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Breast cancer to thyroid gland: An unconventional metastatic site

1 Department of Medical Oncology, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
2 Department of Pathology, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
3 Department of Nuclear Medicine, Cerrahpasa School of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey
4 Department of Medical Oncology, Istanbul University-Cerrahpasa, Istanbul, Turkey

Date of Submission02-May-2020
Date of Decision13-Aug-2020
Date of Acceptance10-Sep-2020
Date of Web Publication22-Jun-2022

Correspondence Address:
Emir Celik,
Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty. Kocamustafapasa Street. No:53 34098 Fatih, Istanbul
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_561_20

 > Abstract 

Thyroid gland blood supply is rich but it is not an open area for metastasis. Only 1%–3% of the neoplastic lesions seen in the thyroid are of extrathyroidal origin. Thyroid, lung, bone, lymph node metastasis were detected at the time of diagnosis in a 78-year-old woman with metastatic breast cancer. Control imaging was performed 3 months after hormone therapy was started. All lesions were regressed except thyroid lesion and neck lymph. Tru-cut biopsy was performed to the lesion in the thyroid. The result is consistent with breast cancer metastasis. With this breast cancer metastasis to thyroid case, we want to emphasize the differential diagnosis of neoplastic lesions in the thyroid is important in those diagnosed with malignancy. If there is clinical suspicion after a nondiagnostic thyroid sampling, repeated biopsies should be performed.

Keywords: Breast cancer, fine-needle aspiration cytology, metastasis, thyroid gland

How to cite this URL:
Celik E, Ozturk T, Samanci NS, Demirci NS, Akovali B, Demirelli FH. Breast cancer to thyroid gland: An unconventional metastatic site. J Can Res Ther [Epub ahead of print] [cited 2022 Aug 16]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=347790

 > Introduction Top

Breast cancer is the most common malignancy and the second-most common cancer leading to mortality in women.[1] Bone, lung, liver, and brain are the frequent sites of metastasis in breast cancer.[2] Although the thyroid gland has a rich blood supply, it is not a typical location for breast cancer metastasis, and invasive ductal carcinomas tend to metastasize to the thyroid gland more frequently than breast cancers with lobular histology.[3] Here, we present a rare case of a patient with breast cancer metastasis in the thyroid gland.

 > Case Report Top

A 78-year-old female patient with no other chronic condition was diagnosed with invasive ductal breast cancer with neuroendocrine differentiation as a result of a trucut biopsy performed to investigate a mass in the left breast. Following the definitive diagnosis of Grade 3, estrogen receptor (ER) 95% positive, progesterone receptor (PR) negative, Her-2-negative breast cancer with Ki–67: 60% [Figure 1], the patient underwent left breast-conserving surgery and left axillary lymph node dissection. The patient, whose surgical pathology result was reported as pT2N2Mx (Tumor-Node-Metastasis staging, 8th ed.ition), was referred to the medical oncology department for adjuvant therapy. The positron emission tomography–computed tomography (PET/CT) scan performed for staging purposes revealed multiple metastatic lesions with fluorodeoxyglucose uptake in bones, mediastinal lymph nodes, bilateral lung parenchyma and the peripheral region of the thyroid gland, where a mid–necrotic gross nodular lesion filled the entire left lobe and a metastatic lymph node was observed in the right cervical region [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d. Fine-needle aspiration cytology (FNAC) was performed from the sacral lesion and the thyroid nodule. The result of the FNAC was reported as “atypia of undetermined significance (Bethesda category III).” The result of the sacral bone FNA revealed extensive neoplastic cells with a positive nuclear staining for GATA-3 and was considered breast cancer metastasis to the bone on comparative evaluation with the primary breast tumor [Figure 3]a and [Figure 3]b.
Figure 1: Immunohistochemical findings of the primary breast tumor. (a) Grade 3, invasive ductal carcinoma, ductal, and solid pattern (HE × 200) with neuroendocrine differentiation (b) (positive synaptophysin staining × 200) (c) 95% positive estrogen receptor staining (ER × 200) (d) Negative progesterone receptor staining (PR × 200) (e) Negative Her-2 staining (×200) (f) 60% ki 67 proliferation index (×200)

