Nexgen Pathology: Predicting Clinical Course and Targeting Disease Causation

Abstract

Overview Pathology is a bridging discipline involving basic and clinical biomedical sciences. This context includes both descriptive and mechanistic approaches, with the goals of understanding the anatomical changes and underlying molecular events involved in disease‐related processes. Neoplastic disorders are a focal point for the further development of this chapter. The two main objectives of pathology are to define disease causation [from “Pathos” (Greek) “Disease”] and categorize disease states to render clinical diagnostic services. A modern academic Department of Pathology encompasses education activities, including teaching students, training residents and fellows, and mentoring faculty; and hospital‐based clinical services usually under three divisions, comprising anatomic pathology (surgical pathology, cytology, and autopsy services); clinical pathology (embodying a variety of laboratory services from blood bank and coagulation to chemistry and microbiology, among others); and molecular pathology (commonly housing somatic genetics, cytogenomics, and flow cytometry). During the past two decades, we have witnessed the transition from descriptive analysis of tissue histology and analyte variables that categorized patients and broad disease stages to more objective and quantitative multidimensional studies aimed at defining individual patient signatures. More traditional population and cohort‐based classifications are turning into patient‐specific profiles that optimize treatment efficacy and outcome: from diagnostic and prognostic approaches that group patients into disease categories to the development of a more precise, predictive, and individualized patient assessment. Such an integrated care model drives selection of evidence‐based treatment protocols to optimize clinical outcome, engendering a cost‐effective and personalized healthcare. Disease classification and assistance in selection of therapy is the focus of this “patient‐centric” pathology approach, expanding into monitoring of therapy (such as assessing therapeutic index and mutational load through tumor genotypes) and managing high‐risk patients through early diagnosis of their disease condition. The ultimate goals are to move from treating symptomatology to treating disease causation once origin of the disease is better understood and to move from a fee‐for‐service to population‐based accountable healthcare management.