Uncovering the WWTR1::NCOA2 Gene fusion in low-grade myoepithelial-rich neoplasm with HMGA2 expression: A case report.

We describe a case of a pleomorphic adenoma (PA) arising from the para-tracheal accessory salivary gland in a 44-year-old male harboring a novel WWTR1::NCOA2 gene fusion. To our knowledge, this novel gene fusion has not been described previously in salivary gland tumors. The patient presented with hoarseness of voice. The radiological exam revealed a mass in the upper third of the trachea involving the larynx. Histologically, the tumor consisted of bland-looking monocellular eosinophilic epithelial cells arranged in cords and sheets separated by thin fibrous stroma, focally forming a pseudo-tubular pattern. In immunohistochemistry, the tumor cells demonstrated positivity for CK7, PS100, SOX10, and HMGA2; and negativity for CK5/6, p40 p63, and PLAG1. In addition, the clustering analysis clearly demonstrates a clustering of tumors within the PA group. In addition to reporting this novel fusion in the PA spectrum, we discuss the relevant differential diagnoses and briefly review of NCOA2 and WWTR1 gene functions in normal and neoplastic contexts.

Genetic Heterogeneity in Cellular Angiofibromas.

BACKGROUND: Cellular angiofibroma, a rare benign mesenchymal neoplasm, is classified within the 13q/RB1 family of tumors due to morphological, immunohistochemical, and genetic similarities with spindle cell lipoma. Here, genetic data reveal pathogenetic heterogeneity in cellular angiofibroma. METHODS: Three cellular angiofibromas were studied using G-banding/Karyotyping, array comparative genomic hybridization, RNA sequencing, and direct cycling sequencing. RESULTS: The first tumor carried a del(13)(q12) together with heterozygous loss and minimal expression of the RB1 gene. Tumors two and three displayed chromosome 8 abnormalities associated with chimeras of the pleomorphic adenoma gene 1 (PLAG1). In tumor 2, the cathepsin B (CTSB) fused to PLAG1 (CTSB::PLAG1) while in tumor 3, the mir-99a-let-7c cluster host gene (MIR99AHG) fused to PLAG1 (MIR99AHG::PLAG1), both leading to elevated expression of PLAG1 and insulin growth factor 2. CONCLUSION: This study uncovers two genetic pathways contributing to the pathogenetic heterogeneity within cellular angiofibromas. The first aligns with the 13q/RB1 family of tumors and the second involves PLAG1-chimeras. These findings highlight the diverse genetic landscape of cellular angiofibromas, providing insights into potential diagnostic strategies.

HMGA2-positive salivary gland neoplasms with prominent trabecular/canalicular morphology: a focus on carcinomas arising within this phenotype.

AIMS: Pleomorphic adenoma (PA) with a prominent trabecular/canalicular morphology has consistent HMGA2 protein expression, and association with HMGA2 fusions. We report our experience with this subtype, with emphasis on the carcinomas that can arise in this context. METHODS AND RESULTS: A retro- and prospective review (2013-2024) of major salivary gland tumours with prominent trabecular/canalicular morphology was performed. Twenty-one parotid tumours met the criteria: 14 benign (66.7%), six carcinomas (28.6%), and one of uncertain behaviour (4.7%). HMGA2 immunohistochemistry (IHC) was performed on all cases. Next-generation sequencing was successfully performed on 18. Seven benign cases had a conventional PA component. In all cases, the tumour cells in these trabecular/canalicular areas demonstrated variable papillary thyroid carcinoma-like nuclear changes, including chromatin clearing, overcrowding, membrane irregularities, and intranuclear pseudoinclusions. Benign tumours were well-demarcated, whereas carcinomas demonstrated either a multinodular pattern of invasion or subtle infiltration. Two carcinomas showed increased cytologic atypia and architectural complexity and one had perineural invasion. By IHC, all were positive for HMGA2. In the trabecular/canalicular areas, there was consistent strong expression of CAM5.2, S-100, and SOX-10 and variable expression of p63 but negative p40. HMGA2 alterations were detected in 16 of 18 cases (89%). Follow-up was available on two carcinomas, with one being locally recurrent. CONCLUSION: While most HMGA2-positive salivary gland neoplasms with a prominent trabecular/canalicular growth pattern are benign, they, like traditional PAs, may give rise to carcinomas that can locally recur. These carcinomas can be deceptively bland, subtly infiltrative, or have a multinodular pattern of invasion.

