Malignant Pheochromocytoma

Pheochro­mo­cy­toma (PPC) and para­gan­gliomas (PGL) are rare neural crest de­rived tu­mors. About 40% of them is caused by a germ-line mu­ta­tion in one of the many sus­cep­ti­bil­ity genes so far dis­cov­ered. More than 90% of PPC/​PGL are be­nign. Ma­lig­nancy is de­fined only by the pres­ence of metas­tases, which means chro­maf­fin tis­sue in sites, as liver, lymph nodes, lungs or bones, nor­mally de­void of it. In fact, pathol­ogy can only pro­vide a risk in­dex of ma­lig­nancy, us­ing his­to­log­i­cal scores, like PASS. The risk of ma­lig­nancy is higher for tu­mors large in size, ex­traa­drenal, dopamine re­leas­ing, and mu­tated in the SDHB gene. SDHB mu­tated tu­mors are ma­lig­nant in more than 40% of cases. Ma­lig­nant PPC/​PGL do not have a cure. Fre­quently ma­lig­nant PPC/​PGL have an in­do­lent clin­i­cal course that al­lows a “wait-and-see” fol­low up. De­pend­ing on the tu­mor func­tion, med­ical ther­apy, mainly with al­pha- and beta-block­ers is piv­otal to re­duce the car­dio­vas­cu­lar risks. Surgery of the pri­mary tu­mor can be per­formed to re­duce the car­dio­vas­cu­lar ef­fects of the cat­e­cholamine ex­cess and/​or to re­duce the tu­mor bur­den and make the ra­diometa­bolic ther­apy more ef­fec­tive. Ra­diometa­bolic ther­apy is gen­er­ally per­formed us­ing 131-Io­dine-metaiodoben­zyl­guani­dine or la­beled so­mato­statin analogs like 90Y-DOTA-TOC or 177Lu-DOTA-TATE. Chemother­apy is gen­er­ally re­served to pro­gres­sive dis­ease, un­re­spon­sive to ra­diometa­bolic ther­apy. Tar­geted ther­apy, es­pe­cially with an­tian­gio­genic drugs, is a fur­ther op­tions but still needs to be val­i­dated in clin­i­cal tri­als.