Random Dermatology MCQ - Multiple Endocrine Neoplasia (MEN)

A 45-year-old man presents with recurrent episodes of facial flushing, explosive watery diarrhea, and wheezing. On examination, you note multiple, firm, flesh-colored papules on his central face and several pink-brown macules on his lips. A workup reveals elevated 24-hour urinary 5-HIAA and a mass in the terminal ileum. What is the most likely underlying genetic syndrome and the associated endocrine neoplasia most pertinent to the skin findings?

A. Multiple Endocrine Neoplasia type 1 (MEN1); associated with facial angiofibromas and collagenomas.
B. Multiple Endocrine Neoplasia type 2A (MEN2A); associated with cutaneous lichen amyloidosis and mucosal neuromas.
C. Multiple Endocrine Neoplasia type 2B (MEN2B); associated with mucosal neuromas and a marfanoid habitus.
D. Neurofibromatosis type 1; associated with café-au-lait macules and axillary freckling.
E. Carney complex; associated with lentigines and cardiac myxomas.

Correct Answer: A. Multiple Endocrine Neoplasia type 1 (MEN1); associated with facial angiofibromas and collagenomas.

Answer and Explanation

The correct answer is A. This question describes a patient with a carcinoid tumor (ileal mass with elevated 5-HIAA causing carcinoid syndrome - flushing, diarrhea, wheezing). Carcinoid tumors are a well-known, albeit less common, component of Multiple Endocrine Neoplasia type 1 (MEN1). The cutaneous findings described—multiple, firm, flesh-colored facial papules—are classic for facial angiofibromas, and the pink-brown macules on the lips are typical mucosal or cutaneous lipomas or collagenomas. These are the hallmark dermatologic manifestations of MEN1. The triad of MEN1 is parathyroid adenomas, pancreatic neuroendocrine tumors (like gastrinoma), and pituitary adenomas, but carcinoid tumors and these specific skin lesions are major diagnostic clues.

Why the Other Options are Incorrect:

• B. Multiple Endocrine Neoplasia type 2A (MEN2A): This syndrome features medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism. The characteristic skin finding is cutaneous lichen amyloidosis, a pruritic, scaly plaque on the upper back, not facial papules or lip macules. Mucosal neuromas are not a feature.

• C. Multiple Endocrine Neoplasia type 2B (MEN2B): This syndrome features MTC, pheochromocytoma, and a distinct phenotype with mucosal neuromas (bumpy lips and tongue), marfanoid habitus, and intestinal ganglioneuromatosis. It does not cause facial angiofibromas or carcinoid tumors.

• D. Neurofibromatosis type 1: While café-au-lait macules and axillary freckling are present, the facial papules in NF1 are cutaneous neurofibromas, which are softer and more pedunculated than the firm, dome-shaped angiofibromas of MEN1. NF1 is not associated with carcinoid syndrome.

• E. Carney complex: This features spotty pigmentation (lentigines, blue nevi), cardiac myxomas, and endocrine overactivity. The facial lesions are lentigines (flat, dark macules), not angiofibromas, and it is not associated with carcinoid tumors.

Additional High-Yield Information for Exams:

• MEN1 (Wermer's Syndrome):

  • Gene: MEN1 tumor suppressor gene.

  • Endocrine Tumors: "3 P's" – Parathyroid adenoma (most common, ~95%), Pancreatic neuroendocrine tumors (gastrinoma, insulinoma), Pituitary adenoma.

  • Dermatologic Features (Present in ~80%): Facial angiofibromas (mimicking acne), collagenomas (firm, skin-colored papules/plaques on trunk/neck), lipomas (cutaneous and visceral), confetti-like hypopigmented macules.

• MEN2 (Sipple Syndrome):

  • Gene: RET proto-oncogene.

  • MEN2A: MTC, Pheochromocytoma, Hyperparathyroidism. Cutaneous lichen amyloidosis is a pathognomonic skin marker.

  • MEN2B: MTC, Pheochromocytoma, Mucosal neuromas, marfanoid habitus, intestinal ganglioneuromatosis. Neuromas give a characteristic facial appearance (bumpy lips).

• Differential Diagnosis: Facial angiofibromas also occur in Tuberous Sclerosis Complex (TSC). The key is the associated findings: in TSC, look for hypomelanotic macules, seizures, and intellectual disability; in MEN1, look for the endocrine tumor triad.

• Prognosis: In MEN1, morbidity and mortality are primarily from malignant pancreatic neuroendocrine tumors (e.g., gastrinoma) and thymic carcinoids. In MEN2, medullary thyroid carcinoma is the leading cause of death, driving the need for prophylactic thyroidectomy.

• Management & Rationale:

  • Rationale: Management revolves around surveillance for early detection of tumors and prophylactic surgery in the case of MEN2.

  • MEN1: Regular screening for hormone excess and tumor growth (annual biochemical testing, imaging). Treatment is surgical or medical for specific tumors.

  • MEN2: Genetic testing at birth is critical. For individuals with a RET mutation, prophylactic total thyroidectomy is recommended, often in early childhood (timing based on specific mutation risk level). Screening for pheochromocytoma before any surgery is mandatory.

  • Dermatologic: Facial angiofibromas can be treated with laser therapy for cosmetic purposes.