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Figure 2: Positron emission tomography–computed tomography images of the breast cancer metastasis to cervical lymph node (a), thyroid gland (b), mediastinal lymph nodes (c), sacrum (d) before aromatase inhibitor treatment. Cervical lymph node (e) progressed after 3 months' hormonotherapy, other metastatic sites (f-h) showed regression

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Figure 3: Sacrum bone biopsy showed (a) ductal and solid pattern carcinoma infiltration (HE × 200) and (b) diffuse staining for GATA-3 (×200). Thyroid lesion biopsy showed (c) solid pattern carcinoma infiltration (HE × 200), (d) diffuse staining for GATA-3 (×400) and negative staining for TTF-1 (x200) (e) and thyroglobulin (x200) (f)

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Treatment with aromatase inhibitor combined with a cyclin-dependent kinase (CDK) 4/6 inhibitor was planned for the hormone receptor positive patient; however, the treatment was started as letrozole 2.5 mg filmcoated tablets once daily plus ibandronic acid 50 mg/day tablets since CDK 4/6 inhibitors were not reimbursed by the state health insurance in Turkey. After 3 months of hormone therapy, a PET/CT scan was performed for the patient who was asymptomatic. Bone metastases, lung parenchymal lesions, and metastatic mediastinal lymph nodes showed significant regression while the lesion in the left lobe of the thyroid gland was stable; however, progression was noted in the right cervical lymph node [Figure 2]e, [Figure 2]f, [Figure 2]g, [Figure 2]h. The current treatment was continued, and a trucut biopsy was performed from the gross nodular thyroid lesion. Thyroid lesion biopsy showed solid pattern carcinoma infiltration and staining results of the biopsy showed extensive strong positive staining for GATA–3, 100% strong positive staining for ER- and PR–negative neoplastic cells were observed [Figure 3]c and [Figure 2]d. Due to negative staining with TTF-1 and thyroglobulin, primary thyroid carcinoma was excluded [Figure 3]e and [Figure 2]f. When evaluated comparatively with the primary breast cancer pathology, immunohistochemical findings were interpreted as consistent with breast cancer metastasis. The patient continued receiving treatment with letrozole + ibandronic acid and a control visit at the outpatient clinic was scheduled on the date of the next PET/CT scan.

 > Discussion Top

Only 1%–3% of neoplastic lesions seen in the thyroid gland are of extrathyroidal origin although there is a rich blood supply in the thyroid gland.[4],[5],[6] The most common source of metastasis to the thyroid gland appears to be renal cell carcinoma (RCC), followed by lung cancer and gastrointestinal tumors, and breast cancer may also metastasize to the thyroid gland.[7],[8],[9],[10] According to postmortem studies, metastasis to the thyroid gland is mostly caused by breast cancer and these occult tumors may not be clinically diagnosed.[3],[11] The follow-up and treatment approaches to thyroid metastasis and primary thyroid cancer differ from each other; therefore, differential diagnosis is critically important in prognosis.

Most cases of breast cancer with metastasis in the thyroid gland are diffuse metastatic disease.[12] After primary breast cancer surgery, thyroid metastasis may occur as late as 12 years and is generally associated with poor prognosis.[3],[13] While FNAC is usually used in the differential diagnosis of thyroid nodules, it may not always be easy to distinguish primary thyroid tumors from metastatic lesions.[14] Immunohistopathological analysis should be performed to confirm the diagnosis of metastatic breast cancer. Negative immunohistochemical staining for thyroglobulin and TTF-1 in the thyroid biopsy, and similar staining results for GATA-3, ER, PR, and HER-2 in breast and thyroid biopsy provides the distinction between primary thyroid cancer and metastatic breast cancer. As shown in [Figure 3]e and [Figure 3]f, malignant cells were not stained for thyroglobulin and TTF-1, which confirms that the lesions were not of thyroid origin.

