Thyroid Metastasectomy

Thyroid Metastasectomy

PABLO H. MONTERO, MD, TIHANA IBRAHIMPASIC, MD, IAIN J. NIXON, MD, AND ASHOK R. SHAHA, MD*Head and Neck Surgery Service, Department of Surgery, Memorial Sloan-Kettering Cancer, New York, New York

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

KEY WORDS: thyroid cancer; thyroid neoplasms/secondary; metastasis; thyroid surgery; metastasectomy

INTRODUCTION

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

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

Many of those patients with metastatic disease will be identified onpre‐operative investigation of a thyroid mass. However, some mayundergo surgery for an assumed thyroid malignancy. The majority ofpatients will have a history of preceding malignancy, although for a few,the metastasis may be the mode of presentation of a disseminatedmalignancy. In select patients with resectable disease, and without anaggressive disseminated malignancy, surgery may be considered toavoid the complications related to uncontrolled central neck disease.

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

EPIDEMIOLOGY

Themost common primary location of metastasis to thyroid gland arethe kidney, lung, breast, gastro‐intestinal tract, and skin, with variationsreported 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 isunknown, an approximation can be drawn from reports of autopsyreviews and cases‐series analysis. The approximate incidence amongpatients without an antecedent history of cancer is between 0.5% and5.2% (Table I) [3–6]. However, if patients with a previous history ofmalignancy 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 ofscrutiny with which the post mortem gland is analyzed.

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

In surgical series, a wide variety of malignancies are reported tometastasize to the thyroid gland. When series of 10 or more patients areanalyzed, renal cell carcinoma, followed by lung and breast carcinoma arethemost commonhistological subtypesdescribed(Table II).This suggestsa slight but significant difference between autopsies and clinical series, asthose patients selected for surgical management are more likely to have aless aggressiveprimarydisease [12].Thegastrointestinal tract and the skinare 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 caseswere metastases from renal cancer, 10.4% from colorectal, 8.3% fromlung, 7.8% were from breast cancer, and 4% from melanoma.

CLINICAL PRESENTATION ANDDIAGNOSTIC WORK UP

While 60–80% of metastases are metachronous (followingpreviously 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 fromprimary treatment to presentation of a metastasis in the thyroid glandvaries from a few months in aggressive malignancies, to many years inless aggressive disease [14,15]. Renal cell carcinomas have beenreported up to 20 years following therapy for the primary lesion [12,16].

The symptoms at presentation are similar to those associated withprimary thyroid malignancies, which can result in a delayed diagnosis.

Disclosure Statement: The authors have no financial interests, disclosures orconflicts of interest regarding the content of this original manuscript. Thecontents of this manuscript have not been presented or published in any otherformat.

*Correspondence to: Ashok R. Shaha, MD, Head and Neck Service,Department of Surgery, Memorial Sloan‐Kettering Cancer Center, 1275York Ave, New York, NY 10065. Fax: 212‐717‐3302. E‐mail: [email protected]

Received 15 January 2013; Accepted 10 September 2013

DOI 10.1002/jso.23452

Published online 4 October 2013 in Wiley Online Library(wileyonlinelibrary.com).

Journal of Surgical Oncology 2014;109:36–41

� 2013 Wiley Periodicals, Inc.

Clinically evident metastases present most commonly as a palpable mass(72%of patients), while aminority of patients (28%) have a thyroidmassincidentally detected by imaging studies [17]. More advancedmetastases may present with dysphagia or dysphonia, associated withinvasion of adjacent structures. Eventually, replacement of normalthyroid parenchyma may result in thyroid dysfunction, with both hypo‐and hyperthyroidism reported [18,19]. It has been suggested that amultinodular architecture may predispose to the metastasis within thethyroid (59%of cases are in abnormal glands), but the reasons for this arenot clear [14].The similarities in presentation between primary thyroiddisease and metastasis highlights the need to enquire about a history ofprevious malignancy during preoperative assessment of the patient witha thyroid mass [12,16].

The diagnostic work up is similar to that used in the assessment of astandard thyroid nodule. Although the development of modern imagingtechniques (ultrasound, CT, MRI, FDG‐PET) has increased the rate ofdetection of thyroid lesions, primary, and secondary disease cannot beeasily differentiated due to the lack of specific imaging features [12,20].

Detection of thyroid enlargement or a thyroid nodule on imagingstudies in a patient with present or past history of another primarymalignant tumor should always raise the suspicion of metastasis to thethyroid.

