@Teal_cfr The only occasion I have seen a similar symptom before is when URL rewrites for or on-the-fly generation of static resources are used and Nginx caching is on.
Example how this could happen (this way or similar, it is just an example to make clear why such things can happen): The website shall deliver a .jpg file to the browser. But that .jpg does not physically exist on the server. It is generated by a script. When the first request hits the server, Nginx looks into its cache if it has seen the same request before. It does not know it yet so it asks Apache for the file. Apache has a URL rewrite for the URL and runs a script that returns a data stream as if it was the file. It hands the data to Nginx, Nginx delivers that data to the browser, the browser displays the image. The second requests comes in for the same file. Now Nginx knows "Hey, I know that file, let's get this one straight from disk ...", but it won't find the file on disk, because the file has never been there, but would need another script request. Now it returns a 404, because Nginx thinks the file doesn't exist. Again, just a rough sketch how these things can happen. Maybe something like this or similar fit your situation?