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Background: The impact of timing of PORT initiation for major salivary gland cancers on survival is unknown. We aim to examine the impact of PORT timeliness on overall survival (OS) of patients with major salivary gland cancers. Methods: This was a cross‐sectional analysis using data from the National Cancer Database (2004–2017) and included patients with major salivary gland cancer treated with surgery and PORT. Results: In total, 5701 patients were included (3133 [55%] male, 4644 [82%] white, mean age 59 ± 16 years). For the overall cohort, PORT >6 weeks was not associated with decreased OS (1.00 aHR, 95% CI 0.89–1.11). When specifically examining patients with mucoepidermoid carcinoma, PORT >6 weeks was associated with a decreased OS (1.27 aHR, 95% CI 1.01–1.58). Conclusions: Overall, this analysis did not demonstrate a survival benefit for initiating PORT within 6 weeks for patients with salivary gland malignancies. Subset analysis did support initiating PORT within 6 weeks after resection for patients with mucoepidermoid carcinomas. This was not demonstrated in other major salivary gland cancer histologies. [ABSTRACT FROM AUTHOR]

Comprehensive information on genetic alterations in salivary gland cancer (SGC) is limited. This study aimed to elucidate the genetic and clinical characteristics of patients with SGC using the Center for Cancer Genomics and Advanced Therapeutics (C‐CAT) database, a Japanese national genomic database. We analyzed data of 776 patients with SGC registered in the C‐CAT database between June 1, 2019, and June 30, 2023. Adenoid cystic carcinoma was the most common histologic type, followed by salivary duct carcinoma (SDC) and adenocarcinoma not otherwise specified. Genetic data of 681 patients receiving FoundationOne® CDx were analyzed. We identified specific features of the combination of TP53 and CDKN2A alterations among the histological types. Specific LYN amplification was mainly detected in carcinoma ex pleomorphic adenoma and myoepithelial carcinoma. For SDC, the frequency of ERBB2 and BRAF alterations were higher in cases with metastatic lesions than in those with primary lesions. Although 28.6% patients were offered recommended treatment options, only 6.8% received the recommended treatments. This study highlights the differences in genetic alterations among the histological types of SGC, with comprehensive genomic profiling tests revealing lower drug accessibility. These findings could contribute to the development of personalized treatment for patients with SGC. [ABSTRACT FROM AUTHOR]

Introduction: Secretory carcinoma, previously known as mammary analog secretory carcinoma, is a rare malignancy of salivary glands. It has a diversity of microscopic patterns and is similar to other salivary gland tumors. Case Report: This report presents the case of a 32-year-old female patient with a painless swelling of the upper lip and a history of recent surgery for an immature ovarian teratoma. The microscopic sections revealed a circumscribed neoplasm composed of macrocystic, papillary-cystic, and microcystic patterns with bland vesicular nuclei and vacuolated cytoplasm. Tumoral cells were strongly positive for mammaglobin, SOX10, GATA3, S-100, and vimentin. The diagnosis of salivary gland secretory carcinoma was made. After 22 months, there has been no recurrence. Conclusions: As secretory carcinoma is a relatively new entity, it is necessary to understand its characteristics. Although the overall incidence of second primary cancer in patients with salivary gland cancers is low, the possibility of its presence in such patients should be considered. [ABSTRACT FROM AUTHOR]

Amaç: İnsan sağlığı açısından önemli morbitidite ve mortalite sabebi olan tükrük bezi karsinomlarında (TBK) birçok histopatolojik alt tipi bulunmaktadır ve ayrımları zordur. Farklı alt tipler, tanının karmaşıklığına ek olarak farklı klinik özellikler sergilemektedir. Klinikopatolojik çeşitlilik nedeniyle doğru teşhis ve prognostik belirteçlerin belirlenmesi önemlidir. Heat shock 70 kDa protein 2 (HSPA2) farklı malignitelerde anormal seviyelerde eksprese edildiği belirtilen potansiyel kanseri teşvik eden protein olarak tanımlanmaktadır. TBK’de HSPA2 ekspresyonunu araştıran yeterli çalışma bulunmamaktadır. Bu nedenle çalışmamızda TBK’de HSPA2 ekspresyonununun varlığını ve bunun prognostik önemini belirlemeyi amaçladık.Materyal Metod: Çalışmamıza anabilim dalımızda Ocak 2012-2022 tarihleri arasında TBK tanısı konmuş 44 olgu dahil edildi. Tümöral ve non tümöral alanlarda HSPA2 ekspresyonu derecesi ve bu ekspresyonun prognostik parametreler ile ilişkisi immünhistokimyasal yöntem kullanılarak araştırıldı.Bulgular: Çalışmamızda 44 olgunun tamamında HSPA2 ile boyanma izlendi. Tümörlü ve tümörsüz alanların histoskor değerleri karşılaştırıldığında istatiksel olarak anlamlı bir şekilde tümörlü alanlarda boyanma daha kuvvetliydi (p0.05).Sonuç: Çalışmamızın sonuçları TBK'lerde HSPA2 ekspresyonunun tümör gelişiminde rol oynayabileceğini akla getirmektedir. Ayrıca her ne kadar çoğu prognostik parametre ile anlamlı ilişki tespit edilmese de sağ kalım ile artmış HSPA2 ekspresyonu arasında anlamlı ilişki bulunması TBK’da yüksek HSPA2 ekspresyonunun prognostik belirteç olarak kullanılabileceğini düşündürmektedir.