Expanding the histological spectrum of salivary gland neoplasms with HMGA2::WIF1 fusion emphasising their malignant potential: a report of eight cases.

AIMS: Recently, HMGA2::WIF1 fusion has been reported in pleomorphic adenoma (PAs) originating from the parotid gland with a characteristic canalicular adenoma (CAA)-like pattern. However, it is unclear whether HMGA2::WIF1 fusion may occur in salivary gland carcinoma or tumours originating from the minor salivary glands. We herein conducted a detailed clinicopathological review of eight salivary gland tumours harbouring HMGA2::WIF1 fusions. METHODS AND RESULTS: The reviewed diagnoses of salivary gland neoplasms with HMGA2::WIF1 fusion were PA (n = four), myoepithelioma (n = one), myoepithelial carcinoma ex PA (n = two) and high-grade carcinoma with basaloid features (n = one). Two tumours originated from the minor salivary glands. Six tumours (80%) contained areas reminiscent of CAA characterised by interconnected trabeculae/canaliculi of monotonous oncocytic or cuboidal tumour cells associated with a hypocellular, hyalinised to myxoid stroma. Areas typical of PA were seen in four (50%) cases. All tumours showed diffuse S100 and CK7 immunopositivity. Adverse events were detected in two cases, including local recurrence in a patient with PA, and local and distant recurrences and disease-related death in a patient with a high-grade carcinoma of the minor salivary gland of the buccal space, showing tumour necrosis and perineural invasion. CONCLUSION: Salivary gland neoplasms with HMGA2::WIF1 fusion are predominantly characterised by CAA/striated duct adenoma-like histology and a S100+/CK7+ immunoprofile. These tumours are not always benign, as among all reported cases approximately 20% showed malignancy (six of 28) and adverse outcome (three of 15), including recurrence, distant metastasis and disease-specific mortality.

Peculiar nuclear atypia associated with MDM2 gene amplification in carcinoma ex-pleomorphic adenoma harbouring an alteration of HMGA2.

AIMS: Salivary gland neoplasms (SGN) exhibiting the HMGA2::WIF1 fusion are recognized by their resemblance to histology found in canalicular adenoma. Recently, ~20% of cases among 28 HMGA2::WIF1-rearranged-SGN showed malignancy and adverse outcomes (recurrence, distant metastasis, and disease-specific mortality). Among them, MDM2/CDK4 amplifications were identified in one case. This outcome suggests that the MDM2/CDK4 amplifications could be useful to predict an aggressive course of carcinoma ex-pleomorphic adenoma (CEPA). METHODS AND RESULTS: We investigated the correlation between HMGA2 fusion and MDM2 amplification in four salivary gland neoplasms, providing detailed clinicopathological features and outcomes. Cases were selected from different institutions. Histological examination, immunohistochemistry, fluorescence in situ hybridization (FISH), RNA sequencing, and whole-exome capture were performed. The cohort included four CEPA cases, all female, aged between 32 and 89 years. Tumours arose from the parotid gland with an average size of 24.5 mm. None exhibited recurrence or distant metastases during the 4-5 months of follow-up. Pathologically, all cases displayed a peculiar atypical nuclei with 'gear-like appearance'. Immunohistochemically, tumours exhibited a biphasic pattern with myoepithelial and ductal differentiation markers. All cases showed HMGA2 overexpression and MDM2 amplification by FISH and RNA sequencing. In a control cohort of MDM2 nonamplified CEPA cases, not exhibiting the peculiar nuclear atypia. CONCLUSIONS: Our findings suggest a strong correlation between HMGA2 alteration/MDM2 amplification and a peculiar nuclear atypia, advocating for their evaluation in biphasic tumours to facilitate accurate diagnosis and tailored posttumour removal monitoring. Further studies are warranted to validate these observations and elucidate their prognostic implications.

