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Keywords:

  • thyroid cancer;
  • thyroid neoplasms/secondary;
  • metastasis;
  • thyroid surgery;
  • metastasectomy

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. EPIDEMIOLOGY
  5. CLINICAL PRESENTATION AND DIAGNOSTIC WORK UP
  6. GENERAL PRINCIPLES OF TREATMENT AND OUTCOME
  7. TREATMENT OUTCOMES IN RENAL CELL CARCINOMA
  8. TREATMENT OUTCOMES IN OTHER CARCINOMAS
  9. DISCUSSION
  10. CONCLUSION
  11. REFERENCES

Metastases to the thyroid gland are uncommon. Renal, lung, breast, and colon cancer and melanoma are the most common primary diseases implicated. Few retrospective series have been reported. Treatment decisions must be individualized, and will depend on the state of systemic disease. Selected patients could benefit from surgical treatment. Although most patients selected for surgery will not be cured, the aim of surgery is to avoid the complications of uncontrolled central neck disease. J. Surg. Oncol. 2014 109:36–41. © 2013 Wiley Periodicals, Inc.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. EPIDEMIOLOGY
  5. CLINICAL PRESENTATION AND DIAGNOSTIC WORK UP
  6. GENERAL PRINCIPLES OF TREATMENT AND OUTCOME
  7. TREATMENT OUTCOMES IN RENAL CELL CARCINOMA
  8. TREATMENT OUTCOMES IN OTHER CARCINOMAS
  9. DISCUSSION
  10. CONCLUSION
  11. REFERENCES

Metastasis to the thyroid gland infrequently presents as a surgical issue. However, the incidence of metastases to the thyroid reported in autopsy series is high. Up to 24% of patients who die of a malignancy have evidence of metastases within the thyroid gland at autopsy (Table I). In our institution, between 1986 and 2005, only 1% of patients who underwent thyroid surgery did so for metastasis to the gland [1].These results are in keeping with those of others groups, which demonstrates the highly select nature of patients treated surgically for metastatic disease to the thyroid.

Table I. Reported Incidence of Metastasis to Thyroid Gland in Autopsies Series
AuthorsYearIncidencePrimary sites
  • *

    Mortensen et al. and Shimaoka et al. primary lymphomas were excluded.

  • **

    Watanabe et al. from Annuals of the Pathological autopsy Cases of Japan (1969–1971). Local invasion of thyroid gland was excluded.

Autopsies of patients with known cancer history
Rice [7]19349/89 (10.1%)Not specified
Abrams et al. [8]194919/1,000 (1.9%)Breast, lung, colon, kidney
Mortensen et al. [10]195613/430 (3%)*Lung, breast, colon, kidney
Shimaoka et al. [11]1962156/1,871 (8.3%)Breast, lung, head and neck, melanoma, kidney
Silverberg et al. [4]196615/62 (24.1%)Lung, breast, prostate, bladder, colon, kidney
Watanabe et al. [72]1980309/13,862 (2%)**Breast, lung, kidney, gastrointestinal
Unselected autopsies
Willis [3]193310/170 (5.2%)Breast, kidney, gastric
Berge et al. [5]1971202/16,924 (1.2%)Breast, lung, kidney, colon, melanoma
Lam et al. [6]199867/12,955 (0.5%)Lung, breast, gastric, colon, kidney

The earliest description of metastasis to the thyroid can be found in Rudolph Virchow's Pathologie des Tumeurs [2], which contains a description of a testicular tumor metastatic to the thyroid. Despite the fact that the thyroid gland has one of the richest blood supplies in the human body, it is not a common site of metastasis. Experts have described factors that make the thyroid microenvironment unsuitable for metastasis [3]. Rupert Willis hypothesized that the fast arterial flow and the high concentration of both oxygen and iodine may act as barriers to the propagation of metastatic cells.

Many of those patients with metastatic disease will be identified on pre-operative investigation of a thyroid mass. However, some may undergo surgery for an assumed thyroid malignancy. The majority of patients will have a history of preceding malignancy, although for a few, the metastasis may be the mode of presentation of a disseminated malignancy. In select patients with resectable disease, and without an aggressive disseminated malignancy, surgery may be considered to avoid the complications related to uncontrolled central neck disease.

The objective of this paper is to review the current literature relating to the epidemiology, presentation, primary sites, and the management of metastasis to the thyroid gland.

