Clinicopathologic Spectrum of Sclerosing Microcystic Adenocarcinoma: A Systematic Review of Newly Classified Salivary Gland Malignancy

Abstract Background: Sclerosing microcystic adenocarcinoma (SMAC) is a rare, low-grade malignant salivary gland tumour newly classified in the 2022 World Health Organization (WHO) classification. Its histopathologic resemblance to other lesions and the scarcity of published cases hinder accurate diagnosis and optimal management. Objectives: To systematically review reported oral and oropharyngeal SMAC cases, summarising clinicopathologic features, treatments, outcomes and study quality. Data Sources: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search of MEDLINE (Ovid), PubMed, PubMed Central, Web of Science, SCOPUS, Google Scholar, BU Library Search, LILACS and LIVIVO was conducted, supplemented by cross-referencing. The protocol was registered in PROSPERO (CRD42023430309). Study Eligibility Criteria: Included were case reports and case series of histologically confirmed SMAC with demographic, clinical, histopathologic and immunohistochemical data. Excluded were reviews, abstracts, letters, opinions and studies lacking full text or English translation. Results: Fifteen studies comprising 21 patients (ages 41–73; female predominance) were included. The tongue was the most frequent site. Tumours displayed biphasic epithelial–myoepithelial differentiation, dense sclerosis, and frequent perineural invasion. CK7, EMA, p63, S100 and SMA were commonly positive; CD117 was negative. Surgical excision, with or without neck dissection or radiotherapy, achieved disease-free status in all patients with follow-up (4 months–5 years). Risk of bias was low to moderate. Limitations: Small sample size, retrospective nature, incomplete follow-up and lack of molecular data limit generalizability. Conclusions: SMAC is an indolent malignancy with favourable prognosis when completely excised. Greater clinical awareness and molecular studies are needed to refine diagnosis and guide long-term management.