Recent developments in the pathology of primary pulmonary salivary gland-type tumours.

Primary pulmonary salivary gland-type tumours are rare neoplasms that are thought to arise from seromucinous glands that are located in the submucosa of large airways. These neoplasms have clinical and pathologic features that are distinct from other pulmonary neoplasms. The majority of primary pulmonary salivary gland-type tumours are malignant, with the most common entities being mucoepidermoid carcinoma, adenoid cystic carcinoma, and epithelial-myoepithelial carcinoma. Less commonly seen are myoepithelial carcinoma, hyalinizing clear cell carcinoma, acinic cell carcinoma, secretory carcinoma, salivary duct carcinoma, intraductal carcinoma, and polymorphous adenocarcinoma. Benign salivary gland-type tumours of the lung include pleomorphic adenoma and sialadenoma papilliferum. Morphologic, immunophenotypic, and molecular features of these neoplasms are largely similar to salivary gland tumours elsewhere, and therefore the exclusion of metastatic disease requires clinical and radiologic correlation. However, the differential diagnostic considerations are different in the lung. The distinction of salivary gland-type tumours from their histologic mimics is important for both prognostication and treatment decisions. Overall, salivary gland type-tumours tend to have a more favourable outcome than other pulmonary carcinomas, although high-grade variants exist for many of these tumour types. Recent advances in our understanding of the spectrum of salivary gland-type tumours reported in the lung and their diversity of molecular and immunohistochemical features have helped to refine the classification of these tumours and have highlighted a few differences between salivary gland-type tumours of the lung and those primary to other sites.

Pleomorphic adenoma and carcinoma ex-pleomorphic adenoma tumorigenesis: A proteomic analysis.

OBJECTIVES: To conduct a comprehensive proteomic analysis of normal salivary gland tissue, pleomorphic adenoma (PA), and carcinoma ex-pleomorphic adenoma (CXPA), and validate the proteomic findings using immunohistochemistry. METHODS: Six normal salivary gland tissues, seven PA and seven CXPA samples underwent laser microdissection followed by liquid chromatography coupled to mass spectrometry. Protein identification and quantification were performed using MaxQuant software. Statistical analysis and functional enrichment were conducted using the Perseus platform and STRING tool, respectively. Immunohistochemistry was used for validation. RESULTS: Comparative proteomic analysis revealed 2680 proteins across the three tissue types, with 799 significantly altered between groups. Translocation protein SEC63 homolog, Annexin A6 and Biglycan were up-regulated in CXPA compared to PA. Decorin was markedly up-regulated in both PA and CXPA compared to normal salivary gland (log2 fold changes of 7.58 and 7.38, respectively). Validation confirmed elevated levels of Biglycan and Decorin in the extracellular matrix of CXPA compared to PA. CONCLUSIONS: Proteomic analysis identified differential protein expression patterns associated with malignant transformation of PA into CXPA. Findings indicate a crucial role for extracellular matrix proteins, specifically Biglycan and Decorin, in the tumorigenic progression of PA and CXPA.

Salivary gland-like tumors of the breast: Histopathologic and genetic features with clinical implications.

Salivary gland-like tumors of the breast are rare neoplasms that share morphologic, immunophenotypic, and/or genetic features with their salivary gland counterparts, highlighting a shared underlying histopathogenesis in most cases. Salivary gland-like carcinomas included in the World Health Organization classification of breast tumors are adenoid cystic carcinoma, secretory carcinoma, mucoepidermoid carcinoma, acinic cell carcinoma, and the exceedingly rare polymorphous adenocarcinoma. These carcinomas are usually triple negative for estrogen receptor and progesterone receptor expression and HER2 overexpression, yet generally have favorable prognosis, in contrast to high-grade triple negative carcinomas of no special type. On the other hand, a small subset, such as solid-basaloid adenoid cystic carcinoma, rare high-grade carcinomas, and those associated with transformation to other types of high-grade invasive carcinoma can behave more aggressively. Other salivary gland-like tumors of the breast, such as pleomorphic adenoma and adenomyoepithelioma, are usually benign but can rarely undergo malignant transformation. Although clinical experience with salivary gland-like breast tumors is overall limited, their recognition and accurate classification has important implications for prognosis and clinical management, especially to avoid overtreatment of salivary gland-like carcinomas. The identification of characteristic genetic alterations and/or immunohistochemical surrogates in many of these tumors has practical applications to establishing an accurate diagnosis and directing clinical management. This review highlights the histopathologic and genetic characteristics of salivary gland-like breast tumors and the implications of the diagnosis for current clinical management.

