Acinic Cell Carcinoma Research Articles

Pancreatic Acinar Cell Carcinoma in the Setting of a BRCA1 Germline Mutation

Pancreatic acinar cell carcinoma (PACC) is a rare neoplasm of the exocrine pancreas. PACC’s molecular and genetic features are poorly elucidated compared with pancreatic ductal cell carcinoma. Here, we present the patient case of a woman in her late 60s, with a BRCA1 germline mutation and a medical history of breast and lung adenocarcinomas diagnosed with PACC. A literature search identified only 2 reported cases of PACC associated with a BRCA1 germline mutation.

660MO Molecular targets in salivary gland cancers: A comprehensive genomic analysis of 1,666 cases

Next Generation Sequencing (NGS) to identify key molecular targets is an important aspect of management in advanced Salivary Gland Carcinomas (SGC). DNA was extracted from tissues of advanced SGC and Comprehensive Genomic Profiling (CGP) was done to evaluate for base substitutions, short insertions, deletions, copy number changes, gene fusions and rearrangements. Tumor Mutation Burden (TMB) was calculated on up to 1.25 Mb. The table shows the descriptive analysis of 1,666 SGC with clinically relevant Genomic Alterations (GA). Adenoid Cystic Carcinoma (ACC) (28.3%) was the commonest subtype. CDKN2A and CDKN2B GA were common in Acinic cell carcinoma (AcCC) (59 and 37.4%) and mucoepidermoid carcinoma (MEC) (52.5 and 30.5%). PIK3CA was common in Ductal Ca (32.6%) and High-grade Ca NOS (21.3%), making agents like Alpelisib, a consideration. ERBB2 amplification/Short Variants (amp/SV) were frequent in Carcinoma ex Pleomorphic Adenoma (Ca ex PA) (17.6/9.8%) and Ductal Ca (16.3/3.6%). ERBB2 directed therapies can play a crucial role in their management. BRAF GA was common in Ductal Ca (5.6%) and ACC (3.6%). Targets including RET, FGFR, NTRK, BRCA and EGFR had a low incidence. TMB >10 was common in High-grade NOS (18.3%) and MEC (16.9%). High PDL1 was also common in High grade NOS (8.9%) making us believe that this subtype may have the best response to immunotherapy (IO).Table: 660MON=1,666GA (%)CDKN2ACDKN2BBRAFPTENPIK3CAERBB2 (amp/SV)FGFR1FGFR2ARTMB > 10PD-L1 HighACC4713.82.413.18.60.2/01.24.100.20AcCC1955937.43.69.72.10.5/000.50.51.53MEC11852.530.51.77.616.95.9/05.10016.94.2Myoepi-thelial Carcinoma5532.723.61.81.89.10/05.57.307.36.3Ductal Ca3372415.45.618.132.616.3/3.62.11.81.29.43AdenoCa NOS15226.319.127.920.410.5/2.60.7205.94.4High Grade Ca NOS24022.914.62.910.821.315.8/2.14.22.10.418.38.9Ca ex PA5113.79.8219.611.817.6/9.811.87.8011.80Basaloid Ca4710.68.502.110.60/02.18.508.50 Open table in a new tab This large dataset reveals many opportunities for IO and targeted therapy contributing to the continuing increased precision in the selection of treatment for these patients.

Profile of Serum Heat Shock Protein-27 Level in Patients with Salivary Gland Tumor.

Heat shock protein 27 (HSP27) plays important roles in many cellular processes and has been implicated in different types of diseases such as cancers. This study aimed to evaluate the serum level of HSP27 in patients with salivary gland tumors and to determine its possible correlation with the prognosis of the disease. This cross-sectional study was performed on 60 patients with sali-vary gland tumor including 16 pleomorphic adenoma, 33 adenoid cystic carcinoma, 6 mu-coepidermoid carcinoma, 5 acinic cell carcinoma, and 28 healthy control subjects. The con-trol cases were healthy blood donors who matched the study group in age and sex. Serum samples were obtained from the clotted blood and HSP27concentrations were measured with sandwich enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed by using one-way ANOVA, post Hoc test, independent sample t-test, and ROC analysis. A p value of less than 0.05 was considered as significant. The mean serum level of HSP27 was 3956.1±3830.1 (pg/ml) in patients with malig-nant salivary gland tumor, which was significantly higher than that in benign salivary gland tumor (752.2±485.6) and healthy controls (602.3±575.8) (p <0.001). However, there was no significant difference in the HSP27 serum levels between the patients with benign salivary gland tumors and healthy controls (p= 0.2). No association was detected between the mean serum levels of HSP27 and clinicopathologic factors such as age, sex, stage and nodal metas-tasis (p > 0.05), except for the tumor size (p= 0.04). The HSP27 concentration increased in patients with malignant salivary gland tumors. Moreover, the HSP27 level was correlated with tumor growth, invasiveness, and diagnosability. Yet, larger clinical studies are required to explore its prognostic value.

