Subacute Thyroiditis with Coexisting Papillary Carcinoma
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1 C A S E REPORT J Korean Thyroid Assoc Vol. 4, No. 1, May 2011 Subacute Thyroiditis with Coexisting Papillary Carcinoma Pil-Soo Sung, MD 1, Min-Hee Kim, MD 1, Dong-Jun Lim, MD 1, Yoon-Hee Choi, MD 1, Moo-Il Kang, MD 1, Bong-Yun Cha, MD 1 and Ja-Seong Bae, MD 2 Division of Endocrinology and Metabolism, Departments of Internal Medicine 1 ; Surgery 2, The Catholic University of Korea College of Medicine, Seoul, Korea Subacute thyroiditis with coexisting papillary carcinoma is very rare. Here, we report a case of 36-year-old Korean female with both thyroid diseases. She presented with acute onset of anterior neck pain and swelling for 2 weeks. Physical examination, laboratory and image findings suggested subacute thyroiditis. Ultrasonographic examination found a 0.8 cm-sized marked hypoechoic nodule surrounded by multiple irregular hypoechoic lesions and central lymph node metastasis was suspected. Subsequent fine needle aspiration cytology for this nodule showed papillary carcinoma. Two months of oral prednisolone therapy relieved clinical symptoms and normalized her thyroid function. Total thyroidectomy was performed along with central neck dissection and the nodule was confirmed to be papillary carcinoma with one metastatic lymph node among ten dissected nodes, otherwise unremarkable. The other portion of the thyroid showed the typical pathologic features of subacute thyroiditis. Thyroid ultrasonography as an ancillary diagnostic tool in subacute thyroiditis may have clinical implications of finding out hidden malignancy, although the association between two diseases is unclear. Key Words: Subacute thyroiditis, Papillary carcinoma, Thyroid nodule Introduction Subacute thyroiditis, which is a self-limited inflammatory disease of thyroid gland, is characterized by neck pain, a tender diffuse goiter, and a predictable course of thyroid function. It is presumed to be caused by a viral infection or a post-viral inflammatory process. The majority of patients have a history of upper respiratory infection. 1-3) During the evaluation of nodular goiter including subacute thyroiditis by ultrasonography, many other thyroid diseases could be found incidentally. Frequency of detecting thyroid cancer in an incidentally found nodule has been increased globally due to widespread use of sensitive diagnostic tools such as ultrasonography. The association between thyroid cancer and thyroiditis, especially subacute thyroiditis is not a finding frequently encountered, and to our knowledge, there were only two case reports to date. 4,5) Both subacute thyroiditis and thyroid cancer occur most frequently in middleaged women, and there is no report that compared the incidence of papillary carcinoma between patients of subacute thyroiditis and general population yet. We herein report a 36-year-old Korean female presented at our endocrinology clinic with painful anterior neck swelling for 2 weeks. She was diagnosed as having subacute thyroiditis, but by ultrasonographic examination, we found a malignant nodule. Received October 11, 2010 / Accepted January 18, 2011 Correspondence: Dong-Jun Lim, MD. Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary s Hospital, The Catholic University of Korea College of Medicine, 505 Banpo-dong, Seocho-gu, Seoul , Korea Tel: , Fax: , ldj6026@catholic.ac.kr 58
2 Subacute Thyroiditis with Papillary Carcinoma Case Report A 36-year-old woman without previous medical history presented with acute onset of anterior neck pain and swelling for 2 weeks. She had no specific symptoms of thyrotoxicosis. Physical examination revealed diffuse enlargement and tenderness of thyroid gland, and there were no palpable cervical lymph nodes. In laboratory investigation, free thyroxine (ft4) was 2.31 ng/dl (normal range: ng/dl), thyroid-stimulating hormone (TSH) was 0.03 miu/l (normal range: miu/l), and erythrocyte Fig. 1. Tc-99m thyroid scan shows marked impaired pertechnetate uptake in both lobes of thyroid. sedimentation rate (ESR) was 93 mm/h (normal range: 0 20 mm/h). Antithyroglobulin and antimicrosomal antibodies were both negative, and TSH receptor stimulating immunoglobulin was not detected. Impaired pertechnetate uptake in both lobes of the thyroid was noted on a Tc-99m thyroid scan (Fig. 1), which suggested thyroiditis. We started oral prednisolone 30 mg per day and beta blocker and then most of clinical symptoms including anterior neck pain improved within several days. However, as mild neck discomfort persisted, thyroid ultrasonography was performed to exclude coexisting other diseases. Thyroid ultrasonography (Fig. 2) showed ill-defined, hypoechoic areas at mid portion of both