Abstract
Objective: We evaluated the association between thyroid autoimmunity and thyroid cancer in a retrospective series of unselected thyroid nodules submitted to fine-needle aspiration (FNA) cytology. Design: Anti-thyroid antibodies (TAb) were measured in patients with multinodular goiter (MNG) and single/isolated thyroid nodule (S/I) submitted to FNA. Thyroid lymphocytic infiltration (LI) on histology was studied in a subgroup of patients submitted to thyroidectomy; 13,021 patients were included: on cytology 622 had papillary thyroid cancer (c-PTC) and 12,399 benign thyroid nodular diseases (c-BTN). LI was evaluated in histological samples of 688 patients: 304 with PTC (h-PTC) and 384 with BTN (h-BTN). Results: TAb prevalence was not different in c-BTN and c-PTC (38.7% vs 35.6%). TAb were more frequent in c-BTN than c-PTC in females with MNG (40.1% vs 32.5%, p=0.02), and in c-PTC than in c-BTN in males with S/I (31.2% vs 20.4%, p=0.02) and, although not significantly, in females younger than 30 yr (35.1% vs 30.7%). The frequency and severity of LI was significantly higher in h-PTC than h-BTN, both in MNG (82.5% vs 45.0%, p<0.001) and S/I (85.6% vs 71.0%, p<0.001), but a higher number of patients with h-PTC had negative circulating TAb, despite the presence of moderate/severe LI. Conclusions: TAb are weakly associated to PTC in males and young females, while they are more frequent in older females with BTN. The frequency and severity of LI is significantly higher in PTC than in BTN, but in cancer patients TAb are frequently negative, despite the evidence of histological thyroiditis. These data suggest that different kinds of immune response may be involved in PTC and BTN.
Similar content being viewed by others
References
Dailey ME, Lindsay S, Skahen R. Relation of thyroid neoplasms to Hashimoto disease of the thyroid gland. AMA Arch Surg 1955, 70: 291–7.
Hirabayashi RN, Lindsay S. The relation of thyroid carcinoma and chronic thyroiditis. Surg Gynecol Obstet 1965, 121: 243–52.
Ott RA, Calandra DB, McCall A, Shah KH, Lawrence AM, Paloyan E. The incidence of thyroid carcinoma in patients with Hashimoto’s thyroiditis and solitary cold nodules. Surgery 1985, 98: 1202–6.
Ott RA, McCall AR, McHenry C, et al. The incidence of thyroid carcinoma in Hashimoto’s thyroiditis. Am Surg 1987, 53: 442–5.
Okayasu I, Fujiwara M, Hara Y, Tanaka Y, Rose NR. Association of chronic lymphocytic thyroiditis and thyroid papillary carcinoma. A study of surgical cases among Japanese, and white and African Americans. Cancer 1995, 76: 2312–8.
Okayasu I. The Relationship of Lymphocytic Thyroiditis to the Development of Thyroid Carcinoma. Endocr Pathol 1997, 8: 225–30.
Mizukami Y, Michigishi T, Nonomura A, et al. Carcinoma of the thyroid at a young age-a review of 23 patients. Histopathology 1992, 20: 63–6.
McConahey WM, Hay ID, Woolner LB, van Heerden JA, Taylor WF. Papillary thyroid cancer treated at the Mayo Clinic, 1946 through 1970: initial manifestations, pathologic findings, therapy, and outcome. Mayo Clin Proc 1986, 61: 978–96.
Singh B, Shaha AR, Trivedi H, Carew JF, Poluri A, Shah JP. Coexistent Hashimoto’s thyroiditis with papillary thyroid carcinoma: impact on presentation, management, and outcome. Surgery 1999, 126: 1070–6.
Baker JR Jr. The immune response to papillary thyroid cancer. J Clin Endocrinol Metab 1995, 80: 3419–20.
Crile G Jr, Hazard JB. Incidence of cancer in struma lymphomatosa. Surg Gynecol Obstet 1962, 115: 101–3.
Holm LE, Blomgren H, Löwhagen T. Cancer risks in patients with chronic lymphocytic thyroiditis. N Engl J Med 1985, 312: 601–4.
Walker RP, Paloyan E. The relationship between Hashimoto’s thyroiditis, thyroid neoplasia, and primary hyperparathyroidism. Otolaryngol Clin North Am 1990, 23: 291–302.
Boi F, Lai ML, Marziani B, Minerba L, Faa G, Mariotti S. High prevalence of suspicious cytology in thyroid nodules associated with positive thyroid autoantibodies. Eur J Endocrinol 2005, 153: 637–42.
Wirtschafter A, Schmidt R, Rosen D, et al. Expression of the RET/PTC fusion gene as a marker for papillary carcinoma in Hashimoto’s thyroiditis. Laryngoscope 1997, 107: 95–100.
