Holland will be without the likes of Michel Vorm, Nigel de Jong, Erik Pieters and Luciano Narsingh through injury, while experienced internationals such as Maarten Stekelenburg, Johnny Heitinga, Rafael van der Vaart, Wesley Sneijder and Arjen Robben were all omitted from the squad.
There could be senior international debuts for Daley Blind, Ola John and Swansea midfielder Jonathan De Guzman come Wednesday.
The midfield trio may well be very inexperienced, with Adam Maher and Jordy Clasie both tipped to add to their 2 caps alongside Kevin Strootman.
Regular internationals Giorgio Chiellini, Federico Balzaretti, Christian Maggio and Claudio Marchisio have all been joined by Sebastian Giovinco on the sidelines for the Azzurri.
Newcastle full-back Davide Santon has received a long awaited recall to the national set-up and could start in a backline that may include Southampton target Davide Astori.
New AC Milan signing Mario Balotelli should spearhead the attack, supported from the left by teammate El Shaarawy, while Lazio's Antonio Candreva and Alessandro Diamanti fight for the final advanced role.
Both teams are without some key players in this match, with the hosts in particular relying on youth in this tough encounter against Cesare Prandelli's Italy.
El Shaarawy has come on leaps and bounds this season and may become a key player for the visitors, and he will look to stretch a fairly unfamiliar Holland backline.
Italy's experience in the middle of the park may also be key and van Gaal's young trio in midfield will need to be at the top of their game to contain Pirlo and co.
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