Abstract
Hashimoto’s thyroiditis (HT), part of the spectrum of autoimmune thyroid diseases is a major cause of thyroid hypofunction worldwide. Papillary thyroid carcinoma (PTC), the most prevalent of all thyroid carcinomas has been associated with HT. Literature on this association are based on preoperative FNA or post thyroidectomy histopathology reports, which are subject to potential biases. Molecular, hormonal and histopathalogical basis of this association has been hypothesized, however a definite causal association has not been proved till date. This review aims to study the basis of this association and clinical features and management of HT concurrent with PTC. There are no distinctive clinical or radiological features that categorically differentiates HT concurrent with PTC from PTC or which can pick up a nodule harboring PTC in setting of HT. Smaller nodule size and radiological features like hypoechogenecity; hyper vascularity and calcification in a clinical setting of hypothyroidism have a higher odds ratio for malignancy and merit further investigations. PTC associated with HT has been seen to be less aggressive with earlier presentation with lesser chances of extra thyroidal extension and lymph nodal metastasis. The management and follow up of PTC in HT is no different from that of PTC alone. The prognosis of PTC concurrent with HT is better compared to age and stage matched PTC in terms of lower recurrence and disease free and overall survival.
Similar content being viewed by others
References
Davies L, Welch HG (2006) Increasing incidence of thyroid cancer in the United States, 1973–2002. J Am Med Assoc 295(18):2164–2167
Burgess JR, Tucker P (2006) Incidence trends for papillary thyroid carcinoma and their correlation with thyroid surgery and thyroid fine-needle aspirate cytology. Thyroid 16(1):47–53
Mazokopakis EE, Chatzipavlidou V (2007) Hashimoto’s thyroiditis and the role of selenium: current concepts. Hell J Nucl Med 10:6–8
Mazokopakis EE, Papadakis JA, Papadomanolaki MG et al (2007) Effects of 12 months treatment with L-selenomethionine on serum anti-TPO levels in patients with Hashimoto’s thyroiditis. Thyroid 17:609–612
Dailey ME, Lindsay S, Skahen R (1955) Relation of thyroid neoplasms to Hashimoto disease of the thyroid gland. Arch Surg 70(2):291–297
Bojana J et al (2013) Hashimoto’s thyroiditis and papillary thyroid carcinoma: is there a correlation? J Clin Endocrinol Metab 98:474–482
Davies L, Welch HG (2006) Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA 295:2164–2167
http://www.ias.ac.in/currsci/oct252000/n%20kochupillai.PDF. Accessed 2 Apr 2011
Jayaram G, Iyengar KR, Sthaneshwar P et al (2007) Hashimoto’s thyroiditis—a Malaysian perspective. J Cytol 24(3):119–124
Bloodworth JMB, Lechago J, Gould VE (1996) Bloodworth’s endocrine pathology, 3rd edn. Williams & Wilkins, Baltimore
Singh B, Shaha AR, Trivedi H et al (1999) Coexistent Hashimoto’s thyroiditis with papillary thyroid carcinoma: impact on presentation, management, and outcome. Surgery 126(6):1070–1077
Ward LS, Assumpcao LVM (2007) The impact of gender in differentiated thyroid cancer. Clin Endocrinol 66(5):752–753
Kilfoy BA, Zheng T, Holford TR et al (2009) International patterns and trends in thyroid cancer incidence, 1973–2002. Cancer Causes Control 20(5):525–531
Cheema Y, Olson S, Elson D et al (2006) What is the biology and optimal treatment for papillary microcarcinoma of the thyroid? J Surg Res 134:160–162
Cheema Y, Repplinger D, Elson D et al (2006) Is tumor size the best predictor of outcome for papillary thyroid cancer? Ann Surg Oncol 13:1524–1528
