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Purpose: Ultrasound-guided fine-needle aspiration cytology (FNAC) is a widely used diagnostic procedure which facilitates the differentiation of salivary gland lesions. Although the performance of salivary gland FNAC (SG-FNAC) has improved since the introduction of the Milan System for Reporting Salivary Gland Cytopathology (MSRSGC), the range of the reported performance is still wide. Therefore, the aim of this study was to determine lesion- and sampling-related factors that influence the success of SG-FNAC., Methods: All SG-FNAC cases performed in a tertiary referral hospital between September 1st, 2011, and August 31st, 2022, were retrospectively identified. Demographic, histopathological, lesion-specific, and sampling-related data were retrieved from the clinical charts. Cytopathological reports were categorized according to the MSRSGC. The risk of malignancy (ROM), the performance measures, and factors influencing the success of SG-FNAC were calculated., Results: Overall, 1289 cases with histopathological follow-up diagnosis (out of 1952 SG-FNACs) were included. The ROM was: non-diagnostic = 23.9%, non-neoplastic = 4.4%, atypia of undetermined significance (AUS) = 34.5%, neoplasm-benign = 1.0%, neoplasm-salivary gland neoplasm of uncertain malignant potential (SUMP) = 15.3%, suspicious for malignancy = 74.1%, malignant = 96.2%. The sensitivity, specificity, accuracy, positive, and negative predictive value for differentiating benign from malignant lesions (excluding lesions categorized as AUS and SUMP) were 87.5%, 97.7%, 96.3%, 85.0%, and 98.1%, respectively. A larger lesion size (OR (95% CI) = 1.21 (1.06-1.39), p = 0.004), a higher number of obtained slides (OR (95% CI) = 1.31 (1.17-1.46), p < 0.001), and the physician performing the FNAC (p = 0.047) were independent predictors for a higher success, while localization of the lesion within the submandibular compared to the parotid gland (OR (95% CI) = 0.38 (0.19-0.77), p = 0.008) was an independent predictor for lower success of SG-FNAC., Conclusion: This is the largest single-center study evaluating SG-FNAC performance to date. It identified independent lesion-and sampling-related factors influencing the success of SG-FNAC. Knowledge of those can improve performance of the procedure., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethical Approval: All procedures performed in this study were in accordance with the ethical standards of the institution or practice at which the studies were conducted. Consent for Publication: All authors approved the final submitted manuscript. Informed Consent: Informed consent was obtained from all individual participants included in this study (no identifying information about participants is available in this article)., (© 2024. The Author(s).)

Background: Primary salivary gland carcinomas (SGC) are rare neoplasms that present therapeutic challenges especially in recurrent tumors. The aim of this study was to investigate the incidence and distribution of tumor recurrence, associated risk factors, and survival., Methods: This analysis includes data from 318 patients treated for SGC between 1992 and 2020. Survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate analyses were used to identify risk factors associated with recurrence., Results: 21.7% of the patients developed recurrent disease after a mean of 38.2 months. In multivariate analysis, positive-resection margins, vascular invasion, and tumor localization in the submandibular gland and small salivary glands were independent factors for recurrence. The 5-year overall survival was 67%, the 5-year disease-free survival was 54%., Conclusion: Tumor recurrence in SGC occurred in one out of five patients. In highly aggressive entities and patients with risk factors, treatment intensification should be considered., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Purpose: This study aims to provide a broad overview of the epidemiology of cancer of the paranasal sinuses (PSC) in Germany. The data include information on incidence, staging, clinicopathological features and survival from one of the largest cancer registries in Europe., Methods: Population-based data on PSC diagnosed from January 1st, 2009 until December 31st, 2019 were retrieved from the German Centre for Cancer Registry Data (ZfKD). Age standardized incidence was calculated and relative survival estimates were