Abstract Background Salivary gland carcinomas (SGCs) represent various groups of tumors that demonstrate marked diversity in their prognosis owing to different histology and clinical characteristics. One of the poor prognostic indicators is distant metastasis which is considered the major reason for death in SGC patients. Discovering new biomarkers is urgently required to aid in the detection of cancer onset and progression. Cathepsin K (CTSK), the lysosomal cysteine protease has a principal role in cancer invasion and progression through interaction with the tumor microenvironment, degradation of extracellular membrane proteins and destruction of the elastic lamina of blood vessels. In the English literature, little information was present about the role of CTSK in SGCs. The current study aimed to assess the immunohistochemical expression of CTSK in SGCs and correlate its expression to different clinicopathologic parameters. Methods The retrospective study applied to 45 cases of SGCs categorized as high-grade (33 cases) and low-grade SGCs (12 cases) following the criteria of WHO classification (2017) of head and neck tumors. All patients` clinicopathological and follow-up records were retrieved. The following statistical tests were used to study the variance of CTSK expression in SGCs concerning different clinicopathological parameters; Pearson`s Chi-square test, unpaired two-tailed student t-test, One-way ANOVA, and Post Hoc tests. Disease-free survival (DFS) and Overall survival (OS) were calculated and displayed with the Kaplan–Meier strategy and analyzed with the log-rank test. Univariate and multivariate survival analyses were performed with Cox regression. A P-value lesser than 0.05 was considered statistically significant. Results Strong CTSK expression was significantly related to high-grade SGCs (P = 0.000), large infiltrating carcinomas (P = 0.000), presence of nodal (P = 0.041) and distant metastasis (P = 0.009), advanced TNM clinical stage (P = 0.000), the incidence of recurrence (P = 0.009), and reduced DFS (P = 0.006). Distant metastasis was the independent predictor for DFS using Cox regression model. Conclusions CTSK has a great role in cancer progression by triggering many signaling pathways. Its level in cancerous tissue is considered an effective index for predicting the severity and prognosis of cancer. Therefore, we indicate its utility as a prognostic tool and therapeutic target for cancer treatment. Trial registration Retrospectively registered.

Podoplanin (D2-40) is a lymphatic endothelial marker that is considered as a specific marker for lymphatic endothelial cells and lymphangiogenesis in salivary gland carcinomas (SGCs). Aim: the present study aimed to investigate the immunohistochemical expression of podoplanin in SGCs and to correlate its expression with the clinicopathological parameters and patients’ survival. Forty-nine SGC cases were electronically selected. Demographic, clinical, laboratory, and survival data were reviewed and tabulated. Immunohistochemistry was performed using antipodoplanin. Cases were divided into low and high expression based on a scoring system. A score of 0 and 1 was considered low expression, while > 1 was considered high expression. Podoplanin high expression was seen in 46.9% of cases, and 53.1% of cases showed low expression. Significant statistical associations were seen between podoplanin expression and tumour grade ( p ≤ 0.001), tumour-nodal- metastasis (TNM) stage (p ≤ 0.001), tumour size (p ≤ 0.001), nodal metastasis (p ≤ 0.001), tumour type (p = 0.03), prognosis (p ≤ 0.001), and mortality (p ≤ 0.001). The overall survival and progression-free survival differed significantly in cases with high and low expression (p ≤ 0.001). Podoplanin overexpression might be a significant prognostic indicator for patients with SGCs, implicating that it is a potential therapeutic target to improve survival in these cancer patients.

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. [ABSTRACT FROM AUTHOR]