While preoperative PET/CT is not routinely recommended in all patients newly diagnosed with breast cancer scheduled for surgery, it should definitely be performed in those with locally advanced or metastatic disease.[15] Because, according to the current literature, the benefit of mastectomy in prolonging overall survival has not been shown in metastatic breast cancer.[16] Although there was no symptom to suggest systemic metastasis before mastectomy in our case, the metastasis in the axillary lymph node warranted systemic staging prior to primary breast surgery. Furthermore, despite the fact that CDK 4/6 inhibitors or other new oncology drugs are included in current treatment guidelines, as in our case, it remains an important problem that not all patients may access these drugs due to high costs.[17]

 > Conclusion Top

The case presented herein emphasizes the importance of known clinical history of cancer in the approach to thyroid lesions with suspected malignancy. Although rare, it should be kept in mind that thyroid lesions may be metastatic, especially in patients diagnosed with RCC and breast cancer. In cases where no neoplastic findings are seen in thyroid FNAC despite a clinical suspicion of malignancy, a repeat biopsy should be considered due to the possibility of falsenegative results. It is critically important to distinguish metastatic lesions from primary thyroid cancer owing to the different treatment and prognosis of these tumors.

Statement of ethics

All diagnostic and therapeutic procedures were in accordance with ethical standards of the Institutional and National Research Committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent for the case to be published (including images, case history, and data) was obtained from the patient for publication of this case report, including accompanying images.

Author contributions

All authors made substantial contributions to the conception and design and/or acquisition of data and/or analysis and interpretation of data, participated in drafting the article or revising it critically for important intellectual content, and gave their final approval of the version to be submitted and any revised version.

Declaration of patient consent

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

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 > References Top

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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. 4
Bayram F, Soyuer I, Atmaca H, Demirci D, Gokce C, Canoz O, et al. Prostatic adenocarcinoma metastasis in the thyroid gland. Endocr J 2004;51:445-8.  Back to cited text no. 5
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Nixon IJ, Coca-Pelaz A, Kaleva AI, Triantafyllou A, Angelos P, Owen RP, et al. Metastasis to the thyroid gland: A critical review. Ann Surg Oncol 2017;24:1533-9.  Back to cited text no. 7
Russell JO, Yan K, Burkey B, Scharpf J. Nonthyroid metastasis to the thyroid gland: Case series and review with observations by primary pathology. Otolaryngol Head Neck Surg 2016;155:961-8.  Back to cited text no. 8
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Moghaddam PA, Cornejo KM, Khan A. Metastatic carcinoma to the thyroid gland: A single institution 20-year experience and review of the literature. Endocr Pathol 2013;24:116-24.  Back to cited text no. 10
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Pensabene M, Stanzione B, Cerillo I, Ciancia G, Cozzolino I, Ruocco R, et al. It is no longer the time to disregard thyroid metastases from breast cancer: A case report and review of the literature. BMC Cancer 2018;18:146.  Back to cited text no. 12
Plonczak AM, DiMarco AN, Dina R, Gujral DM, Palazzo FF. Breast cancer metastases to the thyroid gland-an uncommon sentinel for diffuse metastatic disease: A case report and review of the literature. J Med Case Rep 2017;11:269.  Back to cited text no. 13
Magers MJ, Dueber JC, Lew M, Pang JC, Davenport RD. Metastatic ductal carcinoma of the breast to the thyroid gland diagnosed with fine needle aspiration: A case report with emphasis on morphologic and immunophenotypic features. Diagn Cytopathol 2016;44:530-4.  Back to cited text no. 14
Caresia Aroztegui AP, García Vicente AM, Alvarez Ruiz S, Delgado Bolton RC, Orcajo Rincon J, Garcia Garzon JR, et al. 18F-FDG PET/CT in breast cancer: Evidence-based recommendations in initial staging. Tumour Biol 2017;39:1010428317728285.  Back to cited text no. 15
Tosello G, Torloni MR, Mota BS, Neeman T, Riera R. Breast surgery for metastatic breast cancer. Cochrane Database Syst Rev 2018;3:CD011276.  Back to cited text no. 16
Barrios CH, Reinert T, Werutsky G. Access to high-cost drugs for advanced breast cancer in Latin America, particularly trastuzumab. Ecancermedicalscience 2019;13:898.  Back to cited text no. 17


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