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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 7  |  Page : 1515-1518

Metastases to the thyroid gland: A retrospective analysis of 21 patients


1 Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, P.R. China
2 Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, P.R. China
3 Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, P.R. China

Date of Web Publication19-Dec-2018

Correspondence Address:
Xiaojia Wang
1 Banshandong Road, Hangzhou, Zhejiang 310022
P.R. China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_435_16

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 > Abstract 


Background: Metastases to the thyroid gland are uncommon and often occur in patients with advanced metastatic diseases. The management and prognosis of secondary thyroid malignancies (STMs) are not well established. This retrospective study reported the incidence, clinical characteristics, treatment, and prognosis of STM in patients with metastatic tumors.
Subjects and Methods: A total of 21 cases (1.2% incidence) diagnosed by fine-needle aspiration between January 2006 to December 2014 in a single center were reviewed. Survival analysis was made by Kaplan–Meier method.
Results: The primary malignancies included esophagus cancer (7/21, 33.33%), breast cancer (6/21, 28.57%), head and neck cancer (3/21, 14.29%), unknown primary cancer (3/21, 14.29%), and lung cancer (2/21, 9.52%). The mean overall survival (OS) from diagnosis of primary malignancies was 57.26 months (95% confidence interval [CI]: 31.19–83.34) and the 2-year OS rate was 61.9%, and the mean OS from diagnosis of thyroid metastases was 31.20 months (95% CI: 12.23–50.18) and the 2-year OS rate was 34.3%. Patients with the head and neck cancer and breast cancer had better survival than other patients (from diagnosis of primary malignancies, P < 0.001; from diagnosis of thyroid metastases, P = 0.03). Histological types were also related to OS (from diagnosis of primary malignancies, P = 0.039; from diagnosis of thyroid metastases, P = 0.130). In addition, thyroidectomy may improve OS for patients with isolated metastases.
Conclusion: The prognosis of STMs basically depends on the anatomic sites and histological types of primary cancers, and thyroidectomy may be considered for patients with isolated metastases.

Keywords: Fine-needle aspiration, primary malignancy, secondary thyroid malignancy, thyroidectomy


How to cite this article:
Wang X, Huang Y, Zheng Z, Cao W, Chen B, Wang X. Metastases to the thyroid gland: A retrospective analysis of 21 patients. J Can Res Ther 2018;14:1515-8

How to cite this URL:
Wang X, Huang Y, Zheng Z, Cao W, Chen B, Wang X. Metastases to the thyroid gland: A retrospective analysis of 21 patients. J Can Res Ther [serial online] 2018 [cited 2019 Aug 19];14:1515-8. Available from: http://www.cancerjournal.net/text.asp?2018/14/7/1515/228639




 > Introduction Top


Secondary thyroid malignancies (STMs) are uncommon and usually considered as a terminal event. Most STMs are carcinomas. The primary malignancies could originate from numerous organs, with different biological heterogeneities. Kidney, lung, head and neck, and breast were reported as the frequent sources of metastases.[1],[2],[3],[4],[5],[6],[7] Nevertheless, the prognoses of patients with different primary tumors have not been well studied. The primary aim of the current study was to investigate the incidence and original sites of metastases to thyroid and explore the impact of various primary malignancies on long-term survival in patients with STMs in a cancer hospital in China.


 > Subjects and Methods Top


Patient eligibility

This retrospective study was performed through a review of medical records of 21 patients who had been diagnosed as metastatic malignancies to the thyroid in the Zhejiang Cancer Hospital (Hangzhou, China). These patients were selected from pathology archives of all patients who underwent thyroid nodule fine-needle aspirations (FNAs) between January 2006 and December 2014. Patient inclusion criteria are as follows: (1) Pathologically proved nonthyroidal primary malignancy. (2) The thyroid metastases confirmed by FNAs. Patient exclusion criteria are as follows: (1) All primary thyroid tumors, lymphomas, and sarcomas. (2) Nonthyroidal cancers with direct invasion into thyroid. The study was approved by the Ethics Committee of Zhejiang Cancer Hospital.

