I followed the 5 minute startup guide on the front page of https://piranhacms.org/ and then started working my way through the steps on Microsoft's Host ASP.NET Core on Linux with Nginx. I got as far as Configure Nginx step.

I could launch the app and get to the main content pages, but trying to access the manager pages at (~/manager) would fail to login. I could get as far as the login page, but after entering the out of the box user name and password, Nginx would return a 403 error. After enabling error logging, I discovering that the app was sending too big a header, I used this blog to resolve the issue:
Nginx Proxy: upstream sent too big header while reading response header from upstream

Ironically, I should have pushed through with the rest of Microsoft's page because they later make mention of long request headers and changing buffer sizes, as well as the Microsoft's hardening steps also changes the buffer sizes.

The CMS documentation should make special mention about setting the buffer sizes for Nginx if the users are planning on using it as their reverse proxy.