Thyroid Cancer Clinical Overview
I. The "On-Call" Snapshot
Clinical Significance in Malaysia: Thyroid nodules are common, but cancer is what we can't miss. Differentiated thyroid cancer is the most common endocrine malignancy in Malaysia and is particularly prevalent in women. Your job in the clinic or ED is to identify the high-risk nodule that needs further workup.
High-Yield Definition: Thyroid cancer is a malignancy arising from the epithelial cells (follicular or parafollicular) of the thyroid gland. The vast majority are well-differentiated (papillary or follicular) and have an excellent prognosis if managed correctly.
Clinical One-Liner: Basically, it's a lump in the neck that could be cancerous, so we need to figure out which ones are suspicious enough to stick a needle in.
II. Etiology & Risk Factors
Etiology: The exact cause is often unknown, but it's a result of genetic mutations leading to uncontrolled cell growth. We classify them into:
Differentiated (from follicular cells): Papillary (~80%), Follicular (~15%). These are the ones you'll see most often.
Medullary (from parafollicular C-cells): ~4%. Can be sporadic or part of MEN 2A/2B syndromes.
Anaplastic (undifferentiated): <2%. Aggressive, poor prognosis, typically in the elderly.
Risk Factors:
Non-Modifiable:
Female sex
Age extremes (<30 or >60 years)
Family history of thyroid cancer or related genetic syndromes (e.g., MEN2, FAP)
Modifiable/Environmental:
History of radiation exposure: Especially to the head and neck during childhood. This is a major red flag.
Iodine deficiency (associated more with follicular cancer).
III. Quick Pathophysiology
For differentiated cancers, it's straightforward. Genetic mutations (like BRAF, RAS, RET/PTC rearrangements) disrupt normal cell growth signalling. This leads to clonal proliferation of follicular cells, forming a nodule that can eventually invade locally or metastasize. The key is that these cells often retain the ability to take up iodine, which is the basis for our radioiodine treatment.
IV. Clinical Assessment
Red Flags & Immediate Actions:
Rapidly enlarging neck mass: Action → Urgent ultrasound and specialist referral (ENT/Endocrine Surgery).
Hoarseness (new onset): Action → Suspect recurrent laryngeal nerve involvement. Needs urgent laryngoscopy and referral.
Stridor or dysphagia: Action → Airway or esophageal compression. This is an emergency. Secure airway if needed, NPO, and get an urgent surgical consult.
Hard, fixed neck mass: Action → High suspicion for malignancy with local invasion. Urgent referral.
Cervical lymphadenopathy: Action → Suggests metastatic spread. Needs ultrasound mapping of the neck.
History:
Common: Often asymptomatic, found incidentally or by the patient as a painless neck lump.
Less Common: Local compressive symptoms (discomfort swallowing, tight collar feeling), cosmetic concerns.
Pertinent Negatives: Ask about symptoms of hyper- or hypothyroidism (most nodules are euthyroid), recent travel, or infections to rule out differentials.
Physical Examination:
Inspection: Look for a visible mass, note if it moves with swallowing. Check for scars from previous neck surgery.
Palpation: This is crucial. Assess the thyroid nodule for:
Size: >4 cm is a risk factor.
Consistency: Hard/firm is more suspicious than soft/cystic.
Fixation: Is it fixed to surrounding tissues like the trachea or strap muscles?
Tenderness: Pain is unusual for malignancy; suggests thyroiditis.
Lymph Nodes: Systematically palpate all cervical lymph node chains (anterior, posterior, supraclavicular).
Clinical Pearl: Get the patient to swallow a sip of water. A thyroid mass or nodule will rise with the thyroid cartilage. A thyroglossal cyst will also rise, but often protrudes more on tongue protrusion.
V. Diagnostic Workflow
Differential Diagnosis: For a solitary thyroid nodule:
Benign Colloid Nodule/Adenoma: Most common cause. Points For: Soft, mobile, slow-growing. Points Against: Absence of suspicious features. Differentiate with FNAC.
Thyroid Cyst: Points For: Smooth, fluctuant. Differentiate with Ultrasound (shows fluid content).
Hashimoto's Thyroiditis: Points For: Firm, rubbery goitre, often with hypothyroidism. Differentiate with anti-TPO antibodies and TFT.
Cervical Lymphadenopathy (from another primary): Points For: Not moving with swallowing. Differentiate with clinical context and imaging.
Investigations Plan:
Bedside / Initial (First 15 Mins in Clinic):
Thyroid Function Test (TFT): Primarily to check functional status. A suppressed TSH suggests a "hot" (hyperfunctioning) nodule, which is rarely malignant. An elevated TSH is a minor risk factor for malignancy.
First-Line Imaging:
High-Resolution Neck Ultrasound: This is the single most important initial imaging test. It characterizes the nodule and identifies features suspicious for malignancy (e.g., microcalcifications, irregular margins, taller-than-wide shape, central vascularity). It also assesses cervical lymph nodes. We use a scoring system like TI-RADS (Thyroid Imaging, Reporting and Data System) to stratify risk.
