Thyroid Cancer Management Clinical Overview
I. The "On-Call" Snapshot
Clinical Significance in Malaysia: Thyroid cancer is the 9th most common cancer among women in Malaysia. You will frequently encounter patients with thyroid nodules in both outpatient and inpatient settings, and your job is to identify which ones need urgent workup.
High-Yield Definition: Malignant neoplasms arising from the follicular or parafollicular (C-cells) of the thyroid gland. They are broadly classified into Differentiated Thyroid Cancer (DTC), Medullary Thyroid Cancer (MTC), and Anaplastic Thyroid Cancer (ATC).
Clinical One-Liner: Basically, it's a lump in the neck that could be anything from benign to extremely aggressive, so we work it up systematically to figure out how urgently we need to act.
II. Etiology & Risk Factors
Etiology:
Differentiated (Papillary, Follicular): Arise from thyroid follicular cells. The exact cause is multifactorial, but genetic mutations (e.g., BRAF, RAS, RET/PTC rearrangements) are key drivers.
Medullary: Arises from parafollicular C-cells. About 25% are familial, driven by germline RET proto-oncogene mutations (part of MEN2A and MEN2B syndromes). The rest are sporadic.
Anaplastic: The most aggressive form. Often arises from a pre-existing DTC through the accumulation of further mutations (e.g., TP53).
Risk Factors:
Non-modifiable:
Female sex (3:1 ratio)
Age extremes (very young or >60 years)
Family history of thyroid cancer or related genetic syndromes (e.g., MEN2, FAP)
Modifiable/Environmental:
Radiation Exposure: The single biggest risk factor, especially in childhood or adolescence. Think previous radiotherapy for lymphoma.
Iodine deficiency (associated more with follicular cancer) or excess.
III. Quick Pathophysiology
Think of it this way:
DTC (Papillary & Follicular): These are "well-behaved" because they still resemble normal thyroid cells. They grow slowly, respond to TSH, and most importantly, take up iodine. This iodine uptake is the key to our main adjuvant treatment, Radioactive Iodine (RAI). Papillary spreads via lymphatics. Follicular spreads via blood.
MTC: These come from C-cells, not follicular cells. They don't take up iodine but they do produce calcitonin. Calcitonin is our tumour marker here.
ATC: This is the dedifferentiated, chaotic end-stage. The cells have lost all normal function. They don't respond to TSH or take up iodine, and they grow incredibly fast. It's a true oncologic emergency.
IV. Clinical Assessment
Red Flags & Immediate Actions:
Rapidly enlarging neck mass: Needs urgent ultrasound and specialist review. Could be anaplastic transformation or lymphoma.
Hoarseness (Dysphonia): Suggests recurrent laryngeal nerve involvement. Scope the patient (ENT referral) and expedite workup.
Stridor or Dyspnea: Airway compromise. This is an emergency. Alert your senior and Anesthetics immediately. Secure the airway.
Hard, fixed neck mass: Highly suspicious for malignancy with local invasion.
Cervical lymphadenopathy: Suggests regional spread.
History:
Common (>50%): Painless neck lump, often found incidentally by the patient or during a routine check-up.
Less Common (10-50%): Compressive symptoms (dysphagia, choking sensation), voice changes, neck pain.
Pertinent Negatives: Ask about B symptoms (fever, night sweats, weight loss) to help rule out lymphoma. Ask about palpitations, heat intolerance to rule out a toxic nodule. Ask about family history of thyroid cancer or pheochromocytoma (for MEN syndromes).
Physical Examination:
Inspection: Look for a visible goiter, surgical scars.
Palpation:
Assess the nodule: Size, consistency (firm/hard vs soft), mobility, tenderness.
Palpate for cervical lymph nodes, especially in the central and lateral compartments.
Systemic: Check for signs of hyper/hypothyroidism. Perform a quick vocal cord check by asking the patient to say "ahh" and "eee". Check for Pemberton's sign if it's a large retrosternal goiter.
Clinical Pearl: The majority of thyroid nodules are benign. Our job isn't to diagnose cancer on palpation, it's to risk-stratify using clinical features and investigations to decide who needs a biopsy.
