When opening Lightroom TIFF in Photoshop, something other than metadata has changed?

I keep getting this message when using Lightroom to open a TIFF file I’ve edited in Photoshop:

"This photo has been changed in an external application. Should Lightroom overwrite the settings on disk?"

I searched this forum (and everwhere else via Google) and found many references to "metadata has been changed," but this message just says the "photo" has been changed. My working procedure is to :

1. Make initial "camera raw" adjustments to the DNG in Lightroom
2. Open that DNG in Photoshop
3. Edit with adjustment layers, clone-stamp, etc.
4. Save as TIFF and close the file
5. Later, return to do more work on the file by selecting it in Lightroom, then Edit in... Photoshop, ticking the "Edit Original" button.
6. As the file is opening, I get this "photo has been changed in an external application" message, SOMETIMES, but not always.

What causes this? I’m not doing anything to that TIFF in Lightroom that I’m aware of. At that point I’m just using Lightroom to catalog it with the rest of the shoot. And if something changed in the metadata, wouldn’t that get the metadata changed message? I’m concerned that something other than the metadata is being changed, without my direction (presumably the image itself!).  

Should I select Cancel (where it apparently opens without overwriting) or let Lightroom overwrite the settings on disk? 

Thanks,
Russell