CASE ISSN: 2005-162X Clin Exp Thyroidol 2014 November 7(2): 194-200 REPORT http://dx.doi.org/10.11106/cet.2014.7.2.194 Axillary Node of Papillary Thyroid Carcinoma: A Case Report

Eun Jung Koo1 and Mi Ri Lee2 Department of Surgery, Hallym Sacred Heart Hospital, Seoul1, Department of Surgery, Dong-A University Medical Center, Busan2, Korea

We report a case of axillary metastasis (LNM) as a recurrence of papillary thyroid carcinoma (PTC) in a 68-year-old male. The patient initially presented in 2009 with a 3.4×5.4 cm sized neck swelling and left cervical . He underwent total thyroidectomy and central compartment neck dissection (CCND) with left modified radical neck dissection (MRND). The pathological report confirmed PTC with metastasis of neck lymph node. On a regular follow up of positron emission tomography (PET), LNM was found on the right supraclavicular area and on the left axillary area. It was 17 months after the initial thyroid cancer had been diagnosed. The right MRND and left axillary lymph node dissections were performed in April of 2012. Pathological result confirmed metastatic PTC of left axillary lymph nodes. After recovery from the surgery, the patient got radioactive iodine therapy with I-131 180 mCi.

Key Words: Axillary lymph nodes metastasis, Papillary thyroid carcinoma

Thyroid function tests results including TSH (0.6 μ Introduction IU/mL; reference range, 0.3-4.1 μIU/mL), free T4 (1.44 ng/dL; reference range, 0.78-1.94 ng/dL), Papillary thyroid carcinoma (PTC) is the most common T3-RIA (117.3 ng/dL; reference range, 60-190 ng/dL) thyroid malignancy and an indolent neoplasm with an were normal. But, thyroglobulin antigen (Tg-Ag) was excellent prognosis, despite its characteristically being high (＞500 ng/mL; reference range, 5-45 ng/mL), associated with lymph node metastasis (LNM). Cervical the level of thyroglobulin antibody (Tg-Ab) (28.74 LNM is common, but axillary LNM is rare and very few IU/mL; reference range, 0-70 IU/mL) was normal. The cases have been reported. We report a case of axil- tumor marker CA 19-9 was highly elevated at 459.22 lary LNM from PTC. (normal, 0-37 U/mL), but there was no evidence of another cancer (e.g. colon cancer or pancreatic can- Case Report cer) on computed tomography (CT) and abdominal ultrasonographic finding. Colonoscopy was A 68-year-old male patient visited the Family not performed. The initial neck CT showed 3.4×5.4 Medicine Clinic with a complaint of palpable mass on cm sized mass with heterogeneous enhancement his left neck in 2009. He was transferred to the Depa- over the left lower neck and left supraclavicular area rtment of Otorhinolaryngology for further evaluation. (Fig. 1). Differential diagnosis on CT was metastatic

Received April 20, 2014 / Revised May 19, 2014 / Accepted June 3, 2014 Correspondence: Mi Ri Lee, MD, PhD, Department of Surgery, Dong-A University Medical Center, Daeshin Park road 26, Seo-gu, Busan 602-715, Korea Tel: 82-51-240-2979, Fax: 82-51-247-9316, E-mail: [email protected] This work was supported by the Dong-A University research fund.

Copyright ⓒ 2014, the Korean Thyroid Association. All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http:// creative- commons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