Background: Salivary gland carcinomas (SGCs) represent various groups of tumors that demonstrate marked diversity in their prognosis owing to different histology and clinical characteristics. One of the poor prognostic indicators is distant metastasis which is considered the major reason for death in SGC patients. Discovering new biomarkers is urgently required to aid in the detection of cancer onset and progression. Cathepsin K (CTSK), the lysosomal cysteine protease has a principal role in cancer invasion and progression through interaction with the tumor microenvironment, degradation of extracellular membrane proteins and destruction of the elastic lamina of blood vessels. In the English literature, little information was present about the role of CTSK in SGCs. The current study aimed to assess the immunohistochemical expression of CTSK in SGCs and correlate its expression to different clinicopathologic parameters. Methods: The retrospective study applied to 45 cases of SGCs categorized as high-grade (33 cases) and low-grade SGCs (12 cases) following the criteria of WHO classification (2017) of head and neck tumors. All patients' clinicopathological and follow-up records were retrieved. The following statistical tests were used to study the variance of CTSK expression in SGCs concerning different clinicopathological parameters; Pearson's Chi-square test, unpaired two-tailed student t-test, One-way ANOVA, and Post Hoc tests. Disease-free survival (DFS) and Overall survival (OS) were calculated and displayed with the Kaplan–Meier strategy and analyzed with the log-rank test. Univariate and multivariate survival analyses were performed with Cox regression. A P-value lesser than 0.05 was considered statistically significant. Results: Strong CTSK expression was significantly related to high-grade SGCs (P = 0.000), large infiltrating carcinomas (P = 0.000), presence of nodal (P = 0.041) and distant metastasis (P = 0.009), advanced TNM clinical stage (P = 0.000), the incidence of recurrence (P = 0.009), and reduced DFS (P = 0.006). Distant metastasis was the independent predictor for DFS using Cox regression model. Conclusions: CTSK has a great role in cancer progression by triggering many signaling pathways. Its level in cancerous tissue is considered an effective index for predicting the severity and prognosis of cancer. Therefore, we indicate its utility as a prognostic tool and therapeutic target for cancer treatment. Trial registration: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Podoplanin (D2-40) is a lymphatic endothelial marker that is considered as a specific marker for lymphatic endothelial cells and lymphangiogenesis in salivary gland carcinomas (SGCs). Aim: the present study aimed to investigate the immunohistochemical expression of podoplanin in SGCs and to correlate its expression with the clinicopathological parameters and patients' survival. Forty-nine SGC cases were electronically selected. Demographic, clinical, laboratory, and survival data were reviewed and tabulated. Immunohistochemistry was performed using antipodoplanin. Cases were divided into low and high expression based on a scoring system. A score of 0 and 1 was considered low expression, while > 1 was considered high expression. Podoplanin high expression was seen in 46.9% of cases, and 53.1% of cases showed low expression. Significant statistical associations were seen between podoplanin expression and tumour grade (p = 0.001), tumour-nodal-metastasis (TNM) stage (p = 0.001), tumour size (p = 0.001), nodal metastasis (p = 0.001), tumour type (p = 0.03), prognosis (p = 0.001), and mortality (p = 0.001). The overall survival and progression-free survival differed significantly in cases with high and low expression (p = 0.001). Podoplanin overexpression might be a significant prognostic indicator for patients with SGCs, implicating that it is a potential therapeutic target to improve survival in these cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The correct diagnosis of different salivary gland carcinomas is important for a prognosis. This diagnosis is imprecise if it is based only on clinical symptoms and histological methods. Mass spectrometry imaging can provide information about the molecular composition of sample tissues. Using a deep-learning method, we analyzed the mass spectrometry imaging data of 25 patients. Using this workflow we could accurately predict the tumor type in each patient sample. Salivary gland carcinomas (SGC) are a heterogeneous group of tumors. The prognosis varies strongly according to its type, and even the distinction between benign and malign tumor is challenging. Adenoid cystic carcinoma (AdCy) is one subgroup of SGCs that is prone to late metastasis. This makes accurate tumor subtyping an important task. Matrix-assisted laser desorption/ionization (MALDI) imaging is a label-free technique capable of providing spatially resolved information about the abundance of biomolecules according to their mass-to-charge ratio. We analyzed tissue micro arrays (TMAs) of 25 patients (including six different SGC subtypes and a healthy control group of six patients) with high mass resolution MALDI imaging using a 12-Tesla magnetic resonance mass spectrometer. The high mass resolution allowed us to accurately detect single masses, with strong contributions to each class prediction. To address the added complexity created by the high mass resolution and multiple classes, we propose a deep-learning model. We showed that our deep-learning model provides a per-class classification accuracy of greater than 80% with little preprocessing. Based on this classification, we employed methods of explainable artificial intelligence (AI) to gain further insights into the spectrometric features of AdCys. [ABSTRACT FROM AUTHOR]

Fatty acid synthase (FASN) expression is closely related to cancer progression, in particular, tumor aggressiveness and poor prognosis. This study aimed to analyse the expression of FASN in carcinomas of the salivary glands and correlate it with Ki-67 expression. We analysed by immunohistochemistry the expression of FASN and Ki‐67 on tissue sections from 7 cases of adenocarcinoma, not otherwise specified (AdNOS), 6 cases of polymorphous adenocarcinoma (PAC), 16 cases of acinic cell carcinoma (AcCC), 19 cases of adenoid cystic carcinoma (AdCC), 15 cases of epithelial-myoepithelial carcinoma (EMC); 10 cases of secretory carcinoma (SC), 13 cases of mucoepidermoid carcinoma (MEC), 10 cases of salivary duct carcinoma (SDC) and 7 cases of myoepithelial carcinoma (MC). These carcinomas were classified into aggressive and indolent regarding their biological behaviour. Additionally, MEC and AdCC were also classified according to the histological grade. High expression of FASN was found in SDC (100%), SC (100%), AcCC (68.7%) and AdNOS (57.2%). No association was found between FASN and Ki-67 expression. Aggressive carcinomas showed a higher rate of Ki-67 proliferation (p < 0.001) and greater expression of FASN when compared to indolent carcinomas (p < 0.05). With regards to carcinomas categorized as indolent, FASN expression was much higher in the lesions that presented cell differentiation (SC and AcCC). Also, FASN expression was significantly higher in high-grade AdCC and MEC when compared to low-grade tumors (p < 0.05). We concluded that FASN expression was correlated to tumor aggressiveness and cellular differentiation in salivary gland carcinomas. [ABSTRACT FROM AUTHOR]

B7-H4 (VTCN1), a member of the B7 family, is overexpressed in several types of cancer. Here we investigated the pattern of expression of B7-H4 in salivary gland carcinomas (SGC) and assessed its potential as a prognostic marker and therapeutic target. Immunohistochemistry (IHC) analyses were performed in a cohort of 340 patient tumors, composed of 124 adenoid cystic carcinomas (ACC), 107 salivary duct carcinomas (SDC), 64 acinic cell carcinomas, 36 mucoepidermoid carcinomas (MEC), 9 secretory carcinomas (SC), as well as 20 normal salivary glands (controls). B7-H4 expression was scored and categorized into negative (<5% expression of any intensity), low (5%-70% expression of any intensity or >70% with weak intensity), or high (>70% moderate or strong diffuse intensity). The associations between B7-H4 expression and clinicopathologic characteristics, as well as overall survival, were assessed. Among all tumors, B7-H4 expression was more prevalent in ACC (94%) compared with those of SC (67%), MEC (44%), SDC (32%), and acinic cell carcinomas (0%). Normal salivary gland tissue did not express B7-H4. High expression of B7-H4 was found exclusively in ACC (27%), SDC (11%), and MEC (8%). In SDC, B7-H4 expression was associated with female gender (P = .002) and lack of androgen receptor expression (P = .012). In ACC, B7-H4 expression was significantly associated with solid histology (P < .0001) and minor salivary gland primary (P = .02). High B7-H4 expression was associated with a poorer prognosis in ACC, regardless of clinical stage and histologic subtype. B7-H4 expression was not prognostic in the non-ACC SGC evaluated. Our comparative study revealed distinct patterns of B7-H4 expression according to SGC histology, which has potential therapeutic implications. B7-H4 expression was particularly high in solid ACC and was an independent prognostic marker in this disease but not in the other SGC assessed., (Copyright © 2023 United States & Canadian Academy of Pathology. Published by Elsevier Inc. All rights reserved.)

