Signet-ring cell cytomorphology in breast cancer: Unveiling the overlooked

Signet-ring cell (SRC) cytomorphology in breast carcinomas involves cells distinguished by copious intracellular mucin that displaces the nucleus, imparting a characteristic signet-ring appearance. Although SRC terminology is prevalent within the context of gastrointestinal tumors, its recognition and management in breast cancer lack standardized clinical guidelines. The World Health Organization (WHO) classification of breast tumor does not recognize SRC differentiation in breast carcinoma as a discrete entity, noting the absence of distinct clinical or molecular characteristics. Consequently, many clinicians are unfamiliar with its identification and implications. This oversight might be influenced by the contentious nature of clinical outcomes associated with SRC. Notably, limited studies, including our case series, suggest that the presence of SRC differentiation may independently influence the biological behavior of the primary breast cancer subtype. Significant disparities between the primary tumor's main body and its SRC component primarily involve molecular subtypes and aggressive behavior. Current literature on this subject is scarce and predominantly based on case reports and analyses with small cohorts, providing inadequate data to comprehensively address the phenomenon. This article aims to synthesize existing literature on SRC cytomorphology in breast cancer to provide a thorough review. Our analysis builds upon previous insights, introduces novel findings from our case series based on multicenter experiences, and incorporates original illustrations to enhance understanding of this pathology. The insights offered herein lay the groundwork for further research and aim to enrich the scholarly discourse surrounding SRC cytomorphology in breast cancer.