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 Table of Contents  
Year : 2022  |  Volume : 55  |  Issue : 2  |  Page : 70-74

Case report of delayed metastasis from thyroid micropapillary carcinoma to the deltoid muscle in a patient with thyroglobulin elevated negative iodine scintigraphy (TENIS)

Department of General Surgery, Amrita Institute of Medical Sciences, Kochi, Kerala, India

Date of Submission07-Dec-2021
Date of Decision04-Mar-2022
Date of Acceptance07-Mar-2022
Date of Web Publication25-Apr-2022

Correspondence Address:
Riju Ramachandran
Ag-1, Sterling Sarovar, Kosseri Lane, Edapally, Kochi, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/fjs.fjs_243_21

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Differentiated thyroid cancers are common but distant metastasis to the muscles is rare. We present a case of 64-year-old male who underwent thyroidectomy for a suspicious thyroid lesion. His histopathology was reported as widely invasive follicular carcinoma of the thyroid with a focus of micropapillary carcinoma (MPC). He underwent radioiodine ablation. On follow-up, he had a serial increase in thyroglobulin but a whole-body radioiodine scan failed to detect any lesion. An 18-fluorodeoxyglucose positron emission tomography (PET)-computed tomography scan picked up a lesion in the left deltoid muscle. An intraoperative ultrasound localization was done and the nonpalpable lesion was successfully removed surgically. The deltoid lesion was a delayed metastasis of a thyroid MPC. A rising thyroglobulin level in a patient with negative iodine scintigraphy warrants further evaluation with PET since rare distant metastasis may be present. A surgeon performing intraoperative ultrasound is useful in effectively identifying and removing occult lesions with small incisions.

Keywords: Case report, intraoperative ultrasound, metastasis, thyroglobulin elevated negative iodine scintigraphy syndrome, thyroid cancer

How to cite this article:
Ramachandran R, Pillai AV, Samuel S. Case report of delayed metastasis from thyroid micropapillary carcinoma to the deltoid muscle in a patient with thyroglobulin elevated negative iodine scintigraphy (TENIS). Formos J Surg 2022;55:70-4

How to cite this URL:
Ramachandran R, Pillai AV, Samuel S. Case report of delayed metastasis from thyroid micropapillary carcinoma to the deltoid muscle in a patient with thyroglobulin elevated negative iodine scintigraphy (TENIS). Formos J Surg [serial online] 2022 [cited 2022 May 26];55:70-4. Available from: https://www.e-fjs.org/text.asp?2022/55/2/70/343819

  Introduction Top

Thyroid cancers and their metastatic lesions are being increasingly reported in India. Our geographical region in Southern India, Kerala, has reported a fourfold increase in incidence in the last few years.[1] The cervical lymph node is the most common site of metastasis in differentiated thyroid cancer (DTC). Distant metastasis in DTC has been reported in 4%–15% of cases and indicates a poor prognosis.[2] Common sites for distant metastases in DTC are lung, bones, liver, kidneys, and adrenals. Although rare, skin, and muscle metastasis are reported to decrease 10-year survival.[3] Advanced imaging like 18-fluorodeoxyglucose positron emission tomography (FDG-PET) has increased the rate of detection of these metastases even in asymptomatic patients.[4] We are reporting a case of thyroglobulin elevated negative iodine scintigraphy syndrome (TENIS) patient with an asymptomatic intramuscular lesion in the left deltoid muscle, 2 years after total thyroidectomy. The lesion in the left deltoid has metastasized from the micropapillary carcinoma (MPC) component.

