Morphological control for molecular testing: a practical approach

Abstract

The determination of molecular aberrations within tumours is important for diagnostic, prognostic and predictive purposes. Pathologists play a critical role in the workflow of molecular diagnostics, by assuring accurate pathological diagnosis, requesting appropriate molecular testing, selecting the adequate tissue section for molecular analysis, enriching tumour cell content by manual macrodissection and estimating the tumour cellularity. Particularly, the assessment of the malignant cell fraction within a tumour section is a key determinant for an appropriate interpretation of the molecular findings. Several factors may impact the estimation of tumour cellularity and constitute a potential pitfall for the final interpretation of the molecular analysis. Evidence suggests that the reliability of morphological control could be improved by training. The scope of this commentary is to provide the training morpho-molecular pathologists with the practical tools necessary to master microscopic morphological control for solid tumours, as well as a set of images that could serve as a training set.

Expert opinion on NSCLC small specimen biomarker testing — Part 1: Tissue collection and management

“…Consequently, the proportion of cells may also inform the choice of molecular testing technique. In case of low neoplastic cell content, tumour cell enrichment techniques, such as macro-dissection, are recommended for direct sequencing and NGS, highlighting the critical role of the pathologist [34][35][36]. For NGS, a coverage of 300-500 sequence reads per target is generally adequate for most diagnostics; the exact number of reads required will depend on the neoplastic cell content [37].…”

Morphological Control: Properties and Applications of Metal Nanostructures

“…A diagram of the synthesis of CoPt 3 nanowires during the deposition process of cobalt and platinum atomic clusters is shown in Figure 3 on a thin film of amorphous or noncrystalline gold on the surface of the anodic oxide layer. In the early stages of CoPt 3 growth, the buds are randomly oriented, and the atomic mass is deposited continuously in a completely random direction [101][102][103]. During the cobalt and platinum precipitation process, CoPt 3 nanowires with lower crystallinity are formed with some porosity and internal stress [104].…”

Tissue management in precision medicine: What the pathologist needs to know in the molecular era

“…Suboptimal processing can alter morphological, immunohistochemical and molecular characteristics of histological and cytological samples ( Bass et al, 2014 ; Gullo et al, 2021 ). The magnitude and direction of effects associated with a given pre-analytical factor are dependent on the object of analysis, whether DNA, RNA or protein ( Penault-Llorca et al, 2022 ).…”

“…The percentage of neoplastic cells present in the selected sample must be estimated for morphological control ( Cree et al, 2014 ; Dufraing et al, 2019 ; Gullo et al, 2021 ). Tissue quality is expressed as the percentage of neoplastic cells to the total number of nucleated cells in a sample.…”

“…Therefore, it is critical that the training pathologist understand the framework and basic technical elements of the molecular tests. Its performance, in accordance with current practices and guidelines for the molecular diagnostics workflow, also encompasses the main following phases: pre-analytical; diagnosis and appropriate selection of tissue sample (quality and quantity); use of “ in situ ” based techniques; integrate the molecular data in the original diagnostic report (translation to the clinicians); and educational activity ( Schmitt, 2011 ; Cree et al, 2014 ; Rekhtman and Roy-Chowdhuri, 2016 ; Fassan, 2018 ; Roh, 2019 ; Gullo et al, 2021 ; Ooft et al, 2021 ; Vranic and Gatalica, 2021 ).…”