Cystic Medullary Thyroid Carcinoma: A Case of Undergoing Endoscopic Thyroid Lobectomy
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1 CASE REPORT ISSN (Print) ISSN (Online) Korean J Endocr Surg 2015;15: The Korean Journal of Endocrine Surgery Cystic Medullary Thyroid Carcinoma: A Case of Undergoing Endoscopic Thyroid Lobectomy Dong Hae Chung, Jae Yeon Seok, Yoo Seung Chung 1, Eun Mee Oh 1, Jung Won Ryu 1, Young Don Lee 1 Departments of Pathology, 1 Surgery, Gachon University Gil Medical Center, Incheon, Korea On ultrasonography, medullary thyroid carcinoma (MTC) shows hypoechogenicity, an irregular margin, a predominantly solid composition, and microcalcifications, similar to those observed in papillary thyroid carcinoma (PTC). MTC presenting as a cystic lesion is rare, and endoscopic thyroidectomy can be performed for benign thyroid masses and early stage PTC, however it is inappropriate for MTC regardless of cystic change. The authors report a case of cystic MTC found after endoscopic thyroid lobectomy and provide a review of the literature on this topic. Key Words: Medullary thyroid carcinoma, Thyroid cyst, Endoscopic thyroidectomy Received November 19, 2014, Revised December 12, 2014, Accepted December 29, 2014 Correspondence: Yoo Seung Chung Department of Surgery, Gachon University Gil Medical Center, 1198 Guwol-dong, Namdong-gu, Incheon , Korea Tel: Fax: dryooseung@gilhospital.com INTRODUCTION CASE REPORT MTC is a rare disease in Korea and accounts for only 0.4% of thyroid malignancies.(1) MTCs are usually firm, white-grey to tan in color, gritty in consistency, and well circumscribed in macroscopic view. Sporadic tumors are typically unilateral, whereas familial tumors are multiple and bilateral.(2,3) Cystic change presents in about one third of thyroid nodules and around 9 14% of these lesions are malignant tumors.(4-6) According to recent reports, the malignancies detected in cystic masses are mainly PTC and follicular thyroid carcinoma.(6,7) Besides, all were PTCs in markedly cystic cases (cystic portion >50%).(8) Predominantly cystic MTC is rarely encountered, and thus, only a small number have been described.(9-13) Herein, we report a case of MTC, which presented as a large cystic lesion. A 32-year-old Asian female was referred by a primary health clinic. A left cervical mass had been detected more than a month previously and diagnosed as a thyroid cyst by ultrasonography (USG) at the clinic. The patient did not complain of any symptoms like neck pain, dysphagia, hoarseness, cough, or dyspnea, and did not exhibit systemic symptoms, such as, facial flushing, diarrhea, or weight loss, or any marfanoid features. Her blood pressure was 129/81 mmhg and her heart rate was 90 per minute. There were no specific underlying diseases in her past medical history and thyroid disease or malignancy in her familial medical history. On physical examination, left neck swelling was observed and an oval, soft thyroid mass was palpable without fixation at swallowing. No palpable lymphadenopathy was detected in bilateral cervical areas. USG showed an oval hypoechoic cystic lesion of cm in the left thyroid, which caused the Copyright 2015 Korean Association of Thyroid and Endocrine Surgeons; KATES. All Rights Reserved. cc 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.
