Recent Advances in Follicular Variant of Papillary Thyroid Carcinoma
Keywords:
papillary thyroid carcinoma, follicular variant, thyroid cancer, RET/PTC, BRAFAbstract
The follicular variant of papillary thyroid carcinoma (FVPTC) constitutes a distinct class of papillary thyroid carcinoma (PTC), presenting unique challenges to the clinician and pathologist regarding its diagnosis, prognosis and treatment. Fifty years since its identification as a unique class of thyroid neoplasms, controversies still exist with respect to the histologic diagnosis and categorization of FVPTC. While agreement exists among experts as to its generic place within PTC, FVPTC exhibits biologic and molecular properties that distinguish it from conventional PTC. Many studies and proposals utilizing histopathologic criteria, immunohistochemical and molecular techniques have been brought to bear on the problems posed by these set of tumors with varying degrees of success. Here we examine the clinical and pathologic features of FVPTC, highlighting diagnostic controversies and recent molecular findings that attempt to provide clues to the proper classification of this unique group of thyroid tumors.
[N A J Med Sci. 2012;5(4):212-216.]
References
Correa P, Chen VW. Endocrine gland cancer. Cancer. 1995;75(1 Suppl):338-352.
Ito Y, Miyauchi A. Prognostic factors and therapeutic strategies for differentiated carcinomas of the thyroid. Endocr J. 2009;56(2):177-192.
Chan JK. Strict criteria should be applied in the diagnosis of encapsulated follicular variant of papillary thyroid carcinoma. Am J Clin Pathol. 2002;117(1):16-18.
Williams ED. Two proposals regarding the terminology of thyroid tumors. Int J Surg Pathol. 2000;8(3):181-183.
Zidan J, Karen D, Stein M, Rosenblatt E, Basher W, Kuten A. Pure versus follicular variant of papillary thyroid carcinoma: clinical features, prognostic factors, treatment, and survival. Cancer. 2003;97(5):1181-1185.
Hagag P, Hod N, Kummer E, Cohenpour M, Horne T, Weiss M. Follicular variant of papillary thyroid carcinoma: clinical-pathological characterization and long-term follow-up. Cancer J. 2006;12(4):275-282.
Celestino R, Magalhães J, Castro P, et al. A folicular variant of papillary thyroid carcinoma in struma ovarii. Case report with unique moleualr alterations. Histopathology. 2009;55(4):482-487.
Hari CK, Kumar M, Abo-Khatwa MM, Adams-Williams J, Zeitoun H. Follicular variant of papillary carcinoma arising from lingual thryoid. Ear Nose Throat J. 2009;88(6):E7.
Yu J, Nikiforova MN, Hodak SP, et al. Tumor to tumor Metastses to Follicular Variant of Papillary Thyroid Carcinoma:Histoloic, Immunohistochemical amd molecular studeis of two unusual cases. Endocr Pathol. 2009;20(4):235-242.
Baloch ZW, Livolsi VA. Follicular-patterned lesions of the thyroid:the bane of the pathologist. Am J Clin Pathol. 2002;117(1):143-150.
Lam AK, Lo CY, Lam KS. Papillary carcimoma of thyroid: a 30-yr clicopathologial revview of the histological variants. Endocr Pathol. 2005;16(4):323-330.
Gupta S, Ajise O, Dultz L, et al. Follicular variant of papillary thyroid cancer: encapsulated, nonencapsulated, and diffuse: distinct biologic and clinical entities. Arch Otolaryngol Head Neck Surg. 2012;138(3):227-233.
Ivanova R, Soares P, Castro P, Sobrinho-Simões M. Diffuse (or multinodular) follicular variant of papillary thyroid carcinoma: a clinicopathologic and immunohistochemical analysis of ten cases of an aggressive form of differentiated thyroid carcinoma. Virchows Arch. 2002;440(4):418-424.
Mizukami Y, Nonomura A, Michigishi T, Ohmura K, Noguchi M, Ishizaki T. Diffuse follicular variant of papillary carcinoma of the thyroid. Histopathology. 1995;27(6):575-577.
Chem KT, Rosai J. Follicular variant of thyroid papillary carcinoma: a clinicopathologic study of six cases. Am J Surg Pathol. 1977;1(2):123-130.
Ghossein R. Encapsulated malignant follicular cell-derived thyroid tumors. Endocr Pathol. 2010;21(4):212-218.