  Case Report Top

A 64-year-old gentleman was evaluated for a multinodular goiter in 2011. Ultrasound (US) imaging showed multiple well-defined nodules with echogenicity varying from hypo-to hyperechoic. Fine needle aspiration reported follicular lesion. Total thyroidectomy was done. Histopathology showed follicular thyroid cancer (FTC) 3.3 cm × 2.5 cm × 2 cm in the left lobe with capsular invasion at 2 foci and vascular invasion. There was also a focus of MPC in the right lobe of 1 cm × 1 mm size with a capsular breach [Figure 1]. Iodine-131 whole-body imaging (131I-WBI) scan showed moderate residual thyroid tissue with doubtful uptake in a cervical lymph node. Radioactive iodine (RAI) ablation with 2590 MBq of iodine-131 (I-131) was done.
Figure 1: Histopathology of the thyroidectomy specimen. (a) Low power field (×40 H and E) capsular and vascular invasion classical of follicular carcinoma. (b) High power view (×400 H and E) Follicular epithelial cells arranged predominantly in a microfollicular pattern. (c) Low power field (×40 H and E) Focus of micropapillary carcinoma

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On follow-up at 6 months, stimulated thyroglobulin (sTg) was 123.2 ng/ml [Figure 2]. The patient was given empirical RAI ablation with 4255 MBq of I-131. Posttherapy scan revealed minimal I-131 uptake in the anterior neck but no new abnormal focus.
Figure 2: Thyroglobulin levels with corresponding thyroid-stimulating hormone levels and line diagram of follow-up of our patient with stimulated thyroglobulin levels

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On review at 9 months, stimulated Tg level had increased to 175.1 ng/ml (thyroid-stimulating hormone [TSH] >100uIU/ml) [Figure 2]. The patient was asymptomatic and 131I-WBI scans showed no abnormal uptake. On clinical examination, the thyroidectomy scar was healthy. There were no swellings nor palpable lymph nodes in the neck. Complete physical examination revealed no other swellings.

The details of the case were discussed in the multidisciplinary thyroid tumor board. Progressive elevation of sTg [Figure 2] and 131I-WBI scan not picking up any abnormality suggested the possibility of TENIS. Hence, an 18-FDG PET-CT was considered. It showed focal uptake in left deltoid/infraspinatus muscle (standardized uptake value Max 12.0) and no metabolically active recurrent primary malignancy in the thyroid bed. CT demonstrated no obvious lesion in the infraspinatus muscle. There were no other FDG-avid lymph nodes or distant metastases [Figure 3]a and [Figure 3]b. The patient was planned for excision of the lesion in the left infraspinatus/deltoid muscle under general anesthesia. Since the lesion was small and deeply located within the infraspinatus/deltoid muscle and was not palpable, an intraoperative ultrasound-guided needle localization was performed by the author, the operating surgeon. An echogenic nodule measuring 12 mm × 8 mm with increased vascularity in the deltoid muscle anteriorly was localized [Figure 4]a and [Figure 4]b. This enabled a small incision, minimal dissection, and effective excision of the lesion with a rim of normal muscle around it. The patient was discharged after 24 h. Stimulated thyroglobulin levels decreased after the procedure [Figure 2].
Figure 3: (a) Computed tomography – No lesion in the left deltoid/infraspinatus muscle. (b) 18-fluorodeoxyglucose positron emission tomography-computed tomography showing an 18-fluorodeoxyglucose-avid lesion in deltoid/infraspinatus muscle

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Figure 4: (a) Ultrasonography showing the lesion in the left deltoid muscle. (b) Intraoperative needle within the lesion

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Histopathology of the lesion in the left deltoid muscle showed a neoplasm arranged in a follicular pattern with interspersed dense fibro-collagenous bands surrounded by skeletal muscle [Figure 5]. The follicles were lined by cuboidal cells with nuclear grooves, overlap, and inclusions. Immunohistochemistry was positive for thyroid transcription factor-1, thyroglobulin, and (cytokeratin-19) [Figure 6]. All these suggested metastatic deposits of papillary carcinoma of the thyroid.
Figure 5: Histopathology of the deltoid muscle metastasis. (a) Low power field (×100 H and E) showing follicular and papillary patterns of neoplasm and surrounding skeletal muscle fibers. (b) High power view (×400 H and E) nuclear clearing and intranuclear pseudoinclusions

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Figure 6: Immunohistochemistry of the metastatic deposit (×400). (a) Positivity for thyroglobulin. (b) Nuclear positivity for thyroid transcription factor-1. (c) Diffusely positive for cytokeratin-19

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Neck US, 131I-WBI scan, and 18-FDG-PET-CT done 6 months later revealed no lesion in the thyroid bed nor the deltoid area. Stimulated Tg level came down to 35.89 ng/ml. The patient was on regular follow-up and was reviewed every 6 months for the next 8 years. His thyroglobulin level continues to show biochemical disease without clinical or radiological features for the past 8 years [Figure 2].

