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Incomplete excision of pleomorphic adenoma (PA) may result in recurrent pleomorphic adenoma (RPA). Furthermore, long-term neglected PA may become carcinoma ex pleomorphic adenoma (CXPA). In the present study, the relationships between mast cell-derived chymase and these tumors were examined. The tumor tissues of PA consisted of either or both glandular and fibrotic structures. Histological features of RPA were almost similar to those of PA, except that they showed multinodular structures. CXPA is composed of a mixture of PA and carcinoma. The main stromal cells in PA were myofibroblasts, whereas fibroblasts constituted the main cellular portion in the stromal tissue of RPA. Cancer-associated fibroblasts (CAFs) were present abundantly in CXPA. With increased VEGF expression, neovascularization tended to increase in RPA or CXPA. Compared with PA, chymase-positive mast cells, as well as chymase gene expression, were increased in the tumor tissues from patients with RPA or CXPA. SCF, TGFβ1, and PCNA-positive staining was widely observed in these tumor tissues. The above results suggest that mast cell-derived chymase through its direct or cooperative effects with other mediators may participate in the pathophysiology of RPA and CXPA.

ObjectiveThere is a rich amount of quantitative information in spectral datasets generated from dual-energy CT (DECT). In this study, we compare the performance of texture analysis performed on multi-energy datasets to that of virtual monochromatic images (VMIs) at 65 keV only, using classification of the two most common benign parotid neoplasms as a testing paradigm.MethodsForty-two patients with pathologically proven Warthin tumour (n = 25) or pleomorphic adenoma (n = 17) were evaluated. Texture analysis was performed on VMIs ranging from 40 to 140 keV in 5-keV increments (multi-energy analysis) or 65-keV VMIs only, which is typically considered equivalent to single-energy CT. Random forest (RF) models were constructed for outcome prediction using separate randomly selected training and testing sets or the entire patient set.ResultsUsing multi-energy texture analysis, tumour classification in the independent testing set had accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 92%, 86%, 100%, 100%, and 83%, compared to 75%, 57%, 100%, 100%, and 63%, respectively, for single-energy analysis.ConclusionsMulti-energy texture analysis demonstrates superior performance compared to single-energy texture analysis of VMIs at 65 keV for classification of benign parotid tumours.Key Points• We present and validate a paradigm for texture analysis of DECT scans.• Multi-energy dataset texture analysis is superior to single-energy dataset texture analysis.• DECT texture analysis has high accura\\cy for diagnosis of benign parotid tumours.• DECT texture analysis with machine learning can enhance non-invasive diagnostic tumour evaluation.

This study explores immunophenotypic and angiogenic profiles in salivary gland tumors (SGTs), focusing on epithelial–mesenchymal dynamics and immune–stromal interactions. Immunohistochemical analysis of E-cadherin, Vimentin, mast cell tryptase (MCT), CD300a, CK18, CD31, and vascular endothelial growth factor (VEGF) was performed in normal salivary tissue, pleomorphic adenomas (PA), and squamous cell carcinomas (SCCs) to assess epithelial plasticity, mast cell (MC) involvement, and vascular remodeling. Normal glands showed compartmentalized E-cadherin (epithelial) and Vimentin (mesenchymal) expression, with stromal MCs positive for MCT and CD300a. PA exhibited reduced E-cadherin, increased Vimentin, and atypical co-localization of CK18 with MCT/CD300a in ductal cells, indicating immune–epithelial plasticity. SCC displayed epithelial–mesenchymal transition (EMT), architectural disruption, and reduced MCT/CD300a. Notably, diminished MCT may reflect either decreased MCs density or prior degranulation, with possible diffuse MCT in stroma. Angiogenic profiling showed maximal CD31 in PA and minimal in SCC, while VEGF peaked in normal tissue, suggesting deregulated angiogenesis. SGT progression involves immune–epithelial plasticity, vascular deregulation, and stromal reprogramming. Immune marker localization within epithelial cells challenges histogenetic models and may inform prognostic assessment and targeted therapeutic strategies.