In the absence of clear imaging characteristics, the use of fine needleaspiration (FNA) can help differentiate between benign and malignantthyroid lesions. However, even with cytology, differentiation betweenprimary and secondary thyroid malignancies remains a challenge [21].Although a high sensitivity has been reported for FNA in patients withvarious metastatic carcinomas to the thyroid gland, the accuracy of FNAis around 50% [1,12,22]. Immunohistochemical demonstration ofmarkers specific for thyroid, such as thyroglobulin, can distinguish aprimary thyroid tumor from a metastatic lesion and help improve thisaccuracy [16,23–25]. It can be particularly difficult to differentiatebetween a high grade metastasis and primary anaplastic thyroidcancer [20]. In fact, 20–30% of primary anaplastic thyroid carcinomasare negative for thyroid specific immunohistochemistry [20,26].Therefore, a tumor directed immunohistochemical testing, based on a

TABLE II. Reported Clinical Series of Metastasis to Thyroid Gland with more than 10 Cases

Authors Year Institution n Primary sites

Elliott et al. [77] 1959 Columbia Presbyterian 14 Breast, lung, kidneyWychulis et al. [74] 1964 Mayo Clinic (1907–1962) 14 Kidney, breast, rectum, bladderHarcourt et al. [79] 1965 University of Edinburg 11 Kidney, breast, melanoma, lungBrady et al. [75] 1977 Hospital of Philadelphia 10 LungEriccson et al. [82] 1981 University of Lund Hospital, Sweden, 10 Renal, melanomaCzech et al. [76] 1982 Mayo Clinic (1960–1980) 12 Kidney, breast, lungIvy et al. [78] 1984 Mayo Clinic (1946–1982) 30 Kidney, breast, lungSmith et al. [70] (�) 1987 Mayo Clinic (1980–1985) 15 Breast, lung, kidneyMichelow et al. [80] (�) 1995 South African Institute for Medical Research 21 Lung, gastrointestinal, melanoma, kidneyRosen et al. [22] 1995 University of Toronto 11 Lung, breast, kidney, melanomaNakhjavani et al. [12] (�) 1997 Mayo Clinic (1985–1994) 43 Kidney, lung, breastChen et al. [13] 1999 Johns Hopkins Hospital 10 Kidney, lungHeffess et al. [16] 2002 Armed Forces Institute of Pathology 36 KidneyWood et al. [27] (�) 2004 Royal Marsden Hospital 15 Kidney, othersKim et al. [21] (�) 2005 Asan Medical Centre, Korea 22 Breast, Kidney, Colon, Lung, othersMirallie et al. [33] 2005 Multicentric, France 29 Kidney, lung, gastrointestinalCichon et al. [34] 2006 Jagiellonian University, Poland 17 Kidney, uterusPapi et al. [7] 2007 Multicentric, Italy 36 Lung, kidney, breast, esophagusCalzolari et al. [36] 2008 Multicentric, Italy 25 Renal, lung, colon, breastIesalnieks et al. [29] 2008 Multicentric, Germany 45 KidneyMachens et al. [81] 2010 Martin Luther University, Germany 17 KidneyNixon et al. [1] 2010 MSKCC 21 Kidney, melanoma, gastrointestinal

Note: (�) This table includes patients that were treated mainly with surgery; however, case series marked with (�) include patients that were primarily diagnosed with FineNeedle Aspiration Cytology, and not necessarily treated with surgery.

TABLE I. Reported Incidence of Metastasis to Thyroid Gland in Autopsies Series

Authors Year Incidence Primary sites

Autopsies of patients with known cancer historyRice [7] 1934 9/89 (10.1%) Not specifiedAbrams et al. [8] 1949 19/1,000 (1.9%) Breast, lung, colon, kidneyMortensen et al. [10] 1956 13/430 (3%)� Lung, breast, colon, kidneyShimaoka et al. [11] 1962 156/1,871 (8.3%) Breast, lung, head and neck, melanoma, kidneySilverberg et al. [4] 1966 15/62 (24.1%) Lung, breast, prostate, bladder, colon, kidneyWatanabe et al. [72] 1980 309/13,862 (2%)�� Breast, lung, kidney, gastrointestinal

Unselected autopsiesWillis [3] 1933 10/170 (5.2%) Breast, kidney, gastricBerge et al. [5] 1971 202/16,924 (1.2%) Breast, lung, kidney, colon, melanomaLam et al. [6] 1998 67/12,955 (0.5%) Lung, breast, gastric, colon, kidney

�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.

Journal of Surgical Oncology

Thyroid Metastasectomy 37

knowledge or suspicion of a certain primary location, is necessary toobtain an accurate diagnosis of metastatic thyroid carcinoma.

