You cannot do it on the client side, because you cannot assume the client-side system has any of required software, even if that client sent an Excel file. And on server side it won't be a big problem.
Strictly speaking, you cannot know what is the file exactly, until you try to parse it all. Please see my comment to Solution 1. You can unzip .xlxs and see what inside. Learn what it should be there and do some check up. Or you can use Microsoft Open XML SDK and try to read the file directly via the SDK.
Please see my past answers:
Extract file rar with vb.net
How to add microsoft excel 15.0 object library from Add Reference in MS Visual Studio 2010