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Year : 2019  |  Volume : 15  |  Issue : 3  |  Page : 665-668

Nonthyroidal metastatic lesion in thyroid: A missed diagnosis and a lesson learnt

1 Department of Radiation Oncology, Amrita School of Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Amrita University, Kochi, Kerala, India
2 Department of Radiation Oncology, HCG Institute of Oncology, Bengaluru, Karnataka, India

Date of Web Publication29-May-2019

Correspondence Address:
Dr. Chelakkot G Prameela
Department of Radiation Oncology, Amrita School of Medicine, Amrita Institute of Medical Sciences, Amrita Vishwa Vidyapeetham, Amrita University, Kochi, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_1043_16

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 > Abstract 

Background: Blood supply to the thyroid is relatively high when compared to that of liver. Despite this documented metastatic deposit in thyroid remains a rarity. Synchronous nonthyroidal metastatic deposit in thyroid from a lung primary is relatively rare. Metastasis to thyroid portends to poor prognosis, and hence a metastatic deposit has to be excluded in any suspicious lesion of thyroid.
Materials and Methods: Details of a rare presentation of a malignant thyroid lesion, a secondary deposit from an asymptomatic primary papillary adenocarcinoma of lung, who had presented to this tertiary care center was retrieved and analyzed.
Results: Patient with an initial diagnosis of papillary carcinoma on FNA was taken up for total thyroidectomy and cervical lmphadenectomy. HPR was mucinous carcinoma of thyroid with high lymph nodal metastasis. In view of the exrathyroidal disease an adjuvant external beam radiotherapy was considered for him. Unfortunately, the radiotherapy planning CT scan revealed left sided lung lesions with pleural effusion which was proved to be papillary adenocarcinoma of lung on biopsy, with metastases to thyroid. He was treated with chemotherapy but he succumbed to his illness 9 months from the date of diagnosis.
Conclusion: Although encountered rarely, metastatic lesions in thyroid from nonthyroidal primaries need to be excluded while evaluating thyroid lesions.

Keywords: Adenocarcinoma lung, nonthyroidal thyroid metastasis, papillary carcinoma thyroid, thyroid metastasis

How to cite this article:
Prameela CG, Ravind R, Sruthi K. Nonthyroidal metastatic lesion in thyroid: A missed diagnosis and a lesson learnt. J Can Res Ther 2019;15:665-8

How to cite this URL:
Prameela CG, Ravind R, Sruthi K. Nonthyroidal metastatic lesion in thyroid: A missed diagnosis and a lesson learnt. J Can Res Ther [serial online] 2019 [cited 2021 Dec 4];15:665-8. Available from: https://www.cancerjournal.net/text.asp?2019/15/3/665/243462

 > Introduction Top

Metastatic deposits in thyroid gland are extremely rare, with autopsy series reporting an incidence of 0.5%–24%.[1],[2] Thyroidectomies for malignancies have yielded only 1.25% of metastatic lesions.[2] Nakhjavani from Mayo clinic in 1966 opined metastasis to thyroid to portend poor prognosis.[3] Adenocarcinoma is the most common to have thyroid metastasis. Diagnosis of metastatic lesions poses dilemma, as fine-needle aspiration for cytology (FNAC) is not always conclusive, and require immunohistochemical (IHC) studies, especially in poorly differentiated tumors. Case reported here posed diagnostic dilemma, in spite of modern imaging and laboratory facilities, stressing the importance of complete, diligent evaluation.

 > The Case Top

A 63-year-old man, reformed smoker, presented with bilateral neck swelling of 3-month duration. Outside evaluation showed multi-nodular goiter, with bilateral cervical lymphadenopathy. FNAC from thyroid lesion was reported as papillary carcinoma.

Clinical examination showed enlarged, nodular bilateral thyroid lobes, and bilateral cervical level III and IV lymph nodes. Cytology slides reviewed in-house was reported as: “Suggestive of cellular thyroid lesion. However, the possibility of papillary carcinoma thyroid with cystic degeneration could not be ruled out.” The patient underwent total thyroidectomy after necessary preanesthetic evaluations, including chest radiograph.

Histopathology and IHC showed neoplastic cells positive for thyroid transcription factor 1 (TTF-1) and carcinoembryonic antigen [Figure 1] and [Figure 2]. Thyroglobulin, calcitonin, and high molecular weight keratin were negative. Out of 42, 38 lymph nodes showed metastasis. With the histological and IHC findings, the final diagnosis considered was, poorly differentiated carcinoma with mucin secretion, even though mucin secretion in these tumors is not described in literature. He was staged pT3N1bMx. Second opinion was sought from renowned pathologists, whose differentials were mucoepidermoid carcinoma, mucinous carcinoma, and metastasis, and concluded that based on clinical and histopathological data mucinous carcinoma of thyroid could be the most likely pathology.
Figure 1: Histopathology image of thyroid with poorly differentiated tumor

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Figure 2: Immunohistochemistry image of thyroid showing thyroid transcription factor 1 positivity

