Thyroid gland
Other carcinoma
Secondary tumors / metastases

Topic Completed: 1 June 2017

Revised: 18 March 2019

Copyright: 2003-2018,, Inc.

PubMed Search: metastases thyroid gland

Shuanzeng Wei, M.D., Ph.D.
Page views in 2018: 1,610
Page views in 2019 to date: 813
Cite this page: Wei S. Secondary tumors / metastases. website. Accessed August 24th, 2019.
Definition / general
  • Tumors arising in thyroid by direct extension from adjacent structures or by vascular spread from nonthyroidal sites (Lloyd: WHO Classification of Tumours of Endocrine Organs, 4th Edition, 2017)
  • Despite being highly vascularized, the thyroid is a rare site for distant metastases
  • The frequency of metastasis in routine practice is < 0.2% of thyroid malignancies (Endocr Pathol 2017;28:112)
  • Direct extension common from tumors of larynx, pharynx, trachea, esophagus and neck - usually are squamous cell carcinoma
  • FNA is useful for diagnosis of solitary metastases (Cytojournal 2007;4:5)
  • More than 1400 cases have been published in series and individual case reports (Endocr Pathol 2013;24:116)
  • Tumor to tumor metastasis localized within a primary thyroid neoplasm are very rare with 30+ cases reported
Essential features
  • Thyroid is highly vascularized but secondary metastases to the gland are very uncommon
  • Secondary tumors arise from direction extension of head and neck squamous cell carcinoma and distant metastases from kidney, lung, GI and breast
  • Tumors preoperatively diagnosed by FNA, cytology, histopathology and immunophenotype are matched with a primary tumor
  • Direct invasion of thyroid by head neck malignancies
    • Squamous cell carcinoma originated from the adjacent organs (larynx, esophagus, hypopharynx and trachea)
    • Soft tissue malignancies of the neck
    • Parathyroid carcinoma
  • Primary sites for distant metastases to thyroid are kidney (34%), lung (15%), gastrointestinal tract (14%) and breast (14%) (Endocr Pathol 2013;24:116)
  • Infradiaphragmatic primaries are more common than supradiaphragmatic (Endocr Pathol 2017;28:11)
  • Renal cell carcinoma is the most common primary in clinical series, while lung cancer is the most common in autopsy studies (Ann Surg Oncol 2017;24:1533)
  • Two major hypotheses explain the rarity of metastases in the highly vascularized thyroid (Thyroid 2012;22:258):
    1. Relatively rapid arterial flow through the thyroid may discourage adhesion and seeding of metastases
    2. High oxygen saturation and iodine content of the thyroid gland itself may directly inhibit the growth of malignant cells
  • Fine needle aspiration after incidental discovery by ultrasound (Ann Surg Oncol 2017;24:1533)
  • Accurate morphological diagnosis is facilitated by clinical history
  • Discovered at the time of diagnosis of the primary tumor, after preoperative investigation of a neck mass, on histologic examination of a thyroidectomy specimen or at autopsy (Ann Surg Oncol 2017;24:1533)
Clinical features
Radiology description
  • Solitary hypofunctioning nodule on RAI scan
  • Sonographic characteristics are similar to benign and malignant thyroid diseases (J Ultrasound Med 2017;36:69)
Radiology images

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CT scan



Metastatic renal cell carcinoma

Prognostic factors
  • Determined by the underlying primary tumor (site of origin, aggressiveness, extent of metastatic spread), time interval between initial diagnosis and metastasis, extrathyroidal extent of disease and completeness or resection (Ann Surg Oncol 2017;24:1533)
  • Overall 5 year survival after detection of thyroid metastasis or postthyroidectomy is 20 - 30%
  • Median survival: 20 months
    • Patients who undergo thyroid resection: 30 - 39 months
    • Without thyroid surgery: 12 - 24 months
  • In one study survival was not different from patients diagnosed with the same primary tumours but without thyroid metastases (Clin Endocrinol (Oxf) 2007;66:565)
Case reports
  • Surgical resection (total or subtotal thyroidectomy) if patient presents with an isolated metastasis diagnosed during followup of indolent disease (Thyroid 2007;17:49)
  • For patients with widespread metastases in the setting of an aggressive malignancy, surgery is rarely indicated (Ann Surg Oncol 2017;24:1533)
Gross description
Gross images

Images hosted on PathOut server:


Melanoma metastatic from skin primary

Contributed by Dr. Mark R. Wick

Metastatic renal cell carcinoma

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Invasion by squamous cell carcinoma of larynx

