Momentum for a Melanoma Marker Modality

In March 2015, the Journal of Cutaneous Pathology published a study regarding a novel diagnostic test for melanoma. Using quantitative RT-PCR targeting 23 preselected genes (MyPath Melanoma, Myriad Genetics), 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 that favors either benign or malignant, with sensitivity and specificity of 89% and 93% (training set); and 90% and 91% (validation set) when compared to expert consensus dermatopathology review.

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, the lesions where intra and inter-departmental histopathology results vary across the board. In fact, a recent patient told me that I "missed" her "dangerous" melanoma when our dermatopathology and outside consult opinions stated that a lesion was a dysplastic nevus; upon the patient personally taking her slides to another institution, it was 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 or her predicament? What’s a clinician to do?

Reassuringly, in perusing the exhibit hall at this spring’s American Academy of Dermatology annual meeting, 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 aforementioned melanoma diagnostic test distinguishes itself with its large study set and its measurement parameters, as it quantifies gene expression. Other adjunctive diagnostic modalities have proven useful in atypical melanocytic proliferations, such as fluorescent in situ hybridization (FISH), comparative genomic hybridization (CGH), and microarray technology, with focus on physical chromosomal copy alterations; however it seems as though MyPath 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.

Clarke LE, et al. Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma. J Cutan Pathol. 2015 Mar 2. [Epub ahead of print]