Medullary Carcinoma

Tumour of the parafollicular cells which secrete calcitonin (C-cells)

Aetiology

  • Can be:
    • Sporadic (70%) - seen in adults (40s-50s)
    • Medullary carcinoma associated with Multiple Endocrine Neoplasia Type 2a (MEN2a) can arise in very young patients
      • MTC associated with phaeochromocytoma and hyperparathyroidism in these patients
      • Consider prophlactic thyroidectomy as child
    • Familial non-MEN seen in adults (40s-50s)

Genetic features

  • Germline RET mutations

Pathophysiology

Morphology

  • Sporadic cases - solitary nodule
  • Familial cases - bilateral/multicentric
    • C cell hyperplasia
  • Composed of spindle or polygonal cells arranged in nests, trabeculae or follicles
  • Associated amyloid deposition (abnormally folded calcitonin)

Prognostic factors

Good prognostic factors
  • Young age, female
  • Smaller tumour rise, confined to thyroid, no metastases
Negative prognostic factors
  • Necrosis
  • Many mitosis
  • Squamous metaplasia
  • Small cell morphology
  • <50% cells calcitonin positive
  • Type of RET mutation
  • Some familial forms have more aggressive potential (MEN2B)

Clinical presentation

  • Neck mass with local effects - dysphagia, hoearseness, airway compromise
  • Paraneoplastic syndrome
    • Diarrhoea - VIP production
    • Cushings - ACTH production

Investigations

  • Neck USS and FNA
  • Measure serum base calcitonin
  • 24 hour urinary metanephrines
  • Further imaging to detect localised/advanced disease
  • Check genetics for MEN

Management

Localised disease

  • Total thyroidectomy - curative
  • Local recurrence in 35% of patients

Advanced disease

  • May involve tyrosine kinase inhibitors