Other diagnostic procedures, including a core biopsy or even surgicalexcision (total thyroidectomy, or lobectomy) can be used to obtain tissuefor diagnosis [1,27]. With a combination of immunohistochemicalmarkers, the diagnosis of metastatic carcinoma to the thyroid can beobtained unequivocally For example, the combination of a negativeTTF‐1 and thyroglobulin, with a positive CD 10 in case of renal cellcarcinoma [28]. These diagnostic challenges demonstrate the need tocommunicate a suspicious of metastatic disease to the pathologistinvolved in analyzing diagnostic tissue samples.

GENERAL PRINCIPLES OF TREATMENT ANDOUTCOME

In the diagnostic work‐up of a new thyroidmass in those patients witha previous history of malignancy, the possibility of metastasis to thethyroid should be always considered. Multidisciplinary work‐up ismandatory to distinguish a metastasis from a primary lesion, sincetreatment 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 whencomparedwithmetastasis to other sites [17]. Thirty‐five percent to 80% ofpatientswho present withmetastases to the thyroid havemetastatic diseasein other locations at the time of diagnosis of the thyroid metasta-sis [14,17,29]. Life expectancy depends primarily on the prognosis of theprimary tumor [17]. Select patients with metastatic disease isolated to thethyroid 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 beensurgical, there is no clear consensus on the exact indications forsurgery. The decision to perform a metastasectomy is made on anindividual case basis, depending on the grade and stage of the primarycancer, local extension of the thyroid lesion, and the general conditionof the patient. Surgery may be curative or palliative according to thecompleteness of the resection, the presence of extrathyroidal disease,and the status of disease elsewhere in the body [31]. Surgery iscurrently considered the only treatment with the potential for cureassuming disease is limited to the thyroid [29]. The ideal surgicalcandidate is a patient with minimal disease in the thyroid and noevidence of disease in other sites. In such patients, even those whohave previously had metastasectomy elsewhere, good outcomes havebeen reported [32].

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

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

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

In patients treated surgically, the absence of disease at othermetastatic sites, a renal origin of primary tumor, and an extended periodbetween the presentation of the primary tumor and the development ofthe metastasis to the thyroid are factors that have been associated with animproved 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 theinferior vena cava [37,38]. Venous involvement has also been describedin patients with RCC metastases to bone and the thyroid [39,40]. Up to11% showed jugular vein invasion by metastatic renal cell carcinoma inamulticentric study [29]. It is generally advised that a complete resectionshould be attempted even in patients with tumor thrombus in the jugularvein. Iesalnieks et al. [29] reported tumor recurrence followingincomplete resection, while no recurrence was observed in their seriesfollowing complete resection of the tumor thrombus in the invadedjugular vein.

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

The decision to sacrifice the recurrent laryngeal nerve should bebased on preoperative function, contralateral nerve function and overallprognosis. For aggressive disseminated malignancies such as melanomaand sarcoma, efforts to minimize the impact of surgical interventionshould be made [1].

Patients that have undergone previous metastasectomy at other sites(up to 35%) may still be candidates for surgery [29] depending on thegeneral 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 thyroidmetastasis [27]. Non‐surgical treatments, such as radiotherapy andchemotherapy, 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 ormicroscopically positive, adjuvant external beam radiotherapy can beconsidered in an attempt to improve local control [41]. Unfortunately,the most common metastasis to the thyroid, renal cell carcinoma, isconsidered radio‐resistant, which may limit the impact of such adjuvanttherapy [42]. Kjaer et al. [42] reported no improvement in local tumorcontrol or survival in patients receiving postoperative irradiation whencompared to those treated by nephrectomy alone. Following palliativeradiotherapy, a partial response and reduction in pain has been reportedin up to 86% of patients with metastatic renal cell carcinoma tobone [41]. In thyroid metastases, a small group of patients in amulticenter study who received neck irradiation for local recurrence ofmetastatic renal cell carcinoma showed improved survival compared topatients who did not receive irradiation [29].Therefore, radiation therapyshould be considered in the case of residual disease or local recurrence.

Ultimately, the goal of surgery is to control disease in the central neckwhile recognizing that most patients will go on to die of disseminateddisease [1]. Characteristics of the primary tumor are very important inselection of the appropriate treatment approach for patients withmetastasis to the thyroid gland. Histologies range in terms of grade andtherefore outcome.

TREATMENT OUTCOMES IN RENAL CELLCARCINOMA

In general, 20% of patients with RCCwill present with distant diseaseat the time of diagnosis [43], and a third will subsequently develop


38 Montero et al.

distant disease [44,45], up to 20 years after nephrectomy [46].Metastasisto head and neck sites is extremely rare [47]. The thyroid gland accountsfor most of the cases, but metastasis to both the tongue and sinuses havebeen described [48,49]. In the thyroid gland, metastasis are usuallysingle (77%) and unilateral (71%) [50].

