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Fine-Needle Aspiration Biopsy of Secondary Neoplasms of the Thyroid Gland: A Multi-Institutional Study of 62 Cases

Originally published in Cancer Cytopathalogy, January 2015

By: Dr. Paul Michaels, et al.
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Secondary neoplasms of the thyroid gland (SNTGs) are uncommon, and it is important to recognize them in thyroid fine-needle aspiration biopsy (FNAB). METHODS: The authors report a cohort of 62 SNTGs from 7 institutions in the United States and Europe. Patients were identified retrospectively by searching through medical records of the respective institutions. All initial diagnoses were rendered by FNAB. RESULTS: SNTGs represented 0.16% of all thyroid FNABs and were more frequent among women (ratio of women to men, 1.2:1.0). The mean patient age was of 59 years (range, 7-84 years), the mean tumor size was 3 cm (range, 0.9-7 cm), and the mean interval from diagnosis of the primary tumor was 45 months (range, 0-156 months). Eighty-seven percent of SNTGs were diagnosed as malignant by FNAB, and there was a specific SNTG diagnosis in 93% of patients. Immunocytochemistry and flow cytometry, which were used in 30% of patients, were useful ancillary studies. Adenocarcinomas (n 5 23; 37%) and squamous cell carcinomas (SCCs) (n 5 22; 35.5%) represented the majority of SNTGs, followed by lymphoma (n 5 5; 8%), melanoma (n 5 5; 8%), adenoid cystic carcinoma (n 5 3; 5%), and various sarcomas (n 5 3; 5%). Adenocarcinomas originated from the kidney (n 5 9; 39%), lung (n 5 6; 26%), breast (n 5 5; 22%), and colon (n 5 3; 13%). SCCs originated mostly from the head and neck (n 5 13; 59%), followed by lung (n 5 3; 13%), esophagus (n 5 3; 14%), and unknown primary sites (n 5 3; 14%). CONCLUSIONS: Adenocarcinomas from the kidney, lung, breast, and colon along with SCCs represent the majority of SNTGs. The current results indicate that FNAB is a sensitive and accurate method for diagnosing SNTG; however, diagnostic difficulties can occur. Knowledge of clinical history and the judicious application of ancillary studies can increase the sensitivity and accuracy of FNAB for detecting SNTGs. Cancer (Cancer Cytopathol) 2015;123:19-29. VC 2014 American Cancer Society.

KEY WORDS: thyroid; secondary neoplasm; metastasis; renal cell carcinoma; squamous cell carcinoma; adenocarcinoma; lymphoma; adenoid cystic carcinoma; fine-needle aspiration; cytology.


Secondary neoplasms of the thyroid gland (SNTGs), representing either metastases or direct extension of tumors from adjacent anatomic structures, are uncommon. Their reported incidence varies substantially, however, ranging from 0.1% to 3% in clinical series.1-15 They have been reported as incidental findings in autopsy studies16-18 with a frequency of 4.4% to 24% in patients with a known primary cancer or widespread malignancy in which clinically occult thyroid micrometastases may be detected.4,19-22 In the United States and Europe, the most commonly reported primary tumor resulting in symptomatic SNTG is renal cell carcinoma (RCC), closely followed by carcinomas of the breast, lung, and colon.5,23-25 Secondary lymphoma, melanoma, sarcoma, and head and neck squamous cell carcinoma (SCC) also account for a significant proportion of SNTGs.22,24,25 Over the past 3 decades, fine-needle aspiration biopsy (FNAB) has emerged as the leading test for the initial evaluation of patients with thyroid nodules.27-31 The detected incidence of SNTGs may actually be increasing, akin to papillary thyroid microcarcinomas, as a result of increased surveillance over the last few decades by imaging studies, including ultrasound and ultrasound-guided FNAB,2,4,6 and the longer survival of patients with disseminated cancer. Although the use of FNAB in the workup of primary thyroid tumors has been well studied, only isolated case reports and a few smallseries have detailed the cytologic evaluation of SNTGs in thyroid FNABs.2,4,5,7,8,14,16,26,32,33