EPIDEMIOLOGY

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. EPIDEMIOLOGY
  5. CLINICAL PRESENTATION AND DIAGNOSTIC WORK UP
  6. GENERAL PRINCIPLES OF TREATMENT AND OUTCOME
  7. TREATMENT OUTCOMES IN RENAL CELL CARCINOMA
  8. TREATMENT OUTCOMES IN OTHER CARCINOMAS
  9. DISCUSSION
  10. CONCLUSION
  11. REFERENCES

The most common primary location of metastasis to thyroid gland are the kidney, lung, breast, gastro-intestinal tract, and skin, with variations reported depending on the type of studies (autopsies vs. clinical series), geographical location and time period analyzed.

Although the precise incidence of metastasis to the thyroid is unknown, an approximation can be drawn from reports of autopsy reviews and cases-series analysis. The approximate incidence among patients without an antecedent history of cancer is between 0.5% and 5.2% (Table I) [3-6]. However, if patients with a previous history of malignancy are analyzed, it is more common: between 3.9% and 8.3% (Table I) [7-11]. The incidence in such series depends on the degree of scrutiny with which the post mortem gland is analyzed.

Breast and lung carcinomas are the most common primary sites of metastasis seen at post mortem in western countries [8], reflecting in part the prevalence of these tumors. This is likely to be affected by geographic variation in malignancy prevalence, as in Asia lung and gastrointestinal are the most common sites [6].

In surgical series, a wide variety of malignancies are reported to metastasize to the thyroid gland. When series of 10 or more patients are analyzed, renal cell carcinoma, followed by lung and breast carcinoma are the most common histological subtypes described (Table II). This suggests a slight but significant difference between autopsies and clinical series, as those patients selected for surgical management are more likely to have a less aggressive primary disease [12]. The gastrointestinal tract and the skin are also frequent sites of primary disease [13]. Recently, Chung et al. [14] reviewed all clinical reports available in the literature from 2000 to 2010, including both case reports and case series. In this analysis, 48% of cases were metastases from renal cancer, 10.4% from colorectal, 8.3% from lung, 7.8% were from breast cancer, and 4% from melanoma.

Table II. Reported Clinical Series of Metastasis to Thyroid Gland with more than 10 Cases
AuthorsYearInstitutionnPrimary sites
Note
  1. (*) This table includes patients that were treated mainly with surgery; however, case series marked with (*) include patients that were primarily diagnosed with Fine Needle Aspiration Cytology, and not necessarily treated with surgery.

Elliott et al. [76]1959Columbia Presbyterian14Breast, lung, kidney
Wychulis et al. [73]1964Mayo Clinic (1907–1962)14Kidney, breast, rectum, bladder
Harcourt et al. [78]1965University of Edinburg11Kidney, breast, melanoma, lung
Brady et al. [74]1977Hospital of Philadelphia10Lung
Ericcson et al. [81]1981University of Lund Hospital, Sweden,10Renal, melanoma
Czech et al. [75]1982Mayo Clinic (1960–1980)12Kidney, breast, lung
Ivy et al. [77]1984Mayo Clinic (1946–1982)30Kidney, breast, lung
Smith et al. [70] (*)1987Mayo Clinic (1980–1985)15Breast, lung, kidney
Michelow et al. [79] (*)1995South African Institute for Medical Research21Lung, gastrointestinal, melanoma, kidney
Rosen et al. [22]1995University of Toronto11Lung, breast, kidney, melanoma
Nakhjavani et al. [12] (*)1997Mayo Clinic (1985–1994)43Kidney, lung, breast
Chen et al. [13]1999Johns Hopkins Hospital10Kidney, lung
Heffess et al. [16]2002Armed Forces Institute of Pathology36Kidney
Wood et al. [27] (*)2004Royal Marsden Hospital15Kidney, others
Kim et al. [21] (*)2005Asan Medical Centre, Korea22Breast, Kidney, Colon, Lung, others
Mirallie et al. [33]2005Multicentric, France29Kidney, lung, gastrointestinal
Cichon et al. [34]2006Jagiellonian University, Poland17Kidney, uterus
Papi et al. [7]2007Multicentric, Italy36Lung, kidney, breast, esophagus
Calzolari et al. [36]2008Multicentric, Italy25Renal, lung, colon, breast
Iesalnieks et al. [29]2008Multicentric, Germany45Kidney
Machens et al. [80]2010Martin Luther University, Germany17Kidney
Nixon et al. [1]2010MSKCC21Kidney, melanoma, gastrointestinal