Mammary analogue secretory carcinoma (MASC) is a newly defined entity among salivary gland malignancies which has just been established in the 4th edition of the WHO classification of head and neck tumors. MASC (synonym: secretory carcinoma) are characterized by a specific rearangement of the ETV6 gene locus. Here, we present a series of 3 MASC cases including clinical data with follow-up for up to 26 months. All tumours immunhistochemically displayed strong positivity for cytokeratin 7, and mammaglobin, focal positivity for S100, cytokeratin 5/6 and muc-4. In contrast, immunhistochemical stainings against cytokeratin 14, hormon receptors, Her2/neu, androgen receptor and prostate-specific antigen were consistently negative. FISH analysis showed translocation of the ETV6 gene locus in the majority of tumour cell nuclei. During clinical follow-up, no local relapse or metastasis was detected. As these carcinomas are clinically and radiologically indistinguishable from other salivary gland tumours and as therapeutic approaches and prognosis might differ, we need to be able to diagnose MASC correctly.

Mammary analogue secretory carcinoma (MASC) is a newly defined entity among salivary gland malignancies which has just been established in the 4th edition of the WHO classification of head and neck tumors. MASC (synonym: secretory carcinoma) are characterized by a specific rearangement of the ETV6 gene locus. Here, we present a series of 3 MASC cases including clinical data with follow-up for up to 26 months. All tumours immunhistochemically displayed strong positivity for cytokeratin 7, and mammaglobin, focal positivity for S100, cytokeratin 5/6 and muc-4. In contrast, immunhistochemical stainings against cytokeratin 14, hormon receptors, Her2/neu, androgen receptor and prostate-specific antigen were consistently negative. FISH analysis showed translocation of the ETV6 gene locus in the majority of tumour cell nuclei. During clinical follow-up, no local relapse or metastasis was detected. As these carcinomas are clinically and radiologically indistinguishable from other salivary gland tumours and as therapeutic approaches and prognosis might differ, we need to be able to diagnose MASC correctly. [ABSTRACT FROM AUTHOR]

Aims Cancer/testis antigens ( CTAs) are detected in cancer cells but not in healthy normal tissues, with the exception of gametogenic tissues. CTAs are highly immunogenic proteins, and thus represent ideal targets for cytotoxic T-lymphocyte-mediated specific immune therapy. The aim of this study was to screen CTA expression in various types of salivary gland carcinoma and to clarify clinicopathological significance of MAGE-A and NY- ESO-1 expression in adenoid cystic carcinomas (AdCCs) of the salivary gland, which is one of the most common salivary gland carcinomas, and usually has a fatal outcome. Methods and results We used immunohistochemistry to examine the expression of four CTAs ( MAGE-A, NY- ESO-1, CT7, and GAGE7) in various types of salivary gland carcinoma ( n = 95). When carcinoma cases were divided into low-grade and intermediate/high-grade types, NY- ESO-1 and CT7 were expressed more frequently in intermediate/high-grade carcinomas. We then focused on MAGE-A and NY- ESO-1 expression in a large cohort of adenoid cystic carcinomas (Ad CCs) ( n = 46). MAGE-A and NY- ESO-1 were frequently expressed in Ad CC; specifically, MAGE-A was expressed in >60% of the Ad CC cases. MAGE-A expression and tumour site (minor salivary gland) were identified as independent risk factors for locoregional tumour recurrence. Conclusions These findings suggest that CTAs may be expressed in a variety of salivary gland carcinomas, especially in those with higher histological grades. In addition, MAGE-A, which is frequently expressed in Ad CC cases, may be a useful prognostic factor for poorer locoregional recurrence-free survival. [ABSTRACT FROM AUTHOR]

Objectives: To develop and characterize in vitro salivary duct carcinoma as a surrogate for functional studies.Materials and Methods: Cells were dispersed from tumor tissue fragments under sterile conditions in RPMI media. Disassociated cells were cultivated, immortalized with hTERT and propagated for more than 100 passages. Morphologic, linage, cytogenetic and genomic analyses were performed on different passages of cell line and primary tumor. Soft agar growth was performed.Results: Analysis of cytomorphologic features, growth characteristics and lineage specific markers expression confirmed the epithelial derivation and the neoplastic nature of the cell line. DNA STRs analysis showed identical match of both cell line and primary tumor. Cultivated cells expressed Androgen Receptor (AR), PTEN, and EFGR proteins and the AR-V7 isoform transcript. Comparative exome-sequencing identified common mutated genes in both cell line and primary tumor. In-vitro colony formation of late passages is established.Conclusion: We report the development of the first human salivary duct carcinoma cell line (MDA-SDC-04) that retains critical biological and genomic features of the donor tumor. [ABSTRACT FROM AUTHOR]