  Discussion Top

DTC is being increasingly reported in India. Many of them are subclinical, asymptomatic, and indolent.[1] FTC metastasizes through the bloodstream to distant areas of the body while papillary thyroid cancer (PTC) commonly metastasizes through lymphatics to the cervical nodes. A rising titer of stimulated Tg after thyroidectomy points to recurrence or metastasis and is recommended at our institute as per the American Thyroid Association guidelines. Although suppressed Tg averts the symptoms of hypothyroidism, stimulated-Tg is more reliable than suppressed-Tg for PTC follow-up.[5] Metastasis from FTC is more commonly seen in the bones. Delayed metastasis after thyroidectomy usually involves the lung with 7%–23% incidence.[6]

Bloodstream metastasis from PTC is rarely described.[7] With increasing detection of thyroid malignancy, incidental MPC is now frequently reported during histopathological examinations. These lesions do not warrant any further adjuvant treatment.[8] The possibility of distant metastasis from MPC is rare and is described only with symptomatic primary lesions.[9]

Skeletal muscle constitutes more than 40% of the total human weight, yet tumor metastasis to skeletal muscle is rare. A metaanalysis showed only 11 cases of skeletal metastasis in PTC from a total of 58 cases of skeletal muscle metastasis in DTC described over 110 years.[10] The inhibition of tumor cells by lactic acid produced by the skeletal muscle, variation of tissue pressure in skeletal muscle affecting tumor implantation due to influence of β adrenergic receptors, muscle motion, and unadapted pH could make the environment unsuitable for metastatic cells. Another theory is the presence of protease inhibitors in the extracellular matrix resisting tumor cell invasion of skeletal muscle.[11]

Skeletal muscle metastasis from DTC when present is commonly reported in the gluteus muscle. Only 2 cases of deltoid muscle metastasis from DTC have been described in the literature.[10] Since skeletal muscle metastases are neither painful nor palpable, they tend to be an incidental finding during posttherapeutic 131I-WBI scans. Occasionally, the patient presents with elevated Tg but no detectable lesion on the 131I-WBI scans (TENIS). An 18-FDG-PET-CT is a useful tool in such situations, such is the case with our patient. An ultrasound and needle localization done by the author intraoperatively helped to avoid extensive dissection and effectively excise the lesion with a cuff of normal muscle utilizing a small incision. The availability of intraoperative ultrasound enhances the efficacy gives better and earlier recovery while keeping a sound oncologic outcome. The highlight of our case is that the distant metastases proved to arise from the micropapillary component of the DTC rather than the FTC. The lesion was FDG avid, indicating an aggressive malignant potential. However, our patient had an uneventful recovery and is under follow-up for the past 8 years. Although RAI ablation is not recommended in MPC, cases need to be handled on an individual basis. Clinical acumen and regular follow-up are vital in the management of DTC.

