Neurofibromatosis Type 1 — Café-au-lait Spots

A 16-year-old girl presents with episodic palpitations, sweating, headaches, and paroxysmal hypertension (BP 220/130 mmHg during episodes). On examination, she is noted to have multiple light-brown oval cutaneous macules with smooth borders measuring 1–4 cm scattered over the trunk and limbs, as marked **A** in the diagram. She also has axillary freckling, multiple cutaneous neurofibromas, and a large plexiform neurofibroma over the left thigh. Slit-lamp examination reveals Lisch nodules bilaterally. Plasma free metanephrines are markedly elevated, and imaging confirms a 5-cm right adrenal mass. Which of the following BEST explains the pathophysiologic basis for the multiple cutaneous and systemic manifestations in this patient?