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CLL linked to poorer survival in those with malignant melanoma, MCC

Brewer JD. J Clin Oncol. 2012;doi:10.1200/JCO.2011.34.9605.

Patients who have chronic lymphocytic leukemia before diagnosis of malignant melanoma or Merkel cell carcinoma have significantly worse OS than those who do not have a history of the disease, according to study findings published in the Journal of Clinical Oncology.

Patients with CLL before diagnosis also have significantly worse malignant melanoma cause-specific or Merkel cell carcinoma (MCC) cause-specific survival, according to the results.

Previous research has shown an association between malignant melanoma and non-Hodgkin’s lymphomas, including CLL. Population-based studies have suggested malignant melanoma occurs 2.3 to 3.1 times more often in patients with NHL, according to background information in the study.

However, there is little data about whether CLL or NHL influences malignant melanoma outcomes, researchers said.

Jerry D. Brewer, MD, a dermatologic surgeon with Mayo Clinic in Rochester, Minn., and colleagues used SEER database records from 1990 to 2006 to identify 212,245 patients with malignant melanoma, of whom 1,246 had a prior diagnosis of CLL or NHL. Researchers also identified 3,613 patients with MCC, of whom 90 had a prior diagnosis of CLL or NHL.

Researchers derived expected survival from patients with malignant melanoma or MCC who did not have CLL or NHL.

Patients with malignant melanoma who had a history of CLL had worse-than-expected OS (standard mortality ratio [SMR]=2.6; 95% CI, 2.3-3). The results showed a similar result for melanoma patients with a history of NHL (SMR=2.3; 95% CI, 2.1-2.6).

Patients with a history of CLL had worse-than-expected malignant melanoma cause-specific survival (SMR=2.8; 95% CI, 2.2-3.4). Results showed a similar result for patients with a history of NHL (SMR=2.1; 95% CI, 1.7-2.6).

OS for patients with MCC was worse than expected among those with a history of CLL (SMR=3.1; 95% CI, 2.2-4.3) or NHL (SMR=1.9; 95% CI, 1.3-2.8), study results showed.

MCC cause-specific survival was worse than expected for patients with a history of CLL (SMR=3.8; 95% CI, 2.5-5.9), results showed. Researchers did not observe a difference between MCC cause-specific survival in patients with a history of NHL (SMR=0.9; 95% CI, 0.4-2.1).

“Although we have known that CLL is associated with increased secondary malignancy, with a few reports suggesting increased aggressiveness of skin cancer in the setting of CLL, this is the first study to really solidify that the aggressive forms of skin cancer — namely melanoma and Merkel cell carcinoma — behave worse in people with lymphoma,” Brewer said. “Not only do these patients have worse overall survival, but their chances of dying from metastatic melanoma or metastatic Merkel cell carcinoma is also significantly increased. It would be prudent to educate our patients with lymphoma of this phenomenon and have them be seen by a dermatologist for regular skin examinations.”

The researchers said there were study limitations, including the possibility that CLL may be under-reported in cancer registries, and they were unable to evaluate interactions between clinical outcome and specific treatment modalities.

“Despite these limitations, our analysis provides strong evidence that patients with a history of CLL or NHL are at higher risk for death as a result of [malignant melanoma] or MCC once one of these cancers develops,” the researchers said. “An annual dermatologic skin examination and patient education regarding sun protection and skin self-examinations seem appropriate for patients with these lymphoid malignancies.”

These studies remind one of the unique importance of immune surveillance in inhibiting melanoma severity.  I provided expert opinion in a massive medical malpractice case many years ago that also validates this phenomenon. A young woman suddenly collapsed and died of an acute cerebral hemorrhage. Several of her organs were donated (two kidneys, liver, lungs and heart) to needy recipients — all of whom developed lethal metastatic melanoma in the following year. Reexamination of the original autopsied brain demonstrated her hemorrhage was due to a missed brain tumor that was a melanoma! Subsequent history from the woman's husband revealed that a “black mole” had been removed several years before her death. All recipients of her organs, of course, were treated with immunosuppressant drugs, which allowed the rapid and catastrophic development of metastatic melanoma in all of them.

Harry S. Jacob, MD, FRCPath(Hon)
HemOnc Today Chief Medical Editor

Disclosure: Dr. Jacob reports no relevant financial disclosures.