Patient perspective

I had a swelling in the front of my neck region for which I came and saw the doctor in this hospital in 2011. I had a needle biopsy done from the swelling which came as suspicious for thyroid cancer. Hence, my doctor suggested surgery (thyroidectomy) for my condition. I had my thyroid gland removed. My pathology report came as thyroid cancer. I was referred to a nuclear medicine department under whom I took iodine ablation for the remaining thyroid gland. I came back after 6 months and a blood test done (thyroglobulin) was high. The doctor again advised iodine scan and was found normal. However, as the doctor had a suspicion of recurrence of cancer due to increase in thyroglobulin levels, he advised a repeat iodine ablation. Again after 6 months, the doctor once again tested the thyroglobulin and it was found to be high. At this time, the doctor advised a repeat iodine scan which was also negative. The nuclear medicine doctor, endocrine doctor, and my surgeon had a discussion about my case and they told me that I have to undergo a PET-CT scan. For me, all these were adding to my financial burdens. At this point, I was really confused as to what to do next. I had a detailed discussion with the doctors who reassured me. Later I had to borrow money from my friends and relatives to get the PET-CT done. After the scan, doctor told me that there was a swelling inside the muscle of left arm. However, I did not have any symptoms related to that nor did I felt anything over that region. As per doctors' advice, I underwent surgery again for the swelling in the left arm. My blood test of thyroglobulin became normal after this operation. I was asked to come for regular follow-up once every 6 months. During my further follow-ups, I had no problems. My blood reports were normal. My daughter also had a similar thyroid swelling which was operated 3 years back, which was reported as a thyroid cancer. She has also taken the iodine medicine and is doing well. I felt that it was a good decision by the team of treating doctors to go ahead with the PET-CT scan which helped in diagnosing my condition. I am happy with all the treatment I have received here and happier to write this down for publishing in a journal.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.


The authors would like to thank Department of Nuclear Medicine and Endocrinology for support in Patient Care Department of Pathology.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Mathew IE, Mathew A. Rising thyroid cancer incidence in Southern India: An epidemic of overdiagnosis? J Endocr Soc 2017;1:480-7.  Back to cited text no. 1
Clark JR, Lai P, Hall F, Borglund A, Eski S, Freeman JL. Variables predicting distant metastases in thyroid cancer. Laryngoscope 2005;115:661-7.  Back to cited text no. 2
Song HJ, Xue YL, Xu YH, Qiu ZL, Luo QY. Rare metastases of differentiated thyroid carcinoma: Pictorial review. Endocr Relat Cancer 2011;18:R165-74.  Back to cited text no. 3
Chung JK, So Y, Lee JS, Choi CW, Lim SM, Lee DS, et al. Value of FDG PET in papillary thyroid carcinoma with negative 131I whole-body scan. J Nucl Med 1999;40:986-92.  Back to cited text no. 4
Sunny SS, Hephzibah J, Mathew D, Bondu JD, Shanthly N, Oommen R. Stimulated serum thyroglobulin levels versus unstimulated serum thyroglobulin in the follow-up of patients with papillary thyroid carcinoma. World J Nucl Med 2018;17:41-5.  Back to cited text no. 5
[PUBMED]  [Full text]  
Parameswaran R, Shulin Hu J, Min En N, Tan WB, Yuan NK. Patterns of metastasis in follicular thyroid carcinoma and the difference between early and delayed presentation. Ann R Coll Surg Engl 2017;99:151-4.  Back to cited text no. 6
Pereira F, Pereira SS, Mesquita M, Morais T, Costa MM, Quelhas P, et al. Lymph node metastases in papillary and medullary thyroid carcinoma are independent of intratumoral lymphatic vessel density. Eur Thyroid J 2017;6:57-64.  Back to cited text no. 7
Chae AW, Martinez SR. Too much of a good thing: Radioactive iodine ablation use for micropapillary thyroid carcinoma. Am Surg 2018;84:637-43.  Back to cited text no. 8
Sugitani I, Fujimoto Y, Yamamoto N. Papillary thyroid carcinoma with distant metastases: Survival predictors and the importance of local control. Surgery 2008;143:35-42.  Back to cited text no. 9
Herbowski L. Skeletal muscle metastases from papillary and follicular thyroid carcinomas: An extensive review of the literature. Oncol Lett 2018;15:7083-9.  Back to cited text no. 10
Pauli BU, Schwartz DE, Thonar EJ, Kuettner KE. Tumor invasion and host extracellular matrix. Cancer Metastasis Rev 1983;2:129-52.  Back to cited text no. 11


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]


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