Salivary gland carcinomas of the larynx are uncommon. Adenoid cystic carcinoma is the most prevalent type of salivary gland carcinoma in this region, although other histologies such as mucoepidermoid carcinoma and adenocarcinomas have been reported. These tumors may present with advanced-stage due to nonspecific symptoms and their relatively slow-growing nature. The index of suspicion for a non-squamous cell carcinoma entity should be high when a submucosal mass is present. An accurate diagnosis is mandatory due to the impact each biologic entity has on treatment and outcome. Data concerning treatment and outcome are scarce, but primary surgery with utmost focus on free surgical margins is the treatment of choice. The role of adjuvant radiotherapy has not been well defined, although there is an agreement that it should be considered in advanced-stage or high-grade disease. This review considers only the most common malignant salivary neoplasms of the larynx with a focus on clinical management of these tumors. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To analyze clinical presentations, treatment modalities, and evolution of pediatric cases of salivary gland carcinomas to standardize care for these rare diseases.Study Design: Multicentric, retrospective study.Methods: We included in this retrospective study all children and adolescents (aged ≤18 years) treated from 1992 to 2012 in six pediatric centers in Paris, France. Pathological tumor specimens of these cases were reviewed.Results: Forty-three children were included (sex ratio male/female = 19/24, median age = 13 years). The parotid gland was the most common (37 cases) location for tumors. Histological subtypes were mucoepidermoid carcinomas (n = 20), acinic cell carcinomas (n = 14), and other (n = 9). Initial fine-needle aspiration was performed in 15 cases (33%), and was concordant to final diagnosis in three cases (20%). Primary surgery was performed in 42 patients, leading to a complete microscopic resection in 80%. Associated lymph node dissection was performed in 28 patients (homolateral: 27, bilateral: 1) and showed lymph node metastases in only two patients. One patient had distant metastases. Adjuvant irradiation was delivered to 11 patients (median: 60 Gy; range: 50-65) and chemotherapy in five cases. After a median follow-up of 5 years, six tumors relapsed, but no deaths occurred.Conclusions: Childhood salivary gland carcinomas have a good prognosis despite possible recurrences. Treatment is mainly based on surgery, with simultaneous node dissection in cases of clinical or radiologic node enlargement. Radiation therapy seems to be restricted to inoperable high-grade tumors or after recurrence.Level Of Evidence: 4 Laryngoscope, 127:140-147, 2017. [ABSTRACT FROM AUTHOR]

Primary salivary gland carcinomas are extremely rare neoplastic lesions of the larynx. These tumors arise from the subepithelial minor salivary glands that are found widespread in larynx. There is not an agreement about the treatment procedure of such rare tumors and no report is present in the literature of which series is large enough to determine the prognosis. Reviewing the literature, we present two cases, an adenocarcinoma and an adenoid cystic carcinoma of the larynx, with their diagnosis, treatment approaches and prognostic outcomes in order to contribute to the literature.

Malignant salivary gland tumors are rare and exhibit a broad spectrum of phenotypic heterogeneity. The objective of this study was to investigate prognostic factors in patients with salivary gland carcinomas and review the results in light of other reports. We retrospectively reviewed 40 patients with primary salivary gland carcinomas who were diagnosed and treated at our institution between 1991 and 2014. Of the 40 tumors, 19 (47.5%) were mucoepidermoid carcinomas, 11 (27.5%) were adenoid cystic carcinomas, 7 (17.5%) were acinic cell carcinomas, 2 (5.0%) were myoepithelial carcinomas and 1 (2.5%) was a squamous cell carcinoma. Clinically positive lymph nodes were present in 4 patients (10.0%). As regards clinical stage, 15 cases (37.5%) were stage I, 13 (32.5%) were stage II, 1 (2.5%) was stage III and 11 (27.5%) were stage IVA. The majority of the patients (97.5%) were treated with surgery, of whom 25 (62.5%) received surgery alone and 14 (35.0%) underwent surgery in combination with chemotherapy or chemotherapy and radiotherapy. The median follow-up time for all the patients was 48 months. The disease-specific survival rate at 5 years was 87.1%. We identified a significant correlation between poor survival rate and histological grade (intermediate/high), tumor size (T3/T4), lymph node metastasis (node-positive) and clinical stage (III/IV) using the Kaplan-Meier method (P<0.05 for each). In addition, the Cox proportional hazards regression analysis confirmed that lymph node metastasis and tumor size were independent prognostic factors for disease-specific survival (hazard ratio = 18.7 and 15.1, respectively; P=0.023 and 0.037, respectively). Furthermore, tumor size was found to be a predictive factor regarding recurrence in the multivariate logistic regression analysis (odds ratio = 8.35; P=0.025). Our results suggest that lymph node metastasis and tumor size are significant prognostic factors for patients with salivary gland carcinomas. [ABSTRACT FROM AUTHOR]

Background We compared clinical outcomes between patients with salivary gland carcinomas preoperatively misdiagnosed as benign lesion and properly diagnosed as malignant lesion. Methods The outcomes were compared between patients with benign lesion and malignant lesion (44 each) on preoperative fine-needle aspiration cytology diagnosis who underwent conservative or radical surgery. Results Five-year lesion-free survival (DFS) rates were 86.8% for benign lesion and 76.3% for malignant lesion ( p = .128). Surgical extent did not significantly affect locoregional recurrence and DFS ( p = .360). Univariate analysis showed that sublingual gland tumor, positive resection margin, and extraparenchymal extension (EPE) were significantly associated with DFS ( p < .05 each). On multivariate analysis, EPE remained an independent variable ( p = .047, hazard ratio = 6.621, 95% confidence interval = 1.393-31.474). Conclusions The clinical outcomes of patients with salivary gland carcinomas misdiagnosed as benign are relatively favorable. Conservative surgery may be sufficient for patients with low-grade and T1-2 salivary gland carcinomas. © 2013 Wiley Periodicals, Inc. Head Neck 35: 1764-1770, 2013 [ABSTRACT FROM AUTHOR]

