• molecular genetics
• cancer genetics
• diagnostics

Formalin-fixed paraffin embedded samples for actionable somatic pathogenic variant (SPV) testing should undergo review in order to ensure that the appropriate material has been submitted and the neoplastic cell content (NCC) is sufficient for SPV detection. In samples with suboptimal NCC, light microscopy identification of areas of higher NCC and the provision of a marked H&E slide for precise macrodissection increase the likelihood of detecting an actionable SPV.

While this should reflect common practice, despite requesting this information, our experience is that a significant number of referrals arrive at the laboratory with no indication of NCC and/or are unmarked for macrodissection, necessary on samples with an NCC of less than 10%. This increases the risk of a false-negative result.

Using malignant melanoma as a representative for actionable SPV testing, we audited 231 samples obtained by the laboratory between August and October 2018. Eight per cent (n=19) of the samples were obtained with no estimate of NCC and 7% (n=17) of the samples stated to have <10% NCC were not marked for macrodissection.

Three exemplar cases of malignant melanoma referred for clinical testing of actionable BRAF SPVs are presented to underline the importance of careful review …