Statistical analysis

Overall survival (OS) was calculated from primary diagnosis to date of last follow-up or death and from thyroid metastasis to date of last follow-up or death. The survival curves were plotted based on the Kaplan-Meier method. Differences in survival were compared by the log-rank test. A value of P < 0.05 was considered statistically significant. Analyses were conducted using SPSS version 17.0 (SPSS Inc., Chicago, IL, USA).

Follow-up

Follow-up data were obtained by retrospective review of the patient's medical records and telephone surveys. Patients were followed up at 3- to 6-month intervals for the first 5 years, and after that, at 1-year interval. The last follow-up was on January 30, 2016.


 > Results Top


Clinical characteristics

Overall, 1754 patients were conducted with the thyroid nodule FNAs from 2006 to 2014; 21 of them were identified as having STMs, which accounted for 1.20% of all patients with thyroid nodule FNAs [Table 1]. This group comprised 11 males and 10 females with ages ranging from 42 to 79 years (median age, 58 years). The median interval between the diagnosis of thyroid metastasis and the diagnosis of primary malignancy was 12 months (range, 0–141 months).
Table 1: Clinical characteristics of patients diagnosed with secondary thyroid malignancy

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The most common primary malignancy was esophagus cancer (7/21, 33.33%), followed by breast cancer (6/21, 28.57%), head and neck cancer (3/21, 14.29%), unknown primary cancer (3/21, 14.29%), and the remaining was lung cancer (2/21, 9.52%). Thirteen (61.90%) patients did not have any metastatic disease at the time of their primary tumor diagnosis. Among those patients, 2 (15.38%) developed only thyroid metastases, and 11 (84.62%) finally developed metastases in other sites besides the thyroid. Five (23.81%) patients were diagnosed with a primary malignancy and STM simultaneously. The primary cancers of three (14.29%) cases were unknown.

Following clinical determination of STM, 14 (66.67%) patients received chemotherapy and/or radiotherapy, 1 (4.76%) patient had partial thyroidectomy with no postoperative treatment, and 6 (28.57%) patients quit any anticancer therapy for the poor performance status.

Follow-up and prognosis

Mean follow-up duration was 42 months (range 3–141 months). No patient was lost to follow-up. Fifteen patients died from diseases during the follow-up. For all the patients, the mean OS from diagnosis of primary malignancy was 57.26 months (95% confidence interval [CI]: 31.19–83.34) and the 2-year OS rate was 61.9%, and the mean OS from time diagnosis of thyroid metastasis was 31.20 months (95% CI: 12.23–50.18) and the 2-year OS rate was 34.3%. There were significant differences in OS between patients with different primary malignancies. As demonstrated in [Figure 1], patients with the head and neck cancer and breast cancer had the better survival than other patients (breast cancer vs. esophagus cancer vs. head and neck cancer vs. lung cancer vs. unknown primary cancer: 81.61 vs. 21.71 vs. 96.67 vs. 34.50 vs. 4.0 months, from time of primary malignancy diagnosis, P < 0.001; 20.48 vs. 13.71 vs. 76.00 vs. 28.50 vs. 4.00 months, from time of thyroid metastasis diagnosis, P = 0.03, [Table 2]). Histological type was also related to OS [Figure 2]. The mean OS from time of primary malignancy diagnosis for patients with adenocarcinoma seemed to be longer than those with squamous cell carcinoma or other type (adenocarcinoma vs. squamous cell carcinoma vs. other type: 85.76 vs. 48.09 vs. 12.00 months, from time of primary malignancy diagnosis, P = 0.039; 24.89 vs. 37.91 vs. 8.00 months, from time of thyroid metastasis diagnosis, P = 0.130, [Table 2]).
Figure 1: Kaplan–Meier curves of overall survival of patients with various primary malignancies. (a) Overall survival from primary diagnosis; (b) overall survival from thyroid metastasis diagnosis

