Updated: 10/24/2022

Thyroid Cancer

Review Topic
  • A 32-year-old woman complains of fatigue and difficulty swallowing for the past month. The patient has also noted that her voice has been sounding different for the past 2 weeks. On physical exam there is a palpable, nontender nodule in the front of her neck that moves with swallowing. There is no cervical lymphadenopathy. Ultrasound of the neck shows a 1.9 cm nodule with microcalcifications. 
  • 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
  • Prognosis
    • papillary has very good prognosis
    • anaplastic has very poor prognosis
  • 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 papillary serous cystadenocarcinoma and meningiomas
      • ground glass/empty nuclei  
        • nuclear grooves
        • known as "Orphan Annie" eyes
      • 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 
      • most commonly spreads hematogenously
        • lungs most common location of metastasis
        • can also involve jugular lymph nodes 
      • 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
  • 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
  • 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 > 1 cm and has ≥ 1 suspicious features such as
          • irregular margins
          • microcalcifications 
          • rim calcifications
          • extrathyroidal extension
      • intermediate suspicion of malignancy if
        • hypoechoic nodule > 1 cm with smooth margins
  • 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
  • Benign thyroid nodule
    • key distinguishing factors
      • more likely to be tender
      • associated hypo- or hyperthyroidism
      • typically "hot" on radioactive iodine uptake test
  • 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 
      • risk of hypocalcemia after surgery due to removal of parathyroid glands
        • treat with calcium and vitamin D supplementation 
  • Metastasis to other organs
  • Death 

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(M1.ON.17.4754) A 43-year-old female presents to her primary care physician complaining of a gradually enlarging neck mass. She reports that she first developed a firm nodular midline mass on the anterior aspect of her neck two months ago. She is otherwise healthy and takes no medications. A fine-needle aspiration is performed and a histological sample of the specimen is shown. Which of the following is the most likely diagnosis?

QID: 108711

Medullary thyroid carcinoma



Follicular thyroid carcinoma



Papillary thyroid carcinoma



B-cell lymphoma



Anaplastic thyroid carcinoma



M 2 C

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(M1.ON.14.27) A 27-year-old female presents to her physician with a palpable thyroid nodule. Iodine uptake testing shows that the nodule has decreased iodine uptake compared with the rest of the thyroid gland. A fine-needle aspiration is performed and the physician calls telling the patient that she has a neoplasm of the thyroid. Which of the following diagnoses is the most likely?

QID: 104667

Papillary carcinoma



Medullary carcinoma



Follicular carcinoma



Anaplastic carcinoma



Hurthle cell carcinoma



M 2 D

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Evidence (4)
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