The traditional classification of thyroid tumours is derived from follicular and 'C' cells and based on morphology and clinical features, but molecular studies have shown the involvement of distinct genes in each of these tumours. The high prevalence of papillary microcarcinoma in thyroid glands removed for other reasons underpinned the alteration of the TNM classification of thyroid tumors. Molecular studies showed that the high prevalence of BRAF mutations in papillary carcinomas, reaching ≤70% in some series, contrasts with lower levels of this mutation in cases of follicular variants. Follicular variants of papillary carcinoma share oncogene changes with follicular tumours, making the differential diagnosis of follicular lesions a challenge. Hyalinizing trabecular tumour has the same RET oncogene rearrangement encountered in many papillary carcinomas, raising the possibilty that it is a variant of papillary carcinoma. The 'mixed medullary-follicular cell carcinoma' is of uncertain histogenesis and merits separate classification. © 2008 Elsevier Ltd. All rights reserved.145236246De Lellis, R.A., Williams, E.D., Tumours of the thyroid and parathyroid (2004) World Health Organization Classification of Tumours Pathology & Genetics. Tumours of Endocrine Organs, pp. 50-105. , De Lellis R.A., Lloyd R.V., Heitz P.V., and Eng C. (Eds), Oxford University Press, OxfordRosai, J., Carcangiu, M.L., De Lellis, R.A., (1992) Atlas of tumor pathology. Tumors of the thyroid gland. 3rd edn., , AFIP, Washington DC 19-258Baloch, Z.W., Livolsi, V.A., Pathology of the thyroid gland (2002) Endocrine Pathology, pp. 61-101. , Livolsi V.A., and Asa S.L. (Eds), Churchill Livingstone, EdinburghHazard, J.B., Kenion, R., Atypical adenoma of the thyroid (1954) Arch Pathol Lab Med, 58, pp. 554-563Cheung, C.C., Boerner, S.L., MacMillan, C.M., Ramyar, L., Asa, S.L., Hyalinizing trabecular tumor of the thyroid: a variant of papillary carcinoma proved by molecular genetics (2000) Am J Surg Pathol, 24, pp. 1622-1626Papotti, M., Volante, M., Giuliano, A., RET/PTC Activation in hyalinizing trabecular tumors of the thyroid (2000) Am J Surg Pathol, 24, pp. 1615-1621(1990) Surgical Pathology of the Thyroid, pp. 131-274. , Livolsi V.A. (Ed), WB Saunders, EdinburghChan, J.K.C., Tumors of the thyroid and parathyroid glands (2001) Diagnostic Histopathology of Tumors, pp. 959-1038. , Fletcher C.D.M. (Ed), Churchill Livingstone, EdinburghHarach, H.R., Franssila, K.O., Wasenius, V.M., Occult papillary carcinoma of the thyroid. A "normal" finding in Finland. A systemic autopsy study (1985) Cancer, 56, pp. 531-538Bisi, H., Fernandes, V.S., de Carvalho, R.Y., Koch, L., Abdo, A.H., de Brito, T., The prevalence of unsuspected thyroid pathology in 300 sequential autopsies, with special reference to incidental carcinoma (1989) Cancer, 64, pp. 1888-1893Fink, A., Tomlinson, G., Freeman, J.L., Rosen, I.B., Asa, S.L., Occult micropapillary carcinoma associated with benign disease and unrelated thyroid neoplasms (1996) Mod Pathol, 9, pp. 816-820Rosai, J., Livolsi, V.A., Sobrinho-Simões, M., Williams, E.D., Renaming papillary microcarcinomas of the thyroid gland: the Porto proposal (2003) Int J Surg Pathol, 11, pp. 249-251Matos, P.S., Ferreira, A.P.C., Ward, L.S., Prevalence of papillary microcarcinoma of the thyroid in Brazilian autopsy and surgical series (2006) Endocr Pathol, 17, pp. 165-173Piersanti, M., Ezzat, S., Asa, S.L., Controversies