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Table 2: Overall survival estimates

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Figure 2: Kaplan–Meier curves of overall survival of patients with different histological type. (a) Overall survival from primary diagnosis; (b) overall survival from thyroid metastasis diagnosis

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 > Discussion Top


The majority of thyroid malignancies are primary thyroid cancers, and the most common subtypes are well-differentiated papillary and follicular carcinoma, which often have good prognosis. STMs are rarely observed in clinic; however, they usually exist in patients with advanced metastatic diseases. Their treatment also varies considerably from that of primary thyroid cancers.[8],[9],[10] Therefore, the distinction of STMs from primary thyroid tumors is really important. However, STMs often have difficulties in diagnosis, especially if they present years after primary cancers. As a minimally invasive method, FNA is the preferred process in the evaluation of thyroid nodules.[1] Previous studies have demonstrated the accuracy of FNA in the cytologic diagnosis of STMs.[11],[12],[13],[14] Hegerova et al. reported that the sensitivity of FNA in detecting STMs was 94% and the specificity was 100%.[11] FNA cytology is more feasible than postoperative histopathological examination for earlier diagnosis of STMs. It not only avoids inappropriate thyroid resection in some cases but may also reveal the unknown primary cancer.

The current research demonstrated that STMs were account for 1.20% of patients with the thyroid nodule FNAs in our hospital. It is consistent with prior report that 1.4%–3% of all patients who have surgery for suspected cancer in the thyroid gland were STMs.[15] Nevertheless, in autopsy studies, the incidence rises, which ranges from 1.9% to 24%.[11] Such a noticeable difference between clinical and autopsy studies is closely related to the diagnostic difficulty in clinical practice. Our study confirmed that FNA was a good choice for the diagnosis of STMs. All the cases in our series were diagnosed as STMs by FNA. One case was further confirmed by thyroidectomy. A previous history of nonthyroid malignancy contributes to an accurate diagnosis of STMs; however, they also can be the very first sign of cancer in patients with no symptoms and prior cancer history. Our data revealed 61.90% (13/21) of cases had a history of prior cancer, and metastases progressed 4–111 months after primary diagnosis. About 38.10% (8/21) cases did not have an earlier history of malignancy during FNA. In these eight cases, the primary malignancies of three cases were unknown.

In the present study, the most common primary malignancy site was the esophagus (7/21, 33.33%), followed by breast (6/21, 28.57%), head and neck (3/21, 14.29%), unknown (3/21, 14.29%), and lung (2/21, 9.52%). Esophagus accounted for a large proportion of cases in our series. It is consistent with prior reviews that the gastrointestinal organs, especially esophagus and stomach, are the frequent sites of primary malignancy leading to STMs in the Asian area.[3],[7] Instead, in the USA, cancers of kidney, breast, and lung are the most common cancer types that metastasize to the thyroid.[5],[11],[15] The incidence of those malignancies varies in distinct study populations; consequently, it is difficult to identify which of those malignancies dominates the original source of STMs.

In our series, esophageal and lung carcinomas possess relative poor prognosis, and unknown primary malignancy has the worst outcome with fast disease progression and death within just months of diagnosis. The present study also found that the prognosis was significantly better in patients with adenocarcinoma compared to patients with squamous cell carcinomas or other histological type; although following the diagnosis of STMs, the OS did not have significant differences between them. Therefore, these results indicated that the different outcomes among those patients are determined by high heterogeneity of the biological behavior of primary tumors.

The appropriate management of STMs is controversial. Patients with STMs usually have Stage IV disease or poor performance status, and probably, thyroidectomy would not be considered once the thyroid nodules were detected. In our research, one patient diagnosed as thyroid only metastasis after laryngeal cancer surgery who underwent thyroidectomy over 9 years ago, and he/she is still alive in the last follow-up. From previous studies, improved survival was also observed in patients who underwent thyroidectomy for metastatic disease.[6],[7],[11],[16] Surgery was less commonly performed for metastatic disease, but thyroidectomy may be considered for patients with isolated metastasis to thyroid.


