As the 41st episode of the series, it is said to be about Stan Lee himself joining his favorite character and friends MJ and Harry on a hunt for the Lizard in the Tunnels beneath Midtown High.
It would seem that either Stan Lee asked the creators of the series if they could write an episode where he can join his favorite character in the show to team up on one of his adventures or Marvel planned on making this episode for Stan Lee to honor him for creating the character and many other famous heroes and villains throughout the 1960's which in this case are afterall some of the most popular characters of the Marvel comics for years. He created a variety of characters such as heroes like Spider-Man, Iron Man, Wasp, Thor, Hulk, the Fantastic 4, X-Men, and villians like Doctor Doom, The Mandarin, Loki, Kingpin, Mephisto, and the Green Goblin.
As for the Lizard, the reason for his escape in episode 32 Sinister Six was to return later for Spidey and his friends to deal with because of his appearance in the 2012 Amazing Spider-Man film.
Be sure to tune in for the episode once it premires at the end of the Month