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Pediatric Thyroid Cancer Workup

  • Author: Mark E Gerber, MD; Chief Editor: Arlen D Meyers, MD, MBA  more...
 
Updated: Apr 30, 2015
 

Laboratory Studies

See the list below:

  • Levels of serum triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) are usually within reference ranges in malignancy. Therefore, although these blood studies have no predictive value for thyroid cancer, they help shape the differential diagnosis of a child's thyroid mass.[17]
  • Antithyroid antibodies are helpful in diagnosing chronic lymphocytic thyroiditis. Thyroglobulin levels may be elevated in differentiated thyroid carcinoma and may help in postoperative monitoring. The thyroglobulin level should not be measured until at least 14 days after fine-needle aspiration (FNA) to prevent an artificial level elevation from the needle instrumentation.[40]
  • Traditional screening for both medullary thyroid cancer (MTC) and thyroid C-cell hyperplasia is performed by measuring calcitonin levels before and after pentagastrin stimulation. Screening for multiple endocrine neoplasia 2 (MEN2) is now possible with DNA analysis for specific mutations in the ret protooncogene.
  • Serum carcinoembryonic antigen (CEA) should be measured in those in whom MTC is suspected. Unfortunately, a negative value may be found in advanced stages of the disease.[41]
  • Obtain a 24-hour urine collection to screen for catecholamines metabolites, as a pheochromocytoma or paraganglioma should be surgically removed before thyroidectomy to avoid a hypertension crisis during surgery.
  • Obtain genetic testing at birth in children at risk for MEN2B and no later than age one year in children at risk for MEN2A.[29, 42]
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Imaging Studies

Imaging studies reveal the malignant potential and the extent of disease, and they provide an anatomical roadmap for surgical planning. The following are the imaging studies with the highest yield.

  • Ultrasonography
    • Ultrasonography, a safe and widely available technique, is the first-line screening diagnostic test in all pediatric patients with thyroid nodules.
    • In particular, children with a history of radiation exposure should be observed with serial ultrasonography. Nodules that enlarge even a few millimeters should undergo FNAB.
    • Ultrasonography is useful in differentiating solid from cystic lesions and in revealing nonpalpable lesions. Many investigators consider cystic lesions to be benign lesions that represent hemorrhage into or degeneration of an adenomatous nodular goiter.
    • A solid nodule is more likely to be malignant; however, up to 50% of malignant lesions may have a cystic component, and approximately 8% of cystic lesions represent malignancies.[43, 23]
    • Ultrasonography reveals critical information regarding the risk of benign versus malignant disease. Benign features on ultrasound include multiple, solid isoechogenic or nonechogenic lesions and a uniform peripheral halo.[7] Malignant features include a thick irregular halo.[44]
    • Color-Doppler sonography may aid in the diagnosis in patients with hyperfunctioning nodules (hot on scintigraphy [SC] and usually benign histologically), indicating an intensive vascular flow within a highly vascularized lesion and no visible flow through the remaining suppressed thyroid gland.[45] Color-Doppler sonography is also valuable in distinguishing a cystic lesion (with no vascular flow) from a solid neoplasm (with intranodular flow).[45]
    • One of the most helpful capabilities of ultrasonography is guidance of percutaneous needle biopsy.[10, 11]
  • Radionucleotide scan (scintigraphy)
    • Thyroid scintigraphy is most useful in revealing tissue function in thyroglossal duct cysts (eg, ensuring that thyroid tissue in the normal location is functioning) and in diagnosing ectopic thyroid. However, thyroid scintigraphy has not proven worthwhile in distinguishing malignant from benign disease.
    • Classic hot nodules show uptake only in the nodule area of the thyroid and are associated with about a 6% incidence of malignancy.
    • Harach et al (2002) wrote that untreated hot nodules can progress to carcinoma.[46] Surgical treatment is advisable for all children and adolescents with autonomously functioning thyroid nodules because of the risks of hyperthyroidism and thyroid carcinoma.[47, 7]
    • Cold nodules are usually benign adenomas, although, in children, a larger number of them are carcinomas.[48] Solid lesions that are cold on scintigraphy are malignant in about 30% of children.[49]
    • Total-body radioactive iodine (RAI) scans often reveal pulmonary nodal metastases, which are missed on radiography.
  • CT scan
    • Noncontrast CT scans can be helpful in patients with substernal extension, local invasion, or lymph node metastasis.
    • At initial evaluation, approximately 20% of children have pulmonary metastasis that can be revealed by either chest radiography or CT scan.[14]
    • Children have a much higher incidence of pulmonary involvement than adults.
    • The CT lung findings, which usually consist of diffuse miliary spots and, less often, infiltrating nodules, are often also best noted with RAI scans.[8]
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Procedures

See the list below:

  • Fine-needle aspiration biopsy
    • FNAB is the criterion standard in the diagnostic workup of adult thyroid nodules. Several studies report efficacy in the pediatric population.
    • High diagnostic accuracy with experienced pathologists improves the selection of pediatric patients for surgery and is an adjunct to guide further management.[50, 15, 16, 51]
    • Ultrasonography can be a useful guide for percutaneous needle biopsy when the lesion is difficult to identify with palpation.[10, 11]
    • FNAB is often not practical in children younger than 10 years; excisional biopsy under general anesthesia is recommended in this population.[52]
    • Using molecular polymerase chain reaction (PCR) studies on FNAB aspirate is mostly beneficial in the clinical research setting. It can be used in a very small number of patients for diagnostic purposes, but it remains expensive.[17]
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Histologic Findings

Follicular adenoma is the most common cause of solitary nodules of the thyroid in the pediatric population.[9] Adenomas are solitary, well circumscribed, and well encapsulated and are composed of glandular epithelium. Most are histologically follicular but are occasionally papillary.

