Perineural invasion (PNI) is a well-recognized histopathologic feature in multiple malignancies; however, its significance in breast cancer remains relatively underexplored. This review provides a synopsis of the current knowledge on PNI in breast cancer, discussing its histopathologic features, molecular mechanisms, diagnostic challenges, and clinical relevance. PNI is most frequently observed in high-grade invasive ductal carcinoma (IDC), particularly in triple-negative and HER2-positive subtypes. It is also seen in special histological subtypes such as mixed, metaplastic, and invasive micropapillary carcinomas. Mechanistically, PNI involves tumor–neural interactions, including neurotrophic factor signaling and epithelial–mesenchymal transition, contributing to tumor progression and potential locoregional recurrence (LRR). While PNI is linked to adverse prognosis in other tumors, its independent role remains unclear in breast cancer due to limited large-scale studies. Therefore, further investigation into its prognostic significance and potential therapeutic implications is needed. Future research should focus on refining diagnostic criteria and assessing targeted therapies to mitigate PNI-associated progression. This review summarizes the current knowledge on perineural invasion (PNI) in breast cancer, addressing its histological features, molecular mechanisms, diagnostic challenges, and clinical implications.

Paired box (PAX) genes encode a family of nine transcription factors that function as master regulators of embryogenesis, organogenesis, and lineage specification. Their tightly regulated spatial and temporal expression is essential for the development of multiple organ systems, including the central nervous system, eyes, kidneys, immune system, musculoskeletal system, and endocrine organs. Germline mutations of PAX genes result in a broad and often pleiotropic spectrum of human disease, reflecting the developmental programs governed by each family member. Pathogenic variants in PAX genes underlie diverse congenital disorders such as aniridia (PAX6), renal coloboma syndrome (PAX2), otofaciocervical syndrome with immunodeficiency (PAX1), Waardenburg syndrome (PAX3), maturity-onset diabetes of the young (PAX4), and tooth agenesis (PAX9). These conditions frequently demonstrate variable expressivity, incomplete penetrance, and overlapping phenotypes, which make it challenging to be clinically recognized. Beyond embryogenesis and embryologic development, emerging evidence indicates that several PAX proteins remain active in postnatal tissue maintenance, adult stem cell regulation, immune function, and regenerative responses (particularly PAX7 in skeletal muscle satellite cells and PAX5 in B-cell homeostasis), further expanding their clinical relevance. This review provides a synopsis of the major, clinically relevant, germline PAX gene mutations, emphasizing genotype–phenotype correlations, developmental mechanisms, and disease classification across the organ systems. By integrating molecular genetics with human pathology, we highlight the diagnostic implications of PAX genes as central determinants of congenital disease and provide a framework for understanding how alterations in the developmental transcriptional networks translate into human pathology.