Bloodworth JMB, Lechago J, Gould VE (1997) Bloodworth’s endocrine pathology. Williams & Wilkins, Baltimore, The thyroid; pp. 178–181, pp. 197–206
Kollur SM, El Sayed S, El Hag IA (2003) Follicular thyroid lesions coexisting with Hashimoto’s thyroiditis: incidence and possible sources of diagnostic errors. Diagn Cytopathol 28(1):35–38
Wijayawardena MA, Gunawardane HD, Sheriffdeen AH et al (2004) Medullary carcinoma of the thyroid gland associated with Hashimoto’s thyroiditis. Ceylon Med J 49(3):96
Wartofsky L (2010) Increasing world incidence of thyroid cancer: increased detection or higher radiation exposure? Horm 9(2):103–108
Ostroumova E, Brenner A, Oliynyk V et al (2009) Subclinical hypothyroidism after radioiodine exposure: Ukrainian- American cohort study of thyroid cancer and other thyroid diseases after the chornobyl accident (1998–2000). Environ Health Perspect 117(5):745–750
Gomez Segovia I, Gallowitsch HJ, Kresnik E et al (2004) Descriptive epidemiology of thyroid carcinoma in Carinthia, Austria: 1984–2001. Histopathologic features and tumor classification of 734 cases under elevated general iodination of table salt since 1990: population-based age stratified analysis on thyroid carcinoma incidence. Thyroid 14(4):277–286
Lee JH, Kim Y, Choi JW et al (2013) The association between papillary thyroid carcinoma and histologically proven Hashimoto’s thyroiditis: a meta-analysis. Eur J Endocrinol 168(3):343–349
Laurberg P, Cerqueira C, Ovesen L et al (2010) Iodine intake as a determinant of thyroid disorders in populations. Best Pract Res 24(1):13–27
Nikiforov YE (2006) RET/PTC rearrangement—a link between Hashimoto’s thyroiditis and thyroid cancer…or not. J Clin Endocrinol Metab 91(6):2040–2042
Shands WC (1960) Carcinoma of the thyroid in association with struma lymphomatosa. Ann Surg 151(5):675–680
Anil C, Goksel S, Gursoy A (2010) Thyroglobulin antibody is associated with increased cancer risk in thyroid nodules. Thyroid 20(8):885–891
Boi F, Lai ML, Marziani B et al (2005) High prevalence of suspicious cytology in thyroid nodules associated with positive thyroid autoantibodies. Eur J Endocrinol 153(5):637–642
Fiore E et al (2011) Hashimoto’s thyroiditis is associated with papillary thyroid carcinoma: role of TSH and of treatment with L-thyroxine. Endocr Relat Cancer 18(4):429–437
Fiore E, Rago T, Scutari M et al (2009) Papillary thyroid cancer, although strongly associated with lymphocitic infiltration on histology, is only weakly predicted by serum thyroid autoantibodies in patients with nodular thyroid diseases. J Endocrinol Investig 32(4):344–351
Boelaert K, Horacek J, Holder RL et al (2006) Serum thyrotropin concentration as a novel predictor of malignancy in thyroid nodules investigated by fine-needle aspiration. J Clin Endocrinol Metab 91(11):4295–4301
Rago T, Di Coscio G, Ugolini C et al (2007) 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 67(3):363–369
Fiore E, Rago T, Provenzale MA et al (2009) Lower levels of TSH are associated with a lower risk of papillary thyroid cancer in patients with thyroid nodular disease: thyroid autonomy may play a protective role. Endocr Relat Cancer 16(4):1251–1260
Crile G Jr, Fisher ER (1953) Simultaneous occurrence of thyroiditis and papillary carcinoma; report of two cases. Cancer 6(1):57–62
Hirabayashi RN, Lindsay S (1965) The relation of thyroid carcinoma and chronic thyroiditis. Surg Gynecol Obstet 121:243–252
Schlicke CP, Hill JE, Schultz GF (1960) Carcinoma in chronic thyroiditis. Surg Gynecol Obstet 111:552–556
Clark OH, Greenspan FS, Dunphy JE (1980) Hashimoto’s thyroiditis and thyroid cancer: indications for operation. Am J Surg 140(1):65–71