computed by sex, histological subtype, age group and T-, N-, and M-Stage., Results: In total, 3975 cases were included in this study. The age-adjusted incidence rate (ASR) for PSC was 0.3/100,000 which remained stable during the observation period. The most frequent tumor localization was the maxillary sinus (41.9 %) and the most common histological subtype was keratinizing squamous cell carcinoma (kSCC) (44.3 %). All subtypes were predominantly found in the maxillary sinus except for adenocarcinoma and neuroendocrine carcinomas (SNEC), which were most frequently located in the ethmoidal sinus. The majority of the patients with a known T stage was diagnosed in tumor stage T4 (60.8 %). The overall 5-year relative survival (RS) for all patients with PSC was 52 %. RS dropped from 93 % for T1 stage tumors to 39 % for T4 tumors. RS was 58 % for N0 and 31 % for N+ cases, 54 % for M0 and 27 % for M1 cases., Conclusion: Age-adjusted incidence for PSC is low and has been stable for the observed 11-year period. RS decreases continuously with increasing T-, N- and M-stage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Salivary gland carcinomas are a rare and heterogeneous group of malignant tumors, accounting for 3-6% of all malignant tumors in the head and neck region. The 1-, 3- and 5-year survival rates are 83%, 69% and 63% respectively. Due to new molecular pathological and genetic findings, new entities are constantly being defined as part of the recurring WHO classification of salivary gland carcinomas, so that the incidence rates of the entities are subject to constant change. The only certain risk factor for the development of salivary gland carcinomas is ionizing radiation. In addition, large tumors, cervical lymph node involvement and perineural sheath involvement significantly worsen the prognosis. Today, molecular pathology is coming to the fore, with which potential targets have been identified that can offer prognosis-improving treatment options, particularly in recurrent or distant metastatic stages. Entity-specific tyrosine kinase inhibitors such as axitinib in adenoid cystic carcinoma or larotrectinib in secretory carcinoma and cross-entity therapies such as HER2 inhibition and androgen deprivation can prolong median and progression-free survival with a favorable side effect profile., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: A parotid abscess (PA) is a complication of an acute bacterial parotitis with a potentially life-threatening course. To date, data on the diagnosis and therapy of PA is sparse and mostly consists of case reports or case series. Therefore, this study aimed at comprehensively analyzing the microbiological spectrum and the therapeutic management in a bi-institutional setting., Methods: A retrospective clinical chart review was performed to identify all patients surgically treated for PA at two tertiary care centers in Germany. Data on demographics, clinical management and microbiological data including species identification, pathogenicity, type of antibiotic therapy, adjustment of antibiotics, antibiotic sensitivity testing, and smear test results were extracted. Intervention-related variables and etiology were analyzed for their statistical association with outcome variables., Results: Overall, 85 patients were included. Most patients (92.9%) underwent surgical incision. Around half of the patients (45.9%) were treated under local anesthesia. No facial nerve palsy was observed. The most frequently detected pathogens were Streptococci (n = 23), followed by Staphylococcus aureus (n = 6) including one case of methicillin-resistant Staphylococcus aureus. Most patients (68.2%) received an aminopenicillin ± beta-lactamase inhibitor as empiric antibiotic therapy. In 6 cases the antibiotic therapy was modified after receiving the antibiogram. Four patients (5.2%) presented with recurrent PA. Etiology was idiopathic (42.4%), followed by tumorous (12.9%), obstructive, and immunosuppressive (each 11.8%). Patients with a dental focus (p = 0.007) had a longer duration of hospitalization., Conclusion: The results show that the surgical therapy of PA under local anesthesia is safe. A dental examination should routinely be performed to rule out a dental focus. Obtaining a microbiological specimen in order to modify antibiotic therapy if necessary and a histopathological specimen to rule out a tumorous etiology is obligate., (© 2024. The Author(s).)

