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Diagnostic Applications of Nuclear Medicine: Thyroid Tumors

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Abstract

Thyroid cancer (TC) is the most frequent endocrine malignancy. Its incidency has been growing in the last three decades reaching a mean of 12/100,000 women and 4/100,000 men. Since the mortality is low (0.5%), the prevalence is very high especially among women who have a higher rate compared to men (3:1). TCs are distinguished into well-differentiated thyroid cancer (DTC) (i.e., papillary and follicular), poorly differentiated thyroid cancer (PDTC), anaplastic (ATC), and medullary cancer (MTC). Other very rare TC accounts for non-epithelial tumors, lymphoma, and carcinomas characterized by the presence of mucin-producing cells and keratin.

TC usually presents as a thyroid nodule. Thyroid ultrasonography (US) is useful to detect thyroid nodules, but since only 5% of thyroid nodules are malignant, the diagnosis of malignancy is done by fine-needle aspiration cytology (FNAC). Radioiodide or 99mTc-pertechnetate thyroid scan has a low diagnostic specificity and sensitivity for characterizing thyroid nodules. X-ray of the neck is useful to disclose a deviation of the trachea or lumen restriction, in large nodules and in multinodular goiter. CT and MRI are generally reserved for mediastinal thyroid masses or the identification of regional or distant metastasis.

The most widely used staging system for TC is the TNM classification that has been defined jointly by the Union Internationale Contre le Cancer (UICC) and by the American Joint Committee on Cancer (AJCC). Thyroid remnant ablation with 131I-iodide is indicated in DTC patients with a moderate to high risk of recurrence. Patients are prepared with rhTSH and low iodine diet.

ATC is a rare tumor (<3% of all TCs) derived from follicular cells with a very poor prognosis and almost invariably lethal. The most common clinical presentation of ATC is a new, large, firm thyroid mass, often associated with signs/symptoms of local compression/invasion. Multimodality treatment of ATC includes surgery, EBRT, and combination of chemotherapies. Therapy with 131I-iodide is not useful, since these tumors do not concentrate radioiodide. Preoperative imaging with US, CT, and MRI plays an important role, and [18F]FDG PET is useful to plan the therapeutic strategy.

MTC is a well-differentiated TC arising from the parafollicular, calcitonin-producing C cells. Its prevalence is 5–10% in all TCs. Sporadic and familial forms are recognized. Elevated baseline serum levels of calcitonin (Ct) are suspicious for MTC. Following surgery, MTC patients are monitored with serum Ct and CEA levels, and serial neck US examinations are performed. Ct doubling time in serum is the most sensitive biomarker for MTC progression. Scintigraphy with 123I-MIBG has very high sensitivity for staging patients with MEN II and familial MTC. However, it has a low sensitivity in patients with increased serum Ct but no clinical site of disease. 68Ga-DOTATATE PET/CT is now the best imaging modality in the detection of metastatic MTC lesions in the presence of high levels of serum Ct. Radionuclide therapy with the radiolabeled somatostatin analogue 90Y-DOTA-Tyr3-octreotide (90Y-DOTA-TOC) has been tested in metastatic MTC. The two TKIs, vandetanib and cabozantinib, represent nowadays the best therapy of metastatic and progressive MTC.

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Abbreviations

[18F]FDG:

2-Deoxy-2-[18F]fluoro-d-glucose

123I-MIBG:

123I-meta-Iodobenzylguanidine

18F-DOPA:

2-18F-Fluoro-l-3,4-dihydroxyphenylalanine

AJCC:

American Joint Committee on Cancer

ATC:

Anaplastic thyroid cancer

BRAF:

Gene encoding for the B-Raf protein, a serine/threonine-protein kinase; the gene is also known as the proto-oncogene B-Raf and v-Raf murine sarcoma viral oncogene homolog B

CEA:

Carcinoembryonic antigen, a tumor-associated serum marker

CI:

Confidence interval

Ct:

Calcitonin

CT:

X-ray computed tomography

DMSA:

Dimercaptosuccinic acid, a metal-chelating agent

DOTA-TOC:

DOTA-octreotide

DOTA:

1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid

DOTATATE:

DOTA-octreotate

DTC:

Well-differentiated thyroid cancer

EBRT:

External beam radiation therapy

EFVPTC:

Encapsulated follicular variant of papillary thyroid tumor

FNAC:

Fine-needle aspiration cytology

FT3:

