Are you reading this, Carl? A letter to The New England Journal of Medicine details two dramatic, but potentially cautionary tales about Tysabri, Biogen’s troubled mulitple sclerosis med. And the news prompts one Wall Street analyst to say Biogen’s forecast for growing the number of Tysabri patients is unrealistic, perhaps dampening prospects for the biotech and Carl Icahn’s hopes of boosting the stock price.

A 46-year-old woman with MS received her first dose, but then a mole that had been on her shoulder for years suddenly took on a dangerous new character; it turned out to be a melanoma that spread like wildfire and she has just a few months to live, writes Health Day News. And 45-year-old woman with MS developed melanoma in her retina after receiving several doses. She had a family history of melanoma and had atypical moles on her body; the mole on her retina went back at least nine years.

“I can’t say it’s cause-and-effect definitively because it’s just an observation, but the first patient had had that mole forever. She took the drug and almost instantaneously the lesion changed,” John Thomas Mullen, co-author of the letter and a surgical oncologist at Beth Israel Deaconess Medical Center in Boston, tells Health Day. “We don’t know if the two are related right now,” says Patricia O’Looney, vp of biomedical research at the National Multiple Sclerosis Society. “There are so many people taking Tysabri, we should go forward with caution…”

Investors should also be cautious, suggests David Amsellam of Friedman Billings Ramsey, who writes in an investor note this morning that the NEJM letter “raises new concerns about Tysabri safety.” Ironically, he points out that the letter is published just one day after Biogen execs told analysts that they expect to see “more liberal usage of Tysabri.”

Of course, as Amsellam goes on to note, “Tysabri safety risks, and likely competitive headwinds, played a major role” in Biogen’s failure to find a buyer late last year, even though Biogen and its partner, Elan, played down safety risks. The ‘For Sale’ sign went up, by the way, after Icahn bought a stake in the biotech.

UPDATE: A reader points out that, on yesterday’s earnings call, Cecil Pickett, Biogen’s R&D chief, says Biogen hasn’t had any discussions with the FDA about melanoma risk, and says this about the NEJM letter: “I think it’s important to sort of put those two cases in some kind of context with regard to our clinical trial experience. I think overall the occurrence in our clinical trials of malignancies are similar in Tysabri treated and placebo groups. There has been a single case of melanoma during placebo-controlled clinical trial experience in a male patient, but that patient had a lesion present at first dose. So I think it’s something that we will certainly monitor.”

Tysabri, a monoclonal antibody that helps treat autoimmune disorders such as MS and Crohn’s disease, has had a clouded history, Health Day reminds us. The med was first approved by the FDA in November 2004, but was pulled three months later after several patients in clinical trials developed a rare but deadly viral infection of the brain called progressive multifocal leukoencephalopathy. In June 2006, the FDA allowed the drug back on the market but with strict conditions governing its use. Just last month, the FDA approved Tysabri to treat people with a moderate to severe form of Crohn’s.

But there is basic science to support Mullen’s observations, Health Day writes. One of the participants in an earlier study of Tysabri had developed (and subsequently died of) a metastatic melanoma that appeared as soon as he got his first dose of the drug, Mullen tells the site. And in a study done before Tysabri received FDA approval, melanomas in mice that were given the drug had an increased tendency to detach from the primary tumor and spread.

Tysabari may have a dampening effect on the immune system that encourages the formation of the potentially deadly skin cancer, the letter stated. And now that Tysabri has been approved for people with Crohn’s, more people may be at risk, although those with no family history of melanoma and no moles probably don’t need to worry, Mullen tells Health Day

“Doctors should ask for a family history of melanoma and do a quick skin check,” he says. “Tysabri isn’t the only drug in our arsenal. You could give the patient something else if you were concerned about that.”