Medullary Thyroid Cancer

🦠 Medullary Thyroid Carcinoma (MTC)

• Accounts for ~5% of all thyroid malignancies

• Constitutes 5–10% of pediatric thyroid cancers

• Unlike other thyroid cancers, Medullary Thyroid Carcinoma does NOT arise from follicular cells.

• Male : Female ≈ 1 : 1

What is the most common type of Thyroid cancer?

What cells does Medullary Thyroid Carcinoma originate from?

Which Thyroid cancer has female preponderance?

🧠 Classification of Medullary Thyroid Carcinoma

1️⃣ Sporadic Medullary Thyroid Carcinoma

• Most common type
• Age: 4th–6th decade
• Unifocal
• No associated endocrinopathy

2️⃣ Familial Medullary Thyroid Carcinoma

• Multifocal

• Bilateral

Familial MTC is further divided into:

Which is the most common type of Medullary Thyroid Carcinoma?

What type of inheritance pattern is seen in Familial Medullary Thyroid Carcinoma?

🧠 MEN Syndromes & Medullary Thyroid Carcinoma

MEN 2A (Sipple Syndrome)

🚩 Mnemonic: 1M + 2P

• M → Medullary thyroid carcinoma
• P → Pheochromocytoma
• P → Parathyroid hyperplasia (adenoma most common)

Other associations:

• Hirschsprung disease (rare)
• Cutaneous lichen amyloidosis (interscapular region)

MEN 2B (Most aggressive)

🚩 Mnemonic: 3M + 1P

• M → Medullary thyroid carcinoma
• M → Mucosal ganglioneuromas (tongue, lips, conjunctiva, GIT)
• M → Marfanoid habitus
• P → Pheochromocytoma

Other features:

• Enlarged lips
• Thickened corneal nerves
• Skeletal abnormalities (pectus excavatum, pes cavus, joint laxity)

What mutations are seen in MEN2A & MEN2B?

🩺 Clinical Features of Medullary Thyroid Carcinoma

Local Features

• Painless thyroid nodule (>75%)
• Later:
  • Dysphagia
  • Hoarseness
  • Dyspnea
  • Pain

Metastasis (Common at Diagnosis)

• Cervical nodes: 40–50%

• Distant (hematogenous):

  • Liver
  • Lung
  • Bone
  • Brain
  • Skin

Hormonal Effects

• ↑ Calcitonin → diarrhea, flushing
• Rare:
  • ACTH / CRH secretion → Cushing syndrome (poor prognosis)

🔬 Pathology of Medullary Thyroid Carcinoma

Gross

• Solitary or multifocal
• Usually non-encapsulated
• Upper 2/3 of thyroid
• Less than 1 cm → Medullary microcarcinoma (better prognosis)

Microscopy

• Tumor cells:
  • Round to polygonal
  • Arranged in solid, trabecular, insular, or nested patterns
• Fibrocollagenous stroma
• Amyloid deposition

🔑 Only thyroid cancer associated with amyloidosis

Why does Amyloid deposition occur in Medullary Thyroid Carcinoma?

What does Congo red stain show in Medullary Thyroid Carcinoma?

🔍 Investigations of Medullary Thyroid Carcinoma

• Ultrasound neck
• FNAC (amyloid is diagnostic)
• Serum calcitonin
• CEA
• Serum calcium (MEN 2A)
• Plasma / urine metanephrines (pheochromocytoma)

⚠️ Always rule out pheochromocytoma before thyroid surgery

Why should you always rule out pheochromocytoma before thyroid surgery?

Which is the most sensitive biochemical marker of Medullary Thyroid Carcinoma?

🛠️ Treatment of Medullary Thyroid Carcinoma

Primary Treatment

• Total thyroidectomy
• Central compartment (Level VI ± VII) neck dissection

When is Lateral Neck Dissection indicated in Medullary Thyroid Carcinoma?

Distant Metastasis

• Surgery for airway / esophageal protection

• External beam radiotherapy

• Targeted therapy:

  • Vandetanib
  • Cabozantinib

🧪 Follow-Up of Medullary Thyroid Carcinoma

• Lifelong follow-up

What are the parameters that should be monitored in a case of Medullary Thyroid Carcinoma?

How long does it take for Calcitonin to normalize in Medullary Thyroid Carcinoma postoperatively?

🛡️ Prophylactic Thyroidectomy (RET-positive) in Medullary Thyroid Carcinoma

📊 Prognosis of Medullary Thyroid Carcinoma

• 10-year survival: 56-96%

• Biochemical cure → 97.7% survival

• Children: 95% 5 year survival

What is Calcitonin / CEA Doubling Time? What value has a good prognosis and bad prognosis?

📌 Exam Pearls

• Only thyroid cancer from C cells
• Only thyroid cancer with amyloid
• Calcitonin = diagnostic + prognostic marker
• MEN 2B = most aggressive
• Rule out pheochromocytoma before surgery