Inside the USCAP Journals

The proportion of cases in which molecular testing is needed to inform clinical management is rapidly increasing. The quality of formalin-fixed paraffin-embedded material available for use in such assays can vary widely. One important consideration, as explained by Smits et al in this issue, is the sample’s tumor cellular content (or, more accurately, the percentage of tumor nuclei), which is usually estimated from H&E sections. A reliable estimate is key to ensuring that the tumor falls within the known sensitivity or lowest limit of detection of the assay. Correlation with more quantitative sequencing methods, such as next-generation sequencing, in which the precise percentage of mutated and nonmutated amplicons is known, is increasingly important. The investigators found that estimates by experienced pathologists varied widely, both between observers and as compared with manual nuclei counting. The common overestimation of cellularity could lead to false-negative results. The authors suggest that additional training could increase accuracy.