A patient presents with macroglossia (enlarged tongue). Which systemic condition is classically associated as the most common systemic cause of macroglossia?

Amyloidosis is the most classic systemic cause of macroglossia in the oral medicine context. In primary (AL) amyloidosis, insoluble amyloid protein fibrils deposit throughout body tissues including the tongue, resulting in diffuse, firm enlargement (macroglossia). The enlarged tongue may show indentations from the teeth (scalloped tongue margin). Amyloidosis may be primary or secondary to multiple myeloma. Other causes of macroglossia include hypothyroidism (cretinism/myxedema), acromegaly, Down syndrome, hemangioma, lymphangioma, and Beckwith-Wiedemann syndrome. Candidiasis affects the mucosal surface but does not cause true macroglossia. Medication side effects rarely cause true macroglossia.