In general, the survival of patients with metastatic renal cancer ispoor [48,49]. However, in selected cases the resection of isolated or evenmultiple metastases has been associated with an improvement insurvival [32,51]. Metastasectomies in cases of RCC metastasis in thelung, liver, bone, and brain lesions have been reported, showing overallsurvival around 30% [32,51].The current guidelines of the EuropeanAssociation of Urology recommend metastasectomy in cases of aresectable lesion regardless of the site, be it synchronous ormetachronous [52]. In general, factors that have been associated withimproved survival after metastasectomy include; an interval betweennephrectomy and metastasis of greater than 12 months; a solitarymetastasis; and patient age less than 60 years [32].

In general then, resectable metastatic RCC should be considered forsurgical treatment. Several reports of large series of patients have shownan overall survival of 30–50%, with some individual patients enjoyinglong disease free intervals evenwith repeated resections [53,54].Most ofthese patients will ultimately die from recurrent disease in sites otherthan the neck [16]. Regarding extent of surgery, no difference in survivalhas been reported between total thyroidectomy and less than totalthyroidectomy [16,27–29]. Recurrence in those managed with partialthyroidectomy may be high (20%), which is presumed to be related tothe presence of positive margins at initial surgery or multifocaldisease [29]. This highlights the importance of appropriate preoperativeinvestigation and patient selection. Removal of all gross disease with anegative resection margin is the most important goal of surgery, asshown in a multicenter study which reported that local recurrence is highin patients with a positive margin [29].Subsequent local complicationsare distressing for the patient and difficult to manage.

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

Although limited by low patient numbers, a number of studies havereported favorable outcomes in patients selected to undergo resection ofisolated metachronous thyroid metastases of RCC [12,16,27]. In one ofthe largest study to date, that involved 36 patients with isolated thyroidmetastases of RCC, overall 5‐ and 10‐year survival rates were 51.4% and25.7%, respectively [16].

TREATMENT OUTCOMES IN OTHERCARCINOMAS

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

Non‐small cell lung cancer (NSCLC) is the most common lungcancer, and a relatively common source of metastasis to thyroid gland,especially in geographic areas with high incidence of lung cancer, suchas Italy [17]. Forty percent of cases of lung cancer had metastatic diseaseat the time of diagnosis [57]. However, metastasis to the thyroid isuncommon with only 2 of 62 patients reported by Salah et al. [58]. Ingeneral, treatment decisions are based on the number and resectability ofmetastases, and the time elapsed between initial presentation anddetection of distant disease. A recent pooled analysis of case reportssuggests improved survival for patients following resection of solitarymetastasis when compared to historical survival data from patients withStage IV disease [58]. The survival results in metachronous metastasismay be better, but few sporadic cases are reported [36].

Breast cancer is one of the leading causes of cancer‐related deathamong American women [43]. Synchronous metastases are present in5% 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 thyroidmetastases alone. Most data supporting metastasectomy is drawn fromretrospective analyses, as no randomized clinical trials have beenperformed [60]. Despite this, an improvement in survival has beenreported in patients who undergo metastasectomy with prolongeddisease free intervals (>36 months), estrogen‐receptor positive cancer,original early stage presentation, small size of metastasis, or less thanfour secondary locations [60]. Data regarding metastasis to the thyroidcomes from single case reports and cases series. In these reports, mostpatients presented with multiple metastatic sites at the time of diagnosisand were treated with chemotherapy and/or hormonotherapy, withdismal outcomes [12,21,61].

The incidence of thyroid metastasis among colorectal cancer patientsis quite low: 0.1% [62]. There are multiple single case reports ofcolorectal carcinoma metastatic to the thyroid gland, but just oneinstitutional review with more than two cases. A recent meta‐analysisidentified 31 case reports between 1954 and 2006, showing that solitarymetastases to thyroid gland from colorectal cancer is most commonlymetachronous (27/31 cases), usually associated with both disease inother metastatic sites (24/31) and a poor prognosis (50% cancer‐relateddeath in less than a year).Treatment was usually thyroidectomy (18/31)with adjuvant chemotherapy and/or radiotherapy [25]. Although the roleof thyroid surgery in metastatic colorectal cancer is unknown, the onlyseries with several patients treated in a single institution reported thatpatients treated with thyroidectomy had better palliation of respiratorysymptoms than those who were merely observed [62].