Purpose: The incidence of salivary duct carcinoma (SDC) seems to be underestimated due to inaccurate classification. Further, the frequency of SDC patients with targeted therapy options according to current guidelines is unclear. Therefore, this study aimed at (a) describing the proportion of SDC among salivary gland carcinoma (SGC) before and after reclassification of cases initially classified as adenocarcinoma, not otherwise specified (ANOS); and (b) quantifying the frequency of SDC patients with targeted therapy options., Methods: All patients with SDC or ANOS treated in a tertiary care center between 1996 and 2023 were identified. Histopathological diagnosis was verified for patients primarily diagnosed with SDC and reviewed for patients initially diagnosed with ANOS. Clinical data for SDC patients were retrieved from clinical charts. Immunohistochemical (IHC) androgen receptor (AR) and HER2 staining was performed., Results: Among 46 SDC, 34 were primarily diagnosed as SDC and 12 had initially been classified as ANOS. The proportion of SDC among SGC was 12.1% and was rising when comparing the time periods 2000-2015 (7.1-11.5%) versus 2016-2023 (15.4-18.1%). Nuclear AR staining in > 70% of tumor cells was found in 56.8% and HER2 positivity (IHC 3 +) in 36.4% of cases. 70.5% of patients showed AR staining in > 70% of tumor cells and/or HER2 positivity and therefore at least one molecular target. 5-year overall and disease-free survival (DFS) were 62.8% and 41.0%. Multivariate Cox regression revealed positive resection margins (HR = 4.0, p = 0.03) as independent negative predictor for DFS., Conclusions: The results suggest a rising SDC incidence and show that the extent of the AR and HER2 expression allows for targeted therapy in most SDC cases., (© 2024. The Author(s).)

Objective: The aim of this study was to evaluate the quality and the educational content of YouTube videos showing parotidectomy., Methods: We searched for videos displaying parotidectomy on YouTube. To rate parotidectomy videos, we introduced the "Instructional Videos in Otorhinolaryngology by YO-IFOS (IVORY)-grading-system (GS)" derived from the IVORY Guidelines, which pose established consensus recommendations for the production of educational surgical videos in otolaryngology. The videos were rated using the IVORY-GS, and the total score was tested for statistical association with views, likes, likes/dislikes-ratio, age, and length of the videos for validation of the IVORY-GS., Results: Overall, 50 parotidectomy videos were identified. Sixty-eight (68%) of the videos showed a superficial parotidectomy. The mean IVORY-GS total score was 24.9 (out of a maximum of 44 points). Video education quality was rated as moderate in 22% and high in 4%. There was a statistically significant correlation between the total score and the number of views (p = 0.03), the total score and the number of likes (p < 0.01), and the total score and the likes/dislikes ratio (p < 0.01). A higher total score was a significant predictor of more likes (p = 0.01) and a higher likes/dislikes ratio (p < 0.01)., Conclusion: Our modification of the IVORY Guidelines is otolaryngology-specific, suitable, and recommended to evaluate parotidectomy videos. To date, most videos are of poor educational quality. Future efforts in otolaryngology surgical video education could focus on the establishment of an online video platform., Level of Evidence: NA Laryngoscope, 133:2631-2637, 2023., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Many locally advanced and metastatic salivary gland carcinomas (SGC) lack therapeutic targets. Enfortumab vedotin, an antibody-drug conjugate binding to Nectin-4, recently gained FDA approval for third-line urothelial carcinoma. Therefore, the aim of this study was to assess the expression of Nectin-4 in primary SGC and corresponding lymph node metastases and to correlate it with clinicopathological data. Immunohistochemical staining for Nectin-4 was performed for patients who had undergone surgery with curative intent for primary SGC of the parotid or submandibular gland in a tertiary referral center between 1990 and 2019. One hundred twenty-two primary SGC and twenty corresponding lymph node metastases were included. Nectin-4 was expressed in 80.3% of primary SGC with a mean Histo(H-)score of 61.2 and in 90.0% of lymph node metastases with a mean H-score of 75.6. A moderate or high Nectin-4 expression was found in 25.9% of salivary duct carcinomas (SaDu) and in 30.7% of adenoid cystic carcinomas (ACC). SaDu patients with a lower T-stage (p = 0.04), no loco-regional lymph node metastases (p = 0.049), no vascular invasion (p = 0.04), and no perineural spread (p = 0.03) showed a significantly higher mean Nectin-4 H-score. There was a statistical tendency towards a more favorable disease-free survival among SaDu patients with a higher Nectin-4 expression (p = 0.09). Nectin-4 is expressed in SGC and therefore represents a potential therapeutic target, especially in entities with a high rate of local recurrence and metastatic spread such as SaDu and ACC., (© 2023. The Author(s).)

