A Physicians' Guide to
Thyroid Cancer from A-Z

Thyroid Cancer Screening

A complete medical history is vital in diagnosing thyroid cancer. Of key importance is:

  • a history of head and/or neck irradiation during childhood or adolescence
  • a history of total body irradiation (eg, for bone marrow transplantation)
  • family history of thyroid carcinoma
  • personal/family history (in a first-degree relative) of Cowden’s syndrome, FAP, or MEN II

The diagnostic approach in children is no different than in adults.1

The physical examination focuses on the thyroid gland, nodules and/or masses, and cervical lymph nodes. Palpable nodules are usually 1 cm or larger and require a complete work-up. Physical findings indicative of possible malignancy include lateral cervical lymphadenopathy, nodule(s) fixation to surrounding tissue(s), hoarseness, and vocal cord paralysis.1 Firm nodules may represent thyroid cancer, but this clinical observation is not considered diagnostic.2

The American Thyroid Association (ATA) recommends:1

  • Measure Serum Thyroid-stimulating Hormone (TSH).  If the serum TSH is below normal, a radionuclide thyroid scan should be performed using either technetium 99mTc pertechnetate or 123I. 1 A radionuclide thyroid scan is an imaging test performed to determine the etiology of hyperthyroidism. A “hot” or autonomous nodule carries a very low risk of cancer and does not require a work-up for malignancy. Thyroid scans are not helpful and should not be ordered when the serum TSH is normal or elevated.
  • Diagnostic Ultrasound. Diagnostic ultrasound should be performed for known and suspected thyroid nodules. This includes thyroid nodules detected incidental to a CT scan, MR imaging, or thyroidal update on a fluorodeoxyglucose (FDG)-positron emission tomography (PET) scan (performed to detect or monitor for recurrence of non-thyroid malignancies). Ultrasound is ideal for evaluating thyroid structures and can confirm thyroid nodule size, furnish detail related to tumor characteristics, and identify other nodules requiring biopsy (Figs. 1 and 2).1

Figure 1. Solid thyroid nodule in the right thyroid lobe

Figure 2. Cystic nodule in the left thyroid lobe
  • Fine-needle Aspiration.  Fine-needle aspiration (FNA) is an accurate and cost-effective technique to biopsy thyroid nodules for cytological evaluation. Ultrasound-guided FNA is preferred, as some nodules are difficult or impossible to palpate.1 Furthermore, ultrasound-guided fine-needle aspiration improves diagnostic outcome on smaller nodules when compared to palpation-guided FNA.3

The Bethesda System for Reporting Thyroid Cytopathology classifies the results of FNA into one of six categories.4 Furthermore, it provides terminology consistent for meaningful communication between pathologists, endocrinologists, oncologists, and other physicians involved in the evaluation and diagnosis of thyroid nodules.

Bethesda System for Reporting Thyroid Cytopathology4

  1. Nondiagnostic (ND) or Unsatisfactory (US)
    (Contained no cells, only cyst fluid, or other substances [eg, blood] that render sample ND/US.)
    Clinical Action: Repeat ultrasound-guided FNA
  2. Benign
    Clinical Action: Follow-up
  3. Atypia of Undetermined Significance (AUS) or Follicular Lesion of Undetermined Significance (FLUS)
    Clinical Action: Repeat ultrasound-guided FNA
  4. Follicular Neoplasm or Suspicious of Follicular Neoplasm
    Clinical Action: Surgery
  5. Suspicious for Malignancy
    Clinical Action: Surgery
  6. Suspicious for Malignancy
    Clinical Action: Surgery

Biological Markers: Advances in Thyroid Cancer Diagnosis

Tumor markers specific to thyroid cancers include serum thyroglobulin, calcitonin, and carcinoembryonic antigen (CEA). Serum thyroglobulin is used to monitor patients with differentiated thyroid carcinomas. Serum calcitonin levels can be used to detect and to monitor disease in patients with medullary thyroid cancer. CEA is a protein needed for cellular adhesion and is a useful marker for the follow-up of patients with medullary thyroid carcinoma.

Other markers, both genetic and molecular, show potential to benefit the diagnosis and prognosis of thyroid cancers.5,6 Many markers involve different oncogenes. When a normal gene is altered by mutation, it affects a related aspect of normal cell functionality. Certain oncogenes deregulate cell division, programmed apoptosis, and disrupt tumor cell suppression. Advancement in the area of genetic and molecular markers may benefit patients with a cytological report of indeterminate thyroid cancer by potentially obviating the need for "diagnostic surgery."

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Thyroid Cancer Staging and Initial Treatment Considerations
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