Although physical examination is the primary screening modality for the detection of thyroid cancer, in populations at increased risk, neck ultrasound is an important supplemental approach. Any solitary thyroid nodule should be considered malignant until proved otherwise. Although toxic nodular goiters are less likely to contain carcinoma, a nodule in the setting of hyperthyroidism does not preclude malignancy.

Because most thyroid tumors spread primarily by local extension and regional nodal metastasis, assessment of the extent of disease in the neck is critical. In recent years, ultrasound has become integrated into endocrinology practices and is very helpful in assessing risk of cancer, and in facilitating expeditious outpatient fine needle aspiration (FNA) of suspicious thyroid nodules. FNA does not require local anesthesia and is considered safer and easier to perform than core biopsy, with accuracy between 50% and 97%, depending on the type of cancer, the experience of the pathologist, and the institution; however, there are times when formal core biopsies are required, including when lymphoma is suspected.

Diagnostic RAI imaging is not now commonly used in the primary assessment of thyroid nodules, but remains a mainstay of assessment in patients with high-risk disease or with metastatic radioiodine-avid DTC after primary surgery. Chest radiography should be performed before surgery to rule out macroscopic pulmonary metastasis. If there is any clinical or laboratory suggestion of bone or other metastases, skeletal radiographs, computed tomography (CT) scan, positron emission tomography (PET) scan, and/or a radionuclide bone scan should be considered on a casebycase basis.

Several issues should also be kept in mind in assessing disease extent and response to therapy. First, iodinated contrast materials should not be used in any DTC patients who may be candidates for therapeutic radioiodine, as the iodine load can saturate tumor binding sites and thereby render therapeutic RAI ineffective. In general, a 2-month delay of RAI is preferred after any iodinated contrast. Second, anatomic imaging in surveillance of patients and in following disease course is important. In DTC for instance, a negative iodine/thyroid scan does not exclude the possibility of metastatic disease, as small pulmonary nodules often escape detection using this modality. Further, some DTCs will become radioiodine refractory and will not image even in the presence of bulky metastases. Third, although tumor markers can be very helpful in patient surveillance in the postoperative setting in DTC and MTC, they must be used judiciously. Thyroglobulin can be neutralized by patient antithyroglobulin antibodies, and therefore the two tests should always be measured in tandem. If antithyroglobulin antibody is elevated, thyroglobulin levels are uninterpretable. Moreover, with time and interval therapies, thyroglobulin production by DTCs diminishes concordant with tumor dedifferentiation, thereby yielding misleading results—and again emphasizing the importance of anatomic imaging in highrisk patients or those with advanced disease. Thyroglobulin levels are also less predictable in estimating disease extent in patients receiving novel therapies.

Also worthy of comment is that PET imaging should be used judiciously in thyroid cancer. In ATC, PET can be very helpful; however, some DTCs do not image well via PET. In DTC, PET avidity tends to correlate with more aggressive tumor behavior.

Patients with thyroid carcinoma are typically euthyroid; however, elevated TSH with increased thyroid peroxidase antibodies may be seen with Hashimoto thyroiditis, which may coexist in 20% of patients with thyroid lymphoma and also sometimes in DTC.

The most widely accepted tumor staging system, TNM, uses tumor size and extent, presence of lymph node spread, and distant metastasis (Table 13.2). Any ATC is considered stage IV (A, B, or C), and there are no TNM stage III or IV patients with DTC who are younger than 45 years. This staging system is suboptimal in thyroid cancer, prompting use of algorithms such as the MACIS system discussed above.

Therapeutic approach in thyroid cancer depends considerably on the histologic type, extent of disease, patient symptoms, and rate of disease progression. Careful management of disease residing in the neck so as to protect airway, esophagus, and other critical structures is also of paramount importance.