Journal List > J Korean Thyroid Assoc > v.7(1) > 1056568

J Korean Thyroid Assoc. 2014 May;7(1):57-61. Korean.
Published online May 30, 2014.
Copyright © 2014. the Korean Thyroid Association. All rights reserved.
Hashimoto's Thyroiditis and Papillary Thyroid Cancer
Kee-Hyun Nam
Department of Surgery, Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea.

Correspondence: Kee-Hyun Nam, MD, PhD, Department of Surgery, Institute of Endocrine Research, Yonsei University College of Medicine, 134, Sinchon-dong, Seodaemun-gu, Seoul 120-752, Korea. Tel: 82-2-2228-2100, Fax: 82-2-313-8289, Email:
Received October 08, 2013; Revised November 07, 2013; Accepted November 07, 2013.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


The association of Hashimoto's thyroiditis (HT) with papillary thyroid cancer (PTC) has been still under debate. Some suggest that these two are positively correlated, whereas other studies report no relationship. We performed a systematic literature review of original studies to investigate the correlation between HT and PTC. The existing data provide inconsistent evidence favoring a causal relationship between HT and PTC. The average prevalence rate of PTC in patients with HT was 1.2% in 8 fine needle aspiration (FNA) studies of 18,023 specimens and 27.6% in 8 archival thyroidectomy studies of 9884 specimens. The risk ratio of PTC in HT specimens ranged from 0.39 to 1.00 in the FNA group (average RR 0.69) in contrast to 1.15 to 4.16 from thyroidectomy studies (average RR 1.59). Population-based fine needle aspiration biopsy studies report no relationship, whereas many of the studies using thyroidectomy specimens report a positive relationship, possibly related to selection bias. Several studies identified a few biomolecular markers, including the PI3K/Akt pathway, RET/PTC gene rearrangements, p63 protein, and loss of heterozygosity of hOGG1, that are potentially involved in neoplastic transformation from HT to PTC. So far, no causal genetic linkage has been confirmed. PTC with concurrent HT is associated with female gender, young age, less aggressive disease such as small tumor size, less frequent capsular invasion and nodal metastasis, and better outcome. However, more prospective studies with long term follow-up are needed to further elucidate this relationship and prognosis. Careful observation and follow-up of HT patients is recommended, especially those with nodular variants.

Keywords: Hashimoto's thyroiditis; Papillary thyroid cancer; Prevalence; Risk ratio; Prognosis


Fig. 1
Papillary thyroid carcinoma arising in the background of Hashimoto's thyroiditis. Lymphocytic infiltration with germinal center (thin arrow) and papillary carcinoma (thick arrow) are noted (H&E stain, ×40).
Click for larger image


Table 1
Prevalence of papillary thyroid cancer in patients with Hashimoto's thyroiditis according to FNA and thyroidectomy studies
Click for larger image

Table 2
Risk ratio of papillary thyroid cancer in patients with Hashimoto's thyroiditis according to FNA and thyroidectomy studies
Click for larger image

