How to Screen for Hereditary Cancers in General Pathology Practice

Abstract

Context.—As a pathologist, an awareness of the particular diagnoses that can serve as “sentinels” for an underlying genetic syndrome can be incredibly beneficial to patients and their families. This is a complex and ever-changing field of medicine, where remaining up to date with diagnostic and treatment options is challenging. Simply raising the possibility of an underlying syndrome may not, in itself, be diagnostic; however, this may present an opportunity for genetic assessment, and possibly early intervention or primary prevention of disease in the kindred. In the last decade, immunohistochemistry has emerged as a useful tool in hereditary cancer screening. This is best exemplified by the use of mismatch repair immunohistochemistry as a screening tool in colorectal and endometrioid carcinomas. Reflex testing of all tumors for deficiencies in these proteins is now resulting in superior identification and treatment of Lynch-associated cancers, and families harboring these syndromes. Despite the success and potential value of immunohistochemistry as a genetic screening tool, hematoxylin-eosin morphology remains a valuable tool for hereditary cancer screening and is the focus of this article. Objective.—To highlight the utility of hematoxylin-eosin morphology as a valuable tool for hereditary cancer screening. Data Sources.—Primary literature review with PubMed. Conclusions.—Recognition of tumors associated with cancer predisposition may identify individuals and families at high risk for cancer and may also have peridiagnostic utility with regard to implications for targeted therapy.