CLINICAL PRESENTATION AND DIAGNOSTIC WORK UP

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. EPIDEMIOLOGY
  5. CLINICAL PRESENTATION AND DIAGNOSTIC WORK UP
  6. GENERAL PRINCIPLES OF TREATMENT AND OUTCOME
  7. TREATMENT OUTCOMES IN RENAL CELL CARCINOMA
  8. TREATMENT OUTCOMES IN OTHER CARCINOMAS
  9. DISCUSSION
  10. CONCLUSION
  11. REFERENCES

While 60–80% of metastases are metachronous (following previously treated malignancy), 20–40% are synchronous (simultaneous) with the primary lesion [1, 14]. Indeed, in some cases, thyroid surgery may be the initial diagnostic event. The time from primary treatment to presentation of a metastasis in the thyroid gland varies from a few months in aggressive malignancies, to many years in less aggressive disease [14, 15]. Renal cell carcinomas have been reported up to 20 years following therapy for the primary lesion [12, 16].

The symptoms at presentation are similar to those associated with primary thyroid malignancies, which can result in a delayed diagnosis. Clinically evident metastases present most commonly as a palpable mass (72% of patients), while a minority of patients (28%) have a thyroid mass incidentally detected by imaging studies [17]. More advanced metastases may present with dysphagia or dysphonia, associated with invasion of adjacent structures. Eventually, replacement of normal thyroid parenchyma may result in thyroid dysfunction, with both hypo- and hyperthyroidism reported [18, 19]. It has been suggested that a multinodular architecture may predispose to the metastasis within the thyroid (59% of cases are in abnormal glands), but the reasons for this are not clear [14].The similarities in presentation between primary thyroid disease and metastasis highlights the need to enquire about a history of previous malignancy during preoperative assessment of the patient with a thyroid mass [12, 16].

The diagnostic work up is similar to that used in the assessment of a standard thyroid nodule. Although the development of modern imaging techniques (ultrasound, CT, MRI, FDG-PET) has increased the rate of detection of thyroid lesions, primary, and secondary disease cannot be easily differentiated due to the lack of specific imaging features [12, 20].

Detection of thyroid enlargement or a thyroid nodule on imaging studies in a patient with present or past history of another primary malignant tumor should always raise the suspicion of metastasis to the thyroid.

In the absence of clear imaging characteristics, the use of fine needle aspiration (FNA) can help differentiate between benign and malignant thyroid lesions. However, even with cytology, differentiation between primary and secondary thyroid malignancies remains a challenge [21]. Although a high sensitivity has been reported for FNA in patients with various metastatic carcinomas to the thyroid gland, the accuracy of FNA is around 50% [1, 12, 22]. Immunohistochemical demonstration of markers specific for thyroid, such as thyroglobulin, can distinguish a primary thyroid tumor from a metastatic lesion and help improve this accuracy [16, 23-25]. It can be particularly difficult to differentiate between a high grade metastasis and primary anaplastic thyroid cancer [20]. In fact, 20–30% of primary anaplastic thyroid carcinomas are negative for thyroid specific immunohistochemistry [20, 26]. Therefore, a tumor directed immunohistochemical testing, based on a knowledge or suspicion of a certain primary location, is necessary to obtain an accurate diagnosis of metastatic thyroid carcinoma.

Other diagnostic procedures, including a core biopsy or even surgical excision (total thyroidectomy, or lobectomy) can be used to obtain tissue for diagnosis [1, 27]. With a combination of immunohistochemical markers, the diagnosis of metastatic carcinoma to the thyroid can be obtained unequivocally For example, the combination of a negative TTF-1 and thyroglobulin, with a positive CD 10 in case of renal cell carcinoma [28]. These diagnostic challenges demonstrate the need to communicate a suspicious of metastatic disease to the pathologist involved in analyzing diagnostic tissue samples.

