Updated: 12/26/2021

Thyroid Cancer

Review Topic
  • 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

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(M2.ON.16.37) A 45-year-old woman comes into your office with complaints of a "lump" she found on her neck while showering. She denies any other symptoms and states that she has not gained any weight. On exam, you notice a 2 cm nodule on her anterior neck. Her TSH level is normal, and radionucleotide scan reveals a cold nodule. Fine needle aspiration biopsy (FNAB) reveals follicular architecture suspicious for malignancy. What is the next best step?

QID: 104579

Punch biopsy



Surgical excision



Thyroxine administration






CT scan



M 6 E

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Evidence (3)
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