^^ This. Great post Ben.
Cylinder pressure becomes exponentially higher with more timing and boost, especially on higher compression engines. But if the piston is coming up for the compression stroke and the fuel ignites early due to a hot valve, plug or other hot spot in the chamber, it will need to compress that explosion, cylinder pressure is huge at this point and is similar to hitting the piston with a sledge hammer. Something must give eventually, either the bearing, rod or piston will fail.
I have noticed you can buy spark plugs with pressure transducers in them, for checking cylinder pressures. I guess tuners don't need such tools, but I would be keen to give them a shot myself for interests sake.