A Rare Subglottic Pleomorphic Adenoma: Magnetic Resonance Findings.

No previous study has published magnetic resonance imaging (MRI) findings for a subglottic pleomorphic adenoma. Here, we describe the case of a 62-year-old man with a subglottic pleomorphic adenoma. Endoscopic findings revealed a smooth-surfaced tumor arising from the subglottic posterior wall. MRI revealed the lesion as an isointense region on T1-weighted images, which was homogeneously enhanced. This lesion showed a heterogeneously hyperintense region on T2-weighted images. Diffusion-weighted imaging (DWI) showed slightly high intensity in the same area, with a normal or only slightly high apparent diffusion coefficient (ADC). Laryngomicrosurgery was performed for transoral excision of the subglottic tumor, resulting in a postsurgical diagnosis of pleomorphic adenoma.

Growth rates over time of unoperated parotid benign tumors.

INTRODUCTION: The treatment of parotid benign tumor is in principle surgery, but observation may be necessary in some cases. The purpose of this study was to investigate the growth rates over time of unoperated parotid benign tumors. METHODS: We retrospectively reviewed the medical records of 63 patients with unoperated parotid benign tumors diagnosed at our institution between January 2010 and December 2022. RESULTS: Forty-nine of the 63 patients had a Warthin tumor and 13 patients had a pleomorphic adenoma. On average, the unoperated parotid benign tumors grew 0.02 cm in length and 0.4 cm3 in volume per year. Compared to pleomorphic adenomas, Warthin tumors were more predominant in male patients and in those with a smoking history and a longer duration of smoking history; patients with Warthin tumors were also followed up longer (p < 0.05). However, the length and volume growth rates of unoperated Warthin tumors and pleomorphic adenomas did not significantly differ. CONCLUSION: Surgery is the standard treatment for parotid benign tumors. However, small benign parotid tumors identified during preoperative examination can be observed through close follow-up, taking into account the patient's medical and general condition.

Partial superficial parotidectomy for pleomorphic adenoma of the parotid gland: Early post-operative outcomes.

INTRODUCTION: There has been historical controversy regarding the extent of resection in the management of pleomorphic adenomas. This study aims to evaluate the extent of surgery and short-term postoperative outcomes of partial superficial parotidectomy (PSP) for the management of pleomorphic adenomas at a tertiary, high-volume center. METHODS: A retrospective chart review of patients who underwent PSP was performed. Variables included demographics, pre-operative facial nerve function, operative techniques, postoperative complications/facial nerve function, and recurrence. RESULTS: 151 adults who underwent PSP for pleomorphic adenoma from January 1st, 2000 to December 31st, 2022 were identified. Median age was 55 (IQR 40-66) years with females representing 74 % of the cohort. Median tumor size at presentation was 1.8 (IQR 1.3-2.3) cm. Baseline facial nerve function was excellent for most patients (House-Brackmann I, 99 %). Most patients underwent a superficial inferior parotidectomy (88 %). Modified Blair incision (70 %) was the most common incision. Intraoperatively, the facial nerve was identified in 149 (99 %) patients. The main trunk was identified in 126 (85 %) patients. No patient had tumor spillage. Only two patients required parotid bed reconstruction. The most common complication was ear numbness (60 %). Postoperatively, 114 patients were House-Brackmann grade I at both preoperative and postoperative assessment, 8 went from grade I to II, and 1 went from grade VI to II (Bell's palsy that resolved to grade II following surgery). Median follow-up was 1(IQR 1-5) month. CONCLUSION: PSP is efficacious in the management of pleomorphic adenomas with preservation of facial nerve function, and minimal post-operative complications. Future study is needed to assess long term recurrence risk.