Introduction: Salivary gland carcinomas are rare tumours of heterogeneous morphology that require distinctive surgical and adjuvant therapy. Methods: Relevant studies were electronically searched in PubMed and reviewed for innovative and important information. Results: Recent insights in genetic alterations like chromosomal aberrations, expression of receptor tyrosine kinases, malfunction of tumour suppressor genes or DNA promoter methylations increased the knowledge about aetiology and pathogenesis. New histological subtypes are recognised, and a three-tiered grading system seems reasonable. Ultrasound remains the basic diagnostic imaging procedure. New developments comprise the diffusion-weighed magnetic resonance imaging, while fluorodeoxyglucose positron emission tomography/computed tomography shows good diagnostic accuracy in detecting distant metastases and local recurrence. Fine-needle aspiration cytology helps in differentiating a neoplasia from a non-neoplastic lesion while being unreliable in recognising malignancy. In contrast, additional core needle biopsy and/or intraoperative frozen section diagnosis increase the accuracy in diagnosing a malignant lesion. Conservative parotid surgery with nerve monitoring remains state-of-the-art. Free flaps or musculoaponeurotic flaps are proposed for prevention of Frey's syndrome. As parotid cancer often shows skip metastases, complete ipsilateral neck dissection (level I-V) is indicated particularly in high-grade lesions. Adjuvant radio(chemo)therapy increases local tumour control, whereas overall survival is not necessarily improved. Current results of systemic chemotherapy or targeted therapy in advanced tumour stages are disappointing. Conclusion: Despite several developments, salivary gland carcinomas remain a heterogeneous group of tumours challenging both pathologists and clinicians. [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2010) 40: 451–455 Background:  In several cancer types, osteopontin (OPN) expression has been correlated with tumor progression and prognosis. Two earlier studies have examined OPN expression in salivary gland carcinomas with contradictory results. Methods:  One hundred and seventy‐five patients with a primary salivary gland carcinoma diagnosed from January 1, 1990 to December 31, 2005 were identified in the local pathology register, Odense University Hospital. Criteria as documented by Allred et al. were used to assess OPN immunostaining that was performed on surgical specimens. Results:  Osteopontin was expressed in all salivary gland carcinomas. Adenoid cystic carcinomas had the highest mean sum score (7.3) and a significantly higher proportion of carcinomas with high OPN sum score than both mucoepidermoid carcinoma and acinic cell carcinoma. Correlation of OPN expression with known prognostic factors in salivary gland carcinomas was insignificant. Conclusions:  Salivary gland carcinomas express OPN. The expression does not correlate with known prognostic factors. [ABSTRACT FROM AUTHOR]

Summary: Salivary gland carcinomas (SGC) are rare cancers with poor prognosis and limited response to conventional chemotherapy. New strategies based on molecular targeted therapy are needed and the EGFR signaling cascade is considered a possible key pathway for therapeutic molecules. We have analyzed 65 SGC of the main histopathological types for the expression of EGFR and and the mutation status of its downstream effector KRAS. EGFR overexpression (+2, +3) has been identified by immunohistochemistry in 75.4%. KRAS mutation analysis was performed by direct genomic sequencing and revealed a KRAS wildtype in 98.5% except of one adenoid cystic carcinoma with a GGT–GAT transition at codon 12 (Gly12Asp). EGFR overexpression and KRAS wildtype are prerequisites for a successful anti-EGFR therapy. The results of this study plead in favor of further therapeutic trials with EGFR-targeting monoclonal antibodies in SGC. [Copyright &y& Elsevier]

Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the major and minor salivary glands. Surgical resection is the only curative treatment and there is no effective post-operative therapy for MEC. The present study reports an Institutional Review Board-approved case of a 45-year-old Japanese female diagnosed with low-grade MEC in the hard palate. Radical resection, supraomohyoid neck dissection and antero-lateral thigh flap reconstruction was performed. A MEC cell line was then established from the resected tumor tissue. Short tandem repeat profiling confirmed the origin and authenticity of the cell line, that harbors a CRTC1-MAML2 translocation, which is frequently observed in MEC. Amphiregulin (AREG), identified as one of the targets of the CRTC1-MAML2 fusion gene, was expressed in the cell line. The AREG receptor, epidermal growth factor receptor (EGFR) was also highly phosphorylated. The results predicted that AREG-EGFR signaling, which is required for tumor growth and survival, might be activated in the cell line in a cell-autonomous manner. As AREG expression is associated with EGFR-targeted drug resistance, this cell line might assist with the identification of novel strategies for MEC treatment. [ABSTRACT FROM AUTHOR]

Background. The purpose of this study was to examine the association between 4 Fas single nucleotide polymorphisms (SNPs) and risk of differentiated thyroid carcinoma (DTC) and salivary gland carcinoma (SGC). Methods. We conducted a case-control study including 279 DTC cases, 165 benign thyroid disease (BTD) cases, 154 SGC cases, 61 benign salivary gland disease (BSGD) cases, and 510 controls. Results. The A744G SNP genotype distribution was significantly different between subjects with SGC or BSGD and controls, while that of the A18272G SNP was significantly different between subjects with DTC or SGC and controls. Risk of SGC was significantly elevated for the 22628 heterozygous CT genotype (odds ratio [OR] = 1.5, p = .050), and risk of BSGD was elevated for the 22628 homozygous TT genotype (OR = 2.9, p = .023). Conclusion. Fas C22628T SNP may be associated with risk of SGC and BSGD, but none of the investigated Fas SNPs was associated with risk of DTC. © 2007 Wiley Periodicals, Inc. Head Neck 2008 [ABSTRACT FROM AUTHOR]

