Columbus did not have the supplies to sail across the Pacific without resupplying somewhere. Nor do I see a plausible way which he could unknowingly sail through the Straits of Magellen or south of Cape Horn without noticing there was land nearby.
A more realistic scenario would be; WI Columbus and his ships never returned? I believe Spain, which was already in the process of conquering and colonizing foreign territory, would have made far greater inroads into Muslim North Africa. In many ways, the conquest and Catholization of the New World in OTL was a continuation of the centuries long Reconquista. If not given an outlet for ambition and greater wealth across the Atlantic it seems logical that Spaniards would continue to push against Islam. This would perhaps help to connect southern Italy to Spain more concretely, the Spanish monarchy already claimed the Kingdom of Naples. I can see a TL with a Catholic, Hispanic North Africa from Morocco to Egypt as not that unlikely.
Not that a failure of Columbus' voyage would have kept Europeans unaware of the Americas forever. Or even that long. But it's the Age of Explorers that is perhaps the most susceptible to alternate outcomes. A few failures of successful voyages, a few successful voyages instead of failures, the winds blowing in a different direction, a few different navigation decisions, and the map of the world would look very different.