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Extrathyroid extension mandated adjuvant radiation and simulation computed tomography (CT) scan for radiotherapy planning, revealed left-sided pleural effusion and posterior pleural-based nodule in the left lung, lower lobe. Subsequent contrast-enhanced CT scan showed well-defined mildly enhancing soft-tissue density lesion with spiculated margins, 2.6 cm × 2.4 cm in posterior basal segment of the left lower lobe. Mild left pleural effusion and multiple enlarged nodes at prevascular, upper and lower paratracheal, para-aortic levels, and bilateral hilar nodes were noted. Guided biopsy from lung lesion [Figure 3] showed papillary neoplasm, positive for TTF1 and cytokeratin-7 (CK7), and negative for thyroglobulin. Histopathological and IHC findings of thyroid and lung lesions matched, and diagnosis of papillary adenocarcinoma of lung with metastases to thyroid [Figure 4] was confirmed.
Figure 3: Computed tomography image showing left-sided pleural effusion and lung lesion

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Figure 4: Histopathology image of lung showing papillary adenocarcinoma

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The patient was planned for chemotherapy using carboplatin-etoposide on which he progressed. Second-line paclitaxel-carboplatin combination and salvage single-agent docetaxel also failed, and he developed superior vena cava obstruction. Supportive symptomatic domiciliary care was opted, and he succumbed within 9 months of initial presentation.

 > Discussion Top

About 70%–80% of thyroid tumors are papillary carcinomas, having favorable prognosis even with extensive lymph nodal involvement.[4] Wada quoted high incidence of recurrence in patients with palpable lymph nodes at presentation, especially in elderly (>45 years).[5] Tissue diagnosis of papillary carcinoma of thyroid by two onco-pathologists, justifies radical thyroid surgery in index case.

Virchow in 1871 documented metastatic lesions in thyroid in his autopsy series.[6] Willis, in 1931, observed that [6] despite high arterial blood flow of 560 ml/100 g of tissue per minute, more than half of what entire liver receives; huge disparity exists in reported metastasis to thyroid and that these are not as rare as believed, necessitating thorough pathological evaluation of any thyroid lesion.

Nonthyroidal primaries metastasizing to thyroid is very rare [7] accounting 1.4%–3%. Chung et al. quoted that renal-cell carcinoma tops this list with 48.1% incidence, followed by colorectal with 10.4%. Lung has about 8.3% incidence. Interval between detection of primary disease and metastatic lesion in thyroid was longest in sarcomas (75 months), and shortest in lung malignancies (4.5 months).[7] Synchronous presentation of primary and metastatic lesions in thyroid was observed in renal-cell carcinoma (25 among 69) and lung (15/69).[7] Namad et al. opined that [8] adenocarcinoma of lung is the most common to metastasize to thyroid followed by squamous, small cell and large cell carcinomas. Rare thyroid metastasis from small-cell lung cancer is also reported.[9]

Distant metastasis in head and neck malignancy is 7%–23%,[10] and for papillary thyroid cancer is <10%.[11] Features of thyroid cancer predicting aggressive disease are age >45 years, male gender, and aggressive histological factors such as columnar, tall cell, and insular variants of differentiated thyroid cancers.[12]

Histopathological diagnosis of thyroid malignancy is challenging. Criteria differentiating malignant lesions are features of aggressiveness, nature of tumor capsule, and invasion of surrounding structures such as thyroid parenchyma, vasculature, and skeletal muscles.[13] IHC studies complement morphological findings. One of the first antibodies used in the diagnosis of thyroid malignancies was Hector Battifora mesothelial antigen (HBME1).[14] Since then an array of markers have been in use. Extensively studied markers are, HBME1, CK19, galectin-3, TTF-1, p53, thyroperoxidase, CD57, CD44v6, Rb-1, and CD56 (NCAM).[15] CD56 is highly specific for papillary carcinoma thyroid.[16]

IHC panel for lung includes epithelial markers, CK AE1/AE3 and CK7; neuroendocrine markers chromogranin, synaptophysin, TTF-1 and p53; and mesenchymal markers leukocyte-common antigen and smooth-muscle actin. Primary non-small cell lung cancer is TTF-1 and CK7 positive; and adenocarcinoma CK5/CK6, CK7, and surfactant protein-A positive.[17] Thyroglobulin differentiates primary thyroid tumor from primary lung lesion. Differentiating metastatic lesion in thyroid from lung is difficult, especially with poor differentiation.

Chest radiograph is usually opted instead of CT scan of thorax in thyroid malignancy workup, though far inferior to CT scan in detecting malignant lung lesions.[18] In index case, chest radiograph before surgery had failed to pick up the lesion resulting in wrong diagnosis [Figure 5]. CT scan of thorax has high sensitivity (73%) and specificity (80%) in detecting lung lesions and remains an important tool in screening lung in head and neck malignancies.[19] This is significant when considering high prevalence of pulmonary Koch's (75/100,000 population),[20] and possibility of synchronous second primary in lung, especially with long smoking history.
Figure 5: Initial preoperative chest radiograph

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 > Conclusion Top

Although encountered rarely, metastatic lesions in thyroid from nonthyroidal primaries need to be excluded while evaluating thyroid lesions. Probabilities of detecting coexistent lesions should be judiciously weighed against financial constraints while considering imaging modalities, in countries like India.