Correlation between MRI (DWI and DCE) and cellularity of parotid gland pleomorphic adenomas.

PURPOSE: Parotid pleomorphic adenomas present a risk of recurrence, higher when the tumour is a hypocellular subtype. The aim of the study was to determine whether it is possible to characterize this histological subtype with diffusion and perfusion sequences of the preoperative MRI. METHODS: This retrospective study included 97 patients operated between 2010 and 2020. Histologic slides review was performed to classify tumours into three histologic subtypes: hypocellular, classical and hypercellular. Univariate and multivariate analyses studied the correlation between histology and diffusion and perfusion MRI parameters obtained with OleaSphere® software. RESULTS: The hypocellular subtype had higher apparent diffusion coefficient values than the other two subtypes: 2.13 ± 0.23, 1.83 ± 0.42, and 1.61 ± 0.4 × 10-3 mm2/s for hypocellular, classical and hypercellular subtype respectively (p < 0.0001). Multivariate analysis showed that an ADCmean > 1.88 × 10-3 mm2/s was suggestive of a hypocellular pleomorphic adenoma in 79% of the cases, with a specificity and PPV of 94 and 96% (p < 0.001), respectively. CONCLUSION: The histological subtype of a pleomorphic adenoma can be predicted preoperatively with ADC values. A prospective and multicentric study on a larger cohort is needed to confirm our results.

Evaluation of multiparametric MRI differentiating pleomorphic adenoma from schwannoma in parapharyngeal space.

PURPOSE: This study aimed to investigate whether multiparametric magnetic resonance imaging (MRI) including dynamic contrast-enhanced (DCE) and diffusion weighted (DW) MRI can differentiate pleomorphic adenoma (PA) from schwannoma in the parapharyngeal space. METHODS: Forty-six patients with pathologically proven PAs and 47 schwannomas in the parapharyngeal space were enrolled. All patients underwent conventional MRI, and DW-MRI and DCE-MRI were performed in 30 and 33 patients, respectively. Fisher's exact, Mann-Whitney-U tests and Independent samples t-test were used to compare variables between PAs and schwannomas. Multivariate logistic regression analysis was used to examine the diagnostic performance of MRI parameters. RESULTS: The PAs usually show lobulation sign, posterior displacement of ICA and attached to the parotid gland deep leaf, while bird beak configuration, anterior displacement of ICA and involvement of foramen jugular were more commonly seen in the schwannomas(all p < 0.001). The washout rate of PAs was found to be higher than that of schwannomas (p = 0.035), whereas no significance was found in the other DCE-MRI parameters and in ADCs(p > 0.05). Using a combination of conventional MRI features including lobulation sign, bird beak configuration, direction of internal carotid artery(ICA) displacement and attached to the parotid gland in multivariate logistic regression analysis, sensitivity, specificity, and accuracy in differential diagnosis of PAs and schwannomas were 97.8%, 91.5% and 94.6%, respectively. CONCLUSION: Conventional MRI can effectively differentiate PAs from schwannomas in the parapharyngeal space with a high diagnostic accuracy. The DCE-MRI and DWI have limited added diagnostic value to conventional MRI in the differential diagnosis.

Oral cavity salivary gland pleomorphic adenoma: a histomorphological case series.

