Occurs 70% in adrenal gland and 30% are extra-adrenal in location.
10% are familial and usually bilateral and multifocal.
Occurs mostly in adults; rare in children.
Clinical: Classically associated with paroxysmal sweating attacks, headaches, and tachycardia; hypertension may be intermittent or sustained; these tumors may secrete epinephrine and/ or norepinephrine, ACTH, or parathormone; urinary vanillylmandelic acid (VMA) is elevated in up to 90% of cases.
Gross: encapsulated yellow-white to red-brown, soft, fleshy tumor (image A).
Well-defined nests (zellballen) of polygonal cells surrounded by a delicate fibrovascular stroma (image B) & (image C).
Cells have considerable variation in size and shape, and often demonstrate faintly basophilic (blue) finely granular cytoplasm.
Pleomorphism, hyperchromasia, and mitotic figures may be present and do not necessarily indicate malignancy (image D).
Eosinophilic globules (PAS positive) can be seen.
The only definitive evidence of malignancy is metastatic disease.
Immunohistochemistry: synaptophysin+, chromogranin+ and S100+ (+ only in sustentacular cells intermingled with malignant chromaffin cells).