Rivera M, Tuttle RM, Patel S, Shaha A, Shah JP, Ghossein RA. Encapsulated papillary thyroid carcinoma: a clinico-pathologic study of 106 cases with emphasis on its morphologic subtypes (histologic growth pattern). Thyroid. 2009;19(2):119-127.
Mandal S, Jain S. Adenoid cystic pattern in follicular variant of papillary thyroid carcinoma: a report of four cases. Cytopathology. 2010;21(2):93-96.
Jakubowski M, Hunt JL. BRAF mutational analysis in papillary carcinomas with mixed follicular and papillary growth patterns. 2009;33(11):1590-1593.
Cardenas MG, Kini S, Wisgerhof M. Two patients with highly aggressive macrofollicular variant of papillary thyroid carcinoma. Thyroid. 2009;19(4):413-416.
Elsheikh TM, Asa SL, Chan JK, et al. Interobserver and intraobserver variation among experts in the diagnosis of thyroid follicular lesions with borderline nuclear features of papillary carcinoma. Am J Clin Pathol. 2008;130(5):736-744.
LiVolsi VA, Baloch ZW. Follicular neoplasms of the thyroid: view, biases, and experiences. Adv Anat Pathol. 2004;11(6):279-287.
Saleh HA, Jin B, Barnwell J, Alzohaili O. Utility of immunohistochemical markers in differentiating benign from malignant follicular-derived thyroid nodules. Diagn Pathol. 2010;5:9.
Saleh HA, Feng J, Tabassum F, Al-Zohaili O, Husain M, Giorgadze T. Differential expression of galectin-3, CK19, HBME1, and Ret oncoprotein in the diagnosis of thyroid neoplasms by fine needle aspiration biopsy. Cytojournal. 2009;6:18.
Nikiforov YE. RET/PTC rearrangement in thyroid tumors. Endocr Pathol. 2002;13(1):3-16.
Nikiforova MN, Lynch RA, Biddinger PW, et al. RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab. 2003;88(5):2318-2326.
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(6):2745-2752.
Marques AR, Espadinha C, Catarino AL, et al. Expression of PAX8-PPAR gamma 1 rearrangements in both follicular thyroid carcinomas and adenomas. J Clin Endocrinol Metab. 2002;87(8):3947-3952.
Kroll TG, Sarraf P, Pecciarini L, et al. PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected]. Science. 2000;289(5483):1357-1360. Erratum in Science 2000;289(5484):1474.
Fukahori M, Yoshida A, Hayashi H, et al. The associations between RAS mutations and clinical characteristics in follicular thyroid tumors: new insights from a single center and a large patient cohort. Thyroid. 2012;22(7):683-689.
Soares P, Fonseca E, Wynford-Thomas D, Sobrinho-Simões M. Sporadic ret-rearranged papillary carcinoma of the thyroid: a subset of slow growing, less aggressive thyroid neoplasms? J Pathol. 1998;185(1):71-78.
Soares P, Trovisco V, Rocha AS, et al. BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC. Oncogene. 2003;22(29):4578-4580.
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(7):1454-1457.
Castro P, Rebocho AP, Soares RJ, et al. PAX8-PPARgamma rearrangement is frequently detected in the follicular variant of papillary thyroid carcinoma. J Clin Endocrinol Metab. 2006;91(1):213-220.
Trovisco V, Vieira de Castro I, Soares P, et al. (2004). BRAF mutations are associated with some histological types of papillary thyroid carcinoma. J Pathol. 2004;202(2):247-251.
De Falco V, Giannini R, Tamburrino A, et al. Functional characterization of the novel T599I-VKSRdel BRAF mutation in a follicular variant papillary thyroid carcinoma. J Clin Endocrinol Metab. 2008;93(11):4398-4402.
Couto JP, Prazeres H, Castro P, et al. How molecular pathology is changing and will change the therapeutics of patients with follicular cell-derived thyroid cancer. J Clin Pathol. 2009;62(5):414-421.
Jhiang SM, Caruso DR, Gilmore E, et al. Detection of the PTC/retTPC oncogene in human thyroid cancers. Oncogene. 1992;7(7):1331-1337.
Tallini G, Santoro M, Helie M, et al. RET/PTC oncogene activation defines a subset of papillary thyroid carcinomas lacking evidence of progression to poorly differentiated or undifferentiated tumor phenotypes. Clin Cancer Res. 1998;4(2):287-294.
Cibas ES, Ali SZ. The Bethesda System for Reporting Thyroid Cytopathology. American Journal of Clinical Pathology. 2009;132(5):658-665.