lobes, which were findings compatible with thyroiditis. Additionally, a well-defined, 0.8x0.6 cm sized heterogenous marked hypoechoic nodule was noted in left upper thyroid gland and several central lymph nodes were also observed. A fine needle aspiration of the nodule was done, and the cytologic diagnosis was papillary carcinoma. After two months of steroid therapy, the patient s ft4 level dropped to 1.24 ng/dl and tenderness of thyroid gland improved, and the time was thought to be as an appropriate time for operation. We decided to perform total thyroidectomy and cervical lymph node dissection. Total thyroidectomy was performed because the malignant nodule was thought to be 1.2 cm-sized by surgeon during operation and central lymph node metastasis was suspicious by ultrasonography. At operation, both Fig. 2. Transverse (A) and longitudinal (B) thyroid ultrasonographic images (A) show a well defined, 7x8x9 mm sized heterogenous hypoechoic nodule (thin arrow) in left upper thyroid gland. Longitudinal image (B) shows multiple ill-defined, hypoechoic areas (thick arrows) were noted around the nodule, findings compatible with thyroiditis. 59 J Korean Thyroid Assoc
3 Pil-Soo Sung, et al lobes of the thyroid were firm in consistency, and adjuvant radioactive iodine, and subsequent whole severe perithyroid adhesion was noted as a result of body I-131 scintigraphy after one year revealed no the thyroiditis. Left lobe of thyroid gland was excised iodine and the nodule in upper portion of the left lobe was recurrence confirmed as papillary carcinoma by frozen section. A remained undetectable for one year after operation. uptake. and She her has been serum free of clinical thyroglobulin level 0.8 cm-sized hard whitish nodule was confirmed to be papillary carcinoma without calcification and Discussion necrosis. Lymphatic invasion, vascular invasion, and perineural invasion were absent (Fig. 3A, B). However, Subacute thyroiditis is one of the inflammatory thy- metastatic papillary carcinoma was detected in one of roid diseases that present acute neck pain, low grade ten dissected cervical lymph nodes. The other portion fever, and occasional dysphagia. Symptoms and signs of the thyroid showed diffuse granulomatous inflam- of hyperthyroidism may or may not be present, but a mation with the destruction of follicular epithelial cells painful thyroid swelling following an upper respiratory and colonization of multinucleated giant cells (Fig. 3C, tract infection is possibly a typical sign of subacute D), in consistent with the features of subacute thyroiditis.1,2) To make the diagnosis of subacute thyroiditis. The patient was administered 100 mci of thyroiditis, the basic clinical and laboratory data are Fig. 3. Histopathological findings of the thyroid. A (H&E stain, 40) and B (H&E stain, 200) show papillary carcinoma. Papillary carcinoma is associated with interstitial fibrosis that results from desmoplastic change by carcinoma. C (H&E stain, 40) and D (H&E stain, 400) show granulomatous inflammation and interstitial fibrosis with multinucleated giant cells, which suggest subacute thyroiditis. Vol. 4, No. 1,
4 Subacute Thyroiditis with Papillary Carcinoma needed, and biopsy is rarely required. Imaging studies help diagnose subacute thyroiditis. The 24-hour iodine uptake is low or pertechnetate uptake is impaired in the toxic phase of subacute thyroiditis, distinguishing this disease from Graves disease. 3,6) The diagnosis can be assisted by use of ultrasonography. Typical ultrasonographic features include focal ill-defined hypoechoic areas in one lobe or diffuse hypoechoic areas in both lobes. 7,8) However, diffuse hypoechogenicity by ultrasonography is found in Graves disease or Hashimoto thyroiditis, while both benign nodules and thyroid carcinomas can also exhibit focal hypoechoic areas. 9) In patients with subacute thyroiditis, color-flow doppler ultrasonography can also be used with clinical significance, which shows that the gland has low-to-normal vascularity. 10) The coexistence of subacute thyroiditis and papillary carcinoma is generally regarded as coincidental. However, some reports indicated causal association of both diseases. There was a retrospective observational study that investigated serum selenium level and thyroid disease. 11) In this study, low serum selenium levels were found in subacute and silent thyroiditis and also in papillary and follicular carcinoma. Accordingly, they suggested that low serum selenium level might be the simultaneously associated with subacute thyroiditis and thyroid malignancy. One previous report proposed the possibility of subacute thyroiditis being induced by tissue necrosis and growth factors produced by the carcinoma. 