THYROID CANCER - 06/09/11

Thyroid cancer is the most frequent endocrine malignancy. Although infrequent, it is increasing worldwide and its characteristics are changing.<sup>1 Bacher-Stier C., Riccabona G., Totsch M. , et al. Incidence and clinical characteristics of thyroid carcinoma after iodine prophylaxis in an endemic goiter country Thyroid 1997 ;  7 : 733-741  [cross-ref]

Cliquez ici pour aller à la section Références, 9 Deandra M., Garlone G., Veglio M. , et al. Thyroid cancer histotype changes as observed in a major general hospital in a 21-year period J Endocrinol Invest 1997 ;  20 : 52-58

Cliquez ici pour aller à la section Références</sup> Papillary forms are on the rise, whereas follicular and anaplastic tumors are becoming less frequent. The addition of iodine to the salt, with the ensuing decrease of endemic goiter, and the decrease in the chronic high thyroid stimulating hormone (TSH) stimulation are believed to explain, in part, this trend.<sup>33 Slabe G.B. Etiology of thyroid cancer: An epidemiological overview Thyroidology 1994 ;  6 : 11-19

Cliquez ici pour aller à la section Références</sup> Livolsi et al<sup>18 Livolsi V.A., Asa S.L. The demise of follicular carcinoma of the thyroid gland Thyroid 1994 ;  4 : 233-236  [cross-ref]

Cliquez ici pour aller à la section Références</sup> have emphasized that pathologists still tend to overdiagnose follicular thyroid cancer. Patients with thyroid cancer are presenting with smaller tumors and in earlier stages of the disease (Table 1) Thyroid capsular and extrathyroidal involvement are currently rare although still more frequent in poorer countries and lower socioeconomic levels. The incidence in men is rising, especially in patients over 50 years old in whom the ratio of women to men is similar.

Thyroid cancer presents unique biologic features that set it apart from most of the cancers addressed in this issue of The Surgical Clinics of North America. With the exception of medullary carcinoma that arises in the parafollicular cells, most of the tumors originate in the follicular cells. Although differentiated forms are associated with excellent prognosis, undifferentiated forms tend to be quickly fatal. The unique relationship of differentiated tumors with age presentation results in a completely different prognosis for tumors of similar stage, depending on whether they occur in a young or an older patient. Differentiated thyric cancer also is the only cancer in which lymph node involvement does not relate necessarily to poor prognosis. Adjuvant therapies in differentiated cancers include TSH suppression and radioactive iodine rather than the use of standard chemotherapeutic agents and external beam radiotherapy.

Exposure to ionizing radiation, especially in childhood, is the only verified cause of thyroid carcinogenesis in humans.<sup>13 Hard G.C. Recent developments in the investigation of thyroid regulation and thyroid carcinogenesis Environ Health Perspect 1998 ;  106 : 427-436

Cliquez ici pour aller à la section Références</sup> Specific alterations in gene expression have been identified and linked to tumor phenotype and oncogene gene activation; tumor suppressor gene inactivation also may be a factor in the development and progression of thyroid cancer.<sup>13 Hard G.C. Recent developments in the investigation of thyroid regulation and thyroid carcinogenesis Environ Health Perspect 1998 ;  106 : 427-436

Cliquez ici pour aller à la section Références</sup> Studies are assessing the role of chemically induced neoplasia, the role of oncogene mutations and growth factors, and the effect of persistently elevated TSH levels. Loss of heterozygosity (LOH) studies to identify sites harboring tumor suppressor genes involved in tumor initiation or progression have suggested that regions in chromosomes 3p, 11q, 2p, 2q, 10q, and 1p are deleted more frequently, at least in one site, in follicular (60%) rather than in papillary carcinomas (23%).<sup>39 Ward L.S., Brenta G., Medvedovic M. , et al. Studies of allelic loss in thyroid tumors J Clin Endocrinol Metab 1998 ;  83 : 525-530  [cross-ref]

Cliquez ici pour aller à la section Références</sup> Thyroid tumor development seems correlated with mutation of five alternative genes: RAS, RET, TRK, GSP, and the TSH receptor. Mutation of RAS and RET may be sufficient to initiate tumorigenesis. Progression to undifferentiated cancer may require a p53 mutation together with a switch in the differentiation program.<sup>40 Wynford-Thomas D. Origin and progression of thyroid tumors: Cellular and molecular mechanisms Horm Metab Res 1997 ;  47 : 145-157  [cross-ref]

Cliquez ici pour aller à la section Références</sup> The management of children with medullary carcinoma has been revolutionized by the identification of specific mutations in the RET oncogene that predicts multiple neoplasia syndromes.<sup>16 Laquaglia M.P., Telander R.L. Differentiated and medullary thyroid cancer in childhood and adolescence Semin Pediatr Surg 1997 ;  6 : 42-49

Cliquez ici pour aller à la section Références</sup> Total thyroidectomy can be advised in such cases before the serum calcitonin rises. Other than the standard prognostic factors (age, sex, tumor size, extent of local disease, residual tumor, metastatic disease), aneuploid tumors; tumors with low adenylate cyclase response to TSH; and tumors that are RAS-positive, GSP-positive, p21-positive, and p53-positive seem to behave more aggressively.

Because of its frequency, differentiated thyroid cancer is emphasized in this article.