Nikiforova MN, NIkiforov YE. Molecular Diagnostics and Predictors in Thyroid Cancer. Thyroid. 2009;19(12):1351-1361.
Marchetti I, Lessi F, Mazzanti CM, et al. A morpho-molecular diagnosis of PTC: Braf V600E detection as an important tool in preoperative evaluation of FNA. Thyroid. 2009;19(8): 837-842.
Ito Y, Miyauchi A. Prognostic factors and therapeutic strategies for differentiated carcinomas of the thyroid. Endocr J. 2009;56(2):177-192.
Chan JK. Strict criteria should be applied in the diagnosis of encapsulated follicular variant of papillary thyroid carcinoma. Am J Clin Pathol. 2002;117(1):16-18.
Williams ED. Two proposals regarding the terminology of thyroid tumors. Int J Surg Pathol. 2000;8(3):181-183.
Zidan J, Karen D, Stein M, Rosenblatt E, Basher W, Kuten A. Pure versus follicular variant of papillary thyroid carcinoma: clinical features, prognostic factors, treatment, and survival. Cancer. 2003;97(5):1181-1185.
Hagag P, Hod N, Kummer E, Cohenpour M, Horne T, Weiss M. Follicular variant of papillary thyroid carcinoma: clinical-pathological characterization and long-term follow-up. Cancer J. 2006;12(4):275-282.
Celestino R, Magalhães J, Castro P, et al. A folicular variant of papillary thyroid carcinoma in struma ovarii. Case report with unique moleualr alterations. Histopathology. 2009;55(4):482-487.
Hari CK, Kumar M, Abo-Khatwa MM, Adams-Williams J, Zeitoun H. Follicular variant of papillary carcinoma arising from lingual thryoid. Ear Nose Throat J. 2009;88(6):E7.
Yu J, Nikiforova MN, Hodak SP, et al. Tumor to tumor Metastses to Follicular Variant of Papillary Thyroid Carcinoma:Histoloic, Immunohistochemical amd molecular studeis of two unusual cases. Endocr Pathol. 2009;20(4):235-242.
Baloch ZW, Livolsi VA. Follicular-patterned lesions of the thyroid:the bane of the pathologist. Am J Clin Pathol. 2002;117(1):143-150.
Lam AK, Lo CY, Lam KS. Papillary carcimoma of thyroid: a 30-yr clicopathologial revview of the histological variants. Endocr Pathol. 2005;16(4):323-330.
Gupta S, Ajise O, Dultz L, et al. Follicular variant of papillary thyroid cancer: encapsulated, nonencapsulated, and diffuse: distinct biologic and clinical entities. Arch Otolaryngol Head Neck Surg. 2012;138(3):227-233.
Ivanova R, Soares P, Castro P, Sobrinho-Simões M. Diffuse (or multinodular) follicular variant of papillary thyroid carcinoma: a clinicopathologic and immunohistochemical analysis of ten cases of an aggressive form of differentiated thyroid carcinoma. Virchows Arch. 2002;440(4):418-424.
Mizukami Y, Nonomura A, Michigishi T, Ohmura K, Noguchi M, Ishizaki T. Diffuse follicular variant of papillary carcinoma of the thyroid. Histopathology. 1995;27(6):575-577.
Chem KT, Rosai J. Follicular variant of thyroid papillary carcinoma: a clinicopathologic study of six cases. Am J Surg Pathol. 1977;1(2):123-130.
Ghossein R. Encapsulated malignant follicular cell-derived thyroid tumors. Endocr Pathol. 2010;21(4):212-218.
Rivera M, Tuttle RM, Patel S, Shaha A, Shah JP, Ghossein RA. Encapsulated papillary thyroid carcinoma: a clinico-pathologic study of 106 cases with emphasis on its morphologic subtypes (histologic growth pattern). Thyroid. 2009;19(2):119-127.
Mandal S, Jain S. Adenoid cystic pattern in follicular variant of papillary thyroid carcinoma: a report of four cases. Cytopathology. 2010;21(2):93-96.
Jakubowski M, Hunt JL. BRAF mutational analysis in papillary carcinomas with mixed follicular and papillary growth patterns. 2009;33(11):1590-1593.
Cardenas MG, Kini S, Wisgerhof M. Two patients with highly aggressive macrofollicular variant of papillary thyroid carcinoma. Thyroid. 2009;19(4):413-416.
