Thyroid lumps and nodules

Thyroid nodules

• Clinically detectable in 5% of the population, but radiologically detectable in around 50% (ultrasound can be very sensitive)
• More common in women (4 x as prevalent), older people, areas with low iodine intake
• Often picked up incidentally due to other imaging – found on 16% of CT or MRI neck scans, 9% of carotid duplex scans and 3% of PET scans
• <15% of nodules are clinically relevant
• The problem with nodules
  • • Can cause thyroid dysfunction
      • • Around 5% of nodules are toxic ‘hot nodules’ and are only very rarely cancerous
        • Cold nodules can be malignant (but usually aren’t)
    • Can cause compression – hoarseness, dysphagia, SOB, cough, dysphonia
    • Can be cancer
      • • Around 10% of thyroid nodules >1cm will be cancerous (but palpable nodules are not necessarily suspicious)
        • If PET-positive nodule: around 33% risk of cancer

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Thyroid cancer

• Papillary – 70% of cases. Slow growing and metastases are rare
• Follicular – 15% of cases. More aggressive
• Medullary < 5%. Locally invasive with mets, more aggressive than follicular. MEN 2 association. Check calcitonin – elevated.
• Anaplastic < 10%. The most aggressive
• Lymphoma < 1%

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Assessment of thyroid nodules

• Assess for symptoms and signs of cancer/thyroid disease
• Assess for cancer risk
  • • Personal risk factors
      • • History of neck irradiation, family history (especially of papillary thyroid cancer, medullary thyroid cancer, MEN), history  lymphoma (NHL or HL), age <20 or >70, men, symptoms of compression
    • Examination features
      • • Worrisome features include: firm nodule, rapid growth, fixed to adjacent structures, cervical nodes, vocal cord paralysis
    • Imaging – suspicious features on USS, lymphadenopathy, FDG-PET avidity
• TFTs
  • • If normal TFTs
      • • Do thyroid USS
        • Consider fine needle aspiration on 2ww pathway
    • If low TSH – Consider radioiodine uptake scan (hot nodules virtually never malignant)
• Tumour markers
  • • Serum calcitonin
      • • A marker for medullary thyroid cancer
        • Sensitive, but non-specific, therefore not done routinely and screening not advised (however it is checked routinely in Europe)
    • Serum thyroglobulin
      • • Useful in the follow up for differentiated thyroid cancer, but not sensitive or specific therefore not used to help diagnose thyroid cancer
• Ultrasound scan
  • • Very sensitive test of thyroid nodules – counts nodules, characterises
    • Helps decide who to do a Fine Needle Aspiration for (and increases the yield of FNA)
    • Can be specific for diagnosing papillary thyroid cancer
    • Operator needs to be experienced if assessing possible cancer
• Decide on FNA (fine needle aspiration) – see below

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Ultrasound features

• Echogenicity
  • • Solid and hypoechoic lesions could be medullary or papillary thyroid cancer
    • Hyperechoic/homogenous lesions in follicular thyroid cancer
    • Spongiform or honeycomb – tend to be benign
• Calcification
  • • Egg shell calcifications reassuring for benign lesion
    • Microcalcifications can occur in cancer
• Shape and border
  • • Benign nodules can be cystic
    • Malignant nodules may be irregular
    • Taller than wide suggests cancer
• Internal vascularity
  • • Red flag for medullary or papillary thyroid cancer
    • Peripheral vascularity more common in benign lesions
• Halo – Hypoechoic halo suggest benign lesion, absence of halo can suggest cancer
• Lymphadenopathy – use a grading system

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The U classification and actions

• Based on the characteristics on ultrasound detailed above
  • • U1 normal – very rare as USS not required!)
    • U2 benign-looking – can be discharged
    • U3 indeterminate – can be a follicular lesion
    • U4 suspicious
    • U5 appears malignant
• Do FNA based on U score and size
  • • U1 and U2 – no follow up required
    • U3 and 1-2 cm – repeat USS in 6-12 months (if no changes can be discharged)
    • U3 and >2cm – FNA
    • U4/5 and >1cm – FNA (consider FNA if 0.5cm-1cm)
    • Can also do FNA of abnormal cervical nodes for staging
    • FNA is very difficult if <0.5 cm
    • If PET-positive – always do USS and then FNA if U3 or more (regardless of size)

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Cytology

• ‘Thy’ categories predict malignancy
  • • Thy 1 is non-diagnostic. Consider repeating FNA. This occurs in up to 10% of FNAs
    • Thy 2 is non-cancerous. This occurs in 65% of biopsies
    • Thy 3a – cancer possible but atypical features. Usually repeat the FNA and MDT discussion if Thy 3a again. This result occurs in 10% of biopsies, and confers a risk of cancer of around 20%
    • Thy 3f is a follicular cancer – do diagnostic hemi-thyroidectomy. This occurs in around 10% of biopsies and risk of cancer is around 33%.
    • Thy 4 is suspicious of cancer – do diagnostic hemi-thyroidectomy. This occurs in 3% of biopsies and cancer risk is 60%
    • Thy 5 is diagnostic of cancer. Treat as per tumour type and patient preferences. This occurs in 3% of biopsies and cancer risk is 98%.
    • If thy3 – bear in mind that risk of cancer remains <50% (important to communicate to patients)
• Molecular markers can help refine the diagnosis but may not be available in the UK yet
  • • Check for mutations in the thyroid cell DNA (eg BRAF, RAS, TERT, TP53, fusion genes) – this rules in cancer
    • Check gene expression analysis – this can help rule out cancer (96% positive predictive value)
    • Micro-RNA expression kits. Expensive and not available in UK

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Management

• Consider surgery if
  • • Cancerous, or suspicious cytology
    • Compressive symptoms
    • >2 non-diagnostic FNAs (and sufficient suspicion)
    • For cosmetic reasons
    • Large toxic nodule
    • Graves’ disease
• The risk of hypothyroidism after hemithyroidectomy is around 20%
• Thermal ablation can be used for benign nodules (by radiofrequency, microwaves or lasers). Major complications rare.
• Cystic nodules can be aspirated
• Multinodular thyroids
  • • Bear in mind that there can be multiple nodules, including benign and cancerous ones
    • Only FNA nodules if suspicious on USS
    • 4% of multinodular goitre is complicated by carcinoma
    • Suppressive levothyroxine no longer used to reduce nodule growth (causes subclinical hyperthyroidism)
• Follow up scans
  • • Indicated for
      • • Non-diagnostic FNA (with suspicious USS)
        • Small U3 lesion
        • Suspicious USS and thy 2
    • No need to rescan if USS reassuring (not like colonic polyps which can transform over time, thyroid nodules are either cancer or not)

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Non-malignant thyroid enlargement

• Generally not treated treatment if normal TFTs and no / minimal symptoms
• Consider treatment if SOB /airway narrowing – options are surgery, radioactive iodine ablation (if uptake), percutaneous thermal ablation
• Repeat USS if hoarseness / SOB / red flags for cancer
• Can aspirate cystic lesions if compressive