Lindsay S, Dailey ME, Friedlander J, Yee G et al (1952) Chronic thyroiditis: a clinical and pathologic study of 354 patients. J Clin Endocrinol Metab 12(12):1578–1600
Meier DW, Woolner LB, Beahrs OH, McConahey WM, (1959) Parenchymal findings in thyroidal carcinoma: pathologic study of 256 cases. J Clin Endocrinol Metab 19:162–171
Kebebew E, Treseler PA, Ituarte PHG et al (2001) Coexisting chronic lymphocytic thyroiditis and papillary thyroid cancer revisited. World J Surg 25(5):632–637
Lu H, Ouyang W, Huang C (2006) Inflammation, a key event in cancer development. Mol Cancer Res 4(4):221–233
Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867
Kang DY, Kim KH, Kim JM et al (2007) High prevalence of RET, RAS, and ERK expression in Hashimoto’s thyroiditis and in papillary thyroid carcinoma in the Korean population. Thyroid 17(11):1031–1038
Colotta F, Allavena P, Sica A et al (2009) Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30(7):1073–1081
Crawford S, Belajic D, Wei J et al (2008) A novel B-RAF inhibitor blocks interleukin-8 (IL-8) synthesis in human melanoma xenografts, revealing IL-8 as a potential pharmacodynamics biomarker. Mol Cancer Ther 7(3):492–499
Unger P, Ewart M, Wang B et al (2003) Expression of p63 in papillary thyroid carcinoma and in Hashimoto’s thyroiditis: a pathological link? Hum Pathol 34:764–769
Asioli S, Erickson LA, Lloyd RV (2009) Solid cell nests in Hashimoto’s thyroiditis sharing features with papillary thyroid microcarcinoma. Endocr Pathol 20:197–203
Burstein DE (2004) Immunohistochemical detection of p53 homolog p63 in solid cell nests, papillary thyroid carcinoma, and Hashimoto’s thyroiditis: a stem cell hypothesis of papillary carcinoma oncogenesis. Hum Pathol 35(4):465–473
Cameselle-Teijeiro J et al (2009) BRAF mutation in solid cell nest hyperplasia associated with papillary thyroid carcinoma. A precursor lesion? Hum Pathol 40:1029–1035
Crile GJ, Hazard JB (1962) Incidence of cancer in struma lymphomatosa. Surg Gynecol Obstet 115:101–103
Mukasa K, Noh JY, Kunii Y et al (2011) Prevalence of malignant tumors and adenomatous lesions detected by ultrasonographic screening in patients with autoimmune thyroid disease. Thyroid 21:37–41
Okayasu I, Fujiwara M, Kara Y, Tanaka Y, Rose NR (1995) Association of chronic lymphocytic thyroiditis and thyroid papillary carcinoma. Cancer 76:2312–2318
McLeod DS, Watters KF, Carpenter AD, Ladenson PW, Cooper DS, Ding EL (2012) Thyrotropin and thyroid cancer diagnosis: a systematic review and dose-response meta-analysis. J Clin Endocrinol Metab 97:2682–2692
Daniel R (2008) Is Hashimoto’s thyroiditis a risk factor for papillary thyroid cancer? J Surg Res 150(1):49–52
Yeh HC, Futterweit W, Gilbert P (1996) Micronodulation: ultrasonographic sign of Hashimoto thyroiditis. J Ultrasound Med 15:813–819
Simeone JF, Daniels GH, Mueller PR et al (1982) High-resolution real-time sonography of the thyroid. Radiology 145:431–435
Butch RJ, Simeone JF, Mueller PR et al (1985) Thyroid and parathyroid ultrasonography. Radiol Clin N Am 23:57–71
Pedersen OM, Aardal NP, Larssen TB et al (2000) The value of ultrasonography in predicting autoimmune thyroid disease. Thyroid 10:251–259
Baskin J, Duick D, Guttler R, et al. (2005) Academy of Clinical Thyroidologists. Position paper on FNA for non-palpable thyroid nodules. Academy of Clinical Thyroidologists Web site. www.thyroidologists.com/papers.html
Baloch ZW, Cibas ES, Clark DP et al (2008) The national cancer institute thyroid fine needle aspiration state of the science conference: a summation. Cyto J 5:6
