Salivary Gland Adenoid Cystic Carcinoma: A Systematic Review

Abstract

Background: Adenoid cystic carcinoma (ACC) of the salivary glands is a slow-growing, aggressive malignancy with perineural invasion and late metastasis. Although it has an indolent course, ACC poses a formidable clinical problem due to diagnostic difficulties and limited treatment options.

Materials and Methods: This systematic review was conducted according to PRISMA guidelines. Electronic searches were conducted on PubMed, Scopus, and Web of Science databases, incorporating literature between 2005 and 2025. Included studies varied across clinical, molecular, imaging, and computational studies investigating salivary gland ACC. Selected articles were evaluated based on study type, sample size, diagnostic markers, treatment protocols, and prognostic outcomes.

Results: The final review included six relevant studies. ACC mostly occurs in patients aged between their fifth to seventh decade of life and is more common in females. Tumors most frequently develop in parotid and submandibular glands and show cribriform, tubular, or solid histologic patterns. Molecular studies identified recurrent MYB-NFIB and MYBL1-NFIB gene fusions and NOTCH pathway mutations. Immunohistochemical analysis showed prevalence M2 macrophage invasion and increased angiogenesis. Imaging technologies, especially machine learning-based models of ultrasound, greatly enhanced the diagnostic rate. High survival rates and low recurrence were observed with surgical resection and radiotherapy. MicroRNA profiling also indicated tumor aggressiveness-related miRNAs.

Conclusion: ACC of the salivary glands is a biologically complex neoplasm with unpredictable clinical behavior. Integration of molecular genetics, immunopathology, radiologic innovation, and artificial intelligence maximizes diagnostic accuracy and may dictate future therapeutic directions. Despite promising findings, long-term multicenter trials are essential to validate new strategies.