Purpose: The aim of this project was to provide an overview of the epidemiology of primary salivary gland carcinomas (SGC) in terms of incidence, distribution of clinicopathological features and survival in one of the largest cancer registries in Europe., Methods: Data were collected from patients with SGC of the major salivary glands registered in the population-based state cancer registry (Landeskrebsregister LKR) in North Rhine-Westphalia (NRW), Germany from 01/01/2009 to 12/31/2018. Age standardization of incidence was performed and relative survival estimates were computed by sex, histological group, age group and T-, N-, and M-stage., Results: A total of 1680 patients were included in this analysis. The most frequent tumor localization was the parotid gland (78%). Adenocarcinoma (not otherwise specified) was the most common tumor entity (18.5%). Most tumors were found in stages T1-T3 (29% T1; 29% T2; 28% T3). The age-standardized incidence rate (ASR) for SGC was 0.65/100,000 and remained stable during the observation period. There was an age-dependent incidence increasing especially from the age 70 years and onwards. The overall 5-year relative survival (RS) for all patients with SGC was 69.2%. RS was 80-95.6% for T1-2 stage tumors, 60.3% for T3, 47.3% for T4 stage, 87.4% for N0 and 51.2% for N1-2, 74.4% for M0 and 44.9% for M1., Conclusion: Age-standardized incidence for SGC has been stable for the observed 10-year period. Smaller tumors and those without lymph node or distant metastases had a better RS than more advanced tumors., (© 2022. The Author(s).)

The extracellular matrix (ECM) is an integral part of the tumor microenvironment of carcinomas. Even though salivary gland carcinomas (SGCs) display a range of tumor cell differentiation and distinct extracellular matrices, their ECM landscape has not been characterized in depth. The ECM composition of 89 SGC primaries, 14 metastases, and 25 normal salivary gland tissues was assessed using deep proteomic profiling. Machine learning algorithms and network analysis were used to detect tumor groups and protein modules that explain specific ECM landscapes. Multimodal in situ studies to validate exploratory findings and to infer a putative cellular origin of ECM components were applied. We revealed two fundamental SGC ECM classes which align with the presence or absence of myoepithelial tumor differentiation. We describe the SGC ECM through three biologically distinct protein modules that are differentially expressed across ECM classes and cell types. The modules have a distinct prognostic impact on different SGC types. Since targeted therapy is rarely available for SGC, we used the proteomic expression profile to identify putative therapeutic targets. In summary, we provide the first extensive inventory of ECM components in SGC, a difficult-to-treat disease that encompasses tumors with distinct cellular differentiation. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Background: Secondary malignancies of the parotid gland frequently have a cutaneous origin and the incidence in central Europe is increasing., Objective: The aim of this review article was to present the epidemiology, (differential) diagnostics and treatment of secondary malignancies of the parotid gland., Material and Methods: A literature search of the current guidelines and evidence was carried out in the web-based databank PubMed., Results: The incidence of secondary malignancies of the parotid gland seems to be increasing in Europe, mainly due to a rising incidence of metastases of cutaneous squamous cell carcinomas. Except for malignant lymphomas, parotidectomy is the treatment of choice in the curative situation. In the absence of clear evidence, in the case of an intact facial nerve lateral or total parotidectomy with ipsilateral neck dissection seems to be indicated, depending on the entity of the secondary malignancy., Conclusion: The differential diagnostics of squamous cell carcinoma (in) of the parotid gland can be complicated. When a squamous cell carcinoma of the parotid gland is diagnosed for the first time, a dermatological full body examination