V. Diagnostic Workflow
Differential Diagnosis:
Benign Nodular Goiter (Colloid Nodule, Adenoma):
Points For: Soft, mobile nodule, long history without growth, euthyroid state.
Points Against: Red flag symptoms, suspicious ultrasound features.
How to Differentiate: Fine Needle Aspiration Cytology (FNAC) is the decider.
Thyroiditis (e.g., Hashimoto's, De Quervain's):
Points For: Diffusely enlarged, firm gland (Hashimoto's) or a very tender gland after a viral illness (De Quervain's). Abnormal TFTs.
Points Against: A single, discrete, non-tender nodule.
How to Differentiate: Clinical picture, thyroid autoantibodies (anti-TPO), and FNAC.
Cervical Lymphadenopathy / Other Neck Lumps:
Points For: Mass located outside the typical thyroid anatomical borders.
Points Against: Mass moves with swallowing.
How to Differentiate: Ultrasound will confirm if the mass is intra-thyroidal or extra-thyroidal.
Investigations Plan:
While we don't have a specific national CPG for thyroid cancer, our practice in Malaysia is guided by international standards like the American Thyroid Association (ATA) guidelines.
Initial (Clinic/GP level):
TSH Level: This is your first and most important blood test.
If TSH is low (suppressed), it suggests a hyperfunctioning ("hot") nodule, which is rarely malignant. Proceed to a radionuclide scan.
If TSH is normal or high, the nodule is "cold" or "warm", and risk of malignancy is higher. Proceed to ultrasound.
First-Line Imaging & Biopsy (Hospital setting):
Ultrasound of the Neck: This is the cornerstone of imaging. We use a TIRADS (Thyroid Imaging Reporting and Data System) classification to stratify malignancy risk based on features like microcalcifications, irregular margins, being "taller-than-wide", and extrathyroidal extension.
Fine Needle Aspiration Cytology (FNAC): Guided by ultrasound, this is the main diagnostic tool. We send the sample for cytology, which is reported using the Bethesda System.
Bethesda I: Non-diagnostic (repeat FNAC).
Bethesda II: Benign (follow-up).
Bethesda III/IV: Atypia/Suspicious for follicular neoplasm (needs diagnostic lobectomy).
Bethesda V/VI: Suspicious for/Malignant (proceed to surgical planning).
Staging / Gold Standard:
Contrast-Enhanced CT Scan of Neck & Thorax: Not for initial diagnosis, but crucial for pre-operative planning in confirmed cancer to assess for local invasion and lymph node metastasis.
Histopathology of Surgical Specimen: This is the definitive gold standard. It confirms the cancer type, size, and extent.
VI. Staging & Severity Assessment
We use the AJCC 8th Edition TNM Staging system. The most critical point to remember is that for DTC, age is a major prognostic factor. The cut-off is 55 years.
For Patients <55 years old (DTC):
Stage I: Any T, Any N, M0 (No distant mets).
Stage II: Any T, Any N, M1 (Distant mets present).
It's that simple. Age is protective.
For Patients ≥55 years old (DTC):
Staging is more granular, incorporating T, N, and M status similarly to other cancers. Stage I is for small, contained tumours (T1N0M0), while Stage IV is for distant mets or significant local invasion.
Medullary & Anaplastic Cancer: These have their own staging systems which do not use the age cut-off and are staged based on tumour extent, reflecting their more aggressive biology. Anaplastic is essentially Stage IV by definition.
VII. Management Plan
This is a multidisciplinary team (MDT) decision involving surgeons, endocrinologists, and oncologists.
Differentiated Thyroid Cancer (Papillary & Follicular)
Surgery (Definitive Treatment):
Total Thyroidectomy: Standard of care for tumours >4cm, or those with extrathyroidal extension, clinical nodes, or distant mets. This is the most common procedure we do.
Thyroid Lobectomy: Can be considered for low-risk, small (<4cm), unifocal, intrathyroidal tumours with no suspicious nodes.
Adjuvant Treatment:
Radioactive Iodine (RAI) Ablation: Done post-thyroidectomy for patients with higher risk of recurrence (e.g., large tumours, lymph node mets, aggressive subtypes). The patient swallows an I-131 capsule to destroy any remaining thyroid tissue (remnant ablation) and microscopic cancer cells. This makes follow-up with Thyroglobulin easier.
