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A 9-year-old boy is brought to the office due to oral lesions.  He had been living in a children's home until he was adopted 3 months ago.  He believes the tongue nodules have always been present.  They do not hurt or itch.  He has no taste disturbance and eats a variety of solids and liquids.  He is not bothered by drinking hot or cold liquids.  Vital signs are stable.  He is tall for his age with long arms and fingers.  Tongue examination is shown below.  On palpation, the tongue nodules feel discrete, firm, and rubbery.  They are not tender.  This patient is at greatest risk from which of the following conditions?

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Classification of multiple endocrine neoplasia

Type 1

  • Primary hyperparathyroidism (parathyroid adenomas or hyperplasia)
  • Pituitary tumors (prolactin, visual defects)
  • Pancreatic tumors (especially gastrinomas)

Type 2A

  • Medullary thyroid cancer (calcitonin)
  • Pheochromocytoma
  • Primary hyperparathyroidism (parathyroid hyperplasia)

Type 2B

  • Medullary thyroid cancer (calcitonin)
  • Pheochromocytoma
  • Mucosal neuromas/marfanoid habitus

This patient with an unknown family history, marfanoid habitus (eg, long arms and fingers), and mucosal neuromas (eg, painless, rubbery tongue nodules) likely has multiple endocrine neoplasia type 2B (MEN2B).  MEN2B is caused by a germline RET mutation and is often identified via family history or genetic screening.  Family members of a patient with a known germline RET mutation should undergo genetic testing.

The greatest threat to this patient's life is from medullary thyroid cancer (MTC).  MTC associated with MEN2B tends to occur at a very young age.  Because of this risk, prophylactic thyroidectomy is often performed in infancy (eg, age <1 year) in patients with known MEN2B.  Half of patients with MEN2B also have pheochromocytoma, which needs to be evaluated (ie, with plasma-fractionated metanephrines).

(Choice A)  Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome) leads to diffuse arteriovenous malformations, sometimes with life-threatening complications (eg, massive hemoptysis, gastrointestinal bleeding), and often presents with mucosal telangiectasias.  However, these typically appear as ruby-colored papules that blanch with pressure rather than firm, rubbery neuromas.

(Choice B)  Peutz-Jeghers syndrome is characterized by gastrointestinal tract hamartomatous polyposis.  Although oral lesions develop, they are typically perioral mucocutaneous pigmented macules rather than mucosal neuromas.

(Choice C)  MEN type 1 is characterized by primary hyperparathyroidism, pituitary tumors, and gastrointestinal/pancreatic endocrine tumors (eg, gastrinomas).  It is not associated with marfanoid habitus or mucosal neuromas.

(Choice D)  Tuberous sclerosis is an inherited neurocutaneous syndrome that often includes seizures that gradually worsen over time.  Although it can present with benign tumors, these are typically skin tumors (eg, ash-leaf spots, facial angiofibromas, shagreen patches) rather than mucosal neuromas.

Educational objective:
Multiple endocrine neoplasia type 2B (MEN2B) is characterized by medullary thyroid cancer (MTC), pheochromocytoma, marfanoid habitus, and mucosal neuromas.  MTC associated with MEN2B is often very aggressive, and thyroidectomy is often recommended in infancy.