Pheochromocytomas have been associated with "rule of 10s". 10% extraadrenal, bilateral, biologically malign, are not associatd with hypertension.
Malignancy is more common ( 20-40%) in extra adrenal paragangliomas.
The incidence of malinancy is higher ( 30%) in tumors that arise on the backdrop of germline SDHB mutations. The succinate dehydrogenase complex subunit gense ( SDHB, SDHC and SDHD) encode proteins involved in mitochondrial electron transport and oxygen sensing. The loss of funtion in one or more of these subunit leads to stabilization of the oncogenic transcription factor hypoxia-inducible factor 1a (HIF-1alfa), promoting tumorigenesis.
Incubation of fresh tissue with apotassium dichromate solutıon turns the tumor a dark brown color due to oxidation of stored catecholamines, thus the term chromaffin.
The histologic patern in pheochromocytoma is quite variable. Tumors are composed of polygonal to spindle-shaped chromaffin cellls or chief cells, clustered with sustentecular cells into small nests or alveoli(zellballen) by rich vascular network.
Determinig malignancy in pheo, there is no histologic feature that reliably predicts clinical behaviour. The definitive diagnosis in pheo is based exclusively on the presence of metastases.
Laboratory diagnosis is based on the increased urinary excreation of free catecholamines and their metabolites, such as vanillylmandelic acid and metanephrines.
