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Ectopic thyroid tissue in the breast: A case report

  • Zheng Gong , Yan Yang and Zegang Liu EMAIL logo
Published/Copyright: June 14, 2023
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Open Life Sciences
From the journal Open Life Sciences Volume 18 Issue 1

Abstract

Ectopic thyroid tissue is a rare condition manifested as the appearance of thyroid tissue outside the thyroid gland. Here, we report a case of ectopic thyroid tissue in the breast. A 48-year-old Chinese woman who was diagnosed with breast cancer received modified radical mastectomy. A thyroid tissue was found on subsequent pathological examination. The ectopic thyroid tissue was confirmed by immunohistochemistry staining of thyroid biomarkers, including thyroglobulin, thyroid transcription factor-1, and thyroid peroxidase. Currently, abnormal thyroid anlage descent is the main theory to explain ectopic thyroid tissue, especially lingual thyroid. However, it is far-fetched to explain the pathogenesis of ectopic thyroid tissues existed in organs or tissues far from thyroid such as iris, cardiac, pulmonary, duodenal, adrenal, and vertebral. Here, we reviewed the previous cases of ectopic thyroid tissue in breast and proposed a “entoderm migration” theory to explain distant ectopic thyroid tissues based on embryonic development perspective.

Keywords: ectopic thyroid tissue; breast; embryology; case report

1 Introduction

Ectopic thyroid tissue is a rare condition accounts about 1 case per 100,000 to 300,000 persons, and its pathogenesis is not clear [1]. The majority of patients with thyroid ectopia are asymptomatic and have been considered benign. Since thyroid sarcomas tend to spread to the breast and thoracic cavity, it is important to confirm whether there are thyroid cancer especially thyroid sarcomas when an ectopic thyroid tissue is diagnosed. The current theory considered that abnormal migration of thyroid anlage during the embryonic period resulting ectopic thyroid tissue especially lingual thyroid [2]. However, this theory is defective to explain thyroid tissues existed in the areas which is far from the thyroid anlage migration path. In this case report, we presented a rare case of breast ectopic thyroid tissue and proposed a “entoderm migration” theory to interpret its pathogenesis. We also discussed differential diagnosis between thyroid ectopia and thyroid sarcomas and reviewed the literature associated with ectopic thyroid tissue.

2 Case presentation

In July 2018, a 48-year-old Chinese woman came to our hospital searching for further breast cancer therapy. Before admitted to our hospital, the patient had accepted treatment in other hospital, because of left breast mass. In the previous hospital, she underwent a surgical resection of left breast mass and post-operation pathological examination confirmed left breast invasive ductal carcinoma. For further treatment, she came to our hospital. The patient had no history of other malignancy, smoking, or drinking history. She had no family history of any cancer or thyroid diseases. When she was admitted to our hospital, there were no inflammatory signs and no anemia or dyspnea. Physical examination indicated a surgical incision in the outer lower quadrant of left breast, 5.6 cm away from nipple. There were also touchable enlarged lymph nodes in the left axillary. The thyroid ultrasound scan did not find any nodules. The thyroid function tests were normal: thyrotropin (TSH) 1.51 µIU/mL (0.49–4.91 µIU/mL), free thyroxine (FT4) 10.49 pmol/L (7.64–16.03 pmol/L), and free triiodothyronine (FT3) 4.76 pmol/L (3.28–6.47 pmol/L). Because the patient had been diagnosed as breast carcinoma by pathological examination, she received modified radical mastectomy in our hospital. After surgery, the excised breast tissue went on pathological examination to confirm the pathological type of tumor. A touchable hard area in the outer upper quadrant was found. The transection of this hard area showed colors of sallow, different from the neighboring tissue. To further explore the histological characteristics, this area was sliced and performed HE staining. The HE staining image (Figure 1) showed mammary gland structures including glandular acinus and cystic hyperplasia, which accompanied usual ductal hyperplasia and columnar cell lesions. Moreover, the thyroid-like structures were found besides the breast tissue and was precisely the tissue of the color of sallow which was mentioned above. The thyroid tissue regions had obvious thyroid-like follicles that containing pink colloid and were surrounded by cells with similar character of thyroid follicular epithelial cells (Figure 2a). There were no cancer cells found in all slices. To explore whether the regions were thyroid tissues, immunohistochemistry (IHC) staining was performed. IHC staining indicated that thyroglobulin (TG) distributing in thyroid follicles, suggesting the origin of thyroid tissues (Figure 2b). Thyroid transcription factor-1 (TTF-1) expressed in cells which surrounding follicles revealed follicular cells (Figure 2c). Thyroid peroxidase (TPO) existed in the apical membrane of the thyrocyte further confirmed ectopic thyroid gland (Figure 2d). Negative staining of biomarkers such as Ki67 and Galectin-3 excluded possibility of thyroid cancer (data not shown).