2 16 Korean J Endocr Surg 2015;15:15-19 journal.kates.or.kr Fig. 1. Transverse (A) and longitudinal (B) ultrasonographic views showing a cm sized hypoechoic predominantly cystic lesion with incomplete septa occupying the entire left thyroid gland. trachea to deviate to the right (Fig. 1). Thyroid function tests, including serum thyroid stimulating hormone and free thyroxine, were within normal limits, and so were serum calcium and phosphorus levels. Serum thyroglobulin and calcitonin were not checked. USG-guided fine needle aspiration cytology (FNAC) was carried out using a 23-gauge needle connected to a 20 ml syringe in a syringe holder. After draining 20 ml of a chocolate-colored sticky fluid, a small amount of intracystic material remained. A cytologic examination and cell block were performed on the fluid. After aspiration, the neck swelling decreased. Some macrophages without an epithelial cell component were observed, and resultantly, the lesion was considered a cystic change lesion of uncertain nature. However, 11 days later the lesion reassumed its previous size. We decided on left endoscopic thyroidectomy because the patient wanted to avoid a scar. A bilateral axillo-breast approach (BABA) endoscopic left thyroidectomy was performed without complication. There was no extrathyroidal extension and lymph node enlargement in central cervical area. Grossly, the excised thyroid mass was oval and smooth (Fig. 2). Frozen biopsy was not checked during operation. The left lobe measured cm and weighed 26.2 gm. In section, the mass was found to be a demarcated, encapsulated cystic mass measuring cm. The cystic space contained bloody fluid and its inner surface Fig. 2. Left thyroid gland was easily separated from strap muscle during endoscopic thyroidectomy using BABA. On palpation, the left thyroid gland was soft and smooth after removal using an endoscopic plastic bag via a right areolar incision. was irregular and hemorrhagic. The solid portion was reddish brown, soft, and focally calcified. Microscopically, the tumor consisted of solid sheets of medium-sized polygonal cells traversed by fine vascular septae. Cystic change with hemorrhage and aggregated hemosiderin-laden macrophages were also noted in solid portion. Tumor cells showed relatively uniform, round nuclei, and eosinophilic granular cytoplasm. Amyloid deposition was only focally noted (Fig. 3A-C). By immunohistochemistry, tumor cells were positive for calcitonin (Fig. 3D), chromogranin, synaptophysin, TTF-1, CEA, CD56, cyclin D1, and P53, but negative for thyroglobulin,
3 Dong Hae Chung, et al: Medullary Thyroid Cancer Presenting as a Mainly Cystic Lesion 17 Fig. 3. Photographs of medullary thyroid carcinoma showing prominent cystic change. (A) Low power view showing a large cystic space in the center and in the solid portion at the periphery of the tumor (H&E, 10). (B) In the solid portion, cystic change with hemorrhage and aggregation of hemosiderin-laden macrophages was noted (H&E, 100). (C) High power view showing solid sheets of uniform tumor cells. Note the prominent vasculature and focal amyloid deposition (arrow) (H&E 400). (D) Tumor cells were positive for calcitonin (immunostain, 400). galectin-3, and HBME-1. Based on these features a performed after operation showed no evidence of an diagnosis of MTC was made. abnormal pathologic lesion. Elevated serum calcitonin (10.2 pg/ml; normal value: 1 4.8) and CEA (67.89 ng/ml, normal value: 0 5) levels DISCUSSION th were found on the 8 postoperative day (POD8, on the basis of the first operation). Serum parathyroid hormone MTCs are usually firm in consistency and may feel gritty on POD2 was 26.1 pg/ml (normal value: 10 65). Open when sectioned owing to the presence of fine granular completion thyroidectomy was performed with central calcification. Amyloid accumulation is present in 70 80% neck lymph node dissection on POD14 without compli- or more cases.(2,3) Follicular cell proliferative lesions have cation. No tumor was noted in the opposite lobe of the a prominent thin vascular network and cystic change in thyroid or in cervical lymph nodes. Serum calcitonin and follicular lesions may result from vascular rupture and CEA decreased to 3.4 pg/ml and ng/ml, respectively, hemorrhage in enlarged follicles. MTC exhibit highly on POD16. vascular tumors, and generally dense fibrovascular stroma PET-CT, abdominal CT, chest CT, and bone scan with amyloid deposition, which appears to preclude