and a detailed medical history should be taken with respect to skin tumors of the head and neck region. In addition to surgical treatment of the parotid gland and neck, adjuvant radiotherapy is usually indicated., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Introduction: Obstructive sleep apnea syndrome (OSAS) is the most common sleep disorder in humans. Although OSAS is clearly related to arterial hypertension, coronary artery disease, and heart failure, it remains unknown through which pathomechanisms OSAS influences cardiovascular health. Recent research has pinpointed long non-coding RNAs (lncRNA) as important molecular mediators of various cardiovascular pathologies. In this study, we have identified the lncRNA MRPL20-AS1 to be affected by OSAS in patients as well as by hypoxia in vitro., Methods and Results: A transcriptomic analysis was performed on peripheral blood from four patients with severe OSAS taken after one night of polygraphic assessment. We found that three lncRNAs were significantly dysregulated, of which MRPL20-AS1 was the most significant. In a larger cohort of 22 OSAS patients, MRPL20-AS1 was inversely correlated with the apnea-hypopnea index (AHI). This indicates that OSAS patients with higher AHI levels and therefore more severe OSAS had lower levels of MRPL20-AS1 in the blood. The results were recapitulated in vitro by subjecting endothelial cells to hypoxia. In these experiments, hypoxia led to a significant downregulation of MRPL20-AS1 in endothelial cells., Conclusion: MRPL20-AS1 may serve as a useful tool to identify patients suffering from severe OSAS and further research should be done to evaluate the therapeutic potential of MRPL20-AS1 as a target to counteract the cardiovascular effects of OSAS., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Novel therapeutic options for the treatment of salivary gland malignancies have emerged due to the improvement and distribution of molecular pathological testing methods and the availability of targeted therapies. Since they are less toxic, these new agents are a valuable alternative to conventional cytotoxic chemotherapy. On the one hand, there are new entity-specific therapies such as NTRK inhibitor therapy for secretory carcinomas and axitinib therapy for adenoid cystic carcinomas. Moreover, cross-entity therapeutics such as antiandrogenic therapy, HER2 inhibition, and PI3K inhibition are also coming to the fore. For metastatic/recurrent salivary gland carcinomas that cannot be treated with targeted therapy, platinum-based chemotherapies continue to be therapy of choice., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Advanced salivary gland carcinomas (SGC) often lack therapeutic options. Agents targeting CD138 have recently shown promising results in clinical trials for multiple myeloma and a preclinical trial for triple-negative breast cancer. Immunohistochemistry for CD138 was performed for all patients who had undergone primary surgery for SGC with curative intent. Findings were validated using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging. Overall, 111 primary SGC and 13 lymph node metastases from salivary duct carcinomas (SaDu) were evaluated. CD138 expression was found in 60% of all SGC with differing expression across entities (p < 0.01). A mean of 25.2% of the tumor cells in mucoepidermoid carcinoma (MuEp) were positive, followed by epithelial-myoepithelial carcinoma (20.9%), acinic cell carcinoma (16.0%), and SaDu (15.2%). High-/intermediate-grade MuEp showed CD138 expression in a mean of 34.8% of tumor cells. For SaDu, lymph node metastases showed CD138 expression in a mean of 31.2% of tumor cells which correlated with CD138 expression in their primaries (p = 0.01; Spearman’s ρ = 0.71). MALDI-MS imaging confirmed the presence of the CD138 protein in SGC. No significant association was found between clinicopathological data, including progression-free survival (p = 0.50) and CD138 expression. CD138 is expressed in the cell membrane of different entities of SGC and SaDu lymph node metastases and therefore represents a potential target for CD138 targeting drugs.