194 Axillary Lymph Node Metastasis of Papillary Thyroid Carcinoma: A Case Report lymphadenopathy or neurogenic tumor such as sch- des on the left lower neck and left supraclavicular wannoma or paraganglioma. Fine needle aspiration area confirmed the metastasis of PTC. Small calcifica- (FNA) of neck mass presented a few atypical epithelial tion was seen on the precontrast scan. I-123 5 milli- cell nests in acute inflammatory exudate. To rule out curie (mCi) whole body scan presented normal func- malignancy, incisional biopsy of lymph nodes was tioning thyroid tissue in both thyroid glands and cold carried out. Pathological examination of the lymph no- nodule in the left lobe (Fig. 2). The result of FNA of thyroid was suspicious for malignancy, especially of PTC. Therefore, the patient received a total thyroi- dectomy with central compartment neck dissection (CCND) and left modified radical neck dissection (MRND). Pathological test resulted in the diagnosis of PTC with follicular variant of ossification and metastasis of level III, IV, and V neck lymph node, of central com- partment lymph node, and of external jugular area lymph node. The size of the tumor was 1.5×1.2 cm, but it invaded to perithyroidal soft tissue. So the stage was T3N1bM0. After the surgery, the level of Tg-Ag was 4.26 ng/mL and that of Tg-Ab was 27.44 IU/mL (Table 1). The patient received radioactive iodine ther- apy with I-131 150 mCi. The 150 mCi therapeutic whole body scan at 48 hour, reveals two intense ac-

Fig. 1. Neck CT showing large mass in left lower neck carotid cumulation of the I-131 in the mid thyroid bed and space, metastatic lymphadenopathy and left thyroid nodule. remnant pyramidal lobe, with a focal much less I-131

Fig. 2. I-123 5 mCi whole body scan showing normal functioning thyroid tissue in both thyroid gland and cold nodule in left thyroid lobe.

195 Clin Exp Thyroidol Eun Jung Koo and Mi Ri Lee uptake in the left upper thyroid bed or neck lymph months after a radioiodine ablation therapy. There was node (Fig. 3). Diagnostic I-131 scan performed 6 no longer iodine uptake in the thyroid bed (Fig. 4). Seventeen months later, an enlargement of the left ax- illary and right supraclavicular lymph nodes were de- Table 1. The serial level of Tg-Ag and Tg-Ab tected on chest CT during the regular follow up. Tg-Ag Tg-Ab Moreover, there were hypermetabolic metastatic lymph After the initial surgery 4.26 27.44 nodes in the right supraclavicular and left axillary Follow-up 17.78 43.06 18 After axillary and right ＞1000 36.66 area in F-FDG positron emission tomography (PET) supraclavicular lymph (Fig. 5). Ultrasonography guided FNA diagnosed LNM nodes metastasis of PTC in both in left axillary and right supraclavicular After the second* surgery 314.98 12.05 At present 24.63 8.1 area. Thus, a second operation was urgently required, and the right MRND and left axillary lymph node Tg-Ag: thyroglobulin antigen, Tg-Ab: thyroglobulin antibody *axillary dissection and right modified radical neck dissection dissections were performed in April 2012 (Fig. 6).

Fig. 3. 151 mCi therapeutic whole body scan at 48 hours showing two intense accumulation of the I-131 in the mid thyroid bed and remnant pyramidal lobe, with a focal much less I-131 uptake in the left upper thyroid bed or neck lymph node.

Vol. 7, No. 2, 2014 196 Axillary Lymph Node Metastasis of Papillary Thyroid Carcinoma: A Case Report

Fig. 4. Diagnostic I-131 scan showing no longer iodine uptake in the thyroid bed.

Fig. 5. PET showing hypermetabolic metastatic lymph nodes in right suprclavicular (A) and left axillary area (B).

Pathological results confirmed the metastatic PTC (tall The therapeutic whole body scan reveals well uptake cell variant) of the left axillary lymph nodes (Fig. 7). of residual thyroid tissue in both thyroid bed (Fig. 8). Malignancy was not seen in the right neck lymph It was 9 months after his second surgery when the nodes. After recovery from the surgery, the patient re- metastasis of bone, especially on level 2 of the thora- ceived radioactive iodine therapy with I-131 180 mCi. cic spine (T2), was found on PET CT during the regu-

197 Clin Exp Thyroidol Eun Jung Koo and Mi Ri Lee

lar follow up. At that time the level of Tg-Ag was 376.46 ng/mL and that of Tg-Ab was 4.88 IU/mL. The patient received novalis stereotactic radiotherapy (RT) on T2 (total RT dose: 4000 cGy). One year after RT, 18F-FDG PET shows normal glucose metabolism on bones and soft tissue, the level of Tg-Ag was 24.63 ng/mL and that of Tg-Ab was 8.1 IU/mL.