4 18 Korean J Endocr Surg 2015;15:15-19 journal.kates.or.kr vascular rupture and cystic change.(14) In our case, stromal fibrous and amyloid components comprised a minor portion of the tumor, which might have been related to the observed cystic change. Cystic change in MTC is rare, in fact, only 6 cases such cases have been reported in the English literature.(9-13) Table 1 provides a summary of these cases, which including our case, include five female and two male patients. Patients ages varied widely and no patient had multiple endocrine neoplasia (MEN). Average tumor size was 3.92 cm and lymph node metastasis was absent in all cases. Preoperative FNAC did not reveal the presence of malignancy in 4 of 6 cases (66.7%), and a second operation, including cervical lymph node dissection, was performed in 3 of 7 cases (42.8%). Two patients were diagnosed as MTC preoperatively. In the case of patient no. 4, preoperative serum calcitonin was elevated and MTC was diagnosed by immunocytochemical staining for calcitonin. Patient no. 6 underwent second FNAC because first FNAC resulted in inadequate cytological findings and no serum calcitonin result. The sonographic features of MTC have not been adequately described. The sonographic characteristics of malignant nodules are as follows: the presence of microcalcifications, marked hypoechogenicity, microlobulated or an irregular or spiculated margin, a taller-than-wide shape, absence of a halo, predominantly solid composition, and intranodular vascularity. Sonographic features predictive of MTC are known to be similar to those of PTC, except that the presence of focal cystic change and homogeneous echotexture is more frequent in MTC.(15,16) BABA endoscopic thyroidectomy can be carried out in patients with a benign thyroid mass or early stage thyroid carcinoma.(17,18) The largest benign tumor operated on by BABA endoscopic thyroidectomy was 7 cm by preoperative USG.(18) Accordingly, the 5.26 cm sized cystic thyroid mass in our patient was deemed suitable for BABA endoscopic thyroidectomy. Completion thyroidectomy via the BABA method can be performed after BABA thyroidectomy.(19) Nevertheless, we decided to re-operate using the conventional open method to ensure complete lymph node dissection after serious discussion with the patient. We did not determine whether the presented case was familial or sporadic MTC, but our patient had no familial history of MTC or exhibit any systemic symptoms. Furthermore, physical examination, blood tests, and imaging work up provided no evidence of familial disease. Although we recommended genetic counseling, the patient left Korea for planned study abroad on recovery from completion thyroidectomy. In our case, it was regrettable that MTC was not diagnosed preoperatively. We did not perform a serum calcitonin test preoperatively. Preoperative serum calcitonin test is helpful for diagnosis of MTC. However, the routine measurement of serum calcitonin during thyroid nodule work-up is not recommended obligatorily in Korea because of its lack of sensitivity and specificity and cost.(13,20) As the thyroid mass was mainly cystic, we did not suspect the presence of malignancy. FNAC revealed the presence of only macrophages and degenerated blood component were detected, which are common findings for benign cystic nodules. On reflection, a second FNAC should Table 1. Clinicopathologic features of medullary thyroid carcinoma with prominent cystic change No. Author Year Age/Sex MEN Size (cm) Aspiration cytology Operation LNM 1 Simcic(9) /F NA 6.0 No malignancy ST CT w LND No 2 Simcic(9) /M NA 1.5 Non diagnostic TT w LND No 3 Liberatore(10) /F No 2.5 Not done L CT w LND No 4 Fadda(11) /F No 3.5 MTC TT w LND No 5 Ozkara(12) /F No 6.0 Nodular colloidal goiter NT NA 6 Kim(13) /M NA 3.0 Suspicious for MTC TT w LND No 7 Present case /F No 5.0 Cystic change lesion L CT w LND No F = female; M = male; MEN = multiple endocrine neoplasia; NA = not available; MTC = medullary thyroid carcinoma; ST = subtotal thyroidectomy; CT = complete thyroidectomy; w = with; LND = lymph node dissection; TT = total thyroidectomy; L = lobectomy; NT = near total thyroidectomy; LNM = lymph node metastasis.