Procollagen 11A1 (COL11A1) is a central component of the extracellular matrix in many carcinomas, which is considered to be mainly produced by cancer associated fibroblasts (CAFs). As COL11A1 expression correlates with adverse prognosis and is implicated in chemoresistance, it is a promising putative target. For the first time, we used RNA in-situ hybridization to systematically identify the cells that produce COL11A1 in the ten most prevalent carcinoma types, lymphomas (n = 275) and corresponding normal tissue (n = 55; panCancer cohort). Moreover, as most salivary gland carcinomas (SGC) display distinct stromal architectures, we also analysed 110 SGC. The corresponding protein formation of COL11A1 was determined by MALDI-TOF-MS-Imaging. We report that colon, breast and salivary duct carcinomas are highly infiltrated by COL11A1 positive CAFs (CAFs COL11A1 ) and might thus be promising candidates for antidesmoplastic or COL11A1-targeted therapies. The amount of CAFs COL11A1 correlated significantly with tumour grade, tumour stage and nodal spread in the panCancer cohort. Significant associations between CAFs COL11A1 and vascular invasion, perineural spread and nodal spread were observed in the SGC cohort. Also, we discovered that tumour cells of intercalated duct derived SGC and CAFs produce COL11A1 in a mutually exclusive manner. Our findings represent a novel mode of extracellular matrix production in carcinomas and could be highly relevant in the future. Our findings elucidate the mode of COL11A1 expression in very different carcinoma types and may aid to categorise tumours in the setting of possible future COL11A1-related therapies., (© 2021. The Author(s).)

Introduction: Obstructive sleep apnea syndrome (OSAS) is associated with an increased cardiovascular risk. The underlying mechanisms are largely unclear. MicroRNAs (miRNAs) are RNAs circulating in the blood that can be released into the bloodstream during hypoxia. In the present study, we investigate if OSAS-induced hypoxia results in a release of miRNAs that may mediate OSAS-associated cardiovascular damage., Methods: Blood was sampled from 23 OSAS patients before and after a polygraphically monitored night. Total circulating RNA was isolated from the plasma and quantified using real-time qPCR. Using a Taqman miRNA array, the levels of 384 different miRNAs were compared between evening and morning after polysomnography. The most highly upregulated miRNA (miRNA-505) and four additionally upregulated miRNAs (miRNA-127, miRNA-133a, miRNA-145, and miRNA-181a) were then quantified in a bigger patient cohort individually., Results: Apnea/Hypopnea-Index (AHI) was evaluated and averaged at 26 per hour on nocturnal polygraphy. In an initial miRNA array, a total of 4 miRNAs were significantly regulated. A significant increase of miRNA-145 was observed in the larger patient cohort. No significant changes in concentration were detected for miRNA-127, miRNA-133a, miRNA-181a, and miRNA-505 in this larger cohort., Conclusion: OSAS results in the nocturnal release of miRNAs into the bloodstream. Our collected data may indicate a hypoxia-induced release of miRNAs into the bloodstream of OSAS-patients. In vitro experiments are needed to confirm the secretion of these miRNAs under hypoxia and evaluate the effect on the cardio vasculature., Competing Interests: The authors have declared that no competing interests exist.

Treatment options for unresectable, recurrent or metastatic salivary gland carcinomas (SGC) are scarce. Trophoblast cell surface antigen 2 (Trop-2) is a transmembrane glycoprotein that is involved in a variety of oncogenic cell signaling pathways. Its potential as a target for the antibody-drug conjugate sacituzumab govitecan has already been demonstrated in different tumor entities. The United States Food and Drug Administration approved this antibody-drug conjugate for the treatment of metastatic triple-negative breast cancer. Here, we aimed to investigate Trop-2 protein expression in different entities of SGCs. We retrospectively reviewed the medical records of all patients that underwent surgery for a primary SGC in a tertiary referral center between 1990 and 2014. Immunohistochemical (IHC) staining for Trop-2 was performed and rated as negative, weak, moderate or high using a semiquantitative score. Additionally, representative cases were analyzed using MALDI-mass spectrometry (MS) imaging to confirm the IHC results. The cohort consisted of 114 tumors of the parotid gland (90.4%) and submandibular gland (9.6%). It mainly included mucoepidermoid, salivary duct and adenoid cystic carcinomas. In IHC samples, 44% showed high, 38% moderate and 10% weak expression rates of Trop-2. MALDI-MS imaging confirmed the presence of Trop-2 protein in 80% of the tested tumor samples. This is the first study to demonstrate that several types of SGC express Trop-2 with variable intensity. Since there are currently few systemic treatment options for advanced SGCs, Trop-2 represents a promising target for further clinical studies, for instance, with sacituzumab govitecan., (© 2021. The Author(s).)

