15. The good, the bad, and the ugly of SNP array testing for cutaneous melanocytic neoplasms

Abstract

Cutaneous melanocytic neoplasms (CMNs) with ambiguous histologic features are diagnostically challenging for anatomic pathology practices. Ancillary genomic testing by SNP array can identify copy number abnormalities and allelic imbalances potentially associated with malignancy. We tested 445 formalin fixed, paraffin embedded CMNs by SNP array (OncoScan CNV Plus Assay, Thermo Fisher Scientific). Specimens were reviewed by a pathologist for acceptable amount and percentage of tumor cells. The reportable range included deletions > 1 megabase (Mb), duplications > 2 Mb, copy neutral loss of heterozygosity (cnLOH) > 10 Mb, or any detectable alteration affecting gene regions known to be associated with melanoma; benign alterations were excluded. If SNP array testing could not be completed, our laboratory requested reflex testing with a melanoma panel of FISH probes targeting 6p gain, 6q loss, 8q gain, 9p loss, and 11q gain. SNP array yielded interpretable results on 341 out of 426 specimens tested; abnormalities were reported in a total of 162 (47.5%) arrays, including 134 with abnormalities undetectable by FISH. In 97 specimens converted from SNP array to FISH testing, 92 were successfully tested by FISH, and 29 (31.5%) were abnormal. The combination of SNP array and FISH yielded interpretable results on 97.3% of CMNs. FISH interpretation was confounded by technical artifact, cell overlap, and tetraploidy, whereas SNP array had a higher failure rate (20% vs. <5% for FISH), a tendency toward 'noisy' results, and a higher yield of non-specific copy number alterations. Despite the challenges of SNP array, it is more precise and comprehensive.