in papillary microcarcinoma of the thyroid (2003) Endocr Pathol, 14, pp. 183-191Lindsay, S., (1960) Carcinoma of the Thyroid Gland: A Clinical and Pathologic Study of 293 Patients at the University of California Hospital, , Chares C Thomas, SpringfieldChen, T.K.K., Rosai, J., Follicular variant of thyroid papillary carcinoma: a clinicopathologic study of six cases (1977) Am J Surg Pathol, 1, pp. 123-130Matos, P.S., Ferreira, A.P., Facuri, F.O., Assumpção, L.V.M., Ward, L.S., Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy (2005) Histopathol, 47, pp. 391-401Cheung, C.C., Ezzat, S., Freeman, J.L., Rosen, I.B., Asa, S.L., Immunohistochemical diagnosis of papillary thyroid carcinoma (2001) Mod Pathol, 14, pp. 338-342Beesley, M.F., McLaren, K.M., Cytokeratin 19 and Galectin-3. Immunohistochemistry in the differential diagnosis of solitary thyroid nodules (2002) Histopathol, 41, pp. 236-243Hawk, W.A., Hazard, J.B., The many appearances of papillary carcinoma of the thyroid (1976) Cleve Clin Q, 43, pp. 207-216Ostrowski, M.L., Merino, M.J., Tall cell variant of papillary thyroid carcinoma. A reassessment and immunohistochemical study with comparison to the usual type of papillary carcinoma of the thyroid (1996) Am J Surg Pathol, 20, pp. 964-974Rüter, A., Dreifus, J., Jones, M., Overexpression of p53 in tall cell variants of papillary thyroid carcinoma (1996) Surgery, 120, pp. 1046-1050Evans, H.L., Collumnar cell carcinoma of the thyroid: a report of two cases of an aggressive variant of thyroid carcinoma (1986) Am J Pathol, 85, pp. 77-80Sobrinho-Simões, M., Nesland, J.M., Johannessen, J.V., Columnar cell carcinoma: Another variant of poorly differentiated carcinoma of the thyroid (1988) Am J Clin Pathol, 89, pp. 264-267Wenig, B.M., Thompson, L.D., Adair, C.F., Shmookler, B., Heffess, C.S., Thyroid papillary carcinoma of columnar cell type. A clinicopathologic study of 16 cases (1998) Cancer, 82, pp. 740-753Matos PS. Tumores do Sistema Endócrino: Glândula Tireóide. In: Billis A, Vassallo J eds. Patologia Diagnóstica de Tumores. Impressão Digital do Brasil Gráfica e Editora Ltda. IDB/20041-24Carcangiu, M.L., Bianchi, S., Diffuse sclerosing variant of papillary carcinoma of the thyroid. A histologic and immunohistochemical study of 15 cases (1989) Am J Surg Pathol, 3, pp. 1041-1049Soares, J., Limbert, E., Sobrinho-Simões, M., Diffuse sclerosing variant of papillary carcinoma. A clinicopathologic study of 10 cases (1989) Pathol Res Pract, 185, pp. 200-206Gomez-Morales, M., Alvaro, T., Munoz, M., Diffuse sclerosing papillary carcinoma of the thyroid gland. Immunohistochemical analysis of the host immune response (1991) Histopathology, 18, pp. 427-433Sobrinho-Simões, M., Diffuse follicular variant of papillary carcinoma of the thyroid: report of eight cases of a distinct agressive type of thyroid tumor (1990) Surg Pathol, 3, pp. 189-203Mizukami, Y., Nonomura, A., Michigishi, T., Ohmura, K., Nogushi, M., Ishizaki, T., Diffuse follicular variant of papillary carcinoma of the thyroid (1995) Histopathology, 27, pp. 575-577Apel, R.L., Asa, S.L., Livolsi, V.A., Papillary Hurthle cell carcinoma with lymphocytic stroma (1995) Am J Surg Pathol, 19, pp. 810-814Nikiforov, Y.E., Erickson, L.A., Nikiforova, M.N., Caudill, C.M., Lloyd, R.V., Solid variant of papillary thyroid carcinoma: incidence, clinical-pathologic characteristics, molecular analysis, and biologic behavior (2001) Am J Surg Pathol, 