Free circulating form of the thyroid hormone tri-iodothyronine

FT4:

Free circulating form of the thyroid hormone tetra-iodothyronine

FTC:

Follicular thyroid tumor

FVPTC:

Follicular variant of papillary thyroid tumor

GLUT:

Glucose transporter family

Gy:

Gray unit (ionizing radiation dose in the International System of Units, corresponding to the absorption of one joule of radiation energy per kilogram of matter)

MAP:

Mitogen-activated protein

MEN:

Multiple endocrine neoplasia

MET:

Gene encoding for a protein of the receptor tyrosine kinase family

MIBG:

meta-Iodobenzylguanidine

MIP:

Maximum intensity projection

MRI:

Magnetic resonance imaging

MTC:

Medullary thyroid cancer

mTOR:

Mammalian target of rapamycin

NEFVPTC:

Non-encapsulated follicular variant of papillary thyroid tumor

NIFTP:

Noninvasive follicular variant of papillary thyroid carcinoma

NIS:

Na+/I− symporter

p53:

Tumor protein p53, also known as cellular tumor antigen p53, phosphoprotein p53, tumor suppressor p53, antigen NY-CO-13, or transformation-related protein 53 (TRP53)

PAX8:

A member of the paired box (PAX) family of transcription factors

PDTC:

Poorly differentiated thyroid cancer

PET:

Positron emission tomography

PET/CT:

Positron emission tomography/Computed tomography

PI3K/AKT:

Intracellular signalling pathway regulating the cell cycle

PPA Rγ :

Gene encoding for the peroxisome proliferator-activated receptor gamma (or PPARG, a nuclear receptor), also known as the glitazone receptor, or NR1C3 (nuclear receptor subfamily 1, group C, member 3)

PTC:

Papillary thyroid tumor

RAS:

Oncogene regulating signalling intracellular cascades

RET:

A proto-oncogene encoding for a receptor tyrosine kinase for extracellular signalling molecules (from “rearranged during transfection”)

rhTSH:

Recombinant human TSH

SWI/SNF:

A nucleosome remodeling complex (from “SWItch/Sucrose Non-Fermentable”)

TC:

Thyroid cancer

TERT:

Gene encoding for telomerase reverse transcriptase, a catalytic subunit of the enzyme telomerase

Tg:

Thyroglobulin

TKI:

Thymidine kinase inhibitor

TNM:

AJCC/UICC staging system based on parameters “T” (tumor status), “N” (lymph node status), and “M” (distant metastasis status)

TRK:

Gene encoding for a receptor tyrosine kinase for extracellular signalling molecules

TSH:

Thyroid stimulating hormone or thyrotropin

UICC:

Union Internationale Contre le Cancer (International Union Against Cancer)

US:

Ultrasonography

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Authors and Affiliations

  1. Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Paradisa 1, 56100, Pisa, Italy

    Rossella Elisei, Laura Agate, Valeria Bottici & Eleonora Molinaro

  2. Regional Center of Nuclear Medicine, Department of Translational Research and Advanced Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy

    Sara Mazzarri, Federica Guidoccio, Giuseppe Boni & Giuliano Mariani

  3. Nuclear Medicine Unit, Department of Diagnostics and Public Health, University of Verona, Verona, Italy

    Marco Ferdeghini

Authors
  1. Rossella Elisei
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  2. Laura Agate
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  3. Sara Mazzarri
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  4. Valeria Bottici
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  5. Federica Guidoccio
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  6. Eleonora Molinaro
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  7. Giuseppe Boni
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  8. Marco Ferdeghini
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  9. Giuliano Mariani
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Corresponding author

Correspondence to Rossella Elisei .

Editor information

Editors and Affiliations

  1. Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    H. William Strauss

  2. University of Pisa, Regional Center of Nuclear Medicine, Pisa, Italy

    Giuliano Mariani

  3. University of Pisa, Regional Center of Nuclear Medicine, Pisa, Italy

    Duccio Volterrani

  4. Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA

    Steven M. Larson

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Elisei, R. et al. (2017). Diagnostic Applications of Nuclear Medicine: Thyroid Tumors. In: Strauss, H., Mariani, G., Volterrani, D., Larson, S. (eds) Nuclear Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-26236-9_11

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  • DOI: https://doi.org/10.1007/978-3-319-26236-9_11

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-26234-5

  • Online ISBN: 978-3-319-26236-9

  • eBook Packages: MedicineReference Module Medicine

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