The mechanisms involved with the pathogenesis of carcinoma ex pleomorphic adenoma (CXPA) seem to be associated with the accumulation of molecular alterations in the pleomorphic adenoma (PA). In this sense, using array-based comparative genomic hybridization (aCGH) a rare series of 27 cases of CXPA and 14 residual PA (rPA) adjacent to the transformation area, we investigated the profile of the copy number alterations (CNAs) comparing benign residual and transformed areas. The main findings were correlated with the histopathological classification by histologic subtype and degree of invasion. The distribution of losses ( p  = 0.187) and amplifications ( p  = 0.172) was not statistically different between rPA and CXPA. The number of gains was increased in the transformed areas compared to the benign residual areas ( p  = 0.005). PLAG1 gain was maintained along the malignant transformation, as it was observed in both residual PA and CXPA samples, likely being an earlier event during transformation. The amplification of GRB7 and ERBB2 may also be an initial step in the malignant transformation of PA to CXPA (salivary duct carcinoma subtype). Furthermore, the amplification of HMGA2 and RPSAP52 were the most prevalent alterations among the studied samples. It was noteworthy that amplified genes in the transformed areas of the tumors were enriched for biological processes related to immune signaling. In conclusion, our results underscored for the first-time crucial CNAs in CXPA, some of them shared with the residual benign area adjacent to the transformation site. These CNAs included PLAG1 gain, as well as amplification of GRB7 , ERBB2 , HMGA2 , and RPSAP52 .

Objectives Accurate preoperative discrimination of salivary gland pleomorphic adenoma (SPA) stromal subtypes is essential for therapeutic plannings. We aimed to establish and test machine learning (ML) models for classification of stromal subtypes in SPA based on ultrasound histogram analysis. Methods A total of 256 SPA patients were enrolled in the study and categorized into two groups: stroma-low and stroma-high. The dataset was split into a training cohort with 177 patients and a validation cohort with 79 patients. The least absolute shrinkage and selection operator (LASSO) regression identified optimal features, which were then utilized to build predictive models using logistic regression (LR) and eight ML algorithms. The effectiveness of the models was evaluated using a range of performance metrics, with a particular focus on the area under the receiver operating characteristic curve (AUC). Results After LASSO regression, six key features (lesion size, shape, cystic areas, vascularity, mean, and skewness) were selected to develop predictive models. The AUCs ranged from 0.575 to 0.827 for the nine models. The support vector machine (SVM) algorithm achieved the highest performance with an AUC of 0.827, accompanied by an accuracy of 0.798, precision of 0.792, recall of 0.862, and an F1 score of 0.826. The LR algorithm also exhibited robust performance, achieving an AUC of 0.818, slightly trailing behind the SVM algorithm. Decision curve analysis indicated that the SVM-based model provided superior clinical utility compared to other models. Conclusions The ML model based on ultrasound histogram analysis offers a precise and non-invasive approach for preoperative categorization of stromal subtypes in SPA.

To establish a nomogram model using MRI characteristics for differentiating Warthin’s tumors (WT) from pleomorphic adenomas (PA) in parotid gland tumors, aiming to enhance management strategies. A retrospective observational study included patients with histopathologically confirmed WT or PA who underwent preoperative enhanced MRI from 2010 to 2023. Clinical and MRI data were analyzed to identify independent risk factors using multivariable logistic regression. A nomogram was constructed and internally validated using bootstrap resampling. 56 patients (32 WT, 24 PA) were analyzed. Significant differences in gender, age, degree of enhancement, and enhancement pattern were identified. The nomogram based on these factors demonstrated high predictive accuracy with an area under the ROC curve of 0.9909. The nomogram model presents a standardized quantitative method to differentiate WT from PA based on MRI characteristics, potentially improving diagnostic accuracy and patient management in parotid gland tumor diagnosis.

Pleomorphic adenoma (PA), the most common benign salivary gland tumor, harbors unpredictable risks of recurrence and malignant transformation into carcinoma ex pleomorphic adenoma (CXPA), posing significant clinical challenges. To better delineate the tumor transformation trajectory, we performed single-cell RNA sequencing of normal salivary gland, primary PA, recurrent PA (rPA), and CXPA. Cell trajectory reconstruction, differential expression gene identification, and key gene network analysis were integrated to characterize molecular transitions and intercellular crosstalk driving PA recurrence and malignant transformation. Immunohistochemistry was used to validate key findings. GALNT13 + myoepithelial cells were identified as CXPA-specific malignant progenitors, delineating early malignant conversion. Concurrently, MIF + myoepithelial cells exhibited enhanced tissue-destructive capabilities. Fibroblasts enforced fibrotic restraint in primary PA and drove extracellular matrix degradation in CXPA. The tumor microenvironment exhibited stage-specific adaptations, with CXPA favoring pro-inflammatory MIF-CD74/CD44 signaling and rPA adopting immunosuppressive traits. Stromal reprogramming and immune-editing dynamics collectively orchestrated microenvironmental adaptation, linking cellular heterogeneity to clinical aggressiveness. This study provides the first comprehensive molecular atlas of PA-to-CXPA transformation, revealing malignant specialization of the myoepithelial subpopulation, fibroblast-mediated stromal reprogramming, and immune-editing driven microenvironmental adaptation. These findings provide a framework for precision stratification of the malignant potential of PA, while positioning microenvironmental intervention as a cornerstone of future clinical strategies.

