Momentous Melanoma Marker Modality?

Clarke et al published a study online on March 2 in the Journal of Cutaneous Pathology regarding a novel diagnostic test for melanoma. Using quantitative reverse transcriptase–polymerase chain reaction targeting 23 preselected genes, biopsy samples from a variety of melanocytic skin lesions—464 lesions in a training set and 437 lesions in a separate validation set—were analyzed. The test assigned a single numeric score favoring either benign or malignant with sensitivity and specificity of 89% and 93%, respectively (training set), and 90% and 91%, respectively (validation set), when compared to expert consensus dermatopathology review.

What’s the issue?

Any clinician who biopsies multiple melanocytic lesions per day daydreams about a modality that will consistently and accurately distinguish the neoplasms that haunt us the most: the ones with no clear diagnosis and the lesions where intra- and interdepartmental histopathology results vary across the board. In fact, a patient recently told me that I “missed” her “dangerous” melanoma when our dermatopathology and outside consultant opinions stated that the lesion was a dysplastic nevus. The patient personally took the slides to another institution where they were deemed an “evolving” melanoma in situ. Are they all correct? How do we know that something is evolving? Which tumors will eventually be the sinister ones? If we don’t know, then how can a patient understand his/her predicament? What’s a clinician to do?

Reassuringly, in perusing the exhibit hall at the 73rd Annual Meeting of the American Academy of Dermatology, the climate has shifted somewhat. A new zone of molecular and genetic technology has emerged between the rows of pharmaceutical innovation and office supply hardware. The reverse transcriptase–polymerase chain reaction melanoma diagnostic test distinguishes itself with its large study set and measurement parameters, as it quantifies gene expression. Other adjunctive diagnostic modalities have been proven useful in atypical melanocytic proliferations, such as fluorescence in situ hybridization, comparative genomic hybridization, and DNA microarray technology, with focus on physical chromosomal copy alterations; however, it seems as though this new test provides a functional measure and straightforward plus/minus result that may be more universally and objectively relevant and interpretable from a simple skin biopsy. Perhaps the diagnostic technology has now outpaced our limited and confusing vocabulary for melanocytic lesions. Nonetheless, further clinical follow-up, prospective prognostic data, and cost analysis will define its evolving role. How do you think this gene signature test will ultimately influence our interpretation of melanocytic biopsy results?

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