Objective: To assess data regarding round window (RW) visibility and surgical approaches in cochlear implant cases, and to describe and analyze surgical steps relevant for the RW approach in cochlear implantation., Study Design: Prospective clinical study., Methods: A questionnaire was completed by surgeons after each of altogether 110 cochlear implantations. Round window membrane (RWM) visibility was graded according to the St Thomas Hospital (STH) classification., Results: Performing different surgical steps during the preparation of the RW niche, the RWM could be fully exposed (STH Type I) in 87%. A RW approach could be used for electrode insertion in 89% of the adult and 78% of the pediatric cases. The distribution of RW types differed significantly between adults and children. Drilling of the superior bony lip was the surgical step most frequently needed in adult as well as pediatric cases to obtain optimal RW exposure., Conclusion: In children, optimized surgical exposure of the RW niche resulted in only 52% full RWM visibility; whereas in adults, this could be achieved in 87%. The facial nerve (FN) had to be exposed at the level of the posterior tympanotomy in more than 70% of pediatric cases with full RWM visibility; while in adult cases with 100% visibility, such specific exposure was necessary in only 33%. Thus, surgical preparation of the RW niche seems to be more demanding in children than in adults.

Facial nerve paralysis due to the infiltration by a lymphoma is rare and the prognosis remains poor. If perineural spread and meningeosis are suspected, quick interdisciplinary diagnostic work-up is recommended. It should include magnetic resonance imaging, biopsy of the lesion, bone marrow biopsy, and lumbar puncture. Therapy should be initiated immediately., Competing Interests: There was no conflict of interest during the preparation of this article. The patient’s family approved the publication of this article., (© 2020 The Authors. Clinical Case Reports published by John Wiley & Sons Ltd.)

The composition of the extracellular matrix (ECM) plays a pivotal role in tumour initiation, metastasis and therapy resistance. Until now, the ECM composition of salivary gland carcinomas (SGC) has not been studied. We quantitatively analysed the mRNA of 28 ECM-related genes of 34 adenoid cystic (AdCy; n = 11), mucoepidermoid (MuEp; n = 14) and salivary duct carcinomas (SaDu; n = 9). An incremental overexpression of six collagens (including COL11A1 ) and four glycoproteins from MuEp and SaDu suggested a common ECM alteration. Conversely, AdCy and MuEp displayed a distinct overexpression of COL27A1 and LAMB3 , respectively. Nonhierarchical clustering and principal component analysis revealed a more specific pattern for AdCy with low expression of the common gene signature. In situ studies at the RNA and protein level confirmed these results and indicated that, in contrast to MuEp and SaDu, ECM production in AdCy results from tumour cells and not from cancer-associated fibroblasts (CAFs). Our findings reveal different modes of ECM production leading to common and distinct RNA signatures in SGC. Of note, an overexpression of COL27A1 , as in AdCy, has not been linked to any other neoplasm so far. Here, we contribute to the dissection of the ECM composition in SGC and identified a panel of deferentially expressed genes, which could be putative targets for SGC therapy and overcoming therapeutic resistance.

