Could you post the full stack trace? And full repro steps? Sounds like it could be a potential bug in Update 50.
I don't think a stack trace would be of much help, as nothing in it was from the EPiServer namespaces. As for reproducing the behaviour, I just set a breakpoint in the Index action in one of the page controllers and then inspected the value of RouteData.DataTokens["node"]. On a normal request the type for that object would be PageReference.
Btw, the behaviour was also in Update 40 (I noticed it there first).
When in edit mode and publishing a page, on the following request for the page, the "node" object in the route data dictionary is of type ContentReference and not PageReference. The type is PageReference again if the page is then selected in the page tree.
Is this behaviour by design or a (known) bug? I was able to reproduce it with Alloy with update 50 (latest as of writing) of the Nuget packages.