Confirmatory / Gold Standard:
Ultrasound-Guided Fine Needle Aspiration Cytology (FNAC): This is the gold standard for diagnosis. We perform this on nodules that are suspicious on ultrasound (e.g., TI-RADS 4 or 5) or large (>1-1.5 cm with moderate suspicion). The pathologist reports it using the Bethesda System for Reporting Thyroid Cytopathology, which gives us a risk of malignancy.
VI. Staging & Severity Assessment
Staging is done post-operatively using the AJCC TNM (Tumour, Node, Metastasis) system, 8th Edition. The unique thing about differentiated thyroid cancer is that age at diagnosis is a major prognostic factor and is part of the staging itself.
Prognostic Groups:
Low Risk: Younger patients (<55 years) with disease confined to the neck (even with lymph node mets) are usually Stage I.
Higher Risk: Older patients (>55 years) are upstaged. Any distant metastasis automatically makes it Stage IVB (for younger patients) or IVC (for older patients).
Impact on Management: Staging, along with post-op histology (e.g., extrathyroidal extension, vascular invasion), determines the need for adjuvant therapy like Radioactive Iodine (RAI).
VII. Management Plan
Management is decided by a multidisciplinary team (Endocrinologist, Surgeon, Oncologist, Nuclear Medicine Physician).
Immediate Stabilisation (Rarely needed): Only for advanced, invasive cancers causing airway compromise. Follow the ABCDE plan.
Definitive Treatment (The Ward Round Plan):
Surgery: This is the cornerstone of treatment.
Total Thyroidectomy: Standard procedure for most cancers >1 cm.
Lobectomy: May be an option for small (<1 cm), low-risk, unifocal, intrathyroidal papillary cancers.
Neck Dissection: Performed if there is evidence of lymph node metastasis.
Adjuvant Therapy:
Radioactive Iodine (RAI) Ablation: Done post-thyroidectomy for patients with higher-risk disease (large tumours, extrathyroidal extension, nodal or distant mets). The goal is to destroy any remaining thyroid tissue and cancer cells.
TSH Suppression Therapy: Patients who have had a thyroidectomy are started on lifelong levothyroxine (e.g., Eltroxin). We aim for a suppressed TSH level (<0.1 mIU/L for high-risk, 0.1-0.5 mIU/L for low-risk) to prevent any remaining cancer cells from being stimulated to grow.
Long-Term & Discharge Plan:
Lifelong follow-up with an endocrinologist.
Monitoring with serial serum Thyroglobulin (Tg) levels (should be undetectable after total thyroidectomy and RAI) and anti-Tg antibodies.
Periodic neck ultrasounds.
Counsel on lifelong levothyroxine compliance.
VIII. Complications
Immediate (Post-operative):
Hypocalcemia: Damage to or removal of parathyroid glands. Management: Monitor serum calcium, replace with IV/oral calcium and calcitriol as needed.
Recurrent Laryngeal Nerve Injury: Hoarseness (unilateral) or airway compromise (bilateral). Management: Speech therapy; may need surgical intervention.
Hemorrhage/Hematoma: Can cause airway compression. Management: Emergency evacuation in OT.
Long-Term:
Hypothyroidism: Inevitable after total thyroidectomy. Management: Lifelong levothyroxine.
Disease Recurrence: Can occur locally in the neck or as distant metastases (lungs, bone). Management: Surgery, further RAI, or external beam radiation/tyrosine kinase inhibitors for advanced disease.
IX. Prognosis
For differentiated thyroid cancer, the prognosis is excellent. The 10-year survival rate for localized papillary thyroid cancer is >99%.
Key Prognostic Factors:
Age at Diagnosis: Poorer prognosis for patients >55 years.
Presence of Distant Metastases: This is the single most important factor for mortality.
Histological Subtype: Anaplastic cancer has a dismal prognosis (months), while papillary has an excellent one.
X. How to Present to Your Senior
"Dr., for review please. This is Puan Siti in Clinic Room 2, a 45-year-old lady who presented with a self-palpated neck lump. On exam, she has a 2cm firm, non-tender nodule in the right thyroid lobe and no palpable cervical nodes. She is clinically euthyroid. Her TFT is normal. My main differential is a thyroid nodule requiring further risk stratification. I plan to send her for a neck ultrasound to characterize the nodule and decide on the need for FNAC."
XI. Summary & Further Reading
Top 3 Takeaways:
Any thyroid nodule needs a TFT and a high-resolution ultrasound.
Suspicious ultrasound features warrant an FNAC to rule out malignancy.
The majority of thyroid cancers are well-differentiated with an excellent prognosis after surgery and appropriate adjuvant therapy.
Key Resources:
Local Guideline: Management of Thyroid Disorders, 2nd Edition (2019) by the Malaysian Endocrine and Metabolic Society (MEMS) & Ministry of Health. This covers the initial workup of nodules. (While a dedicated cancer CPG is less prominent, the principles align with international standards).
International Guideline: American Thyroid Association (ATA) Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. This is the global standard.
For Quick Reference: UpToDate or Amboss articles on "Differentiated thyroid cancer" and "Evaluation of a thyroid nodule".
Now, go and clerk your patient properly.