Salivary gland carcinomas (SGCs) are rare and can be subdivided into distinct entities, some of which confer a poor prognosis. As targets for effective systemic therapy are warranted, some studies investigated the role of immune-checkpoint proteins PD-L1 and CTLA-4 in SGC. Our study depicts the expression of lymphocyte activation gene 3 (LAG3) in a test cohort and a larger validation cohort, totaling 139 SGCs. LAG3 is expressed on tumor-infiltrating lymphocytes (TILs), mediates T cell exhaustion and is subject to numerous currently recruiting clinical studies. Overall, one-third of SGCs were infiltrated by LAG3-expressing TILs with a strikingly high concordance between the test cohort and the validation cohort (30% and 28.2%, respectively). In the validation cohort, entity-wise LAG3 expression frequencies were highly variable. The highest rates were observed in salivary duct carcinoma (SDC; 66.7%) and adenocarcinoma not otherwise specified (ANOS; 50.0%). We observed LAG3 expression on effector T cells and in smaller frequencies also on FOXP3- T helper cells and FOXP3+ Tregs. LAG3 expression significantly correlated with advanced nodal metastases, cytotoxic T cell infiltrate and TP53 mutations. In the group of adenoid cystic carcinomas, LAG3 expression was also associated with a shorter event-free survival (EFS). Tumors with TP53 nonsense mutations (TP53 null type) exhibited higher LAG3 frequencies and a shorter EFS compared to TP53 wild type. This is the first report of LAG3 expression in SGC, a promising target for immunotherapy. LAG3 blockage could be distinctly applicable for SDC and ANOS, two SGC types with a particularly poor outcome.

Mucoepidermoid carcinoma is the most common primary salivary gland malignancy and its tumor grading has an important prognostic significance. The 5 year overall survival rate is significantly higher for low grade mucoepidermoid carcinomas than for intermediate grade and high grade mucoepidermoid carcinomas. The translocation of t(11;19)(q21;p13) with the resulting CRTC1-MAML2 transfusion appears to be of prognostic relevance in patients with mucoepidermoid carcinoma. The translocation is detectable in 38-82 % of all mucoepidermoid carcinomas. Study results have shown a significantly better prognosis for patients with fusion-positive mucoepidermoid carcinomas than fusion-negative mucoepidermoid carcinomas. The t(11;19)(q21;p13) translocation can be found more often in low and intermediate grade mucoepidermoid carcinomas than in high grade tumors of the same entity. Moreover, fusion positive mucoepidermoid carcinoma were found more frequently in younger patients, smaller tumors, lower tumor stages and less frequently lymph node and distant metastases. Up to now, the translocation has not been of therapeutic importance. In selected cases, the lack of t(11;19)(q21;p13) translocation might facilitate the decision towards further escalation of therapy. More studies will be necessary to evaluate the individual prognostic and therapeutic value of CRTC1-MAML2 transfusion., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: Sialendocopy is a minimal-invasive technique used for the diagnosis and treatment of salivary gland diseases. The minimal-invasive character of sialendoscopy can be modified by using different surgical techniques. This is why both general and local anaesthesia are applied to perform this procedure and can be of great influence regarding the postoperative pain of those patients. The following study was performed to investigate the level of postoperative pain after sialendoscopy and its pain management., Material and Methods: 103 patients who were treated with a sialendoscopy of the parotid gland or submandibular gland in local anaesthesia between 2013-2015 were included in the study. The postoperative pain level was evaluated at rest and during periods of stress on the day of surgery and the first and second day after surgery. The pain level was analysed according to the numeric rating scale (NRS 0-10), which is used in the QUIPS project (Quality improvement of postoperative pain)., Results: The pain level on the day of surgery was 0,9 ± 1,9 at rest and 0,7 ± 1,4 during periods of stress. On the first postoperative day, pain levels of 1,2 ± 1,8 at rest and 0,9 ± 1,9 during stress were evaluated. On the second day after surgery there was a decrease of pain with a level of 0,75 ± 1,6 at rest and 0,73 ± 1,5 during stress. The analgesic therapy that was mostly used was Metamizol and Ibuprofen. 37,9 % of all patients received analgesic therapy on the day of surgery whereas on the first day after surgery only 26,2 % of all patients and on the second day after surgery only 12,6 % received pain medication., Conclusion: Sialendoscopy of the parotid gland and the submandibular gland is associated with moderate postoperative pain, which can be managed by using non-opioid analgesic therapy., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)