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Thyroid Cancer Table 1: The Different Subtypes of Thyroid Cancer Subtype Percentage of Cases Prognosis Differentiation Characteristics Papillary 80–85 Good: up to stage II 5-year survival is 100 % Well differentiated Tumor cell form finger-like or papillary structures Follicular 10–15 Good: up to stage II 5-year survival is 100 % Well differentiated Tumor cells have follicles that are similar to normal thyroid follicles Medullary 3–4 Good: up to stage II 5-year survival is 98 % Well differentiated Tumors arise from the parafollicular C cells of the thyroid gland that produce calcitonin and secrete this peptide into the bloodstream. Tumor cannot concentrate radioiodine, do not secrete thyroglobulin and are unresponsive to serum thyroid-stimulating hormone level Anaplastic 1–2 Very poor: 5-year survival is only 9 % Undifferentiated, with marked epithelial to mesenchymal transition Tumor cells do not resemble normal thyroid cells or form follicles. Unresponsive to radioactive iodine, serum thyroid-stimulating hormone level and all currently available treatment modalities TSH = thyroid-stimulating hormone follicular cancers, 9,10 which can be difficult to treat. Histologic Characteristics of Thyroid Cancer Papillary carcinomas have characteristic nuclear features, 11 with large, ovoid, crowded, ground-glass ‘Orphan Annie eyed’ nuclei and nuclear grooves with pseudo inclusions. The demonstration of invasion is not required for diagnosis; therefore, this tumor is often diagnosable by fine-needle aspiration (FNA) and cytologic examination. Mitoses are usually sparse. The papillae are usually arborizing, with a delicate fibro vascular core. Follicular carcinomas are malignant epithelial tumors showing follicular cell differentiation and often lacking the diagnostic nuclear features of papillary thyroid carcinoma. 11 Follicular neoplasms demonstrate signs of vascular or capsular invasion, but neither architectural nor cytologic atypia are reliable criteria of malignancy. Therefore, the distinction from follicular adenoma cannot be easily based on FNA cytology resulting in the appellation ‘follicular neoplasm.’ ATCs exhibit wide variations in appearance with several morphologic patterns recognized and many tumors manifesting a mixed morphology. 12 A common morphologic presentation, and one that is most easily recognized as an anaplastic carcinoma of thyroid, is that of the biphasic spindle and giant cell tumor. 13 All variations of anaplastic carcinoma of On col ogy & Hemato lo gy Revi ew 16 14 New diagnoses 16 12 14 10 New diagnoses 12 8 10 6 8 4 6 2 0 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 Deaths 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2 Deaths 1992 1993 4 0 1992 1993 The well-differentiated thyroid cancers often have an indolent clinical course with low morbidity and mortality. With some exceptions, these are among the most curable of cancers and, as a consequence, patients are sometimes ill advised that thyroid cancer is not a serious problem. Although anaplastic thyroid cancer (ATC), which is highly aggressive and accounts for ~50  % of all thyroid cancer-related deaths, remains uncommon, more malignant forms of differentiated thyroid cancer exist, such as the tall cell variant of papillary thyroid cancer 8 and the Hurtle cell Figure 1: A) The Thyroid Cancer Epidemic Number Number per 100,000 persons per 100,000 persons differentiated thyroid cancer are the papillary and follicular types. The papillary form tends not to metastasize outside the neck compared with follicular thyroid cancers, which have a propensity to spread further. This histologic differentiation is now supported by molecular studies (see below). The vast majority of thyroid tumors arise from thyroid follicular epithelial cells but the 3–5  % of medullary cancers originate from the C cells, which secrete calcitonin and are outside the purview of this review. Hawaii Figure (ethnic 1: population) B) Geographic Variation of Thyroid Cancer Iceland Cali, Colombia Hawaii (caucasian population) Hawaii (ethnic population) Israel Iceland Sweden Cali, Colombia Miyagi, Japan Hawaii (caucasian population) 5 provinces, Canada Israel New York State, US Sweden Chile Miyagi, Japan Kingston, Jamaica 5 provinces, Canada The Netherlands New York State, US 4 regions, England and Wales Chile Hamburg, Germany Kingston, Jamaica The Netherlands 0 1 2 3 4 5 6 7 8 9 4 regions, England and Wales Age-adjusted incidence of thyroid carcinoma Hamburg, Germany 0 per 100,000 women 1 2 3 4 5 6 7 8 Age-adjusted incidence of thyroid carcinoma per 100,000 women 9 Source: http://seer.cancer.gov/statfacts/html/thyro.html the thyroid are highly proliferative with numerous mitotic figures and atypical mitoses. 14 There is usually extensive necrosis with inflammatory infiltrate, and, in some cases, the necrosis may be so widespread that the only viable tumor is preserved around blood vessels. Macrophages form a major component of the inflammatory infiltrate. 15 In approximately 50  % of cases, histologic examination of ATC identifies a component of papillary, follicular, or poorly differentiated carcinoma, or patients have a history of previously resected well-differentiated or poorly differentiated thyroid carcinoma. 12,16,17 This supports the notion that ATC can arise by dedifferentiation of a preexisting well-differentiated thyroid carcinoma. 145