IN THIS issue of the ARCHIVES, Burden et al1 compare the risk factors and the prognosis in a large sample of patients with multiple melanomas and in controls with a single melanoma. They also test the hypothesis of a possible link between CDKN2A mutations and the multiplicity of melanomas in the same patient.
Patients with multiple primary melanoma (MPM) are the individuals who have already developed successively or concomitantly several primary melanomas. This definition needs, however, several comments. Multiple melanoma should be distinguished from melanoma with metastases and melanoma with atypical nevi. This statement may appear useless, but the differential diagnosis is probably more confusing than expected. First, there is no reliable criterion to separate MPMs from a melanoma with an epidermotropic metastasis.2 Second, the differential diagnosis between benign melanocytic lesions and melanomas is probably a source of bias for the inclusion in multiple melanoma series. After a melanoma diagnosis, patients are more closely followed up, and nevi more frequently removed than in the general population. Physicians probably tend to lower their threshold for positive melanoma diagnosis when there is a histological doubt, since there is no new negative consequence for a patient who is already under surveillance. Therefore, one can suspect that there are more false-positive diagnoses of melanoma and more in situ melanoma diagnoses in patients who have already developed a melanoma than in other individuals. Whether in situ melanomas are true melanomas is still debated; their prognosis if not removed is unknown, but some of them are probably not true cancers. False diagnosis of multiple melanoma is probably even higher in concomitant melanoma. The fact that 2 primary melanomas are detected at the same time suggests that at least one of them has grown slowly enough to be detected only when the other one develops. This probably increases the risk that the slowly growing one is not a true melanoma. A multiple melanoma population is thus probably biased by patients with a single melanoma associated with skin metastases or with a benign melanocytic lesion (atypical nevi), or else with uncertainly malignant lesions (melanoma in situ).
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