4,5) Until now, there is no report that compared the incidence of papillary carcinoma between the patients of subacute thyroiditis and the general population. To evaluate the possibility of causal linkage between subacute thyroiditis and thyroid carcinoma, this comparative study should be preceded. When a patient is diagnosed as subacute thyroiditis, thyroid ultrasonography was reported to be useful for evaluation of the degree of inflammation. 12) In one previous report, the hypoechoic area measured by ultrasonography was well correlated with neck pain, ft4 levels, and thyroglobulin levels in patients with subacute thyroiditis. 12) In another aspect, both the subacute thyroditis and papillary carcinoma occur most frequently in middle-aged women. According to a report in Korea, thyroid ultrasonography performed in 61 patients diagnosed as subacute thyroiditis showed ill-defined hypoechoic areas in one lobe or diffuse hypoechoic areas in both lobes. 22 patients (36.0%) among 61 study patients had coexisting thyroid nodule. 13) As mentioned earlier, there were two other case reports describing subacute thyroiditis with coexisting papillary carcinoma. In the cases, thyroid ultrasonography was done by the clinician s preference as an ancillary diagnostic tool, leading to finding out malignancy incidentally. 4,5) In both cases, total thyroidectomy was done due to suspicious metastatic lymph nodes on ultrasonography. Therefore, for patients with subacute thyroiditis, ultrasonography could detect coexisting malignancy incidentally, without regard to the association with increased frequency of thyroid malignancy in subacute thyroditis. It can be suggested that thyroid ultrasonography may be useful as an ancillary diagnostic tool, especially when thyroid nodule and/or cervical lymph nodes are palpable, or the patient has a family history of thyroid malignancy, or the patient has undergone neck irradiation before. However, the prognostic significance of incidentally detected malignant nodule in subacute thyroiditis remains unclear, although presumed not to be affected by the existence of subacute thyroiditis. In summary, we report a rare case of subacute thyroiditis with coexisting papillary carcinoma. When subacute thyroiditis is suspected clinically and by laboratory findings, thyroid ultrasonography may help identify hidden thyroid malignancy, although clinical association might be unclear. References 1) Pearce EN, Farwell AP, Braverman LE. Thyroiditis. N Engl J Med 2003;348(26): ) Fatourechi V, Aniszewski JP, Fatourechi GZ, Atkinson EJ, Jacobsen SJ. Clinical features and outcome of subacute thyroiditis in an incidence cohort: Olmsted county, Minnesota, study. J Clin Endocrinol Metab 2003;88(5): ) Benbassat CA, Olchovsky D, Tsvetov G, Shimon I. Subacute thyroiditis: Clinical characteristics and treatment outcome in fifty-six consecutive patients diagnosed between 1999 and J Korean Thyroid Assoc
5 Pil-Soo Sung, et al J Endocrinol Invest 2007;30(8): ) Lam KY, Lo CY. Papillary carcinoma with subacute thyroiditis. Endocr Pathol 2002;13(3): ) Nishihara E, Hirokawa M, Ohye H, Ito M, Kubota S, Fukata S, et al. Papillary carcinoma obscured by complication with subacute thyroiditis: Sequential ultrasonographic and histopathological findings in five cases. Thyroid 2008;18(11): ) Nishihara E, Ohye H, Amino N, Takata K, Arishima T, Kudo T, et al. Clinical characteristics of 852 patients with subacute thyroiditis before treatment. Intern Med 2008;47(8): ) Park SY, Kim EK, Kim MJ, Kim BM, Oh KK, Hong SW, et al. Ultrasonographic characteristics of subacute granulomatous thyroiditis. Korean J Radiol 2006;7(4): ) Lee SK, Kwon SY. Temporary nonvisualization of biopsyproven papillary thyroid carcinoma. J Ultrasound Med 2009; 28(4): ) Bennedbaek FN, Hegedüs L. The value of ultrasonography in the diagnosis and follow-up of subacute thyroiditis. Thyroid 1997;7(1): ) Hiromatsu Y, Ishibashi M, Miyake I, Soyejima E, Yamashita K, Koike N, et al. Color Doppler ultrasonography in patients with subacute thyroiditis. Thyroid 1999;9(12): ) Moncayo R, Kroiss A, Oberwinkler M, Karakolcu F, Starzinger M, Kapelari K, et al. The role of selenium, vitamin C, and zinc in benign thyroid diseases and of selenium in malignant thyroid diseases: Low selenium levels are found in subacute and silent thyroiditis and in papillary and follicular carcinoma. BMC Endocr Disord 2008;8:2. 12) Omori N, Omori K, Takano K. Association of the ultrasonographic findings of subacute thyroiditis with thyroid pain and laboratory findings. Endocr J 2008;55(3): ) Kim JY, Lee SJ, Jung ED, Lee JH, Shon HS. Diagnostic efficacy of thyroid ultrasonography in subacute thyroiditis. Endocrinol Metab 2010:25(Suppl 3):510. Vol. 4, No. 1,
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