Objectives: Our aim is to investigate the expression of kit protein (KIT) and epidermal growth factor receptor (EGFR) in parotid carcinomas in order to correlate the expression to histology and prognosis. Further we want to perform mutation analysis of KIT-positive adenoid cystic carcinomas. Patients and Methods: Formalin-fixed paraffin-embedded sections from 73 patients with parotid gland carcinomas were used for the study. The sections were stained with both KIT and EGFR polyclonal antibodies. Twelve KIT-positive adenoid cystic carcinomas were examined for c-kit mutation in codon 816. Results: Of all carcinomas 25% were KIT-positive and 79% were EGFR-positive. Ninety-two percentage of the adenoid cystic carcinomas were KIT-positive. None of the adenoid cystic carcinomas had mutations in codon 816 of the c-kit gene. Conclusion: Neither KIT- nor EGFR-expression seem to harbour significant prognostic information. Adenoid cystic carcinomas express KIT, but no mutations in codon 816 of the c-kit gene were identified. [ABSTRACT FROM AUTHOR]

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P53 protein and vascular endothelial growth factor (VEGF) expression, and mean intratumoral microvessel density (IMVD) were studied by immunohistochemistry in 31 salivary gland carcinomas, consisting of 11 adenoid cystic carcinomas (AdCCs), 10 mucoepidermoid carcinomas (MECs), 7 acinic cell carcinomas (AcCCs), and 3 squamous cell carcinomas (SCCs). Cases with p53 protein in more than 20% of tumor cells were detected in one AdCC, four MECs, one AcCC, and two SCCs. Both frequency of p53 and VEGF expression, and mean IMVD, were higher in the MECs and SCCs than in the AdCCs and AcCCs. Similarly, both VEGF expression and mean IMVD were significantly higher (P<0.05) in the eight p53-positive tumors than in the 23 negative tumors. Six cases with survival periods less than 5 years showed significantly higher frequency of p53 and VEGF expression and of mean IMVD than those with longer survival periods. These results indicate that p53 expression might partly correlate with VEGF expression and mean IMVD, and be a factor in the survival of patients with salivary gland carcinomas. [ABSTRACT FROM AUTHOR]

Abstract Background Astrocyte elevated gene-1 (AEG-1) is associated with tumorigenesis and progression in diverse human cancers. The present study was aimed to investigate the clinical and prognostic significance of AEG-1 in salivary gland carcinomas (SGC). Methods Real-time PCR and western blot analyses were employed to examine AEG-1 expression in two normal salivary gland tissues, eight SGC tissues of various clinical stages, and five pairs of primary SGC and adjacent salivary gland tissues from the same patient. Immunohistochemistry (IHC) was performed to examine AEG-1 protein expression in paraffin-embedded tissues from 141 SGC patients. Statistical analyses was applies to evaluate the diagnostic value and associations of AEG-1 expression with clinical parameters. Results AEG-1 expression was evidently up-regulated in SGC tissues compared with that in the normal salivary gland tissues and in matched adjacent salivary gland tissues. AEG-1 protein level was positively correlated with clinical stage (P < 0.001), T classification (P = 0.008), N classification (P = 0.008) and M classifications (P = 0.006). Patients with higher AEG-1 expression had shorter overall survival time, whereas those with lower tumor AEG-1 expression had longer survival time. Conclusions Our results suggest that AEG-1 expression is associated with SGC progression and may represent a novel and valuable predictor for prognostic evaluation of SGC patients.

Abstract Background The pathogenesis of salivary gland carcinomas is very complex and prognostic markers are difficult to find in these carcinomas of which the different subtypes have varying malignant potential. The study was conducted to examine the cellular distribution of maspin and MCM2 in salivary gland carcinomas and their value to predict lymph node metastasis. Materials and methods Fifty three paraffin blocks of different lesions (15 muco-epidermoid carcinoma, 14 adenoid cystic carcinoma, 3 epi-myoepithelial carcinoma, 5 salivary duct carcinoma, 5 malignant pleomorphic adenoma, 6 polymorphous low grade adenocarcinoma and 5 acinic cell carcinoma) were prepared for immunohistochemical staining with maspin and MCM2 antibodies. ANOVA and Pearson correlation tests were used for the statistical analysis of the results. Results All salivary gland carcinomas express maspin and MCM2 with variable cellular localization. There was a significant difference in the expression of each antibody between mucoepidermoid carcinoma, adenoid cystic carcinoma and polymorphous low grade adenocarcinoma. No association was found between examined markers and lymph node metastasis. Conclusions Salivary gland carcinomas express maspin and MCM2 with variable levels and cellular localization, consisting important markers of biological behavior in these tumors. The level of MCM2 expression can be used in the differential diagnosis of adenoid cystic carcinoma and polymorphous low grade adenocarcinoma. Further study with large sample size is recommended to assess their value in prediction of lymph node metastasis.

Podoplanin (D2-40) is a lymphatic endothelial marker that is considered as a specific marker for lymphatic endothelial cells and lymphangiogenesis in salivary gland carcinomas (SGCs). Aim: the present study aimed to investigate the immunohistochemical expression of podoplanin in SGCs and to correlate its expression with the clinicopathological parameters and patients' survival. Forty-nine SGC cases were electronically selected. Demographic, clinical, laboratory, and survival data were reviewed and tabulated. Immunohistochemistry was performed using antipodoplanin. Cases were divided into low and high expression based on a scoring system. A score of 0 and 1 was considered low expression, while > 1 was considered high expression. Podoplanin high expression was seen in 46.9% of cases, and 53.1% of cases showed low expression. Significant statistical associations were seen between podoplanin expression and tumour grade ( p ≤ 0.001), tumour-nodal- metastasis (TNM) stage (p ≤ 0.001), tumour size (p ≤ 0.001), nodal metastasis (p ≤ 0.001), tumour type (p = 0.03), prognosis (p ≤ 0.001), and mortality (p ≤ 0.001). The overall survival and progression-free survival differed significantly in cases with high and low expression (p ≤ 0.001). Podoplanin overexpression might be a significant prognostic indicator for patients with SGCs, implicating that it is a potential therapeutic target to improve survival in these cancer patients.