A higher incidence of melanoma metastatic to the thyroid gland hasbeen described in autopsy analyses (up to 39%) than in some recentreviews of clinical series [11,14]. This finding has been explained to bedue a high prevalence of subclinical disease. Distant metastasis at themoment of diagnosis is not uncommon [63].The incidence of distantmetastasis during the follow up is high, even for thin melanomas [64].The published literature on melanoma metastatic to the thyroid gland islimited to case reports or small case series [33,65–67]. The specific roleof thyroidectomy in this setting is unknown: and it is likely to be limitedto the relief of local symptoms, and only rarely surgery be curative in thisaggressive malignancy [68]. Unfortunately, there is a lack of effectiveadjuvant therapy for metastatic melanoma patients. Metastasectomy inmelanoma patients is supported by clinical randomized trials such asMSLT‐I [69], which shown a significant increase in survival for patientstreated with metastasectomy compared with patients without surgicalresection [69].

DISCUSSION

Clinically evident metastatic disease to the thyroid gland is rare.Despite a high prevalence in autopsy series, few present for managementto the thyroid surgeon. Clinical presentation is similar to any primarythyroid neoplasm, usually an asymptomatic neck mass. Therefore, ahigh index of suspicion is required among patients with a recentdiagnosis of cancer or with an antecedent history of malignancy, evenyears after initial treatment. Although most cases will be detected duringfollow up of the primary tumor, there are no specific imagingcharacteristics which can reliably diagnose metastatic thyroid diseasepreoperatively. Even with the extensive use of PET and PET/CTscanning in the staging of cancer, the most common finding is primarythyroid carcinoma, and very rarely metastatic disease.

In a review at our institution, the incidence of PET incidentalomaswas reported as 2.9% of 8,800 patients. Ultimately, just 20 cases weremalignant, none of them distant metastases [70]. In another institutionalanalysis of 4,136 patients who underwent PET scanning with knownnon‐thyroid malignancies, only two cases of metastasis in the thyroidgland were detected, one from a breast primary and one from anesophageal cancer [71].



FNAcan be used as an adjunct to imaging to identify those lesions thataremetastatic, but accuracy rates are lower than those reported in primarythyroid disease. The most common malignancies reported to metastasizeto the thyroid include: renal cell carcinoma, bronchial carcinoma, breastcarcinoma, colon carcinoma, and malignant melanoma.

Because of its rarity, clinical decisions on the management ofmetastasis to the thyroid must be based on highly selected retrospectivereviews and case reports. Most experts agree that in a patient withresectable disease, and an otherwise reasonable prognosis, surgery isappropriate. Although no survival advantage has been associated withthyroid metastasectomy, surgery remains appropriate to avoid deathfrom central neck disease. Long‐term survival may be achieved in selectpatients with solitary renal cell carcinomametastasis, particularly if thereis a long interval between initial primary treatment and metastasis. Along interval may also be an advantage for metastatic lung and breastcancer. The extent of surgery required remains unclear; however thesurgeon should aim for complete resection of disease and minimizationof complications related to surgery. In those patients with grossly ormicroscopically positive margins, external beam radiotherapy may beconsidered as an adjunct to surgery; however, there is little evidence tosupport this approach.

Ultimately, the outcome of patients with metastatic disease to thethyroid is most strongly influenced by their primary histology andconcurrent disease. Those patients with relatively indolent tumors,isolated metastases and long pre‐metastasis disease free intervals mightbenefit from surgery. In contrast, those with aggressive histologies whohave distant disease at initial presentation have little to gain fromadditional surgery.

Whenmanaging such patients, surgeons should balance the trajectoryof systemic disease against the potential for both disease and treatmentrelated complications. Thyroidectomy may not improve overall survivalinmost of this patient group; however, it offers the only chance to controldisease in the central neck. In turn this can allow patients to avoid thecomplications of airway hemorrhage and asphyxiation, which areamongst the most distressing modes of death.

CONCLUSION

Metastasis to the thyroid gland is a rare occurrence that represents achallenge to the thyroid surgeon as well as the multidisciplinarymanagement team. Surgery remains the cornerstone of treatment;however, decision‐making should balance surgical issues such asresectability of the tumor versus the prognosis of the primary tumor. Inmost cases, improvement in survival is limited; however, palliative aimssuch as the prevention of asphyxiation and other local complicationmustbe considered when selecting appropriate therapy for patients withmetastasis to the thyroid.

REFERENCES

1. Nixon IJ, Whitcher M, Glick J, et al.: Surgical management ofmetastases to the thyroid gland. Ann Surg Oncol 2011;18:800–804.

2. Virchow R: Pathologie des Tumeurs (Aronssohn’s French transla-tion). 1871:243.

3. Willis RA: Metastatic tumours in the thyreoid gland. Am J Pathol1931;7:187–208.

4. Silverberg SG, Vidone RA: Carcinoma of the thyroid in surgical andpostmortemmaterial. Analysis of 300 cases at autopsy and literaturereview. Ann Surg 1966;164:291–299.

