-catenin gene. J Pathol. 2003;199:58-67.
Google Scholar | Crossref | Medline | ISI
9. McDonald, BT, Tamai, K, He, X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009;17:9-26.
Google Scholar | Crossref | Medline | ISI
10. Carcangiu, ML, Zampi, G, Rosai, J. Poorly differentiated (“insular”) thyroid carcinoma. A reinterpretation of Langhans’ “wucherne Struma.” Am J Surg Pathol. 1984;8:655-668.
Google Scholar | Crossref | Medline | ISI
11. Sakamoto, A, Kasai, N, Sugano, H. Poorly differentiated carcinoma of the thyroid. A clinocopathological entity for a high risk group of papillary and follicular carcinomas. Cancer. 1983;52:1849-1855.
Google Scholar | Crossref | Medline | ISI
12. Sobrinho-Simões, M, Albores-Saavedra, J, Tallini, G. Poorly differentiated carcinoma. In: DeLellis, RA, Lloyd, RV, Heitz, PU, Eng, C, eds. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Endocrine Organs. Lyon, France: IARC Press; 2004: 73-76.
Google Scholar
13. Volante, M, Collini, P, Nikiforov, YE. Poorly differentiated thyroid carcinoma: the Turin proposal for the use of uniform diagnostic criteria and an algorithmic diagnostic approach. Am J Surg Pathol. 2007;31:1256-1264.
Google Scholar | Crossref | Medline | ISI
14. Cameselle-Teijeiro, J, Menasce, LP, Yap, BK. Cribriform-morular variant of papillary thyroid carcinoma: molecular characterization of a case with neuroendocrine differentiation and aggressive behavior. Am J Clin Pathol. 2009;131:134-142.
Google Scholar | Crossref | Medline | ISI
15. Ito, Y, Miyauchi, A, Ishikawa, H. Our experience of treatment of cribriform morular variant of papillary thyroid carcinoma: difference in clinicopathological features of FAP-associated and sporadic patients. Endocr J. 2011;58:685-689.
Google Scholar | Crossref | Medline | ISI
16. Soravia, C, Sugg, SL, Berk, T. Familial adenomatous polyposis-associated thyroid cancer: a clinical, pathological, and molecular genetics study. Am J Pathol. 1999;154:127-135.
Google Scholar | Crossref | Medline | ISI
17. Perrier, ND, van Heerden, JA, Goellner, R. Thyroid cancer in familial adenomatous polyposis. World J Surg. 1998;22:738-743.
Google Scholar | Crossref | Medline | ISI
18. Fenton, PA, Clarke, SE, Owen, W, Hibbert, J, Hodgson, SV. Cribriform variant papillary thyroid cancer: a characteristic of familial adenomatous polyposis. Thyroid. 2001;11:193-197.
Google Scholar | Crossref | Medline | ISI
19. Garcia-Rostan, G, Camp, RL, Herrero, A, Carcangiu, ML, Rimm, DL, Tallini, G. Beta-catenin dysregulation in thyroid neoplasms: down-regulation, aberrant nuclear expression, and CTNNB1 exon 3 mutations are markers for aggressive tumour phenotypes and poor prognosis. Am J Pathol. 2001;158:987-996.
Google Scholar | Crossref | Medline | ISI
20. Garcia-Rostan, G, Tallini, G, Herrero, A, D’Aquila, TG, Carcangiu, ML, Rimm, DL. Frequent mutation and nuclear localization of beta-catenin in anaplastic thyroid carcinoma. Cancer Res. 1999;59:1811-1815.
Google Scholar | Medline | ISI
21. Zhang, J, Gill, AJ, Issacs, JD. The Wnt/β-catenin pathway drives induced cyclin D1 levels in lymph node metastasis in papillary thyroid cancer. Hum Pathol. 2012;43:1044-1050.
Google Scholar | Crossref | Medline | ISI
22. Jung, CK, Choi, YJ, Lee, KY. The cytological, clinical, and pathological features of the cribriform-morular variant of papillary thyroid carcinoma and mutation analysis of CTNNB1 and BRAF genes. Thyroid. 2009;19:905-913.
Google Scholar | Crossref | Medline | ISI
23. Curtis, L, Wyllie, AH, Shaw, JJ. Evidence against involvement of APC gene mutation in papillary thyroid carcinoma. Eur J Cancer. 1994;30A:984-987.
Google Scholar | Crossref | Medline | ISI
24. Colletta, G, Sciacchitano, S, Palmirotta, R. Analysis of adenomatous polyposis coli gene in thyroid tumours. Br J Cancer. 1994;70:1085-1088.
Google Scholar | Crossref | Medline | ISI
25. Zeki, K, Spambalg, D, Sharifi, N, Gonsky, R, Fagin, JA. Mutations of the adenomatous polyposis coli gene in sporadic thyroid tumours. J Clin Endocrinol Metab. 1994;79: 1317-1321.
Google Scholar | Medline | ISI
26. Uchino, S, Noguchi, S, Yamashita, H. Mutational analysis of the APC gene in cribriform-morular variant of papillary thyroid carcinoma. World J Surg. 2006;30:775-779.
Google Scholar | Crossref | Medline | ISI
27. Subramaniam, MM, Putti, TC, Anuar, D. Clonal characterization of sporadic cribriform-morular variant of papillary thyroid carcinoma by laser microdissection-based APC mutation analysis. Am J Clin Pathol. 2007;128:994-1001.
Google Scholar | Crossref | Medline | ISI
28. 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.
Google Scholar | Medline | ISI
29. Nikiforova, MN, Kimura, ET, Gandhi, M. BRAF mutations in thyroid tumours are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab. 2003;88:5399-5404.
Google Scholar | Crossref | Medline | ISI
30. Soares, P, Trovisco, V, Rocha, AS. BRAF mutations typical of papillary thyroid carcinoma are more frequently detected in undifferentiated than in insular and insular-like poorly differentiated carcinomas. Virchows Arch. 2004;444:572-576.
Google Scholar | Crossref | Medline | ISI
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