Activating mutations within the epidermal growth factor (EGFR) tyrosine kinase domain identify non-small cell lung cancer patients with improved clinical response to tyrosine kinase inhibitor therapy. Recently, we identified two EGFR mutations in a cohort of 25 salivary gland carcinomas (SGCs) by screening the tumour samples for the both most common hotspot mutations in exons 19 and 21 by allele-specific PCR. Here, we present a comprehensive sequencing analysis of the entire critical EGFR tyrosine kinase domain in 65 SGC of the main histopathological types. We found EGFR mutations in the tyrosine kinase domain to be a rare event in SGCs. No additional mutations other than the two known exon 19 deletions (c.2235_2249del15) in a mucoepidermoid carcinoma and an adenoid cystic carcinoma have been detected. Other putative predictive markers for EGFR-targeted therapy in SGCs might be relevant and should be investigated. [ABSTRACT FROM AUTHOR]

In recent years, increased molecular testing and improved immunohistochemical panels have facilitated more specific classification of salivary gland carcinomas, leading to recognition of several novel tumor types and unique histologic variants. Sclerosing microcystic adenocarcinoma, microsecretory adenocarcinoma, and secretory myoepithelial carcinoma are three such recently described entities that demonstrate low-grade cytology, production of prominent secretory material, and variable amounts of sclerotic stroma. This review provides a practical overview of these important and overlapping emerging entities in salivary gland pathology with a focus on distinctive histologic features and helpful ancillary studies that differentiate them from a wide range of familiar morphologic mimics., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Malignant salivary gland tumors are rare and exhibit a broad spectrum of phenotypic heterogeneity. The objective of this study was to investigate prognostic factors in patients with salivary gland carcinomas and review the results in light of other reports. We retrospectively reviewed 40 patients with primary salivary gland carcinomas who were diagnosed and treated at our institution between 1991 and 2014. Of the 40 tumors, 19 (47.5%) were mucoepidermoid carcinomas, 11 (27.5%) were adenoid cystic carcinomas, 7 (17.5%) were acinic cell carcinomas, 2 (5.0%) were myoepithelial carcinomas and 1 (2.5%) was a squamous cell carcinoma. Clinically positive lymph nodes were present in 4 patients (10.0%). As regards clinical stage, 15 cases (37.5%) were stage I, 13 (32.5%) were stage II, 1 (2.5%) was stage III and 11 (27.5%) were stage IVA. The majority of the patients (97.5%) were treated with surgery, of whom 25 (62.5%) received surgery alone and 14 (35.0%) underwent surgery in combination with chemotherapy or chemotherapy and radiotherapy. The median follow-up time for all the patients was 48 months. The disease-specific survival rate at 5 years was 87.1%. We identified a significant correlation between poor survival rate and histological grade (intermediate/high), tumor size (T3/T4), lymph node metastasis (node-positive) and clinical stage (III/IV) using the Kaplan-Meier method (P<0.05 for each). In addition, the Cox proportional hazards regression analysis confirmed that lymph node metastasis and tumor size were independent prognostic factors for disease-specific survival (hazard ratio = 18.7 and 15.1, respectively; P=0.023 and 0.037, respectively). Furthermore, tumor size was found to be a predictive factor regarding recurrence in the multivariate logistic regression analysis (odds ratio = 8.35; P=0.025). Our results suggest that lymph node metastasis and tumor size are significant prognostic factors for patients with salivary gland carcinomas.

Unlabelled: Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from (18)F-FDG PET/CT are emerging prognostic biomarkers in various human cancers. This study examined the prognostic value of these metabolic tumor parameters measured by pretreatment (18)F-FDG PET/CT in patients with salivary gland carcinomas., Methods: Forty-nine patients with intermediate- or high-grade salivary gland carcinomas who underwent definitive surgery with or without radiotherapy or chemoradiotherapy were evaluated preoperatively by (18)F-FDG PET/CT. Maximum standardized uptake values (SUV max), MTV, and TLG were measured for each patient. Univariate and multivariate analyses were used to identify clinicopathologic and imaging variables associated with progression-free survival (PFS) and overall survival (OS). Univariate analyses included the following variables: age, sex, pT and pN classifications, overall pTNM stage, histologic grade, resection margin, tumor lymphovascular invasion and perineural invasion, postoperative adjuvant therapy, gross total volume, SUV max, MTV, and TLG., Results: The 3-y PFS and OS rates for all study patients were 66.9% and 81.6%, respectively. The median SUV max, MTV, and TLG were 5.1 (range, 1.7-21.5), 16.2 mL (1.0-115.1 mL), and 24.4 g (2.1-224.4 g), respectively. Univariate analyses showed that there were significant correlations between pT classification, pN classification, MTV, and TLG and both PFS and OS (P < 0.05). However, SUV max was not associated with either PFS (P = 0.111) or OS (P = 0.316). Multivariate analyses revealed that MTV (P = 0.011; hazard ratio, 11.50; 95% confidence interval, 1.45-91.01) and TLG (P = 0.038; hazard ratio, 3.55; 95% confidence interval, 1.07-11.76) were independent variables for PFS., Conclusion: Pretreatment values of MTV and TLG are independent prognostic factors in patients with intermediate or high-grade salivary gland carcinomas.