5 Dong Hae Chung, et al: Medullary Thyroid Cancer Presenting as a Mainly Cystic Lesion 19 have been performed after aspiration of cystic fluid. Had the preoperative diagnosis indicated MTC, conventional open total thyroidectomy would have been performed rather than endoscopic thyroidectomy. Furthermore, if we had checked frozen biopsy intraoperatively, operation could have been performed at a time. In conclusion, we describe a case of MTC presenting as a mainly cystic lesion. Although cystic MTC is rare, we urge that the possibility be considered. REFERENCES 1. The Korea Central Cancer Registry, Ministry of Health and Welfare. National Cancer Registration and Statistics in Korea DeLellis RA, Lloyd RV, Heitz PU, Eng C. WHO Classification of Tumors, Pathology and genetics of tumors of endocrine organs. Lyon, France: IARCpress; Nikiforov YE, Biddinger PW, Thompson LD. Diagnostic pathology and molecular genetics of the thyroid. 2nd ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; Cusick EL, McIntosh CA, Krukowski ZH, Matheson NA. Cystic change and neoplasia in isolated thyroid swellings. Br J Surg 1988;75: Hiromura T. Ultrasonography of cystic thyroid nodules: sonographic-pathologic correlation. Nihon Igaku Hoshasen Gakkai Zasshi 1994;54: Lin JD, Hsuen C, Chen JY, Liou MJ, Chao TC. Cystic change in thyroid cancer. ANZ J Surg 2007;77: Lee MJ, Kim EK, Kwak JY, Kim MJ. Partially cystic thyroid nodules on ultrasound: probability of malignancy and sonographic differentiation. Thyroid 2009;19: Henrichsen TL, Reading CC, Charboneau JW, Donovan DJ, Sebo TJ, Hay ID. Cystic change in thyroid carcinoma: Prevalence and estimated volume in 360 carcinomas. J Clin Ultrasound 2010;38: Simcic KJ, Bowland WF. Cystic medullary thyroid cancer. Surgery 1995;117: Liberatore E, Emmolo I. Cystic medullary thyroid cancer. Surgery 1996;120: Fadda G, Muie A, Rufini V, Ardito G, Revelli L, Fiorino MC, et al. Cystic medullary thyroid carcinoma: report of a case with morphological and clinical correlations. Endocr Pathol 2000;11: Ozkara SK, Gürbüz Y, Müezzinoğlu B, Yumbal Z. Encapsulated cystic papillary variant of medullary carcinoma of thyroid gland. Endocr Pathol 2002;13: Kim JY, Choi JJ, Kim AH, Moon HJ, Kim EK, Kwak JY, et al. medullary thyroid carcinoma presenting as a predominantly cystic mass on ultrasonography: a case report. J Korean Soc Ultrasound Med 2012;31: Rosai J, Carcangiu ML, DeLellis RA. Tumors of thyroid gland. Atlas of tumors pathology 3rd Series, Fascicle 5. Washington, DC: Armed Forces Institute of Pathology; Kim SH, Kim BS, Jung SL, Lee JW, Yang PS, Kang BJ, et al. Ultrasonographic findings of medullary thyroid carcinoma: a comparison with papillary thyroid carcinoma. Korean J Radiol 2009;10: Lee S, Shin JH, Han BK, Ko EY. Medullary thyroid carcinoma: comparison with papillary thyroid carcinoma and application of current sonographic criteria. AJR Am J Roentgenol 2010;194: Chung YS, Choe JH, Kang KH, Kim SW, Chung KW, Park KS, et al. Endoscopic thyroidectomy for thyroid malignancies: comparison with conventional open thyroidectomy. World J Surg 2007;31: Choi JY, Lee KE, Chung KW, Kim SW, Choe JH, Koo do H, et al. Endoscopic thyroidectomy via bilateral axillo-breast approach (BABA): review of 512 cases in a single institute. Surg Endosc 2012;26: Kim SJ, Lee KE, Choe JH, Lee J, Koo do H, Oh SK, et al. Endoscopic completion thyroidectomy by the bilateral axillo-breast approach. Surg Laparosc Endosc Percutan Tech 2010;20: Yi KH, Park YJ, Koong SS, Kim JH, Na DG, Ryu JS, et al. Revised Korean thyroid association management guidelines for patients with thyroid nodules and thyroid cancer. J Korean Thyroid Assoc 2010;3:65-96.
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