GENERAL PRINCIPLES OF TREATMENT AND OUTCOME

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. EPIDEMIOLOGY
  5. CLINICAL PRESENTATION AND DIAGNOSTIC WORK UP
  6. GENERAL PRINCIPLES OF TREATMENT AND OUTCOME
  7. TREATMENT OUTCOMES IN RENAL CELL CARCINOMA
  8. TREATMENT OUTCOMES IN OTHER CARCINOMAS
  9. DISCUSSION
  10. CONCLUSION
  11. REFERENCES

In the diagnostic work-up of a new thyroid mass in those patients with a previous history of malignancy, the possibility of metastasis to the thyroid should be always considered. Multidisciplinary work-up is mandatory to distinguish a metastasis from a primary lesion, since treatment and prognosis are significantly different.

Although in general distant metastases are a poor prognostic sign, metastasis to the thyroid does not seem to result in a worse outcome when compared with metastasis to other sites [17]. Thirty-five percent to 80% of patients who present with metastases to the thyroid have metastatic disease in other locations at the time of diagnosis of the thyroid metastasis [14, 17, 29]. Life expectancy depends primarily on the prognosis of the primary tumor [17]. Select patients with metastatic disease isolated to the thyroid gland may expect a better outcome, and even cure on occasion, when the underlying malignancy is treatable [13, 30].

Although for select patients treatment has traditionally been surgical, there is no clear consensus on the exact indications for surgery. The decision to perform a metastasectomy is made on an individual case basis, depending on the grade and stage of the primary cancer, local extension of the thyroid lesion, and the general condition of the patient. Surgery may be curative or palliative according to the completeness of the resection, the presence of extrathyroidal disease, and the status of disease elsewhere in the body [31]. Surgery is currently considered the only treatment with the potential for cure assuming disease is limited to the thyroid [29]. The ideal surgical candidate is a patient with minimal disease in the thyroid and no evidence of disease in other sites. In such patients, even those who have previously had metastasectomy elsewhere, good outcomes have been reported [32].

Those patients, who are deemed not suitable for surgery due to burden of disease, have a poor prognosis [17]. The selection bias in surgical series makes any comparison unreliable.

Our institutional data shows that the median overall survival of patients following surgical treatment of thyroid metastasis was 2 years. The 5-year survival rate of 42% is similar to that reported by other groups [1, 29, 33]. However, in contrast to the poor survival rates, control of the central neck was achieved in 90% of cases. No patients in our series died of uncontrolled central neck disease [1].

There is no clear consensus about the extent of the surgical procedure that should be performed in patients with thyroid metastases [13]. Thyroid lobectomy is the most common procedure reported, in an attempt to control the disease with minimal complications [1, 12, 17, 27]. However, lobectomy may be associated with positive margins, and therefore, an increased risk of local recurrence [29]. Some authors argue that total thyroidectomy may be a safer option. This argument is based on the presumption that total thyroidectomy will better achieve negative surgical margins, and also will address the issue of multifocal metastatic disease [34, 35]. However, no significant benefit from more extensive surgery has been proven [1, 12, 13, 16, 36]. Thus, a decision on the extent of surgery should be based on the ability to completely remove the metastatic tumor from the central neck [29].

In patients treated surgically, the absence of disease at other metastatic sites, a renal origin of primary tumor, and an extended period between the presentation of the primary tumor and the development of the metastasis to the thyroid are factors that have been associated with an improved prognosis [33, 34].

Metastatic lesions maintain their tumor characteristics. For example, 21–35% of primary RCCs extend into the renal vein and 4–10% into the inferior vena cava [37, 38]. Venous involvement has also been described in patients with RCC metastases to bone and the thyroid [39, 40]. Up to 11% showed jugular vein invasion by metastatic renal cell carcinoma in a multicentric study [29]. It is generally advised that a complete resection should be attempted even in patients with tumor thrombus in the jugular vein. Iesalnieks et al. [29] reported tumor recurrence following incomplete resection, while no recurrence was observed in their series following complete resection of the tumor thrombus in the invaded jugular vein.

Associated lymphadenopathy is rare, particularly in patients considered suitable for surgery. The use of neck ultrasonography in suspected or confirmed metastasis to the thyroid gland is recommended to identify nodal metastases and allow pre-operative planning for neck dissection. In those patients with evidence of nodal disease, who remain surgical candidates, neck dissection may be performed. Elective neck dissection is not recommended [33, 36].

The decision to sacrifice the recurrent laryngeal nerve should be based on preoperative function, contralateral nerve function and overall prognosis. For aggressive disseminated malignancies such as melanoma and sarcoma, efforts to minimize the impact of surgical intervention should be made [1].