  • Most thyroid cancers (papillary, follicular, anaplastic) originate from follicular cells. Medullary thyroid cancers (25% hereditary vs 75% sporadic) are of C-cell (calcitonin-producing) origin.[53]
  • Thyroid malignancies in children are usually well-differentiated papillary or papillary-follicular subtypes, but all histologic types have been observed. Papillary carcinoma lesions, which comprise an estimated 72% of pediatric thyroid cancers, are irregular, solid, or cystic masses that arise from follicular epithelium.
  • Microscopically, these masses have fronds of epithelium and distinct uniform cells with rare mitoses. Most contain both papillary and follicular components. The cells contain pink, finely granular cytoplasm with large pale nuclei (Orphan Annie eyes) and nuclear grooves. Psammoma bodies are rounded calcified deposits and can be found in approximately 50% of the lesions. Papillary carcinoma has frequent lymphatic and pulmonary metastases.
  • Follicular carcinoma lesions, which comprise 18% of pediatric thyroid cancers, are usually encapsulated and have highly cellular follicles and microfollicles with compact dark-staining nuclei of fairly uniform size, shape, and location. Pathologic diagnosis can be made only when invasion of the capsule, adjacent glands, lymphatics, or blood vessels is seen. Follicular carcinoma metastasizes intravascularly to the lungs, brain, and bones. When a portion of the cells in the tumor are found to be oxyphilic (Hürthle cells), it is called a Hürthle cell tumor. These lesions tend to have a less favorable prognosis.
  • MTC arises from the thyroid parafollicular or C cells, which secrete calcitonin and are derived from the neural crest and ultimobranchial body. Hyperplasia of the C cells is thought to represent a precancerous state. Histologically, MTC is composed of columns of epithelial cells and dense stroma that typically stain for amyloid and collagen. The nuclei are hyperchromatic, and mitoses are common. The cells have a fusiform shape and may form a whirling pattern. Calcifications are observed in 50% of these lesions.
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Staging

Definition

The American Joint Committee on Cancer (AJCC) created the following staging system:[54, 55]

  • T1 - Tumor diameter 2 cm or smaller
  • T2 - Primary tumor diameter greater than 2-4 cm
  • T3 - Primary tumor diameter greater than 4 cm limited to the thyroid or with minimal extrathyroidal extension
  • T4a - Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve
  • T4b - Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
  • TX - Primary tumor size unknown, but without extrathyroidal invasion
  • NO - No metastatic nodes
  • N1a - Metastases to level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes)
  • N1b - Metastasis to unilateral, bilateral, contralateral cervical, or superior mediastinal mode metastases
  • NX - Nodes not assessed at surgery
  • MO - No distant metastases
  • M1 - Distant metastases
  • MX - Distant metastases not assessed

Stage I (any T, any N, M0)

Stage II (any T, any N, M1)

See Thyroid Cancer Staging for information on stage groupings.

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Contributor Information and Disclosures
Author

Mark E Gerber, MD Clinical Associate Professor of Surgery, University of Chicago Pritzker School of Medicine; Division Head, Otolaryngology-Head and Neck Surgery; Director, Pediatric Otolaryngology-Head and Neck Surgery, NorthShore University Health System

Mark E Gerber, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Bronchoesophagological Association, American Society of Pediatric Otolaryngology, Society for Ear, Nose and Throat Advances in Children, American Academy of Pediatrics, American Rhinologic Society

Disclosure: Nothing to disclose.

Coauthor(s)

Brian Kip Reilly, MD Assistant Professor of Otolaryngology and Pediatrics, Department of Otolaryngology, Children's National Medical Center, George Washington University School of Medicine

Brian Kip Reilly, MD is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery

Disclosure: Nothing to disclose.

Mihir K Bhayani, MD Clinical Assistant Professor, Department of Surgery, University of Chicago Division of the Biological Sciences, The Pritzker School of Medicine; Consulting Surgeon, Head and Neck Surgical Oncology Section, Department of Otolaryngology, NorthShore University Health System

Mihir K Bhayani, MD is a member of the following medical societies: American Head and Neck Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Nader Sadeghi, MD, FRCSC Professor, Otolaryngology-Head and Neck Surgery, Director of Head and Neck Surgery, George Washington University School of Medicine and Health Sciences

Nader Sadeghi, MD, FRCSC is a member of the following medical societies: American Head and Neck Society, American Thyroid Association, American Academy of Otolaryngology-Head and Neck Surgery, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Chief Editor

Arlen D Meyers, MD, MBA Professor of Otolaryngology, Dentistry, and Engineering, University of Colorado School of Medicine

Arlen D Meyers, MD, MBA is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, American Academy of Otolaryngology-Head and Neck Surgery, American Head and Neck Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cerescan;RxRevu;SymbiaAllergySolutions<br/>Received income in an amount equal to or greater than $250 from: Symbia<br/>Received from Allergy Solutions, Inc for board membership; Received honoraria from RxRevu for chief medical editor; Received salary from Medvoy for founder and president; Received consulting fee from Corvectra for senior medical advisor; Received ownership interest from Cerescan for consulting; Received consulting fee from Essiahealth for advisor; Received consulting fee from Carespan for advisor; Received consulting fee from Covidien for consulting.

Acknowledgements

Russell A Faust, MD, PhD Consulting Staff, Department of Otolaryngology, Columbus Children's Hospital

Disclosure: Nothing to disclose.

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A monomorphous cell population of Hürthle cells arranged in loosely cohesive clusters and single cells. The cells are polyhedral and have abundant granular cytoplasm with well-defined cell borders. The nuclei are enlarged and have a central prominent macronucleolus.
 
 
 
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