How to read large number of analog-in fast and effectively with Arduino-Compatible Hardware
In general, multiplex in digital, not analog.  Someplace somewhere you're going to have 50 separate signals.  Whether these go into a bunch of analog muxes then a small number of A/Ds, or into a bunch of A/Ds and a small number of digital ports doesn't change the complexity much.

You need to get your priorities straight.  You don't do these kinds of things by picking the microcontroller first, then figuring how to kludge stuff on to eventually do what you want despite the micro.  You start with the requirements, then pick a suitable micro.

Your logic for dismissing one digital muxing approach makes no sense:

But that would end up in having at least 9 ATSAMD21G18 and in having to connect them with SPI or I2C.

Um, OK, but how is that a problem?  Again, you're going to have 50 separate pins somewhere somehow.  Having these be inputs to a bunch of 8-channel (or whatever) A/Ds sounds like a reasonable approach.  Then using SPI to mux the data from those chips sounds quite reasonable.  Other than dismissing this, you haven't actually given any reason why this isn't a reasonable approach.