Discussion

Axillary masses suggest various diseases involving tumors, inflammatory conditions, and infections. cancer is a major disease of axillary metastasis, so the

Fig. 6. Intraoperative finding of axillary lymph node dissection.

Fig. 7. The tumor shows papillary growths with numerous branches (H&E stain, x10) (A). The papillae of the tumor are lined by single layer or pseudostratified tall columnar cells with elongated nuclei (H&E stain, x200) (B).

Fig. 8. The therapeutic whole body scan reveals well uptake of residual thyroid tissue in both thyroid bed.

Vol. 7, No. 2, 2014 198 Axillary Lymph Node Metastasis of Papillary Thyroid Carcinoma: A Case Report probability of breast malignancy must be ruled out disease.6) There was no synchronous distant meta- when the axillary masses are detected. Other tumors stasis in our report, but metachronous bone metastasis may involve the axillary lymph nodes, such as in developed. However, the patient is still alive with lymphoma, melanoma, cancers of the head and neck, disease after RT. and occasionally carcinomas from various primary Krishnamurthy et al.7) summarized 7 reports written sites.1,2) Metastasis in commonly occurs in English, describing the axillary LNM in PTC. The in the axillary lymph node; however, it is not known patients with axillary metastatic lesions predominantly as the potential site for thyroid cancer metastasis. had poorly differentiated tumors. He also mentioned A case diagnosed with PTC synchronous with that the axillary LNM of PTC might be related to poor breast cancer has been reported.3) In our case, meta- prognosis. stasis of axillary lymph nodes and contralateral lymph Rouvière12) reported about the communication be- node occurred 17 months after the first diagnosis of tween the cervical and axillary lymphatics in 1932, but PTC. There was no evidence of breast cancer on concluded that the physiologic flow is centripetal to the chest CT and 18F-FDG PET. Breast ultrasonography jugulosubclavian junction. However, malignant tumors was not performed. However, pathologic morphologic can change and partially block lymphatic pathways, characteristics of axillary LNM in this case are different potentially resulting in axillary LNM in a retrograde from those of papillary type of breast cancer. Furthe- direction. Although the altered lymphatic flow is mainly rmore, after left axillary lymph node dissections and due to blockage of the lymph nodes by metastasis, right MRND, the level of Tg-Ag was decreased fibrosis at the jugulosubclavian junction due to ex- significantly (Table 1). tensive lymph node dissection or RT can also result Axillary lymph nodes are a rare manifestation of in anomalous lymphatic dissemination to the ax- thyroid carcinoma; only 18 cases are in the published illa.5-10,13) Moreover, with repeated recurrences, PTCs literature. Eighteen reports of axillary LNM from thyroid can be transformed into poorly differentiated carcino- cancer exist in the literature: 12 PTC, 2 mucoepidermoid mas or into histological variants associated with worse carcinoma variants, 2 medullary thyroid carcinoma, and prognosis,7) as seen in our patient. 1 each of follicular thyroid carcinoma, and poorly In our case, metastasis of axillary lymph node and differentiated mucin-producing adenocarcinoma.4-11) contralateral lymph node occurred 17 months after the Our study reports the case of PTC metastatic to axil- first diagnosis of PTC on chest CT and 18F-FDG PET. lary lymph nodes. Papillary carcinoma of follicular variant and mixed Some authors reported a case of the axillary lymph histologic type thyroid carcinomas tend to cause node recurrence in papillary thyroid microcarcinoma. distant lymph node and organ metastases more fre- The patient had severe swelling of the cervical lateral quently than papillary carcinomas of classic type. lymph node preoperatively, which is indicative of a About 20% of patients with high serum Tg have neg- poor prognosis.5) Our report is also agreement with ative 131I whole body scans which may be due to this studies. Nine month after of the second surgery, small size of the metastatic tumor, loss of differentiation the bone metastasis developed. of cancer cells leading to low iodine uptake, or poor Other authors reviewed 9 cases of PTC with axillary TSH stimulation. 18F-FDG PET can detect foci of me- LNM and described poor outcomes of the axillary LNM tastasis in patients with negative 131I whole body scan in PTC patients. In the 6 reports, all of the patients had and high serum thyroglobulin.11) Therefore, 18F-FDG poorly differentiated components, suggesting that the PET is very important during follow-up period as well axillary LNM may be associated with poorly differentiated as 131I whole body scans. Moreover, 9 month after of thyroid carcinoma. Seven out of the nine patients had the second surgery, the bone metastasis developed. synchronous or metachronous distant metastasis, and However, the patient is still alive with disease after RT. only one patient was reported to survive without the Axillary LNM of PTC is rare, but its possibility should