Sheils OM, O’eary JJ, Uhlmann V, Lättich K, Sweeney EC. ret/PTC-1 Activation in Hashimoto Thyroiditis. IntJ Surg Pathol 2000, 8: 185–9.
Di Pasquale M, Rothstein JL, Palazzo JP. Pathologic features of Hashimoto’s-associated papillary thyroid carcinomas. Hum Pathol 2001, 32: 24–30.
Nikiforov YE. RET/PTC Rearrangement—a link between Hashimoto’s thyroiditis and thyroid cancer…or not. J Clin Endocrinol Metab 2006, 91: 2040–2.
Rhoden KJ, Unger K, Salvatore G, et al. RET/papillary thyroid cancer rearrangement in nonneoplastic thyrocytes: follicular cells of Hashimoto’s thyroiditis share low-level recombination events with a subset of papillary carcinoma. J Clin Endocrinol Metab 2006, 91: 2414–23.
Rago T, Di Coscio G, Ugolini C, et al. Clinical features of thyroid autoimmunity are associated with thyroiditis on histology and are not predictive of malignancy in 570 patients with indeterminate nodules on cytology who had a thyroidectomy. Clin Endocrinol (Oxf) 2007, 67: 363–9.
Guidelines of the Papanicolaou Society of Cytopathology for the Examination of Fine-Needle Aspiration Specimens from Thyroid Nodules. The Papanicolaou Society of Cytopathology Task Force on Standards of Practice. Mod Pathol 1996, 9: 710–5.
Hedinger C, Williams ED, Sobin LH. The WHO histological classification of thyroid tumors: a commentary on the second edition. Cancer 1989, 63: 908–11.
Mariotti S, Caturegli P, Piccolo P, Barbesino G, Pinchera A. Antithyroid peroxidase autoantibodies in thyroid diseases. J Clin Endocrinol Metab 1990, 71: 661–9.
Mariotti S, Franceschi C, Cossarizza A, Pinchera A. The aging thyroid. Endocr Rev 1995, 16: 686–715.
Loviselli A, Velluzzi F, Mossa P, et al. The Sardinian Autoimmunity Study: 3. Studies on circulating antithyroid antibodies in Sardinian schoolchildren: relationship to goiter prevalence and thyroid function. Thyroid 2001, 11: 849–57.
Olivieri A, Pinna G, Lai A, et al; Sardinian Newborn Study Group. The sardinian autoimmunity study. 4. Thyroid and islet cell autoantibodies in sardinian pregnantwomen at delivery: a cross-sectional study. J Endocrinol Invest 2001, 24: 570–4.
Kebebew E, Treseler PA, Ituarte PH, Clark OH. Coexisting chronic lymphocytic thyroiditis and papillary thyroid cancer revisited. World J Surg 2001, 25: 632–7.
Bagnasco M, Venuti D, Paolieri F, Torre G, Ferrini S, Canonica GW. Phenotypic and functional analysis at the clonal level of infiltrating T lymphocytes in papillary carcinoma of the thyroid: prevalence of cytolytic T cells with natural killer-like or lymphokine-activated killer activity. J Clin Endocrinol Metab 1989, 69: 832–6.
Castellone MD, Guarino V, De Falco V, et al. Functional expression of the CXCR4 chemokine receptor is induced by RET/PTC oncogenes and is a common event in human papillary thyroid carcinomas. Oncogene 2004, 23: 5958–67.
Puxeddu E, Knauf JA, Sartor MA, et al. RET/PTC-induced gene expression in thyroid PCCL3 cells reveals early activation of genes involved in regulation of the immune response. Endocr Relat Cancer 2005, 12: 319–34.
Borrello MG, Alberti L, Fischer A, et al. Induction of a proinflammatory program in normal human thyrocytes by the RET/PTC1 oncogene. Proc Natl Acad Sci U S A 2005, 102: 14825–30.
Russell JP, Shinohara S, Melillo RM, Castellone MD, Santoro M, Rothstein JL. Tyrosine kinase oncoprotein, RET/PTC3, induces the secretion of myeloid growth and chemotactic factors. Oncogene 2003, 22: 4569–77.
Powell DJ Jr, Eisenlohr LC, Rothstein JL. A thyroid tumor-specific antigen formed by the fusion of two self proteins. J Immunol 2003, 170: 861–9.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Fiore, E., Rago, T., Scutari, M. et al. Papillary thyroid cancer, although strongly associated with lymphocitic infiltration on histology, is only weakly predicted by serum thyroid auto-antibodies in patients with nodular thyroid diseases. J Endocrinol Invest 32, 344–351 (2009). https://doi.org/10.1007/BF03345725
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03345725