Cystic Salivary Gland Neoplasms: Diagnostic Approach With a Focus on Ancillary Studies.

Cystic salivary gland cytology can be challenging due to the fact that a cystic mass can be the clinical presentation of both non-neoplastic and neoplastic conditions. Neoplastic lesions consist of both benign and malignant neoplasms. The cytomorphologic features of these entities can overlap and the cystic background may additionally contribute to the complexity of these lesions and their interpretation. Ancillary studies have been reported in several studies to be beneficial in further characterization of the cellular components and subsequent diagnosis of the cystic lesions of the salivary gland. Fluorescence in situ hybridization, real-time polymerase chain reaction, and next-generation sequencing are now being utilized to detect molecular alterations in salivary gland neoplasms. MALM2 rearrangement is the most common gene fusion in mucoepidermoid carcinoma. PLAG1 rearrangement is present in more than half of pleomorphic adenomas. AKT1:E17K mutation is the key diagnostic feature of the mucinous adenocarcinoma. NR4A3 overexpression is highly sensitive and specific for the diagnosis of acinic cell carcinoma. MYB fusion is noted in adenoid cystic carcinoma. ETV6:NTRK3 fusion is helpful in diagnosis of secretory carcinoma. p16 and human papillomavirus (HPV) studies differentiate HPV-related squamous cell carcinoma from non-HPV-related neoplasms with overlapping features. NCOA4:RET fusion protein is the main fusion in intraductal carcinoma.

Identification of Fusion Genes and Targets for Genetically Matched Therapies in a Large Cohort of Salivary Gland Cancer Patients.

Simple SummarySalivary gland cancer (SGC) is a rare and heterogeneous cancer for which limited treatment options are available in the palliative treatment setting. Characterization of the SGC genetic landscape to identify actionable aberrations is therefore important. This research aimed to comprehensively assess the prevalence of various types of actionable aberrations, including gene fusions, in a large cohort of patients with different SGC subtypes. The combined approach using RNA- and DNA-based targeted next-generation sequencing panels revealed the presence of gene fusions in half of the cases, including several fusions not previously described in SGC. Targets for genetically matched therapies were identified in 28.3–81.8% of cases, depending on the SGC subtype (overall 53.7% of the cases). This highlights the potential of molecular diagnostics to select systemic treatment in SGC.Introduction: Salivary gland cancer (SGC) is a rare cancer for which systemic treatment options are limited. Therefore, it is important to characterize its genetic landscape in search for actionable aberrations, such as NTRK gene fusions. This research aimed to identify these actionable aberrations by combining NGS-based analysis of RNA (gene fusions) and DNA (single and multiple nucleotide variants, copy number variants, microsatellite instability and tumor mutational burden) in a large cohort of SGC patients. Methods: RNA and DNA were extracted from archival tissue of 121 patients with various SGC subtypes. Gene fusion analysis was performed using a customized RNA-based targeted NGS panel. DNA was sequenced using a targeted NGS panel encompassing 523 cancer-related genes. Cross-validation of NGS-based NTRK fusion detection and pan-TRK immunohistochemistry (IHC) was performed. Results: Fusion transcripts were detected in 50% of the cases and included both known (MYB-NFIB, MYBL1-NFIB, CRTC1-MAML2) and previously unknown fusions (including transcripts involving RET, BRAF or RAD51B). Only one NTRK fusion transcript was detected, in a secretory carcinoma case. Pan-TRK IHC (clone EPR17341) was false positive in 74% of cases. The proportion of patients with targets for genetically matched therapies differed among subtypes (salivary duct carcinoma: 82%, adenoid cystic carcinoma 28%, mucoepidermoid carcinoma 50%, acinic cell carcinoma 33%). Actionable aberrations were most often located in PIK3CA (n = 18, 15%), ERBB2 (n = 15, 12%), HRAS and NOTCH1 (both n = 9, 7%). Conclusions: Actionable genetic aberrations were seen in 53.7% of all SGC cases on the RNA and DNA level, with varying percentages between subtypes.

DOG1 as an Immunohistochemical Marker of Acinic Cell Carcinoma: A Systematic Review and Meta-Analysis.