Elsheikh TM, Asa SL, Chan JK, et al. Interobserver and intraobserver variation among experts in the diagnosis of thyroid follicular lesions with borderline nuclear features of papillary carcinoma. Am J Clin Pathol. 2008;130(5):736-744.
LiVolsi VA, Baloch ZW. Follicular neoplasms of the thyroid: view, biases, and experiences. Adv Anat Pathol. 2004;11(6):279-287.
Saleh HA, Jin B, Barnwell J, Alzohaili O. Utility of immunohistochemical markers in differentiating benign from malignant follicular-derived thyroid nodules. Diagn Pathol. 2010;5:9.
Saleh HA, Feng J, Tabassum F, Al-Zohaili O, Husain M, Giorgadze T. Differential expression of galectin-3, CK19, HBME1, and Ret oncoprotein in the diagnosis of thyroid neoplasms by fine needle aspiration biopsy. Cytojournal. 2009;6:18.
Nikiforov YE. RET/PTC rearrangement in thyroid tumors. Endocr Pathol. 2002;13(1):3-16.
Nikiforova MN, Lynch RA, Biddinger PW, et al. RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab. 2003;88(5):2318-2326.
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(6):2745-2752.
Marques AR, Espadinha C, Catarino AL, et al. Expression of PAX8-PPAR gamma 1 rearrangements in both follicular thyroid carcinomas and adenomas. J Clin Endocrinol Metab. 2002;87(8):3947-3952.
Kroll TG, Sarraf P, Pecciarini L, et al. PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected]. Science. 2000;289(5483):1357-1360. Erratum in Science 2000;289(5484):1474.
Fukahori M, Yoshida A, Hayashi H, et al. The associations between RAS mutations and clinical characteristics in follicular thyroid tumors: new insights from a single center and a large patient cohort. Thyroid. 2012;22(7):683-689.
Soares P, Fonseca E, Wynford-Thomas D, Sobrinho-Simões M. Sporadic ret-rearranged papillary carcinoma of the thyroid: a subset of slow growing, less aggressive thyroid neoplasms? J Pathol. 1998;185(1):71-78.
Soares P, Trovisco V, Rocha AS, et al. BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC. Oncogene. 2003;22(29):4578-4580.
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(7):1454-1457.
Castro P, Rebocho AP, Soares RJ, et al. PAX8-PPARgamma rearrangement is frequently detected in the follicular variant of papillary thyroid carcinoma. J Clin Endocrinol Metab. 2006;91(1):213-220.
Trovisco V, Vieira de Castro I, Soares P, et al. (2004). BRAF mutations are associated with some histological types of papillary thyroid carcinoma. J Pathol. 2004;202(2):247-251.
De Falco V, Giannini R, Tamburrino A, et al. Functional characterization of the novel T599I-VKSRdel BRAF mutation in a follicular variant papillary thyroid carcinoma. J Clin Endocrinol Metab. 2008;93(11):4398-4402.
Couto JP, Prazeres H, Castro P, et al. How molecular pathology is changing and will change the therapeutics of patients with follicular cell-derived thyroid cancer. J Clin Pathol. 2009;62(5):414-421.
Jhiang SM, Caruso DR, Gilmore E, et al. Detection of the PTC/retTPC oncogene in human thyroid cancers. Oncogene. 1992;7(7):1331-1337.
Tallini G, Santoro M, Helie M, et al. RET/PTC oncogene activation defines a subset of papillary thyroid carcinomas lacking evidence of progression to poorly differentiated or undifferentiated tumor phenotypes. Clin Cancer Res. 1998;4(2):287-294.
Cibas ES, Ali SZ. The Bethesda System for Reporting Thyroid Cytopathology. American Journal of Clinical Pathology. 2009;132(5):658-665.
Nikiforova MN, NIkiforov YE. Molecular Diagnostics and Predictors in Thyroid Cancer. Thyroid. 2009;19(12):1351-1361.
Marchetti I, Lessi F, Mazzanti CM, et al. A morpho-molecular diagnosis of PTC: Braf V600E detection as an important tool in preoperative evaluation of FNA. Thyroid. 2009;19(8): 837-842.
Downloads
Published
2012-10-31
How to Cite
Chen, MD, H., Izevbaye, MD, PhD, I., Chen, MD, F., & Weinstein, MD, B. (2012). Recent Advances in Follicular Variant of Papillary Thyroid Carcinoma. North American Journal of Medicine and Science, 5(4). Retrieved from https://najms.com/index.php/najms/article/view/213
Issue
Section
Review