5, pp. 1478-1484Carcangiu, M.L., Zampi, G., Rosai, J., Poorly differentiated (insular) thyroid carcinoma. A reinterpretation of Langhans ''Wuchernde Struma" (1984) Am J Surg Pathol, 8, pp. 655-668Carcangiu, M.L., Steeper, T., Zampi, G., Rosai, J., Anaplastic thyroid carcinoma. A study of 70 cases (1985) Am J Clin Pathol, 83, pp. 135-158Vickery, A.L., Carcangiu, M.L., Johannessen, J.V., Sobrinho-Simões, M., Papillary carcinoma (1985) Sem Diagn Pathol, 2, pp. 90-100Haigh, P.I., Ituarte, R.H., Wu, H.S., Completely resected anaplastic thyroid carcinoma combined with adjuvant chemotherapy and irradiation is associated with prolonged survival (2001) Cancer, 91, pp. 2335-2342Albores-Saavedra, J., Housini, I., Vuitch, F., Snyder III, W.H., Macroffolicular variant of papillary thyroid carcinoma with minor insular component (1997) Cancer, 80, pp. 1110-1116Lang, W., Georgii, A., Stauch, G., Kienzle, E., The differentiation of atypical adenomas and encapsulated follicular carcinoma in the thyroid (1980) Virchow Arch A (Pathol Anat Histol), 385, pp. 125-141Franssila, K.O., Ackerman, L.V., Brown, C.L., Hedinger, C.E., Follicular carcinoma (1985) Semin Diagn Pathol, 2, pp. 101-122Lang, W., Choritz, H., Hundeshagen, H., Risk factors in follicular thyroid carcinomas. A retrospective follow up covering a 14-year period with emphasis on morphological findings (1986) Am J Surg Pathol, 10, pp. 246-255Langhans, T., Über die epithelialen formen der malignen struma (1907) Virchows Arch Pathol Anat, 189, p. 69Nishida, T., Katayama, S., Tsujimoto, M., Nakamura, J., Matsuda, H., Clinicopathological significance of poorly differentiated thyroid carcinoma (1999) Am J Surg Pathol, 23, pp. 205-211Giuffrida, D., Gharib, H., Cardiac metastasis from primary anaplastic thyroid carcinoma: report of three cases and review of the literature (2001) Endocr Relat Cancer, 8, pp. 71-73Papotti, M., Negro, F., Carney, J.A., Bussolati, G., Lloyd, R.V., Mixed medullary-follicular carcinoma of the thyroid. A morphological, immunohistochemical and in situ hybridization analysis of 11 cases (1997) Virchows Arch, 430, pp. 397-405Fusco, A new oncogene in human thyroid papillary carcinomas and their lymph node metastasis (1987) Nature, 328, p. 170Zhu, Z., Gandhi, M., Nikiforowa, M.N., Fischer, A.H., Nikiforov, Y.E., Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations (2003) Am J Clin Pathol, 120, pp. 71-77Nikiforova, M.N., Biddinger, P.W., Caudill, C.M., Kroll, T.G., Nikiforov, Y.E., PAX 8-PPAR γ Rearrangement in thyroid tumors. RT-PCR and immunohistochemical analyses (2002) Am J Surg Pathol, 26, pp. 1016-1023Kimura, E.T., Nikiforova, M.N., Zhu, Z., Knauf, J.A., Nikiforov, Y.E., Fagin, J.A., High prevalence of BRAF mutations in thyroid câncer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma (2003) Cancer Res, 63, pp. 1454-1457Xu, X., Quiros, R.M., Gattuso, P., Aun, K.B., Prinz, R.A., High prevalence of BRAF gene mutation in papillary thyroid carcinoma and thyroid tumor cell lines (2003) Cancer Res, 63, pp. 4561-4567Kebebew, E., Clark, O.H., Medullary thyroid Câncer (2003) Endocrine Tumours. Atlas of clinical oncology, pp. 37-48. , Clark O.H., Duh Q.-Y., Perrier N.D., and Jahan T. (Eds), BC Decker, ChicagoSoares, P., Cameselle- Teijeiro, J., Sobrinho-Simões, M., Immunohistochemical detection of p53 in differentiated, poorly differentiated and undifferentiated carcinomas of the thyroid (2004) Histopathology, 24, pp. 205-210