Medullary Thyroid Cancer (MTC): Overview

Medullary Thyroid Cancer (MTC)

• MTC is a neuroendocrine tumor originating from C cells in the thyroid, producing calcitonin. Unlike other thyroid cancers, it's more aggressive.
• It occurs sporadically in about 75% of cases, or as part of familial syndromes like MEN 2A and 2B.
• Originates from neural crest-derived C cells producing calcitonin, which serves as a tumor marker.
• Associated with RET proto-oncogene mutations.
• Metastasizes commonly to cervical and mediastinal lymph nodes, lungs, liver, and bones.
• Typical presentation includes a neck mass (often firm and painless), dysphagia (difficulty swallowing), hoarseness, diarrhea (due to calcitonin), flushing (due to vasoactive peptides), and potential endocrine symptoms.
• MEN 2A can present with hyperparathyroidism and pheochromocytoma, while MEN 2B includes marfanoid habitus, mucosal neuromas, and pheochromocytoma.

Diagnostic Evaluation of MTC

• Biochemical Markers: Serum calcitonin (highly sensitive, correlating with tumor burden), carcinoembryonic antigen (CEA) often elevated in advanced disease, RET proto-oncogene mutation testing is crucial for hereditary cases.
• Imaging: Thyroid ultrasound (first-line), fine-needle aspiration (FNA) with calcitonin staining for confirmation, CT/MRI for metastases (especially for suspected widespread disease), PET-CT (advanced cases), and MIBG/Octreotide scan (other neuroendocrine tumors).

Management of MTC

• Surgical Treatment (Localized): Total thyroidectomy with central lymph node dissection standard. Prophylactic thyroidectomy in MEN2. Lateral neck dissection for positive nodes.
• Adjuvant Treatment (Metastatic/Advanced): Targeted therapy (tyrosine kinase inhibitors like cabozantinib/vandetinib for progressive disease), radiation therapy (palliation for unresectable/metastatic), calcitonin monitoring post-surgery (residual/recurrence), and annual screening (neck ultrasound, serum calcitonin, CEA).

Prognosis of MTC

• Sporadic MTC: ~75% 10-year survival.
• Familial MTC (MEN 2A/2B): Poorer prognosis for MEN 2B (early onset, aggressive).
• Prognosis dependent on stage: Localized disease (good) vs. metastatic disease (poor).

Multiple Endocrine Neoplasia (MEN)

• MEN syndromes are autosomal dominant disorders of genes controlling cell growth in multiple endocrine organs.

MEN 2 (RET-Related)

• MTC is the hallmark of MEN 2.

MEN 2A

• MTC (100%)
• Pheochromocytoma (~50%): Potentially life-threatening hypertension.
• Primary hyperparathyroidism (~20-30%): Often parathyroid hyperplasia.
• RET mutations in specific exons (10, 11, 13, 14, 15, 16).

MEN 2B

• MTC (aggressive, early-onset, 100%)
• Pheochromocytoma (~50%)
• Marfanoid habitus, mucosal neuromas (lips, tongue, eyelids, GI).
• No hyperparathyroidism.
• RET mutations (exons 15, 16), M918T mutation associated with worse prognosis.
• Prophylactic thyroidectomy at a young age.

Medullary Thyroid Cancer (MTC) is an aggressive neuroendocrine tumor derived from thyroid C cells, which produce calcitonin. It can occur sporadically or as part of familial syndromes like MEN 2A/2B, often linked to RET mutations. Diagnosis involves biochemical markers and imaging to assess tumor stage and metastasis.