Figure 1 Ectopic thyroid tissue found in breast. Hematoxylin and eosin (HE) staining shows thyroid-like structure (*) and breast structure (triangles). The scale bar is 1 mm.
Figure 1

Ectopic thyroid tissue found in breast. Hematoxylin and eosin (HE) staining shows thyroid-like structure (*) and breast structure (triangles). The scale bar is 1 mm.

Figure 2 IHC staining of ectopic thyroid tissue. (a) HE staining shows TFCs and colloids. (b) Positive immunohistochemistry staining of TG. (c) Positive staining of TTF-1. (d) Positive staining of TPO. The scale bar is 100 μm.
Figure 2

IHC staining of ectopic thyroid tissue. (a) HE staining shows TFCs and colloids. (b) Positive immunohistochemistry staining of TG. (c) Positive staining of TTF-1. (d) Positive staining of TPO. The scale bar is 100 μm.

  1. Informed consent: Informed consent has been obtained from all individuals included in this study.

  2. Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenets of the Helsinki Declaration, and has been approved by the authors’ institutional review board or equivalent committee.

3 Discussion

An ectopic thyroid is first described by Hickman in 1869 and is defined as thyroid tissue that is not located in the second to fourth tracheal cartilages [3]. Ectopic thyroid is a rare condition and has been reported in tracheal, submandibular, lateral cervical region, etc. [4,5,6]. However, there are only a few reports about ectopic thyroid tissue in breast. Teixeria et al. first reported a case of ectopic thyroid tissue in breast [7]. In this case, the 85-year-old woman with surgical history of total thyroidectomy was diagnosed with ectopic thyroid in breast and received surgical excision. The author raised the question of whether the mild hyperthyroid status was an iatrogenic hyperthyroidism or a result of functioning residual ectopic thyroid tissue. Based on our case here, although ectopic thyroid tissue existed in breast, the thyroid function of the patient was normal. Ectopic thyroid tissue in the breast seems not affect thyroid function. Joseph et al. reported an ectopic intrathoracic thyroid tissue with breast carcinoma [8]. They proposed that it is important to confirm the nature of intrathoracic mass, because the treatment plan should be entirely changed if the mass is a metastatic lymph node. It has been reported that thyroid sarcomas tend to spread to the breast, so it is crucial to distinguish ectopic thyroid tissue from thyroid sarcoma. The diagnosis of thyroid sarcoma relies mainly on IHC staining. Thyroid follicular dendritic cell sarcoma (FDCS) is a malignancy originates from follicular dendritic cells. Seyed-Alagheband et al. reported that this tumor showed positive dendritic cell markers including CD21, CD23, CD35, CD45, and clusterin. Moreover, CD21 and CD35 have higher sensitivity and specificity [9]. Besides FDCS, primary thyroid synovial cell sarcoma (SVS) is another tumor need to be considered. Primary thyroid SVS is a malignancy with poor biological behavior. The tumor is aggressive and shows evidence of distant metastasis. The expression of EMA, CK17, CK19, BCL-2, and TLE1 can help to confirm Primary thyroid SVS [10].

