Snapshot A 36-year-old woman complains of several weeks of hoarseness and difficulty swallowing. She also feels a sense of fullness in her neck. On physical exam there is a palpable, nontender swelling in the front of her neck that moves with swallowing. There is no cervical lymphadenopathy. Lab studies show decreased TSH. Ultrasound of the neck reveals a 2.5 cm hypoechoic thyroid nodule with calcifications and thyroid scintigraphy shows decreased iodine uptake of the nodule compared to surrounding tissues. Introduction Overview primary malignancy of thyroid gland secondary metasteses can occur from other cancers breast, colon, renal, and melanoma Epidemiology Incidence increasing in past 15 years papillary thyroid cancer (most common) has incidence of 15 per 100,000 Demographics papillary more common in women anaplastic more common in elderly Risk factors < 30 or > 70 years of age history of radiation to head/neck family history of medullary thyroid cancer multiple endocrine neoplasia (MEN) syndrome type 2 Cowden syndrome familial adenomatous polyposis Classification Papillary overview 85% of all thyroid cancers female dominance often multifocal risk factors include radiation exposure to the head and neck spreads via lymphatics very good prognosis histology psammoma bodies (calcifications) also seen in ovarian dysgerminomas and meningiomas ground glass/empty nuclei/"orphan Annie nuclei" nuclear grooves cells organized into papillary "fingers" Follicular carcinoma overview usually unifocal small number evolved from a benign follicular adenoma requires surgical excision to differentiate between adenoma and carcinoma follicular carcinoma shows invasion into capsule and vessels spreads hematogenously lungs most common location of metastasis good prognosis histology preservation of normal thyroid follicular architecture but with proliferation uniform follicles Medullary overview derived from calcitonin-synthesizing C cells may present with hypocalcemia may produce ACTH 10% of cases associated with MEN syndrome type 2a or 2b associated with a RET mutation typically unifocal thyroid nodule patients have elevated serum calcitonin (tumor marker) risk factors previous radiation to neck family history histology amyloid (consisting of calcitonin) Anaplastic overview more common in elderly can be superimposed on multinodular goiter or follicular cancer very poor prognosis Presentation Symptoms dysphagia and hoarseness can be due to direct compression by mass can indicate tumor invasion/nerve involvement Physical exam neck mass or palpable thyroid nodule +/- cervical lymphadenopathy suggests metastasis Imaging Thyroid scintigraphy (radioactive iodine uptake test) indications patients with decreased thyroid stimulating hormone (TSH) levels findings "hot" nodule increased uptake of iodine compared to surrounding thyroid tissue suggests autonomously functioning thyroid typically benign no fine needle aspiration (FNA) required "cold" nodule less uptake of iodine compared to surrounding thyroid tissue concern for malignancy perform FNA Ultrasonography indications all patients with thyroid nodule findings hypoechoic nodule >1 cm more likely to be malignant high suspicion of malignancy if hypoechoic nodule > 1cm and has ≥ 1 suspicious features such as irregular margins microcalcifications rim calcifications extrathyroidal extension intermediate suspicion of malignancy if hypoechoic nodule > 1cm with smooth margins Studies TSH levels decreased TSH more concerning for malignancy follow up with thyroid scintigraphy (radioactive iodine uptake test) normal/elevated TSH less concerning for malignancy follow up with ultrasound Serum calcitonin tumor marker for medullary thyroid cancer Fine needle aspiration (FNA) indications all "cold" nodules on radioactive iodine uptake scan nodules that meet high or intermediate suspicion criteria based on ultrasound nodules that are low suspicion on ultrasound but have all of the following properties isoechoic, hyperechoic solid nodule, or partially cystic nodule has eccentric solid areas size > 1.5 cm Differential Benign thyroid nodule key distinguishing factors more likely to be tender associated hypo- or hyperthyroidism typically "hot" on radioactive iodine uptake test Treatment Medical iodine radiotherapy indications papillary thyroid cancer following surgical management in high-risk and some intermediate-risk patients thyroid hormone supplementation indications almost all patients following initial medical/surgical management prevents hypothyroidism minimizes potential TSH stimulation of tumor growth modalities daily oral levothyroxine Surgical thyroidectomy indications FNA findings that either confirm malignancy or are suspicious for malignancy risk of damage to recurrent laryngeal nerve during surgery persistent hoarseness Prognosis Papillary very good prognosis Anaplastic very poor prognosis