Final answer:
The enlargement of the periapical lesion might most likely be due to leakage from a poorly filled root canal, as this can cause persistent or recurrent infection.
Step-by-step explanation:
The most likely cause of failure in the described scenario, where a periapical lesion increased in size two years after periapical curettage following an uncondensed, single-cone root canal filling, is E. Leakage from a poorly filled canal. Inadequate sealing and leakage can allow bacteria to persist or re-enter the periapical area, leading to continued or recurrent infection, which can manifest as an enlarging lesion. Issues like inadequate curettage or failure to resect the apex might contribute to treatment failure, but they typically don't cause an increase in lesion size if the canal itself was properly sealed. An undiagnosed periodontal lesion could also cause problems, but the initial success of the surgery suggests the issue lies with the endodontic treatment itself.