Patients that have undergone previous metastasectomy at other sites (up to 35%) may still be candidates for surgery [29] depending on the general condition of the patient.

Thyroidectomy also has a palliative role. The relief of local symptoms, including airway compromise by compression, invasion or hemorrhage, is the main goal in the surgical treatment for many patients with thyroid metastasis [27]. Non-surgical treatments, such as radiotherapy and chemotherapy, have been used for those patients deemed inoperable, although the impact of these modalities remains uncertain [27, 29].

In cases where surgical margins are considered grossly or microscopically positive, adjuvant external beam radiotherapy can be considered in an attempt to improve local control [41]. Unfortunately, the most common metastasis to the thyroid, renal cell carcinoma, is considered radio-resistant, which may limit the impact of such adjuvant therapy [42]. Kjaer et al. [42] reported no improvement in local tumor control or survival in patients receiving postoperative irradiation when compared to those treated by nephrectomy alone. Following palliative radiotherapy, a partial response and reduction in pain has been reported in up to 86% of patients with metastatic renal cell carcinoma to bone [41]. In thyroid metastases, a small group of patients in a multicenter study who received neck irradiation for local recurrence of metastatic renal cell carcinoma showed improved survival compared to patients who did not receive irradiation [29].Therefore, radiation therapy should be considered in the case of residual disease or local recurrence.

Ultimately, the goal of surgery is to control disease in the central neck while recognizing that most patients will go on to die of disseminated disease [1]. Characteristics of the primary tumor are very important in selection of the appropriate treatment approach for patients with metastasis to the thyroid gland. Histologies range in terms of grade and therefore outcome.

TREATMENT OUTCOMES IN RENAL CELL CARCINOMA

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. EPIDEMIOLOGY
  5. CLINICAL PRESENTATION AND DIAGNOSTIC WORK UP
  6. GENERAL PRINCIPLES OF TREATMENT AND OUTCOME
  7. TREATMENT OUTCOMES IN RENAL CELL CARCINOMA
  8. TREATMENT OUTCOMES IN OTHER CARCINOMAS
  9. DISCUSSION
  10. CONCLUSION
  11. REFERENCES

In general, 20% of patients with RCC will present with distant disease at the time of diagnosis [43], and a third will subsequently develop distant disease [44, 45], up to 20 years after nephrectomy [46]. Metastasis to head and neck sites is extremely rare [47]. The thyroid gland accounts for most of the cases, but metastasis to both the tongue and sinuses have been described [48, 49]. In the thyroid gland, metastasis are usually single (77%) and unilateral (71%) [50].

In general, the survival of patients with metastatic renal cancer is poor [48, 49]. However, in selected cases the resection of isolated or even multiple metastases has been associated with an improvement in survival [32, 51]. Metastasectomies in cases of RCC metastasis in the lung, liver, bone, and brain lesions have been reported, showing overall survival around 30% [32, 51].The current guidelines of the European Association of Urology recommend metastasectomy in cases of a resectable lesion regardless of the site, be it synchronous or metachronous [52]. In general, factors that have been associated with improved survival after metastasectomy include; an interval between nephrectomy and metastasis of greater than 12 months; a solitary metastasis; and patient age less than 60 years [32].

In general then, resectable metastatic RCC should be considered for surgical treatment. Several reports of large series of patients have shown an overall survival of 30–50%, with some individual patients enjoying long disease free intervals even with repeated resections [53, 54]. Most of these patients will ultimately die from recurrent disease in sites other than the neck [16]. Regarding extent of surgery, no difference in survival has been reported between total thyroidectomy and less than total thyroidectomy [16, 27-29]. Recurrence in those managed with partial thyroidectomy may be high (20%), which is presumed to be related to the presence of positive margins at initial surgery or multifocal disease [29]. This highlights the importance of appropriate preoperative investigation and patient selection. Removal of all gross disease with a negative resection margin is the most important goal of surgery, as shown in a multicenter study which reported that local recurrence is high in patients with a positive margin [29].Subsequent local complications are distressing for the patient and difficult to manage.

Results of surgical resection of metastases in atypical sites like the thyroid, are comparable with results of the treatment of lung metastasis [55]. Further recurrence either in the neck or at additional sites may be treated surgically depending on the overall patient status [56].