5. Berge T, Lundberg S: Cancer in Malmö 1958–1969. An autopsystudy. Acta Pathol Microbiol Scand Suppl 1977;260:1–235.

6. LamKY, Lo CY:Metastatic tumors of the thyroid gland: A study of79 cases in Chinese patients. Arch Pathol Lab Med 1998;122:37–41.

7. Rice CO: Microscopic metastases in the thyroid gland. Am J Pathol1934;10:407–412.

8. Abrams HL, Spiro R, Goldstein N: Metastases in carcinoma;analysis of 1000 autopsied cases. Cancer 1950;3:74–85.

9. Hull OH: Critical analysis of two hundred twenty‐one thyroidglands; study of thyroid glands obtained at necropsy in Colorado.AMA Arch Pathol 1955;59:291–311.

10. Mortensen J, Woolner LB, Bennett WA: Secondary malignanttumors of the thyroid gland. Cancer 1956;9:306–309.

11. Shimaoka K, Sokal JE, Pickren JW: Metastatic neoplasms in thethyroid gland. Pathological and clinical findings. Cancer1962;15:557–565.

12. Nakhjavani MK, Gharib H: Goellner JR, et al.: Metastasis to thethyroid gland. A report of 43 cases. Cancer 1997;79:574–578.

13. Chen H, Nicol TL, Udelsman R: Clinically significant, isolatedmetastatic disease to the thyroid gland. World J Surg 1999;23:177–180;discussion 181.

14. Chung AY, Tran TB, BrumundKT, et al.: Metastases to the thyroid:A review of the literature from the last decade. Thyroid2012;22:258–268.

15. Mattavelli F, Collini P, Pizzi N, et al.: Thyroid as a target ofmetastases. A case of foregut neuroendocrine carcinoma withmultiple abdominal metastases and a thyroid localization after 21years. Tumori 2008;94:110–113.

16. Heffess CS, Wenig BM, Thompson LD: Metastatic renal cellcarcinoma to the thyroid gland: a clinicopathologic study of 36cases. Cancer 2002;95:1869–1878.

17. Papi G, Fadda G, Corsello SM, et al.: Metastases to the thyroidgland: Prevalence, clinicopathological aspects and prognosis: a 10‐year experience. Clin Endocrinol (Oxf) 2007;66:565–571.

18. BaeWK, Shim HJ, Choi YD, et al.: Severe hypothyroidism inducedby thyroid metastasis of cholangiocarcinoma. Cancer Res Treat2009;41:56–58.

19. Shimaoka K: Thyrotoxicosis due to metastatic involvement of thethyroid. Arch Intern Med 1980;140:284–285.

20. Peparini N, Di Matteo FM, Maturo A, et al.: Unusual metastasis ofgastrointestinal stromal tumor misdiagnosed as anaplastic thyroidcarcinoma. Int J Surg 2008;6:415–417.

21. Kim TY, Kim WB, Gong G, et al.: Metastasis to the thyroiddiagnosed by fine‐needle aspiration biopsy. Clin Endocrinol (Oxf)2005;62:236–241.

22. Rosen IB, Walfish PG, Bain J, et al.: Secondary malignancy of thethyroid gland and its management. Ann Surg Oncol 1995;2:252–256.

23. Burt A, Goudie RB: Diagnosis of primary thyroid carcinoma byimmunohistological demonstration of thyroglobulin. Histopatholo-gy 1979;3:279–286.

24. Mattavelli F, Collini P, Gervasoni C, et al.: Double, metachronousthyroid metastases of colon cancer. Tumori 2006;92:249–251.

25. Kumamoto K, Utsumi Y, Sugano K, et al.: Colon carcinomametastasis to the thyroid gland: Report of a case with a review of theliterature. Tumori 2006;92:252–256.

26. Hurlimann J, Gardiol D, Scazziga B: Immunohistology ofanaplastic thyroid carcinoma. A study of 43 cases. Histopathology1987;11:567–580.

27. Wood K, Vini L, Harmer C: Metastases to the thyroid gland:The Royal Marsden experience. Eur J Surg Oncol 2004;30:583–588.

28. May M, Marusch F, Kaufmann O, et al.: Solitary renal cellcarcinoma metastasis to the thyroid gland—A paradigm ofmetastasectomy? Chirurg 2003;74:768–774.

29. Iesalnieks I, Winter H, Bareck E, et al.: Thyroid metastases of renalcell carcinoma: clinical course in 45 patients undergoing surgery.Assessment of factors affecting patients’ survival. Thyroid 2008;18:615–624.

30. Lin JD, Weng HF, Ho YS: Clinical and pathological characteristicsof secondary thyroid cancer. Thyroid 1998;8:149–153.