Frates MC, Benson CB, Doubilet PM, Cibas ES, Marqusee E (2003) Can color doppler sonography aid in the prediction of malignancy of thyroid nodules? J Ultrasound Med 22:127–131
Cooper DS, Doherty GM, Haugen BR et al (2006) Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 16:109–142
Gharib H, Papini E, Valcavi R et al (2006) AACE/AME task force on thyroid nodules. American association of clinical endocrinologists and associazione Medici endocarinologi medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. Endocr Pract 12:63–102
Nariko O et al (2007) Ultrasonographic findings of papillary thyroid carcinoma with Hashimoto’s thyroiditis. Intern Med Tokyo Jpn 46(9):547–550
Makhdoomi R et al (2013) Coexistent papillary carcinoma of thyroid and Hashimoto’s thyroiditis—diagnosis on fine needle aspiration cytology. Int J Endocrinol Metab 11(3):191–194
Su DH, Liao KM, Hsiao YL et al (2004) Determining when to operate on patients with Hashimoto’s thyroiditis with nodular lesions: the role of ultrasound-guided fine needle aspiration. Acta Cytol 48:622–629
Rosai J, Carcangiu ML, DeLellis RA (1992) Tumors of the thyroid gland. Armed Forces Institute of Pathology, Washington
Baloch Z, LiVolsi VA (2003) Diagnostic dilemmas in thyroid pathology: follicular variant of papillary thyroid carcinoma and classic papillary thyroid carcinoma arising in lymphocytic thyroiditis. Pathol Case Rev 8:47–56
Baloch ZW, LiVolsi VA (2000) Warthin-like papillary carcinoma of the thyroid. Arch Pathol Lab Med 124:1192–1195
V. Krishna (2014) Textbook: Pathology of Thyroid gland p 1901–1909
Crile GJ (1978) Struma lymphomatosa and carcinoma of the thyroid. Surg Gynecol Obstet 147:350–352
Holm LE, Blomgren H, Lowhagen T (1985) Cancer risks in patients with chronic lymphocytic thyroiditis. N Engl J Med 312:601–604
Carson H, Castelli M, Gattuso P (1996) Incidence of neoplasia in Hashimoto’s thyroiditis: a fine-needle aspiration study. Diagn Cytopathol 14:38–42
Erdogan M, Erdem N, Cetinkalp S et al (2009) Demographic, clinical, laboratory, ultrasonographic, and cytological features of patients with Hashimoto’s thyroiditis: a result of a university hospital of 769 patients in Turkey. Endocrine 36:486–490
Matesa-Anic’ D, Matesa N, Dabelic’ N, Kusic’ Z (2009) Coexistence of papillary carcinoma and Hashimoto’s thyroiditis. Acta Clin Croat 48:9–12
Anil C, Goksel S, Gursoy A (2010) Hashimoto’s thyroiditis is not associated with increased risk of thyroid cancer in patients with thyroid nodules: a single-center prospective study. Thyroid 20:601–606
Mazakopakis E, Tzortzinis A, Dalieraki-Ott E et al (2010) Coexistence of Hashimoto’s thyroiditis with papillary thyroid carcinoma. A retrospective study. Horm (Athens) 9:312–318
Cipolla C, Sandonato L, Graceffa G et al (2005) Hashimoto thyroiditis coexistent with papillary carcinoma. Am Surg 71:874–878
Larson SD, Jackson L, Riall T et al (2007) Increased incidence of well-differentiated thyroid cancer associated with Hashimoto’s thyroid- itis and the role of the PI3K/AKT pathway. J Am Coll Surg 204:764–775
Kurukahvecioglu O, Taneri F, Yuksel O, Aydin A, Tezel E, Onuk E (2007) Total thyroidectomy for treatment of Hashimoto’s thyroiditis coexisting with papillary thyroid carcinoma. Adv Ther 24:510–516
Bradly D, Reddy V, Prinz RA, Gattuso P (2009) Incidental papillary carcinoma in patients treated surgically for benign thyroid diseases. Surgery 146:1099–1104
Siriweera EH, Ratnatung NV (2010) Profile of Hashimoto’s thyroiditis in Sri Lankans: is there an increased risk of ancillary pathologies in Hashimoto’s thyroiditis. J Thyroid Res 2010:124264
Ott RA, Calandra DB, McCall A, Shah KH et al (1985) The incidence of thyroid carcinoma in patients with Hashimoto’s thyroiditis and solitary cold nodules. Surgery 98:1202–1206