BACKGROUND: Pleomorphic adenoma (PA), the most common benign salivary gland epithelial lesion, has a biphasic epithelial-mesenchymal pattern and great histopathological diversity. METHODS: This study's objective was to conduct a retrospective clinicopathological analysis, focusing on the histopathology characteristics of salivary gland PA. RESULTS: There were ten cases of pleomorphic adenoma. The mean age was 33.5 years and no gender predilection was observed. All the patients presented with an asymptomatic mass and the duration of presentation was 31.2 ± 19.4 months. The cellular subtype (50 %) of PA was the most common. Capsular infiltration and incomplete capsules occurred in 20 % of cases. All the cases had round (100 %) and myxoid stroma. The cellular subtype was more common in the major salivary glands; showed capsular abnormalities (incomplete capsule, absent capsule, and tumor infiltration); and had more plasmacytoid, angular, spindled non-luminal cells as well as inflammation and cystic degeneration. The classic subtype had more clear and oncocytic cells along with sebaceous and squamous differentiation. The stroma-rich subtype had the shortest duration of complaints (three months) and showed giant cell reaction. CONCLUSIONS: These findings confirm previous studies on the clinicopathological features of pleomorphic adenomas and highlight important morphologic characteristics like capsular invasion and squamous metaplasia, which can otherwise indicate malignancy.

Pleomorphic Parotid Adenoma in a Child Affected with Cri du Chat Syndrome: Clinical, Cytogenetic, and Molecular Analysis.

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.

An ultrasound-based histogram analysis model for prediction of tumour stroma ratio in pleomorphic adenoma of the salivary gland.

OBJECTIVES: Preoperative identification of different stromal subtypes of pleomorphic adenoma (PA) of the salivary gland is crucial for making treatment decisions. We aimed to develop and validate a model based on histogram analysis (HA) of ultrasound (US) images for predicting tumour stroma ratio (TSR) in salivary gland PA. METHODS: A total of 219 PA patients were divided into low-TSR (stroma-low) and high-TSR (stroma-high) groups and enrolled in a training cohort (n = 151) and a validation cohort (n = 68). The least absolute shrinkage and selection operator regression algorithm was used to screen the most optimal clinical, US, and HA features. The selected features were entered into multivariable logistic regression analyses for further selection of independent predictors. Different models, including the nomogram model, the clinic-US (Clin + US) model, and the HA model, were built based on independent predictors using logistic regression. The performance levels of the models were evaluated and validated on the training and validation cohorts. RESULTS: Lesion size, shape, cystic areas, vascularity, HA_mean, and HA_skewness were identified as independent predictors for constructing the nomogram model. The nomogram model incorporating the clinical, US, and HA features achieved areas under the curve of 0.839 and 0.852 in the training and validation cohorts, respectively, demonstrating good predictive performance and calibration. Decision curve analysis and clinical impact curves further confirmed its clinical usefulness. CONCLUSIONS: The nomogram model we developed offers a practical tool for preoperative TSR prediction in PA, potentially enhancing clinical decision-making.

Recurrence rate of pleomorphic adenoma of the lacrimal gland: systematic review and meta-analysis.

PURPOSE: The aim is to increase the understanding of lacrimal gland pleomorphic adenoma's recurrence rate and the factors that influence it. METHODS: A systematic search of PubMed, SCOPUS, Cochrane Library, and CINAHL was conducted following PRISMA guidelines. The data in the included studies were extracted and analyzed. RESULTS: Twenty-two studies were included representing 963 patients from 12 different countries. The pooled analysis of the recurrence rate was 8.83% (95% CI: 5.08-13.50). In the event of recurrence, there was a 75.17% (95% CI: 65.98-82.94) chance of benign recurrence and a 28.35% (95% CI: 19.66-38.41) chance of malignant recurrences, with malignant recurrence occurring almost exclusively after a benign recurrence. The results showed that 47.09% (95% CI: 24.60 to 70.22) of recurrent tumors had a ruptured pseudocapsule and 6.35% (95% CI: 0.82 to 16.54) had an intact pseudocapsule with a significant difference between the two. Of the recurrent tumors, 51.50% (95% CI: 9.28 to 92.39) were biopsied compared to 8.83% (95% CI: 3.40 to 16.49) of the total; the difference between these two proportions was also found to be significant. CONCLUSION: There was a statistically significant difference in the rates of recurrence between tumors that were either biopsied or had a ruptured pseudocapsule compared to those that did not. This evidence adds additional support for excisional biopsy being the procedure of choice for LGPA and reinforces the importance of keeping the pseudocapsule intact during surgical resection.