Although limited by low patient numbers, a number of studies have reported favorable outcomes in patients selected to undergo resection of isolated metachronous thyroid metastases of RCC [12, 16, 27]. In one of the largest study to date, that involved 36 patients with isolated thyroid metastases of RCC, overall 5- and 10-year survival rates were 51.4% and 25.7%, respectively [16].

TREATMENT OUTCOMES IN OTHER CARCINOMAS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. EPIDEMIOLOGY
  5. CLINICAL PRESENTATION AND DIAGNOSTIC WORK UP
  6. GENERAL PRINCIPLES OF TREATMENT AND OUTCOME
  7. TREATMENT OUTCOMES IN RENAL CELL CARCINOMA
  8. TREATMENT OUTCOMES IN OTHER CARCINOMAS
  9. DISCUSSION
  10. CONCLUSION
  11. REFERENCES

Unfortunately, there is little information about the behavior of thyroid metastasis from primaries other than RCC.

Non-small cell lung cancer (NSCLC) is the most common lung cancer, and a relatively common source of metastasis to thyroid gland, especially in geographic areas with high incidence of lung cancer, such as Italy [17]. Forty percent of cases of lung cancer had metastatic disease at the time of diagnosis [57]. However, metastasis to the thyroid is uncommon with only 2 of 62 patients reported by Salah et al. [58]. In general, treatment decisions are based on the number and resectability of metastases, and the time elapsed between initial presentation and detection of distant disease. A recent pooled analysis of case reports suggests improved survival for patients following resection of solitary metastasis when compared to historical survival data from patients with Stage IV disease [58]. The survival results in metachronous metastasis may be better, but few sporadic cases are reported [36].

Breast cancer is one of the leading causes of cancer-related death among American women [43]. Synchronous metastases are present in 5% of cases at diagnosis, and at 10-year, the distant metastasis rate is over 20% [59]. Metastasectomy has been studied in patients with liver, lung, and brain metastases. However, no such studies exist for thyroid metastases alone. Most data supporting metastasectomy is drawn from retrospective analyses, as no randomized clinical trials have been performed [60]. Despite this, an improvement in survival has been reported in patients who undergo metastasectomy with prolonged disease free intervals (>36 months), estrogen-receptor positive cancer, original early stage presentation, small size of metastasis, or less than four secondary locations [60]. Data regarding metastasis to the thyroid comes from single case reports and cases series. In these reports, most patients presented with multiple metastatic sites at the time of diagnosis and were treated with chemotherapy and/or hormonotherapy, with dismal outcomes [12, 21, 61].

The incidence of thyroid metastasis among colorectal cancer patients is quite low: 0.1% [62]. There are multiple single case reports of colorectal carcinoma metastatic to the thyroid gland, but just one institutional review with more than two cases. A recent meta-analysis identified 31 case reports between 1954 and 2006, showing that solitary metastases to thyroid gland from colorectal cancer is most commonly metachronous (27/31 cases), usually associated with both disease in other metastatic sites (24/31) and a poor prognosis (50% cancer-related death in less than a year).Treatment was usually thyroidectomy (18/31) with adjuvant chemotherapy and/or radiotherapy [25]. Although the role of thyroid surgery in metastatic colorectal cancer is unknown, the only series with several patients treated in a single institution reported that patients treated with thyroidectomy had better palliation of respiratory symptoms than those who were merely observed [62].

A higher incidence of melanoma metastatic to the thyroid gland has been described in autopsy analyses (up to 39%) than in some recent reviews of clinical series [11, 14]. This finding has been explained to be due a high prevalence of subclinical disease. Distant metastasis at the moment of diagnosis is not uncommon [63].The incidence of distant metastasis during the follow up is high, even for thin melanomas [64]. The published literature on melanoma metastatic to the thyroid gland is limited to case reports or small case series [33, 65-67]. The specific role of thyroidectomy in this setting is unknown: and it is likely to be limited to the relief of local symptoms, and only rarely surgery be curative in this aggressive malignancy [68]. Unfortunately, there is a lack of effective adjuvant therapy for metastatic melanoma patients. Metastasectomy in melanoma patients is supported by clinical randomized trials such as MSLT-I [69], which shown a significant increase in survival for patients treated with metastasectomy compared with patients without surgical resection [69].

