Microscopic description and IHC:
Grossly, this is a 9 x 4.5 x 2.5 cm dark brown mass with focal areas of necrosis. Histologically, the mass is composed of nests of amphophilic polygonal cells surrounded by a fine capillary network (Zellballen pattern). Intermixed with this are groups of mature ganglion cells surrounded by fascicles of Schwann cells and collagen. There are areas of marked pleomorphism, cellular spindling and necrosis, with approximately 2 mitoses per 30 HPF.
Immunohistochemically, the pheochromocytoma component exhibits strong positivity for synaptophysin and chromogranin. S-100 highlights the ganglioneuroma component and the sustentacular cells surrounding the nests of chromaffin cells. Melan-A is negative.
Discussion:
Composite pheochromocytoma is the terminology used when a tumor consists of a pheochromocytoma with a component of neuroblastoma, ganglioneuroblastoma, ganglioneuroma, or malignant peripheral nerve sheath tumor. These are rare tumors and comprise less than 3% of adrenal pheochromocytomas. They have rarely been associated with neurofibromatosis type 1, MEN2A or MEN2B. Usually, these tumors are associated with typical signs and symptoms of catecholamine hypersecretion such as hypertension, headache, diaphoresis, palpitations, and weight loss. Some tumors have been associated with Verner-Morrison syndrome with watery diarrhea and hypokalemia. The pheochromocytoma component stains positive for synaptophysin, chromogranin, and GATA3, with S-100 highlighting the sustentacular cells. The ganglioneuroma component is highlighted by S-100. Benign tumors typically average no more than 1 mitosis per 30 high power fields. Other factors such as capsular invasion, vascular invasion, peri-adrenal adipose invasion, cellular spindling, cellularity, hyperchromasia, pleomorphism and necrosis can be used to predict malignant potential.
References:
G. Mangray, S, DeLellis, RA. Adrenal glands. In: Mills, SE, Greenson JK, Hornick JL, Longacre TA, Reuter VE, editors. Sternberg’s diagnostic surgical pathology. 6th edition. Philadelphia: Wolters Kluwer Health; c2015. p 595-646.
Rao RN, Singla N, Yadav K. Composite pheochromocytoma-ganglioneuroma of the adrenal gland: A case report with immunohistochemical study. Urol Ann. 2013; 5(2): 115-118.