Molecular Factors in Carcinoma Ex Pleomorphic Adenoma: Systematic Review and Meta‐Analysis

Abstract

ObjectiveCarcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor. Although multiple reviews have been published on salivary gland malignancies, it has been a decade since the last dedicated systematic review pertaining to CXPA alone was published. This study examines molecular factors in CXPA diagnosis.Data SourcesMEDLINE, CINAHL, Embase, Scopus, Web of Science (BIOSIS), Cochrane CENTRAL, Health Collection (Informit), OpenDOAR, and GreyNet International.Review MethodsSystematic review and meta‐analysis from inception to October 31, 2022 for all English language studies pertaining to “carcinoma ex pleomorphic adenoma.” Predicted incidence of each biomarker was calculated with meta‐analysis. Comparison against pleomorphic adenoma (PA) and salivary duct carcinoma (SDC) when reported within the same study are performed. Risk of bias performed with JBI tool for prevalence studies.ResultsOf 19151 unique studies undergoing abstract screening, 55 studies (n = 1322 patients) underwent data analysis. Biomarkers with >3 studies were p53, HER2, AR, EGFR, PLAG1, ERBB, ER, PR, HMGA2, p16, p63, a‐SMA, RAS, PTEN, PDL1, BRAF, PIK3CA, and c‐kit. Highest incidence was seen in AR, EGFR, p16, and p53. Significant differences were demonstrated compared with PA and SDC. There was high heterogeneity and overall high risk of bias within studies.ConclusionMolecular factors are an area of interest in the diagnosis of CXPA. Our study results support examining CXPA as a discrete cohort in future targeted therapy trials. Laryngoscope, 2023

MicroRNA copy number alterations in the malignant transformation of pleomorphic adenoma to carcinoma ex pleomorphic adenoma

“…In a recent systematic review and meta-analysis focusing on the molecular factors involved in the diagnosis of CXPA was conducted by Key and colleagues. 95 This study identified important biomarkers such as p53, PLAG1, and PTEN. 95 Similarly, our results showed CNA in the miR-NAs p53, PLAG1 and PTEN genes.…”

“…95 This study identified important biomarkers such as p53, PLAG1, and PTEN. 95 Similarly, our results showed CNA in the miR-NAs p53, PLAG1 and PTEN genes. This may support the role of these genes in the pathogenesis of this pathology and reinforces that these target genes are not only the result of genetic alterations but also of epigenetic alterations.…”

PTEN Deregulation Mechanisms in Salivary Gland Carcinomas

“…Similarly, PTEN mutations/deletions characterize a subset of the Carcinoma ex pleomorphic adenoma (CXPA). Additionally, hyalinising clear cell carcinoma (HCCC) subtype demonstrate similar genetic signatures (50,51). In conjunction, another genetic analysis in secretory myoepithelial carcinomas (SMCA) -a very rare, signet ringlike mucinous carcinoma with a myoepithelial componentrevealed very specific and unique PTEN mutation and splicing variant (c.655C>T p. Q219*, and c.1026+1G>A p. K342, respectively) (52).…”

Deep learning based ultrasound analysis facilitates precise distinction between parotid pleomorphic adenoma and Warthin tumor

“…The conventional belief is that the majority of primary parotid tumors (75% -85%) are benign, with pleomorphic adenoma (PA) and Warthin tumor (WT) accounting for up to 93% of benign parotid tumors (1)(2)(3)(4). However, PA is not so innocent and harmless because carcinoma ex pleomorphic adenoma (CXPA), a malignant salivary gland tumor typically found in the parotid gland, arises from the "benign" tumor PA (5)(6)(7). Early on, this tumor appears benign.…”