Lacrimal gland pleomorphic adenomas (LGPAs) are common, benign, and intraorbital tumours that cause exophthalmos, ptosis, and visual disturbances. The curative treatment for LGPAs is gross total resection, and radiotherapy is considered adjunctive for recurrence or an alternative for inoperable LGPAs. Stereotactic radiosurgery (SRS) can be used for precise delivery of high radiation doses to the tumour, crucial in the treatment of intra-and extracranial neoplasms. Here, we present a 95-year-old woman who had a rapidly growing, recurrent LGPA and was successfully treated with SRS. The tumour was controlled without any adverse events over 21 months following SRS. SRS is a potential alternative treatment for recurrent LGPA.

Salivary gland pleomorphic adenoma (SGPA) is the most common type of benign epithelial tumor; it is observed more commonly in females (with a female-to-male ratio of 1.43:1), and the age at diagnosis ranges between 40 and 59 years, with only 2% of cases diagnosed before age 18. Cri du Chat (CdC) is a rare syndrome caused by deletions of various sizes in the short arm of chromosome 5. Tumors in CdC patients are extremely rare: in Danish, Spanish, Australian, and Japanese groups of cases, no tumors have been reported, while a few cases have been described among 321 CdC patients collected in Italy and Germany. These cases all involve tumors that appear at a young age. We here report the case of a parotid pleomorphic adenoma in an 8-year-old boy with CdC. Exome analysis did not identify variants certainly significant for the development of SGPA. A CGH array, analyzed both in peripheral blood and tumor samples, failed to recognize anomalies previously associated with SGPA but identified a de novo duplication in 7p15.2, which contains part of a gene, SKAP2, in which the increased copy number is associated with the development of a different type of tumor such as pancreatic duct adenocarcinoma. The assumption that the duplication in 7p15.2 is relevant for the development of SGPA in our patient implies that CGH array studies must be included early in life in routine work-ups of CdC to identify CNVs with possible pathogenic roles for tumor development. This is particularly also relevant in relation to the severely impaired possibility for patients with CdC to report discomfort or pain related to tumor development. Constitutional CNVs in addition to the deletion in 5p should also be extensively studied to verify if their presence in some patients could explain why, in these cases, tumors develop at an age younger than expected.

Purpose Pleomorphic adenoma (PA) is the most common benign parotid tumor, with a well-known propensity to recur. Many factors have been advocated as prognostic, but there is no consensus on how they affect local control. We studied how PA recurrence-free survival (RFS) may be affected by the most relevant risk factors in a time-to-event analysis, comparing them with those observed in a population of non-PA (NPA). Methods Patients undergoing parotidectomy for benign lesions between 2002 and 2018 in a single academic tertiary referral center were included. A description of patients, tumors, and treatment characteristics was performed, highlighting differences between PA and NPA. Analysis of PA RFS and relative risk factors was also conducted. Results Eight hundred fifty patients underwent parotidectomy for benign lesions, 455 (53.5%) for PA and 57 (6.7%) for NPA. Significant differences between PA and NPA were age at surgery, surgical procedure, and resection margins. Recurrence occurred in 3.1% of PA, with a median disease-free interval of 54 months. 2-, 5-, and 10-year RFS were 99.2, 98.5, and 93.9%, respectively. Age < 18 years (HR = 31.31, p  < 0.001), intraoperative tumor spillage (HR = 6.57, p  = 0.041), extensive pseudo-capsule interruption (HR = 5.85, p  = 0.023), and resection margins < 1 mm (HR = 3.16, p  = 0.085) were associated with RFS. Conclusion Patients affected by NPA were significantly older and treated with more conservative surgical procedures compared to those with PA. In PA, younger age, major pseudo-capsule defects, and surgical margins were the most relevant factors affecting local control. These results confirm the importance of an appropriate surgical management and long-term follow-up in PA.