The FNAB diagnosis of an SNTG is important because it has critical implications for patients’ clinical management and prognosis. Patients who have metastasis to the thyroid have a poor prognosis in general, and most die shortly after the confirmation of distant metastasis,1-5,16,23,25 although prolonged survival has been reported in a rare subset of patients after surgery for an isolated thyroid metastasis.1,3,6,25,34 On occasion, thyroid metastases can also represent the first clinical manifestation of an occult, nonthyroid primary tumor.33-35

In the current report, we present a large FNAB series of SNTGs, consisting of 62 cases from 7 tertiary care medical centers in the United States and Europe. We discuss the major cytologic features of SNTG in thyroid FNAB specimens and the diagnostic challenges that selected SNTGs can cause.


Seventy-six cases of SNTG were collected from 7 major teaching hospitals, including 5 in the United States (Mas- sachusetts General Hospital [MGH] and Brigham and Women’s Hospital [BWH], Boston, Mass; Johns Hop- kins Hospital [JHH], Baltimore, Md; Virginia Common- wealth University Health System [VCU], Richmond, Va; and State University of New York [SUNY] Upstate Medical University, Syracuse, NY) and 2 in Europe (Geneva University Hospital [HUG], Geneva and Canto- nal Institute of Pathology [CIP], Locarno, Switzerland).

Patients with SNTG were identified retrospectively by searching the electronic medical records of the respec- tive institutions. The time frame of the searches varied for the different institutions (MGH, VCU, and HUG, 1992- 2014; BWH, JHH, SUNY, and CIP, 1992-2006). The average number of thyroid FNABs performed annually during this time frame and the prevalence of malignant FNABs in each center was as follows: 1309 FNABs with 3.9% malignant for MGH, 525 FNABs with 4.8% malig- nant for BWH, 534 FNABs with 15% malignant for JHH, 400 FNABs with 9% malignant for VCU, 212 FNABs with 5.2% malignant for SUNY, 390 FNABs with 5.3% malignant for HUG, and 380 FNABs with 5.1% malignant for CPI.

Fourteen cases were excluded for the following rea- sons: 9 were primary or possible primary thyroid lympho- mas; 2 were primary Langerhans cell histiocytosis of the thyroid; 2 were diagnosed as poorly differentiated carcino- mas, but a primary thyroid carcinoma could not be entirely excluded; and 1 was diagnosed as leiomyosar- coma, but undifferentiated thyroid carcinoma (UTC) could not be entirely excluded. For the 62 remaining cases, including 21 from MGH, 13 from JHH, 12 from BWH, 6 from SUNY, 4 from VCU, 4 from CIP, and 2 from HUG, correlation was made with previous or con- current histologic specimens when available. Forty-eight of 62 patients (77%) had a primary tumor site available for histologic comparison at the time of the review, and several had corresponding thyroid histology specimens or cell blocks. All cases included in the cohort had some form of tissue confirmation either through prior known primary tumor histology, concurrent biopsy of the SNTG, or post-FNAB follow-up biopsy of the SNTG. In addition, for all cases included in our FNAB cohort, the combined clinical, radiologic, and pathologic evidence was compelling enough to conclude that they were SNTGs, and these patients were managed clinically based on a diagnosis of SNTG. The following information was collected and analyzed for each patient: patient age and sex; the number, size, and location of the thyroid nod- ule(s) (based on ultrasound); concurrent and previous sur- gical pathologic diagnosis; interval between initial cancer diagnosis and SNTG FNAB diagnosis; cytologic features of SNTG;...

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Paul J. Michaels, MD, is a nationally renowned Anatomical and Clinical Pathologist with over 20 years of experience in his field. Dr. Michaels completed his medical residency and earned a Fellowship in Cytopathology from Massachusetts General Hospital / Harvard Medical School. He offers expert witness services to attorneys representing plaintiff and defense. He has written over 100 general causation reports focusing on pathology and providing an extensive differential diagnosis in order to provide an opinion with a reasonable degree of medical certainty. Dr. Michaels has participated in numerous MDLs, been deposed over 60 times, and testified in court 6 times.

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