Funny enough, my grandmother sort of called me on it, though I plan to sit down with her over the holidays when I go to visit and talk it out with her. She's in her late 60's, and is very much a southern belle in a lot of ways. She also went to baptist churches when she was younger, but the last pastor ticked her off when he went on his 'what will send you to hell' rant. My grandmother has the motto of 'nothing surprises me anymore, which is good because you learn something new every day'. I am really close with her, as she and my grandfather raised me when I was younger for a few years.
My best advice is to sit down, explain calmly and answer any questions as honestly as possible. I will be taking a lot of info down with me so she can read over it in her own time. I told her that I wasn't comfortable with my physical body and that I have never felt like a girl (after she pressed) and the worst response I got from her was "Are you sure? Not just a tomboy? Oh, okay then. I always wondered why you liked all boy things and destroyed those dresses."
Actually, I was less afraid of telling Gramma than I am of telling my Dad. You know your grandmother best, but I can honestly say mine surprised me. She really is an unconditional love sort of woman.