The world's first face transplant recipient, Frenchwoman Isabelle Dinoire, died of a cancer unrelated to medicine she was taking to stop her body rejecting the graft, doctors said Wednesday.
Maimed by her dog, Dinoire received part of a brain-dead person's face in a historic operation in 2005, aged 38.
On Tuesday, doctors announced she had died in April after a "long illness."
The blonde, blue-eyed mother of two suffered many complications over the years related to the strong immunosuppressant drugs all transplant patients have to take.
She had infections, a tumor which was successfully treated, diminished kidney function, and high blood pressure, the Amiens-Picardie university hospital in northern France, where the transplant was done, said in a statement.
Then in November 2014, Dinoire's immune system started rejecting the graft and she reportedly lost partial control of her lips, despite the anti-rejection medicine.
The drugs rein in the immune system, which is prone to identify a transplant organ as an intruder that needs to be got rid of. But in doing so, the patient is also left exposed to infections and cancers.
Dinoire had a new operation in January this year which was able to fix some of the damage, the statement said.
But a few months later, during a checkup, doctors found that a malignant tumour which had been operated on in 2015, had returned.
"This time, unfortunately, it was beyond remedy of any available treatment," said the hospital statement.
It described the killer as a "rare tumor, which cannot be scientifically linked to immunosuppressant treatment."
Dinoire, the statement added, died in hospital on April 22 "surrounded by her loved ones and medical team."
The divorcee gave a remarkable news conference in February 2006, just three months after receiving the nose, lips and chin of a donor in a 15-hour operation.
Dinoire appeared to be wearing thick makeup to disguise the scars, her lips heavy and inflexible.
She spoke with a pronounced lisp as she recounted how she had fainted after "taking medicines to forget" personal problems.
"When I woke up, I tried to light a cigarette and I couldn't understand why it didn't stay between my lips. Then I saw the pool of blood and the dog next to me," she said.
"I went to look in the mirror and was horrified."
But the ground-breaking operation gave her a new lease of life.
"Since my operation I have a face, like everyone... I will be able to resume a normal life."
The ground-breaking procedure had raised hopes for people with faces disfigured in accidents or assaults, and surgeons in the United States, Spain, China, Belgium, Poland and Turkey started conducting similar procedures.
But the initial enthusiasm was soon tempered by the daunting rejection risk.