L’insorgenza di tumori sincroni e metacroni nei pazienti affetti da GIST è un fenomeno ancora poco studiato, la cui patogenesi è attualmente sconosciuta.
Nel nostro studio abbiamo riportato una frequenza di GIST associati ad altre neoplasie del 17% e i tumori sincroni o metacroni riscontrati nella nostra casistica sono rappresentati nel 25% dei casi da tumori del colon, nel 25% dei casi da melanomi, nel 25% dei casi da tumori pancreatici, nel 12.5% dei casi da tumori della vescica e nel 12.5% dei casi da tumori della mammella.
In letteratura la frequenza con la quale sono state riscontrate altre neoplasie nei pazienti affetti da GIST varia da 5.5% a 56.6% e le neoplasie riscontrate in associazione ai GIST sono prevalentemente rappresentate da tumori gastrointestinali, ai quali fanno seguito in ordine di frequenza tumori della prostata, tumori della mammella, linfomi o leucemie, tumori renali e delle vie urinarie, tumori del tratto genitale femminile, tumori polmonari, tumori della pelle, tumori dell’esofago, sarcomi e tumori dei tessuti molli, tumori del distretto epatobiliarepancreatico, tumori neuroendocrini, tumori del testicolo e tumori della tiroide.
La maggior parte dei tumori riscontrati in associazione ai GIST sono di natura epiteliale. In letteratura sono stati studiati diversi fattori che potessero spiegare la maggior frequenza di tumori sincroni o metacroni nei pazienti affetti da GIST rispetto alla popolazione generale e tra questi si possono annoverare fattori genetici, come le mutazioni di c-KIT e l’alterata espressione delle metallotioneine, fattori ambientali, come la N-metil-N-nitroguanidina e l’Helicobacter pylori, e fattori iatrogeni, come il trattamento con Imatinib, la radioterapia e la chemioterapia.
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Nel nostro studio inoltre è stata riscontrata un’evidente tendenza dei GIST associati ad altri tumori a presentare una mutazione del PDGFRA e questo ci ha portato a ipotizzare un possibile coinvolgimento della via del PDGFR nell’associazione dei GIST con altre neoplasie.
Il riscontro di un’alterazione della via PDGF-PDGFR in numerose neoplasie, anche in assenza di GIST associato, e il fatto che gran parte di queste ultime rientri nello spettro dei tumori riscontrati in associazione ai GIST avvalorano ulteriormente la nostra ipotesi. Ulteriori studi sono comunque necessari per definire i fattori che possono contribuire
all’insorgenza di tumori sincroni o metacroni nei pazienti affetti da GIST e per capire in primo luogo se tale fenomeno sia un evento casuale oppure sia determinato da un meccanismo patogenetico attualmente sconosciuto.
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