The etiology of ectopic thyroid tissue is not fully understood. Moon et al. reported an ectopic thyroid tissue in breast and indicated that it is difficult to explain this condition by common abnormal migration theory, because breast is distant from the path of thyroid gland embryological development [11]. The thyroid gland contains two cell types, which are thyroid follicular cells (TFCs) and C cells. During embryo development, these cells come from different places of blastoderm and develop in different period [12]. As is known, thyroid gland development mainly contains three processes [13]. First, the thyroid anlage appears at a 3-week human embryo. Second, the anlage migrates to the thyroid place during 6–7 weeks. Third, the ultimobranchial body migrates to thyroid gland and differentiates to C cells and then the development of thyroid gland is finished. To understand the pathogenesis, most research and theories focused on the migration path of thyroid anlage and could explain ectopic thyroid gland around thyroglossal duct. But the migration theory hardly gives explanation to distant ectopic thyroid, such as esophageal thyroid [14].

The embryonic development is a complex and precisely regulated process. It involves many biological activities including cell migration and differentiation. For example, primitive streak cells move away from the original positions and develop into endoderm and mesoderm. In the period of 3-week embryo, paraxial mesoderm develops into somites and begins to differentiate in the period of 4-week embryo accompanied by cell position changing. Through the analysis of embryonic development, we found that the time of thyroid anlage formation and migration overlaps with somite formation and differentiation. Hence, we proposed a theory to explain distant ectopic thyroid. The thyroid anlage appears in entoderm and forms a small hole toward the mesoderm. At this stage, two cell layers of entoderm and mesoderm are very closed in space, giving the possibility for abnormal cell exchanging. During cardiovascular system development, dorsal aorta and primitive heart tube are close to endoderm in space and may explain why the thyroid tissue could occur in aorta or heart. In the period of 3-week embryo, some cells from thyroid anlage may abnormally leave from the position and migrate into mesoderm and mix with somite cells. Then, the thyroid anlage cells will move to different areas following somite developmental processes. Also, a small number of thyroid anlage cells could move through mesoderm to ectoderm, which will develop into epidermis and breast gland. Considering the probability of reaching the ectoderm through the mesoderm is lower than that of directly reaching the mesoderm, the incidence of breast ectopic thyroid tissue is lower than other parts of the body.

This theory could explain the etiology of breast ectopic thyroid tissue and other types of distant ectopic thyroid. Because thyroid anlage cells in entoderm migrate to different positions and move along with another structure, ectopic thyroid will exist in tracheal, lateral cervical, axillary, carotid, duodenal, vertebral body, and other distant places [15,16,17].

In addition to the correlation between breast and ectopic thyroid in embryonic development, some clinical researches have indicated relationships in breast cancer and thyroid cancer [18,19]. It has been reported that breast cancer patient is more likely occurred by thyroid cancer [20]. Thus, more researches need to be done to clarify the molecular mechanisms of ectopic thyroid tissue in the breast.

4 Conclusion

Overall, we reported a rare case of ectopic thyroid tissue in breast, reviewed the literature, and indicated the importance of distinguishing from sarcomas. More importantly, we proposed the “entoderm migration” theory to explain the etiology of distant thyroid ectopia. This article raises awareness of the causes and diagnosis of ectopic thyroid tissues.

Acknowledgments

We thank the patient who contributed to this study, as well as the staff of each department.

  1. Funding information: Authors state no funding involved.

  2. Author contributions: Z.G.L. designed the research. Z.G. and Y.Y. analyzed and interpreted the data. Z.G. drafted the article. Z.G.L. and Y.Y. revised the article.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2023-03-16
Revised: 2023-05-01
Accepted: 2023-05-15
Published Online: 2023-06-14