31. Ishikawa M, Hirano S, Tsuji T, et al.: Management of metastasis tothe thyroid gland. Auris Nasus Larynx 2011;38:426–430.

32. Kavolius JP, Mastorakos DP, Pavlovich C, et al.: Resection ofmetastatic renal cell carcinoma. J Clin Oncol 1998;16:2261–2266.

33. Mirallie E, Rigaud J, Mathonnet M, et al.: Management andprognosis of metastases to the thyroid gland. J Am Coll Surg2005;200:203–207.


40 Montero et al.

34. Cichon S, Anielski R, Konturek A, et al.: Metastases to the thyroidgland: Seventeen cases operated on in a single clinical center.Langenbecks Arch Surg 2006;391:581–587.

35. Stevens TM, Richards AT, Bewtra C, et al.: Tumors metastatic tothyroid neoplasms: A case report and review of the literature. PatholRes Int 2011;2011:238693.

36. Calzolari F, Sartori PV, Talarico C, et al.: Surgical treatment ofintrathyroid metastases: Preliminary results of a multicentric study.Anticancer Res 2008;28:2885–2888.

37. Davits RJ, Blom JH, Schroder FH: Surgical management of renalcarcinoma with extensive involvement of the vena cava and rightatrium. Br J Urol 1992;70:591–593.

38. Kontak JA, Campbell SC: Prognostic factors in renal cellcarcinoma. Urol Clin North Am 2003;30:467–480.

39. Davison BD, Mammen L, Ritchie J, et al.: Descending tumorthrombus from renal cell carcinoma metastases with SVCsyndrome. Cardiovasc Intervent Radiol 2006;29:687–690.

40. Strugnell M, Gibson M, Hopkins R, et al.: Case report. Renal cellcarcinoma vertebral body metastasis extending into the azygosvenous system causing superior vena cava obstruction. Br J Radiol2005;78:65–67.

41. DiBiase SJ, Valicenti RK, Schultz D, et al.: Palliative irradiation forfocally symptomatic metastatic renal cell carcinoma: Support for doseescalation based on a biological model. J Urol 1997;158:746–749.

42. Kjaer M, Frederiksen PL, Engelholm SA: Postoperative radiother-apy in stage II and III renal adenocarcinoma. A randomized trial bythe Copenhagen Renal Cancer Study Group. Int J Radiat Oncol BiolPhys 1987;13:665–672.

43. Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CACancer J Clin 2012;62:10–29.

44. Rabinovitch RA, Zelefsky MJ, Gaynor JJ, et al.: Patterns of failurefollowing surgical resection of renal cell carcinoma: Implicationsfor adjuvant local and systemic therapy. J Clin Oncol 1994;12:206–212.

45. Maldazys JD, deKernion JB: Prognostic factors in metastatic renalcarcinoma. J Urol 1986;136:376–379.

46. RuutuM,Bono P, TaariK:Resection ofRenal Cell CancerMetastases:Where Do We Stand in 2008? Eur Urol Suppl 2008;7:436–442.

47. Ganini C, Lasagna A, Ferraris E, et al.: Lingual metastasis fromrenal cell carcinoma: A case report and literature review. RareTumors 2012;4:e41.

48. Zegarelli DJ, Tsukada Y, Pickren JW, et al.: Metastatic tumor to thetongue. Report of twelve cases. Oral Surg Oral Med Oral Pathol1973;35:202–211.

49. Nahum AM, Bailey BJ: Malignant tumors metastatic to theparanasal sinuses: Case report and review of the literature.Laryngoscope 1963;73:942–953.

50. Sindoni A, Rizzo M, Tuccari G, et al.: Thyroid metastases fromrenal cell carcinoma: Review of the literature. Scientific WorldJournal 2010;10:590–602.

51. Alt AL, Boorjian SA, Lohse CM, et al.: Survival after completesurgical resection of multiple metastases from renal cell carcinoma.Cancer 2011;117:2873–2882.

52. Ljungberg B, Cowan NC, Hanbury DC, et al.: EAU guidelines onrenal cell carcinoma: The 2010 update. Eur Urol 2010;58:398–406.

53. Thelen A, Jonas S, Benckert C, et al.: Liver resection for metastasesfrom renal cell carcinoma. World J Surg 2007;31:802–807.

54. Fourquier P, Regnard JF, Rea S, et al.: Lung metastases of renal cellcarcinoma: Results of surgical resection. Eur J Cardiothorac Surg1997;11:17–21.

55. Antonelli A, Arrighi N, Corti S, et al.: Surgical treatment of atypicalmetastasis from renal cell carcinoma (RCC). BJU Int 2012;110:559–563.

