Słowa kluczowe
przyzwojak
guz neuroendokrynny
PPGL
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Abstrakt
Ostatnie lata przyniosły znaczny postęp w poznaniu patofizjologii rzadkich guzów neuroendokrynnych – guzów chromochłonnych i przyzwojaków (pheochromocytomas and paragangliomas (PPGLs)). Około 70 % PPGL związanych jest z mutacjami: germinalną lub somatyczną w jednym z ponad 25 poznanych genów związanych z rozwojem PPGL. W oparciu o rolę kodowanych białek, geny te zostały podzielone na trzy klastry.
Klaster 1 obejmuje geny kodujące białka o aktywności enzymatycznej biorące udział w cyklu Krebsa oraz białka związane ze szlakiem hipoksji. PPGLs związane z mutacjami genów należących do klastra 1 zazwyczaj rozwijają się z autonomicznych zwojów współczulnych lub przywspółczulnych (przyzwojaki głowy i szyi), charakteryzują się zwiększoną sekrecją metabolitów noradrenaliny i/lub dopaminy oraz znacznym ryzykiem tworzenia przerzutów. Klaster 2 to geny kodujące białka związane ze szlakiem sygnałowym kinaz – u chorych z PPGL uwarunkowanymi mutacjami należącymi do tego klastra zazwyczaj stwierdza się guzy chromochłonne, podwyższone stężenie metabolitów adrenaliny w diagnostyce biochemicznej, a rozsiana postać występuje rzadko. Najmniej poznany klaster 3 skupia geny związane ze szlakiem sygnałowym Wnt – wśród tych pacjentów dominują guzy zlokalizowane w nadnerczach o agresywnym przebiegu.
W tym artykule poglądowym zostały przedstawione uwarunkowania molekularne podziału PPGLs na klastery, a także kliniczne, biochemiczne, obrazowe oraz terapeutyczne implikacje proponowanej klasyfikacji.
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