Thyroid Cancer

Snapshot

• 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. 

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
• Prognosis
  • papillary has very good prognosis
• anaplastic has very poor prognosis

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 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

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 > 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

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

Complications

• Metastasis to other organs
• Death