We likely need a lot more context here. This is as much a user experience issue as it is graphic design.
My gut reaction upon hearing "requires 50 items at the top-level navigation" is to stop things immediately and get some content experts in to make sure that's truly a requirement (vs. an arbitrary want).
As it is now, it seems like a shotgun approach and no visual design will really fix that.
All that said, I think scrolling or a tag cloud might be perfectly acceptable. But we'd need a lot more details to say one way or the other.
Some other ideas:
- long vertical list. Nothing wrong with lists. People know how to scroll.
- focus on search. make that the primary navigation tool.
- A broader 'TOC' or 'Site Map' approach and see you can visually segregate them into groups.