Pathologists at the Leading Edge of Optimizing the Tumor Tissue Journey for Diagnostic Accuracy and Molecular Testing

Abstract

Objectives: Tumor biomarker analyses accompanying immuno-oncology therapies are coupled with a tumor tissue journey aiming to guide tissue procurement and allow for accurate diagnosis and delivery of test results. The engagement of pathologists in the tumor tissue journey is essential because they are able to link the preanalytic requirements of this process with pathologic evaluation and clinical information, ultimately influencing treatment decisions for patients with cancer. The aim of this review is to provide suggestions on how cancer diagnosis and the delivery of molecular test results may be optimized, based on the needs and available resources of institutions, by placing the tumor tissue journey under the leadership of pathologists.

Methods: Literature searches on PubMed and personal experience provided the necessary material to satisfy the objectives of this review.

Results: Pathologists are usually involved across many steps of the tumor tissue journey and have the requisite knowledge to ensure its efficiency.

Conclusions: The expansion of oncology diagnostic testing emphasizes the need for pathologists to acquire a leadership role in the multidisciplinary effort to optimize the accuracy, completeness, and delivery of diagnoses guiding personalized treatments.

Keywords: Diagnosis; Molecular testing; Pathologist; Sampling; Tumor tissue journey.

Figure 1

Representative stages of the tumor tissue journey. The tumor tissue journey starts with collecting the biopsy specimen, which then undergoes a series of diagnostic assessments to obtain the final clinical report incorporating diagnostic and prognostic data that will ensure a personalized approach in treating patients with cancer. Every stage comes with specific considerations that should be taken into account to ensure diagnostic accuracy. Considerations surrounding tumor sampling should dictate the sampling procedure employed on a case-by-case basis. Morphologic assessment is coupled with ancillary studies to ensure requirements for tissue adequacy and nucleic acid yield are met. Finally, treatment decisions are informed by careful interpretation of molecular testing after considering the analytic parameters affecting the final result. CNB, core needle biopsy; dMMR, mismatch repair deficiency; FACS, fluorescence-activated cell sorting; FFPE, formalin-fixed, paraffin-embedded; FISH, fluorescence in situ hybridization; FNA, fine-needle aspiration; IHC, immunohistochemistry; ISH, in situ hybridization; MSI, microsatellite instability; NGS, next-generation sequencing; PCR, polymerase chain reaction; PD-L1, programmed death ligand 1; RNA-seq, RNA sequencing; RT-qPCR, quantitative reverse transcription polymerase chain reaction; SNV, single nucleotide variant; TMB, tumor mutational burden.

Figure 2

Suggested tumor tissue journey workflow for cancer diagnosis. Pathologists can lead a multidisciplinary team involved in cancer diagnosis by coordinating the interactions between the different personnel and ensuring that the right processes and methods are performed in a timely manner. We propose a diagnostic workflow whereby a pathologist is present throughout the tumor tissue journey and liaises with all the various personnel involved, ranging from interventional physicians at the time of tissue sampling to laboratory scientists during the interpretation of molecular testing. Pathologists can be engaged during every stage of the diagnostic workflow, advising on optimal tissue sampling, triage, and processing to ensure efficiency, diagnostic accuracy, and the delivery of the clinical report in a timely manner.