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. EPIDEMIOLOGY
  5. CLINICAL PRESENTATION AND DIAGNOSTIC WORK UP
  6. GENERAL PRINCIPLES OF TREATMENT AND OUTCOME
  7. TREATMENT OUTCOMES IN RENAL CELL CARCINOMA
  8. TREATMENT OUTCOMES IN OTHER CARCINOMAS
  9. DISCUSSION
  10. CONCLUSION
  11. REFERENCES

Clinically evident metastatic disease to the thyroid gland is rare. Despite a high prevalence in autopsy series, few present for management to the thyroid surgeon. Clinical presentation is similar to any primary thyroid neoplasm, usually an asymptomatic neck mass. Therefore, a high index of suspicion is required among patients with a recent diagnosis of cancer or with an antecedent history of malignancy, even years after initial treatment. Although most cases will be detected during follow up of the primary tumor, there are no specific imaging characteristics which can reliably diagnose metastatic thyroid disease preoperatively. Even with the extensive use of PET and PET/CT scanning in the staging of cancer, the most common finding is primary thyroid carcinoma, and very rarely metastatic disease.

In a review at our institution, the incidence of PET incidentalomas was reported as 2.9% of 8,800 patients. Ultimately, just 20 cases were malignant, none of them distant metastases [70]. In another institutional analysis of 4,136 patients who underwent PET scanning with known non-thyroid malignancies, only two cases of metastasis in the thyroid gland were detected, one from a breast primary and one from an esophageal cancer [71].

FNA can be used as an adjunct to imaging to identify those lesions that are metastatic, but accuracy rates are lower than those reported in primary thyroid disease. The most common malignancies reported to metastasize to the thyroid include: renal cell carcinoma, bronchial carcinoma, breast carcinoma, colon carcinoma, and malignant melanoma.

Because of its rarity, clinical decisions on the management of metastasis to the thyroid must be based on highly selected retrospective reviews and case reports. Most experts agree that in a patient with resectable disease, and an otherwise reasonable prognosis, surgery is appropriate. Although no survival advantage has been associated with thyroid metastasectomy, surgery remains appropriate to avoid death from central neck disease. Long-term survival may be achieved in select patients with solitary renal cell carcinoma metastasis, particularly if there is a long interval between initial primary treatment and metastasis. A long interval may also be an advantage for metastatic lung and breast cancer. The extent of surgery required remains unclear; however the surgeon should aim for complete resection of disease and minimization of complications related to surgery. In those patients with grossly or microscopically positive margins, external beam radiotherapy may be considered as an adjunct to surgery; however, there is little evidence to support this approach.

Ultimately, the outcome of patients with metastatic disease to the thyroid is most strongly influenced by their primary histology and concurrent disease. Those patients with relatively indolent tumors, isolated metastases and long pre-metastasis disease free intervals might benefit from surgery. In contrast, those with aggressive histologies who have distant disease at initial presentation have little to gain from additional surgery.

When managing such patients, surgeons should balance the trajectory of systemic disease against the potential for both disease and treatment related complications. Thyroidectomy may not improve overall survival in most of this patient group; however, it offers the only chance to control disease in the central neck. In turn this can allow patients to avoid the complications of airway hemorrhage and asphyxiation, which are amongst the most distressing modes of death.

CONCLUSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. EPIDEMIOLOGY
  5. CLINICAL PRESENTATION AND DIAGNOSTIC WORK UP
  6. GENERAL PRINCIPLES OF TREATMENT AND OUTCOME
  7. TREATMENT OUTCOMES IN RENAL CELL CARCINOMA
  8. TREATMENT OUTCOMES IN OTHER CARCINOMAS
  9. DISCUSSION
  10. CONCLUSION
  11. REFERENCES

Metastasis to the thyroid gland is a rare occurrence that represents a challenge to the thyroid surgeon as well as the multidisciplinary management team. Surgery remains the cornerstone of treatment; however, decision-making should balance surgical issues such as resectability of the tumor versus the prognosis of the primary tumor. In most cases, improvement in survival is limited; however, palliative aims such as the prevention of asphyxiation and other local complication must be considered when selecting appropriate therapy for patients with metastasis to the thyroid.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. EPIDEMIOLOGY
  5. CLINICAL PRESENTATION AND DIAGNOSTIC WORK UP
  6. GENERAL PRINCIPLES OF TREATMENT AND OUTCOME
  7. TREATMENT OUTCOMES IN RENAL CELL CARCINOMA
  8. TREATMENT OUTCOMES IN OTHER CARCINOMAS
  9. DISCUSSION
  10. CONCLUSION
  11. REFERENCES