199 Clin Exp Thyroidol Eun Jung Koo and Mi Ri Lee be kept in mind. Axillary LNM may be an indicator of 6)Nakayama H, Wada N, Masudo Y, Rino Y. Axillary lymph systemic disease and a poor prognosis. Thus the pa- node metastasis from papillary thyroid carcinoma: report of a case. Surg Today 2007;37(4):311-5. tients with axillary LNM of PTC need intensive strat- 7) Krishnamurthy A, Vaidhyanathan A. Axillary lymph node egies to treat a chain of metastasis or the recurrence metastasis in papillary thyroid carcinoma: report of a case and of disease. review of the literature. J Cancer Res Ther 2011;7(2):220-2. 8) Chiofalo MG, Losito NS, Fulciniti F, Setola SV, Tommaselli A, Marone U, et al. Axillary node metastasis from differentiated References thyroid carcinoma with Hurthle and signet ring cell differentiation. A case of disseminated thyroid cancer with peculiar histologic findings. BMC Cancer 2012;12:55. 1) Ers V, Galant C, Malaise J, Rahier J, Daumerie C. Axillary 9) Kepenekci I, Demirkan A, Cakmak A, Tug T, Ekinci C. lymph node metastasis in recurrence of papillary thyroid carcinoma: Axillary lymph node metastasis as a late manifestation of papillary a case report. Wien Klin Wochenschr 2006;118(3-4):124-7. thyroid carcinoma. Thyroid 2009;19(4):417-9. 2)Jaffer S, Goldfarb AB, Gold JE, Szporn A, Bleiweiss IJ. 10) Wada N, Duh QY, Sugino K, Iwasaki H, Kameyama K, Contralateral axillary lymph node metastasis as the first evidence Mimura T, et al. Lymph node metastasis from 259 papillary of locally recurrent breast carcinoma. Cancer 1995;75(12):2875-8. thyroid microcarcinomas: frequency, pattern of occurrence and 3)Banzo J, Ubieto MA, Gonzalez C, Razola P, Tardin L, recurrence, and optimal strategy for neck dissection. Ann Surg Andres A, et al. [Papillary thyroid carcinoma synchronous with 2003;237(3):399-407. breast cancer: an incidental finding in an (18)F-FDG PET-CT 11) Elboga U, Kalender E, Yilmaz M, Celen YZ, Aktolun C. study carried out in a search for occult breast cancer]. Rev Esp Axillary lymph node metastasis of papillary thyroid carcinoma Med Nucl Imagen Mol 2012;31(4):213-5. detected by FDG PET/CT in a thyroglobulin-positive patient 4) Cummings AL, Goldfarb M. Thyroid carcinoma metastases to with negative whole-body 131I scan. Clin Nucl Med 2012; axillary lymph nodes: report of two rare cases of papillary and 37(11):1120-2. medullary thyroid carcinoma and literature review. Endocr Pract 12) Rouvière H. Anatomie des lymphatiques de L'homme. Paris: 2014;20(3):e34-7. Masson; 1932. 5) Koike K, Fujii T, Yanaga H, Nakagawa S, Yokoyama G, 13) Mazzaferri EL, Young RL. Papillary thyroid carcinoma: a 10 Yahara T, et al. Axillary lymph node recurrence of papillary year follow-up report of the impact of therapy in 576 patients. thyroid microcarcinoma: report of a case. Surg Today 2004; Am J Med 1981;70(3):511-8. 34(5):440-3.

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