1. Mazokopakis EE, Tzortzinis AA, Dalieraki-Ott EI, Tsartsalis AN, Syros PK, Karefilakis CM, et al. Coexistence of Hashimoto's thyroiditis with papillary thyroid carcinoma. A retrospective study. Hormones (Athens) 2010;9(4):312–317.
2. Cipolla C, Sandonato L, Graceffa G, Fricano S, Torcivia A, Vieni S, et al. Hashimoto thyroiditis coexistent with papillary thyroid carcinoma. Am Surg 2005;71(10):874–878.
3. Anderson L, Middleton WD, Teefey SA, Reading CC, Langer JE, Desser T, et al. Hashimoto thyroiditis: Part 2, sonographic analysis of benign and malignant nodules in patients with diffuse Hashimoto thyroiditis. AJR Am J Roentgenol 2010;195(1):216–222.
4. Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA 2006;295(18):2164–2167.
5. Hanafusa T, Pujol-Borrell R, Chiovato L, Russell RC, Doniach D, Bottazzo GF. Aberrant expression of HLA-DR antigen on thyrocytes in Graves' disease: relevance for autoimmunity. Lancet 1983;2(8359):1111–1115.
6. Todd I, Pujol-Borrell R, Hammond LJ, Bottazzo GF, Feldmann M. Interferon-gamma induces HLA-DR expression by thyroid epithelium. Clin Exp Immunol 1985;61(2):265–273.
7. Dayan CM, Daniels GH. Chronic autoimmune thyroiditis. N Engl J Med 1996;335(2):99–107.
8. Salmaso C, Bagnasco M, Pesce G, Montagna P, Brizzolara R, Altrinetti V, et al. Regulation of apoptosis in endocrine autoimmunity: insights from Hashimoto's thyroiditis and Graves' disease. Ann N Y Acad Sci 2002;966:496–501.
9. Spencer CA. Clinical review: Clinical utility of thyroglobulin antibody (TgAb) measurements for patients with differentiated thyroid cancers (DTC). J Clin Endocrinol Metab 2011;96(12):3615–3627.
10. Shih ML, Lee JA, Hsieh CB, Yu JC, Liu HD, Kebebew E, et al. Thyroidectomy for Hashimoto's thyroiditis: complications and associated cancers. Thyroid 2008;18(7):729–734.
11. Dailey ME, Lindsay S, Skahen R. Relation of thyroid neoplasms to Hashimoto disease of the thyroid gland. AMA Arch Surg 1955;70(2):291–297.
12. Crile G Jr, Hazard JB. Incidence of cancer in struma lymphomatosa. Surg Gynecol Obstet 1962;115:101–103.
13. Crile G Jr. Struma lymphomatosa and carcinoma of the thyroid. Surg Gynecol Obstet 1978;147(3):350–352.
14. Holm LE, Blomgren H, Lowhagen T. Cancer risks in patients with chronic lymphocytic thyroiditis. N Engl J Med 1985;312(10):601–604.
15. Carson HJ, Castelli MJ, Gattuso P. Incidence of neoplasia in Hashimoto's thyroiditis: a fine-needle aspiration study. Diagn Cytopathol 1996;14(1):38–42.
16. Erdogan M, Erdem N, Cetinkalp S, Ozgen AG, Saygili F, Yilmaz C, et al. Demographic, clinical, laboratory, ultrasonographic, and cytological features of patients with Hashimoto's thyroiditis: results of a university hospital of 769 patients in Turkey. Endocrine 2009;36(3):486–490.
17. Matesa-Anic D, Matesa N, Dabelic N, Kusic Z. Coexistence of papillary carcinoma and Hashimoto's thyroiditis. Acta Clin Croat 2009;48(1):9–12.
18. Anil C, Goksel S, Gursoy A. Hashimoto's thyroiditis is not associated with increased risk of thyroid cancer in patients with thyroid nodules: a single-center prospective study. Thyroid 2010;20(6):601–606.
19. Mukasa K, Noh JY, Kunii Y, Matsumoto M, Sato S, Yasuda S, et al. Prevalence of malignant tumors and adenomatous lesions detected by ultrasonographic screening in patients with autoimmune thyroid diseases. Thyroid 2011;21(1):37–41.
20. 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(6):1202–1206.
21. Repplinger D, Bargren A, Zhang YW, Adler JT, Haymart M, Chen H. Is Hashimoto's thyroiditis a risk factor for papillary thyroid cancer? J Surg Res 2008;150(1):49–52.
22. Larson SD, Jackson LN, Riall TS, Uchida T, Thomas RP, Qiu S, et al. Increased incidence of well-differentiated thyroid cancer associated with Hashimoto thyroiditis and the role of the PI3k/Akt pathway. J Am Coll Surg 2007;204(5):764–773.
discussion 73-5.
23. Kurukahvecioglu O, Taneri F, Yuksel O, Aydin A, Tezel E, Onuk E. Total thyroidectomy for the treatment of Hashimoto's thyroiditis coexisting with papillary thyroid carcinoma. Adv Ther 2007;24(3):510–516.
24. Bradly DP, Reddy V, Prinz RA, Gattuso P. Incidental papillary carcinoma in patients treated surgically for benign thyroid diseases. Surgery 2009;146(6):1099–1104.
25. Siriweera EH, Ratnatunga NV. Profile of Hashimoto's thyroiditis in Sri Lankans: is there an increased risk of ancillary pathologies in Hashimoto's thyroiditis? J Thyroid Res 2010;2010:124264.
26. 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(6):1070–1076.
discussion 6-7.
27. Tamimi DM. The association between chronic lymphocytic thyroiditis and thyroid tumors. Int J Surg Pathol 2002;10(2):141–146.
28. McLeod DS, Watters KF, Carpenter AD, Ladenson PW, Cooper DS, Ding EL. Thyrotropin and thyroid cancer diagnosis: a systematic review and dose-response meta-analysis. J Clin Endocrinol Metab 2012;97(8):2682–2692.
29. Mechler C, Bounacer A, Suarez H, Saint Frison M, Magois C, Aillet G, et al. Papillary thyroid carcinoma: 6 cases from 2 families with associated lymphocytic thyroiditis harbouring RET/PTC rearrangements. Br J Cancer 2001;85(12):1831–1837.
30. Unger P, Ewart M, Wang BY, Gan L, Kohtz DS, Burstein DE. Expression of p63 in papillary thyroid carcinoma and in Hashimoto's thyroiditis: a pathobiologic link? Hum Pathol 2003;34(8):764–769.
31. Royer MC, Zhang H, Fan CY, Kokoska MS. Genetic alterations in papillary thyroid carcinoma and hashimoto thyroiditis: An analysis of hOGG1 loss of heterozygosity. Arch Otolaryngol Head Neck Surg 2010;136(3):240–242.
32. Kebebew E, Treseler PA, Ituarte PH, Clark OH. Coexisting chronic lymphocytic thyroiditis and papillary thyroid cancer revisited. World J Surg 2001;25(5):632–637.
33. Lun Y, Wu X, Xia Q, Han Y, Zhang X, Liu Z, et al. Hashimoto's thyroiditis as a risk factor of papillary thyroid cancer may improve cancer prognosis. Otolaryngol Head Neck Surg 2013;148(3):396–402.
34. Muzza M, Degl'Innocenti D, Colombo C, Perrino M, Ravasi E, Rossi S, et al. The tight relationship between papillary thyroid cancer, autoimmunity and inflammation: clinical and molecular studies. Clin Endocrinol (Oxf) 2010;72(5):702–708.
35. Jeong JS, Kim HK, Lee CR, Park S, Park JH, Kang SW, et al. Coexistence of chronic lymphocytic thyroiditis with papillary thyroid carcinoma: clinical manifestation and prognostic outcome. J Korean Med Sci 2012;27(8):883–889.
36. Dvorkin S, Robenshtok E, Hirsch D, Strenov Y, Shimon I, Benbassat CA. Differentiated thyroid cancer is associated with less aggressive disease and better outcome in patients with coexisting Hashimotos thyroiditis. J Clin Endocrinol Metab 2013;98(6):2409–2414.