56. Tosco L, Van Poppel H, Frea B, et al.: Survival and impact ofclinical prognostic factors in surgically treated metastatic renal cellcarcinoma. Eur Urol 2013;63:642–652.

57. Quint LE, Tummala S, Brisson LJ, et al.: Distribution of distantmetastases from newly diagnosed non‐small cell lung cancer. AnnThorac Surg 1996;62:246–250.

58. Salah S, Tanvetyanon T, Abbasi S:Metastatectomy for extra‐cranialextra‐adrenal non‐small cell lung cancer solitary metastases:Systematic review and analysis of reported cases. Lung Cancer2012;75:9–14.

59. Arriagada R, Rutqvist LE, Johansson H, et al.: Predicting distantdissemination in patients with early breast cancer. Acta Oncol2008;47:1113–1121.

60. Ruiterkamp J, Ernst MF: The role of surgery in metastatic breastcancer. Eur J Cancer 2011;47:S6–S22.

61. Chung SY, Kim EK, Kim JH, et al.: Sonographic findings ofmetastatic disease to the thyroid. Yonsei Med J 2001;42:411–417.

62. Lievre A, Leboulleux S, Boige V, et al.: Thyroid metastases fromcolorectal cancer: The Institut Gustave Roussy experience. Eur JCancer 2006;42:1756–1759.

63. Chang AE, Karnell LH,Menck HR: The National Cancer Data Basereport on cutaneous and noncutaneous melanoma.

64. Murali R, Haydu LE, Long GV, et al.: Clinical and pathologicfactors associated with distant metastasis and survival in patientswith thin primary cutaneous melanoma. Ann Surg Oncol2012;19:1782–1789.

65. Gherardi G, Scherini P, Ambrosi S: Occult thyroid metastasisfrom untreated uveal melanoma. Arch Ophthalmol 1985;103:689–691.

66. Bozbora A, Barbaros U, Kaya H, et al.: Thyroid metastasis ofmalignant melanoma. Am J Clin Oncol 2005;28:642–643.

67. Basu S, Alavi A:Metastatic malignant melanoma to the thyroid glanddetected by FDG‐PET imaging. Clin Nucl Med 2007;32:388–389.

68. Kung B, Aftab S, Wood M, et al.: Malignant melanoma metastaticto the thyroid gland: A case report and review of the literature. EarNose Throat J 2009;88:E7.

69. Howard JH, Thompson JF, Mozzillo N, et al.: Metastasectomy fordistant metastatic melanoma: Analysis of data from the firstMulticenter Selective Lymphadenectomy Trial (MSLT‐I). AnnSurg Oncol 2012;19:2547–2555.

70. Smith SA, Gharib H, Goellner JR: Fine‐needle aspiration.Usefulness for diagnosis and management of metastatic carcinomato the thyroid. Arch Intern Med 1987;147:311–312.

71. Kim TY, Kim WB, Ryu JS, et al.: 18F‐fluorodeoxyglucose uptakein thyroid from positron emission tomogram (PET) for evaluation incancer patients: High prevalence of malignancy in thyroid PETincidentaloma. Laryngoscope 2005;115:1074–1078.

72. Watanabe I, Tsuchiya A: Secondary carcinoma of the thyroid gland.Jpn J Surg 1980;10:130–136.

73. Wychulis AR, Beahrs OH,Woolner LB:Metastasis of carcinoma tothe thyroid gland. Ann Surg 1964;160:169–177.

74. Brady LW, O’Neill EA, Farber SH: Unusual sites of metastases.Semin Oncol 1977;4:59–64.

75. Czech JM, Lichtor TR, Carney JA, et al.: Neoplasms metastatic tothe thyroid gland. Surg Gynecol Obstet 1982;155:503–505.

76. Elliott RH, Jr Frantz VK: Metastatic carcinoma masquerading asprimary thyroid cancer: A report of authors’ 14 cases. Ann Surg1960;151:551–561.

77. Ivy HK: Cancer metastatic to the thyroid: A diagnostic problem.Mayo Clin Proc 1984;59:856–859.

78. Harcourt‐Webster JN: Secondary neoplasm of the thyroid present-ing as a goitre. J Clin Pathol 1965;18:282–287.

79. Michelow PM, Leiman G:Metastases to the thyroid gland: Diagnosisby aspiration cytology. Diagn Cytopathol 1995;13:209–213.

80. Machens A, Dralle H: Outcome after thyroid surgery for metastasisfrom renal cell cancer. Surgery 2010;147:65–71.

81. Ericsson M, Biorklund A, Cederquist E, et al.: Surgical treatmentof metastatic disease in the thyroid gland. J Surg Oncol 1981;17:15–23.



Thyroid Metastasectomy

Documents

Transcript of Thyroid Metastasectomy