Declaration of patient consent

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


We would like to acknowledge the support rendered by all our colleagues in the Department of Radiation Oncology, and Head and Neck Surgery. We also acknowledge the help offered by our colleagues in the Department of Pathology in procuring the required images.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 > References Top

Lin JD, Weng HF, Ho YS. Clinical and pathological characteristics of secondary thyroid cancer. Thyroid 1998;8:149-53.  Back to cited text no. 1
Lam KY, Lo CY. Metastatic tumors of the thyroid gland: A study of 79 cases in chinese patients. Arch Pathol Lab Med 1998;122:37-41.  Back to cited text no. 2
Nakhjavani MK, Gharib H, Goellner JR, van Heerden JA. Metastasis to the thyroid gland. A report of 43 cases. Cancer 1997;79:574-8.  Back to cited text no. 3
Gonzalez-Gonzalez R, Bologna-Molina R, Carreon-Burciaga RG, Gómezpalacio-Gastelum M, Molina-Frechero N, Salazar-Rodríguez S, et al. Papillary thyroid carcinoma: Differential diagnosis and prognostic values of its different variants: Review of the literature. ISRN Oncol 2011;2011:915925.  Back to cited text no. 4
Wada N, Masudo K, Nakayama H, Suganuma N, Matsuzu K, Hirakawa S, et al. Clinical outcomes in older or younger patients with papillary thyroid carcinoma: Impact of lymphadenopathy and patient age. Eur J Surg Oncol 2008;34:202-7.  Back to cited text no. 5
Willis RA. Metastatic tumours in the thyreoid gland. Am J Pathol 1931;7:187-208.3.  Back to cited text no. 6
Chung AY, Tran TB, Brumund KT, Weisman RA, Bouvet M. Metastases to the thyroid: A review of the literature from the last decade. Thyroid 2012;22:258-68.  Back to cited text no. 7
Namad T, Wang J, Shipley R, Abdel Karim N. Thyroid metastasis from nonsmall cell lung cancer. Case Rep Oncol Med 2013;2013:208213.  Back to cited text no. 8
Can AS, Köksal G. Thyroid metastasis from small cell lung carcinoma: A case report and review of the literature. J Med Case Rep 2015;9:231.  Back to cited text no. 9
Chelakkot GP, Ravind R, Sruthi K, Nair HM, Dinesh M. Surgical resection of solitary distant metastasis from locoregionally controlled advanced hypopharyngeal malignancy: A ray of hope. J Cancer Res Ther 2016;1-4. [Ahead of Publication].  Back to cited text no. 10
Shaha AR, Shah JP, Loree TR. Patterns of nodal and distant metastasis based on histologic varieties in differentiated carcinoma of the thyroid. Am J Surg 1996;172:692-4.  Back to cited text no. 11
Brown RL. Standard and emerging therapeutic approaches for thyroid malignancies. Semin Oncol 2008;35:298-308.  Back to cited text no. 12
Fadda G, Rossi ED. Immunohistochemical diagnosis of thyroid tumors. Surgical Pathology Clinics 2014;7:491-500.  Back to cited text no. 13
de Matos PS, Ferreira AP, de Oliveira Facuri F, Assumpção LV, Metze K, Ward LS, et al. Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the diagnosis of thyroid malignancy. Histopathology 2005;47:391-401.  Back to cited text no. 14
Nechifor-Boila A, Borda A, Sassolas G, Hafdi-Nejjari Z, Borson-Chazot F, Lifante JC, et al. Immunohistochemical markers in the diagnosis of papillary thyroid carcinomas: The promising role of combined immunostaining using HBME-1 and CD56. Pathol Res Pract 2013;209:585-92.  Back to cited text no. 15
El Demellawy D, Nasr AL, Babay S, Alowami S. Diagnostic utility of CD56 immunohistochemistry in papillary carcinoma of the thyroid. Pathol Res Pract 2009;205:303-9.  Back to cited text no. 16
Capelozzi VL. Role of immunohistochemistry in the diagnosis of lung cancer. J Bras Pneumol 2009;35:375-82.  Back to cited text no. 17
Fukuhara T, Fujiwara K, Fujii T, Takeda K, Matsuda E, Hasegawa K, et al. Usefulness of chest CT scan for head and neck cancer. Auris Nasus Larynx 2015;42:49-52.  Back to cited text no. 18
Brouwer J, de Bree R, Hoekstra OS, Golding RP, Langendijk JA, Castelijns JA, et al. Screening for distant metastases in patients with head and neck cancer: Is chest computed tomography sufficient? Laryngoscope 2005;115:1813-7.  Back to cited text no. 19
Moitra S, Sen S, Mukherjee S, Das P, Sinha S, Bose M. Study of prevalence and outcome of standardized treatment on category I pulmonary tuberculosis cases in North India: A single center experience. Commun Acquir Infect 2015;2:83-92.  Back to cited text no. 20


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

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