Nguyen GK, Ginsberg J, Crockford PM, Villanueva RR (1997) Hashimoto’s thyroiditis: cytodiagnostic accuracy and pitfalls. Diagn Cytopathol 16:531–536
Ravinsky E, Safneck JR (1988) Differentiation of Hashimoto’s thyroiditis from thyroid neoplasms in fine needle aspirates. Acta Cytol 32:854–861
Kumarasinghe MP, De Silva S (1999) Pitfalls in cytological diagnosis of autoimmune thyroiditis. Pathology 31:1–7
MacDonald L, Yazdi HM (1999) Fine needle aspiration biopsy of Hashimoto’s thyroiditis. Sources Diagn Acta Cytol 43:400–406
Seifman M, Grodski S, Bailey M, Yeung M, Serpell J (2011) Surgery in the setting of Hashimoto’s thyroiditis. ANZ J Surg 81:519–523
Eisenberg BL, Hensley SD (1989) Thyroid cancer with coexistent Hashimoto’s thyroiditis. Clinical assessment and management. Arch Surg 124:1045–1047
Hall FT, Freeman JL, Asa SL et al (2003) Intra-tumoral lymphatics and lymph node metastasis in papillary thyroid carcinoma. Archives of Otolaryngology—Head and Neck. Surgery 129(7):716–719
Machens A, Hinze R, Thomusch O, Dralle H (2002) Pattern of nodal metastasis for primary and reoperative thyroid cancer. World J Surg 26(1):22–28
Gimm O, Rath FW, Dralle H (1998) Pattern of lymph node metastases in papillary thyroid carcinoma. Br J Surg 85(2):252–254
Noguchi S, Noguchi A, Murakami N (1970) Papillary carcinoma of the thyroid. I. Developing pattern of metastasis. Cancer 26(5):1053–1060
Loh KC et al (1999) Influence of lymphocytic thyroiditis on the prognostic outcome of patients with papillary thyroid carcinoma. J Clin Endocrinol Metab 84(2):458–463
Kim SS (2011) Coexistence of Hashimoto’s thyroiditis with papillary thyroid carcinoma: the influence of lymph node metastasis. Head Neck Vol 33(9):1272–1277
Kim EY et al (2009) Coexistence of chronic lymphocytic thyroiditis is associated with lower recurrence rates in patients with papillary thyroid carcinoma. Clin Endocrinol (Oxford) 71(4):581–586
Thomas CG Jr, Rutledge RG (1981) Surgical intervention in chronic (Hashimoto’s) thyroiditis. Ann Surg 193(6):769–776
Matsubayashi S, Kawai K, Matsumoto Y et al (1995) The correlation between papillary thyroid carcinoma and lymphocytic infiltration in the thyroid gland. J Clin Endocrinol Metab 80(12):3419–3424
Kashima K, Yokoyama S, Noguchi S et al (1998) Chronic thyroiditis as a favorable prognostic factor in papillary thyroid carcinoma. Thyroid 8(3):197–202
Schaffler A, Palitzsch KD, Seiffarth C et al (1998) Coexistent thyroiditis is associated with lower tumour stage in thyroid carcinoma. Eur J Clin Investig 28(10):838–844
Ozaki O, Ito K, Mimura T, Sugino K et al (1996) Papillary carcinoma of the thyroid. Tall-cell variant with extensive lymphocyte infiltration. Am J Surg Pathol 20(6):695–698
Segal K, Ben-Bassat M, Avraham A (1985) Hashimoto’s thyroiditis and carcinoma of the thyroid gland. Int Surg 70(3):205–209
Dongbin A et al (2011) Clinical relationship between Hashimoto’s thyroiditis and papillary thyroid cancer. Acta Oncol 50(8):1228–1234
Huang BY et al (2011) Well-differentiated thyroid carcinoma with concomitant Hashimoto’s thyroiditis present with less aggressive clinical stage and low recurrence. Endocr Pathol 22(3):144–149
Conflicts of interest
The authors declare that there is no conflict of interest.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Anand, A., Singh, K.R., Kushwaha, J.K. et al. Papillary Thyroid Cancer and Hashimoto’s Thyroiditis: An Association Less Understood. Indian J Surg Oncol 5, 199–204 (2014). https://doi.org/10.1007/s13193-014-0325-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13193-014-0325-4