 > Conclusion Top


STMs are uncommon; however, it should be considered in patients with thyroid nodules and a history of cancer, and FNA is recommended for the diagnosis. Although this study is limited by its retrospective nature and the small sample size, it has demonstrated that the prognosis of STMs mainly depend on the type of primary cancers; it is really vital for making a precise diagnosis of the primary malignancy for patients with STMs.

Acknowledgment

The authors are thankful to Dr. Sheng Dai for helping in the editing of the manuscript.

Financial support and sponsorship

This study is financially supported by Grants LQ16H160012 from Zhejiang Provincial Natural Science Foundation of China and NSFC-81502618 from National Natural Science Foundation of China.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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Ko HM, Jhu IK, Yang SH, Lee JH, Nam JH, Juhng SW, et al. Clinicopathologic analysis of fine needle aspiration cytology of the thyroid. A review of 1,613 cases and correlation with histopathologic diagnoses. Acta Cytol 2003;47:727-32.  Back to cited text no. 1
    
2.
Smith SA, Gharib H, Goellner JR. Fine-needle aspiration. Usefulness for diagnosis and management of metastatic carcinoma to the thyroid. Arch Intern Med 1987;147:311-2.  Back to cited text no. 2
    
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Kim TY, Kim WB, Gong G, Hong SJ, Shong YK. Metastasis to the thyroid diagnosed by fine-needle aspiration biopsy. Clin Endocrinol (Oxf) 2005;62:236-41.  Back to cited text no. 3
    
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Ivy HK. Cancer metastatic to the thyroid: A diagnostic problem. Mayo Clin Proc 1984;59:856-9.  Back to cited text no. 4
    
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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. 5
    
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Calzolari F, Sartori PV, Talarico C, Parmeggiani D, Beretta E, Pezzullo L, et al. Surgical treatment of intrathyroid metastases: Preliminary results of a multicentric study. Anticancer Res 2008;28:2885-8.  Back to cited text no. 6
    
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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. 7
    
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Nguyen QT, Lee EJ, Huang MG, Park YI, Khullar A, Plodkowski RA, et al. Diagnosis and treatment of patients with thyroid cancer. Am Health Drug Benefits 2015;8:30-40.  Back to cited text no. 8
    
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Kim TY, Kim WG, Kim WB, Shong YK. Current status and future perspectives in differentiated thyroid cancer. Endocrinol Metab (Seoul) 2014;29:217-25.  Back to cited text no. 9
    
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Padma S, Sundaram PS. Radioiodine as an adjuvant therapy and its role in follow-up of differentiated thyroid cancer. J Cancer Res Ther 2016;12:1109-13.  Back to cited text no. 10
    
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Hegerova L, Griebeler ML, Reynolds JP, Henry MR, Gharib H. Metastasis to the thyroid gland: Report of a large series from the Mayo Clinic. Am J Clin Oncol 2015;38:338-42.  Back to cited text no. 11
    
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Aron M, Kapila K, Verma K. Role of fine-needle aspiration cytology in the diagnosis of secondary tumors of the thyroid – Twenty years' experience. Diagn Cytopathol 2006;34:240-5.  Back to cited text no. 12
    
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HooKim K, Gaitor J, Lin O, Reid MD. Secondary tumors involving the thyroid gland: A multi-institutional analysis of 28 cases diagnosed on fine-needle aspiration. Diagn Cytopathol 2015;43:904-11.  Back to cited text no. 13
    
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Michelow PM, Leiman G. Metastases to the thyroid gland: Diagnosis by aspiration cytology. Diagn Cytopathol 1995;13:209-13.  Back to cited text no. 14
    
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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. 15
    
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Papi G, Fadda G, Corsello SM, Corrado S, Rossi ED, Radighieri E, et al. Metastases to the thyroid gland: Prevalence, clinicopathological aspects and prognosis: A 10-year experience. Clin Endocrinol (Oxf) 2007;66:565-71.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2]



 

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