Renal papillary carcinoma

Metastatic renal cell carcinoma

Surgical specimens

Surgical specimens

Microscopic (histologic) description
  • May involve multiple areas of thyroid gland
  • Can be small deposits within lymphovascular spaces or large mass
  • Often moderate or poorly differentiated adenocarcinoma (Arch Pathol Lab Med 1998;122:37)
  • Tumor to tumor metastasis appears as thyroid neoplasm (usually follicular adenoma) containing a nodule with contrasting morphology
Microscopic (histologic) images

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Images hosted on PathOut server:

Breast carcinoma, AFIP images:

Lobular carcinoma and entrapped thyroid follicles

ER stains breast tumor but not papillary carcinoma

Falsely positive thyroglobulin staining

Kidney: renal cell carcinoma:

Contributed by Dr. Mark R. Wick

Metastatic renal cell carcinoma

CD10, Keratin 8, RCC, thyroglobulin

Clear cell type

Cytoplasm is abundant and completely clear

Oil Red O stains cytoplasm strongly

False positive thyroglobulin staining

Contributed by Gabriel B.W. Lerner, MS4, Case of the Week #461:

Clear cell RCC metastatic to the thyroid

CD10, 400x

RCC, 400x

Lung, AFIP images:

Carcinoid tumor with well defined nesting pattern

Carcinoma metastatic to mediastinal thyroid gland




Case of the Week #342: metastatic leiomyosarcoma (frozen section slides)

Case of the Week #342: metastatic leiomyosarcoma (permanent sections)

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From rectum

Metastatic HCC in the thyroid gland

HCC stains for AFP

Metastatic breast carcinoma

Kidney - renal cell carcinoma metastatic to thyroid:

Clear cell type

Metastasis to goiter

Concurrent RCC and thyroid carcinoma


Central lesions inside
hyperplastic adenomatoid

FNA, histology and stains

CD10 and H&E


Lung-small cell carcinoma

Lung-squamous cell carcinoma


Parotid adenoid cystic carcinoma

Rectal carcinoma
to poorly differentiated
thyroid carcinoma

Tumor to tumor metastases

Virtual slides

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Metastatic renal clear cell carcinoma

Metastatic squamous cell carcinoma

FNA of metastatic breast carcinoma

Cytology description
Cytology images

Images hosted on PathOut server:

Contributed by Dr. Mark R. Wick

FNA: metastatic renal cell carcinoma

Images hosted on other servers:

Breast carcinoma metastatic to thyroid

Esophageal squamous cell carcinoma

Kidney: metastatic renal cell carcinoma, clear cell type

Kidney: bloody background with clusters of atypical cells; nuclei are somewhat pleomorphic with prominent nucleoli

Lung squamous cell carcinoma


Melanoma - HMB45

Parotid gland adenoid cystic carcinoma

Positive stains
  • Primary tumor specific markers e.g. Napsin A for lung, RCC for kidney, mammaglobin and BRST2 for breast, CK20 and CDX2 for gastrointestinal cancers
  • Mucin+ in metastatic adenocarcinoma, which is not seen in primary thyroid tumor
Negative stains
  • Thyroglobulin (may be spuriously positive due to the permeating colloid), TTF1 (but is positive in lung or small cell carcinoma)
Molecular / cytogenetics description
Differential diagnosis
Board review question #1
Which statement is False for metastatic clear cell renal cell carcinoma to the thyroid?

  1. Metastasis from renal cell carcinoma is generally a solitary mass.
  2. Metastatic clear cell renal cell carcinoma can have a very long latency after nephrectomy.
  3. Metastatic clear cell renal cell carcinoma can have a spurious thyroglobulin stain.
  4. TTF1 and PAX8 can be used to differentiate tumors of renal and thyroid origins.
  5. Metastatic tumor to the thyroid gland is the initial manifestation of renal cell carcinoma in 1/3 of cases.
Board review answer #1
D. TTF1 and PAX8 can be used to differentiate renal and thyroid origins.

Explanation: tumors from both thyroid and kidney can be positive for PAX8.
Board review question #2
Which of the following statements is true?

A. Metastases to the thyroid are a common finding.
B. Most patients with thyroid metastases have no known primary.
C. Melanoma is a common primary that metastasizes to the thyroid.
D. PAX8 may be positive in both thyroid and renal tumors.
Board review answer #2
D. PAX8 may be positive in both thyroid and kidney tumors.
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