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
https://doi.org/10.1515/biol-2022-0628
Keywords for this article
ectopic thyroid tissue; breast; embryology; case report
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  217. Bamboo charcoal affects soil properties and bacterial community in tea plantations
  218. Optimization of biogas potential using kinetic models, response surface methodology, and instrumental evidence for biodegradation of tannery fleshings during anaerobic digestion
  219. Understory vegetation diversity patterns of Platycladus orientalis and Pinus elliottii communities in Central and Southern China
  220. Studies on macrofungi diversity and discovery of new species of Abortiporus from Baotianman World Biosphere Reserve
  221. Food Science
  222. Effect of berrycactus fruit (Myrtillocactus geometrizans) on glutamate, glutamine, and GABA levels in the frontal cortex of rats fed with a high-fat diet
  223. Guesstimate of thymoquinone diversity in Nigella sativa L. genotypes and elite varieties collected from Indian states using HPTLC technique
  224. Analysis of bacterial community structure of Fuzhuan tea with different processing techniques
  225. Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta
  226. Mycobiota in Slovak wine grapes: A case study from the small Carpathians wine region
  227. Elemental analysis of Fadogia ancylantha leaves used as a nutraceutical in Mashonaland West Province, Zimbabwe
  228. Microbiological transglutaminase: Biotechnological application in the food industry
  229. Influence of solvent-free extraction of fish oil from catfish (Clarias magur) heads using a Taguchi orthogonal array design: A qualitative and quantitative approach
  230. Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine
  231. The potential for the use of leghemoglobin and plant ferritin as sources of iron
  232. Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM
  233. Bioengineering and Biotechnology
  234. Biocompatibility and osteointegration capability of β-TCP manufactured by stereolithography 3D printing: In vitro study
  235. Clinical characteristics and the prognosis of diabetic foot in Tibet: A single center, retrospective study
  236. Agriculture
  237. Biofertilizer and NPSB fertilizer application effects on nodulation and productivity of common bean (Phaseolus vulgaris L.) at Sodo Zuria, Southern Ethiopia
  238. On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies
  239. Exopolysaccharides from Pseudomonas tolaasii inhibit the growth of Pleurotus ostreatus mycelia
  240. A transcriptomic evaluation of the mechanism of programmed cell death of the replaceable bud in Chinese chestnut
  241. Melatonin enhances salt tolerance in sorghum by modulating photosynthetic performance, osmoregulation, antioxidant defense, and ion homeostasis
  242. Effects of plant density on alfalfa (Medicago sativa L.) seed yield in western Heilongjiang areas
  243. Identification of rice leaf diseases and deficiency disorders using a novel DeepBatch technique
  244. Artificial intelligence and internet of things oriented sustainable precision farming: Towards modern agriculture
  245. Animal Sciences
  246. Effect of ketogenic diet on exercise tolerance and transcriptome of gastrocnemius in mice
  247. Combined analysis of mRNA–miRNA from testis tissue in Tibetan sheep with different FecB genotypes
  248. Isolation, identification, and drug resistance of a partially isolated bacterium from the gill of Siniperca chuatsi
  249. Tracking behavioral changes of confined sows from the first mating to the third parity
  250. The sequencing of the key genes and end products in the TLR4 signaling pathway from the kidney of Rana dybowskii exposed to Aeromonas hydrophila
  251. Development of a new candidate vaccine against piglet diarrhea caused by Escherichia coli
  252. Plant Sciences
  253. Crown and diameter structure of pure Pinus massoniana Lamb. forest in Hunan province, China
  254. Genetic evaluation and germplasm identification analysis on ITS2, trnL-F, and psbA-trnH of alfalfa varieties germplasm resources
  255. Tissue culture and rapid propagation technology for Gentiana rhodantha
  256. Effects of cadmium on the synthesis of active ingredients in Salvia miltiorrhiza
  257. Cloning and expression analysis of VrNAC13 gene in mung bean
  258. Chlorate-induced molecular floral transition revealed by transcriptomes
  259. Effects of warming and drought on growth and development of soybean in Hailun region
  260. Effects of different light conditions on transient expression and biomass in Nicotiana benthamiana leaves
  261. Comparative analysis of the rhizosphere microbiome and medicinally active ingredients of Atractylodes lancea from different geographical origins
  262. Distinguish Dianthus species or varieties based on chloroplast genomes
  263. Comparative transcriptomes reveal molecular mechanisms of apple blossoms of different tolerance genotypes to chilling injury
  264. Study on fresh processing key technology and quality influence of Cut Ophiopogonis Radix based on multi-index evaluation
  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
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