TSH Suppression Therapy: All patients post-thyroidectomy are started on lifelong Levothyroxine. In cancer patients, we give a slightly higher dose to suppress TSH below the normal range. The goal is to remove the TSH growth stimulus from any potential remaining cancer cells. The degree of suppression depends on the recurrence risk.
Medullary Thyroid Cancer (MTC)
Surgery: The absolute mainstay of treatment. Requires total thyroidectomy AND central neck lymph node dissection. Lateral neck dissection is done if nodes are involved there.
Genetic Testing: All patients with MTC must be tested for a germline RET mutation to rule out MEN2. If positive, family members must be screened.
Adjuvant Therapy: MTC does not take up iodine, so RAI is useless. External beam radiotherapy (EBRT) may be used for residual disease.
Systemic Therapy: For advanced/metastatic disease, Tyrosine Kinase Inhibitors (TKIs) like Vandetanib or Cabozantinib, and newer selective RET inhibitors like Selpercatinib, are options. Availability in Malaysian government hospitals needs to be confirmed with the oncologist and pharmacist; access is often limited.
Anaplastic Thyroid Cancer (ATC)
This is an emergency. Management is often palliative from the start.
Secure the Airway: Tracheostomy is often required.
Surgery: Rarely curative. Debulking may be done if feasible to relieve airway compression.
Combined Modality Therapy: The best chance of any response is with a combination of EBRT and systemic therapy (chemotherapy or targeted therapy like Dabrafenib/Trametinib if BRAF V600E mutated).
VIII. Complications
Immediate (Post-op):
Hypocalcemia: Damage to or removal of parathyroid glands. Manage with IV/oral calcium and Vitamin D. This is why you must check the post-op calcium level.
Recurrent Laryngeal Nerve Injury: Hoarseness (unilateral) or airway compromise (bilateral).
Hematoma: Neck swelling, can compromise airway. Needs immediate return to theatre.
Short-Term (Post-RAI):
Sialadenitis: Painful swollen salivary glands. Management: Sour candies, hydration.
Long-Term:
Disease Recurrence: Can be local, regional, or distant.
Complications of TSH suppression: Osteoporosis, atrial fibrillation.
IX. Prognosis
DTC: Excellent. 5-year survival for localised disease is >99%. Even with regional spread, it's >98%. Prognosis is worse in patients >55 years and with distant metastasis.
MTC: Good if caught early. 5-year survival for localised disease is >95%, but drops to ~40% with distant mets.
ATC: Dismal. Median survival is 3-6 months. 1-year survival is <20%.
Top 3 Prognostic Factors: Age at diagnosis, presence of distant metastasis, and completeness of surgical resection.
X. How to Present to Your Senior
"Dr, for review please. This is Puan Siti in Bed 10, a 45-year-old lady with no past medical history, who presented with a painless neck lump for 6 months. On examination, there is a 3cm, firm, mobile nodule in the right thyroid lobe with a palpable 1cm right cervical lymph node. Her TSH is normal. Ultrasound showed a TIRADS 5 nodule and FNAC came back as Bethesda VI: Papillary Thyroid Carcinoma. My main diagnosis is Stage I Papillary Thyroid Cancer. I have sent off the pre-op bloods and referred her to the surgical and endocrine teams. I would like to ask about getting a pre-operative staging CT scan of the neck."
XI. Summary & Further Reading
Top 3 Takeaways:
The first step for any thyroid nodule is a TSH level. This dictates your next move.
FNAC is the main diagnostic tool, but surgical histopathology is the gold standard.
Age (<55 vs ≥55) is the single most important factor in staging and prognosis for Differentiated Thyroid Cancer.
Key Resources:
Local Context: Management of Thyroid Disorders (3rd Edition) - Ministry of Health Malaysia. While not a cancer CPG, it covers the initial approach to nodules. (Link: MOH Thyroid Disorders CPG)
The International Gold Standard: 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer. This is the main reference we use in practice. (Search PubMed: PMID 26462967)
Quick Reference: UpToDate - Search for "Differentiated thyroid cancer: Initial treatment" and "Medullary thyroid cancer: Clinical manifestations, diagnosis, and staging".
Now go and clerk that patient properly.
