I'm new to the DX50 (1 week) and I use iTunes exclusively (on Macbook) to manage my music and have all of my lossless files as ALAC up to 24/96. The DX50 plays the ALAC just fine. No issues I'm aware of other than a slight UI bug that dislays them as 32 bit instead of 24 bit.
I have had zero problems with the DX50 reading and playing my entire library. No media scanning issues, no hang-ups, all artwork showing etc. I have ALAC, AAC and some old MP3. All play fine.
When loading up my Sandisk 64GB micro SDXC card, I simply dragged and dropped all of my artist files that are in the "Music" folder. Using the DX50 directory function, I navigate by the artist folders. Simple. The "all Music" sorted by artist, album etc. works too, but I prefer the directory.
I'm more than happy wth the performance of the DX50 and leveraging the files iTunes creates keeps my life simple.
PS, after re-reading your post, you mention that iTunes only supports 16/44. It supports the 24bit high res files too but Airplay only supports 16/44 and if you want to use an external DAC (with Mac) you'll need an App like Bitperfect to automatically control the MIDI settings to output the proper bitrate to the USB DAC. It's wierd that iTunes doesn't do that but Bitperfect does.
Edited by FlyinMN - 11/5/13 at 10:10am