Central Pleomorphic Adenoma of Mandible Mimicking Ameloblastoma - A Rare Case Report.

Salivary gland neoplasms account for 3% of all head and neck tumours. Pleomorphic adenoma (PA) is the most common salivary gland tumour that mainly occurs in the parotid gland, followed by minor salivary glands of the oral cavity, however, the occurrence of PA inside the jaw bones is exceedingly rare and very few cases have been reported in the literature. Inside jaw bones these lesions tend to imitate large osteolytic lesions encompass a diagnostic challenge. An exhaustive review of the literature revealed only 10 cases of central pleomorphic adenoma. We present a rare case of primary PA that occurred inside the mandible and was provisionally diagnosed as ameloblastoma.

Differential Expression of Mucin in Salivary Gland Tumours.

Background and Objectives: Mucin has been implicated via various mechanisms in the development and growth of tumour cells. However, mucin expression studies in salivary gland tumours are limited, especially with samples from minor salivary glands. This study aims to investigate and compare mucin expression in benign and malignant salivary gland tumours of minor and major salivary gland origins. Materials and Methods: Special stains were used to stain neutral mucin (Periodic acid Schiff), sialomucin (Alcian Blue) and sulfomucin (Aldehyde Fuschin) within tissues from six normal salivary glands and 73 salivary gland tumours including 31 pleomorphic adenomas, 27 mucoepidermoid carcinomas, and 15 adenoid cystic carcinomas. A semi-quantitative approach was used to evaluate mucin expression within ductal lumens. Sialomucin was the most expressed mucin in all salivary gland tumours, regardless of origin. Results: A significant difference was observed in the mucin expression between benign and malignant salivary gland tumours, as pleomorphic adenoma showed three times significantly higher expression of sialomucin compared to mucoepidermoid carcinoma and adenoid cystic carcinoma (p = 0.028). Pleomorphic adenomas of major glands showed 42 times significantly higher expression of sialomucin compared to those of minor glands (p = 0.000). Conclusions: Sialomucin content in pleomorphic adenomas of major glands was vastly increased compared to that in minor glands. Differential sialomucin expression in benign and malignant salivary gland tumours suggests a role in diagnosing of borderline salivary gland tumours.

Salivary carcinosarcoma: insight into multistep pathogenesis indicates uniform origin as sarcomatoid variant of carcinoma ex pleomorphic adenoma with frequent heterologous elements.

AIMS: The formal pathogenesis of salivary carcinosarcoma (SCS) remained unclear, both with respect to the hypothetical development from either preexisting pleomorphic adenoma (PA) or de novo and the clonal relationship between highly heterogeneous carcinomatous and sarcomatous components. METHODS AND RESULTS: We performed clinicopathological and molecular (targeted RNA sequencing) analyses on a large series of 16 cases and combined this with a comprehensive literature search (111 cases). Extensive sampling (average 11.6 blocks), combined with immunohistochemistry and molecular studies (PA-specific translocations including PLAG1 or HMGA2 proven in 6/16 cases), enabled the morphogenetic identification of PA in 15/16 cases (93.8%), by far surpassing a reported rate of 49.6%. Furthermore, we demonstrated a multistep (intraductal/intracapsular/extracapsular) adenoma-carcinoma-sarcoma-progression, based on two alternative histogenetic pathways (intraductal, 56.3%, versus myoepithelial pathway, 37.5%). Thereby, early intracapsular stages are identical to conventional carcinoma ex PA, while later extracapsular stages are dominated by secondary, frequently heterologous sarcomatous transformation with often large tumour size (>60 mm). CONCLUSION: Our findings strongly indicate that SCS (almost) always develops from PA, with a complex multistep adenoma-carcinoma-sarcoma-sequence, based on two alternative histogenetic pathways. The findings from this novel approach strongly suggest that SCS pathogenetically is a rare (3-6%), unique, and aggressive variant of carcinoma ex PA with secondary sarcomatous overgrowth. In analogy to changes of terminology in other organs, the term "sarcomatoid carcinoma ex PA with/without heterologous elements" might be more appropriate.