DOG1 is a transmembrane protein originally discovered on gastrointestinal stromal tumors and works as a calcium-activated chloride channel protein. There are a limited number of articles on the potential utility of this antibody in the diagnosis of salivary gland tumors in routine practice. In this study, we aimed to investigate the role of DOG1 as an immunohistochemical marker in patients with salivary acinic cell carcinoma (ACC) through meta-analysis. A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2010 to September 2021. The literature search revealed 148 articles, of which 20 were included in the study. The overall rate of DOG1 expression in salivary acinic cell carcinoma was 55% (95% CI = 0.43–0.58). Although ACC is a challenging diagnosis, paying careful attention to the cytomorphological features in conjunction with DOG1 immunostaining can help to reach an accurate diagnosis.

1053 Primary Acinic Cell Carcinoma in a Young Female: A Case Report

Abstract Background Acinic cell carcinoma (ACC) is a rare, low-grade tumour, accounting for about 5% of all primary salivary gland malignancies. ACCs predominate in the parotid gland, seen in the fifth and sixth decades of life and has a female predilection. Well-differentiated and low-grade tumours are associated with a favourable prognosis. Case Description We report a case of a 16-year-old female, presenting with a right parotid lump, slowly increasing over the last year. Clinical examination revealed a 1.5cm right parotid nodule with no facial nerve involvement and presence of cervical lymphadenopathy. Past medical history was unremarkable. Findings Radiological investigations revealed a well-circumscribed lobulated lesion in the anterior right parotid gland with presence of reactive lymph nodes bilaterally. Differential diagnoses included Warthin's tumour, which would have been unusual in this age group, and the patient underwent a right partial parotidectomy. Histological examination showed a multinodular appearance with some marked granular cytoplasm with oncolytic and lymphoid infiltrate. Immunohistochemistry was negative for S100, positive with DOG-1. There were widespread PAS-D-resistant granules throughout the tumour cells, with ki67 proliferation index of approximately 5%. Results The tumour was completely excised, and the patient made a full recovery and considered to have a good long-term prognosis. Conclusion This is an unusual case of ACC seen in this age group and gender, where less than 4% of cases of ACC have been reported in patients younger than 20. It is important to consider differential diagnoses of salivary gland pathology, such as ACC in the young female patient.

Clinico-Epidemiological Analysis of Most Prevalent Parotid Gland Carcinomas in Poland over a 20-Year Period.

(1) Background: Malignant tumours of the salivary glands have different clinical and histopathological characteristics. They most commonly involve the parotid gland. Histopathologically, the most common are mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (AdCC), acinic cell carcinoma (AcCC), adenocarcinoma, carcinoma in pleomorphic adenoma (CPA), and squamous cell carcinoma (SCC). (2) Methods: We analysed 2318 patients with malignant parotid gland tumours reported to the National Cancer Registry (NCR) in Poland over 20 years (1999–2018). The demographic characteristics of patients, clinical factors, and overall survival (OS) were analysed. (3) Results: The average age was 61.33 ± 16.1 years. The majority were males (55%) and urban citizens (64%). High percentage of carcinomas was diagnosed in locoregional (33.7%) and systemic (10.4%) stadium. The most prevalent diagnoses were SCC (33.3%) and adenocarcinoma (19.6%). Surgical resection with adjuvant RT (42.1%) was the most common treatment. The OS analysis showed a median survival time of 5.6 years. The most favorable median OS was found in patients with AcCC (18.30 years), the worst for SCC (1.58 years). (4) Conclusion: AcCC has the best prognosis and SCC the worst. Tumour stadium, treatment, and demographic factors affect prognosis. Improvements in diagnosis and re-evaluation of treatment standards are necessary to enhance the outcome of patients with parotid gland cancers in Poland.

Predictors of surgical complications in surger y of disseminated skull base tumors

Post-surgical complications are rather important, and, perhaps, more significant factors determining the efficiency of the provided treatment together with the natural oncological disease course, accompanying pathology, and peculiarities of the adjuvant therapy. The decrease in the frequency and severity of these complications, revealing of modifiable and non-modifiable risk factors, their prevention and reduction are definitely of scientific and practical interest. The aim of the work is the search for predictors of post-surgical complications in the patients with disseminated malignant skull base tumors. The retro-prospective single-center cohort study based on the analysis of the results of surgical treatment of 161 patients with such neoplasms was carried out. The study covered the patients at the age of 19–84 years, with the average age of 55 years (statistical deviation: +\- 1.2). There were 78 women and 83 men. Accordingly, the sex distribution was 1:1.064. The pre-surgical radical radiotherapy was made for 43 patients (26.71 %); 21 patients (13.04 %) underwent one or several cycles of multiagent chemotherapy. Morphologically, there were 16 different types of tumors, among which the epithelial tumors 40.37 % (n=65) prevailed: epidermoid cancer — 16.15 % (n=26), sinonasal cancer — 8.07 % (n=13), and acinic cell carcinoma 5.59 % (n=9). Sarcomas were diagnosed in 12 patients (7.45 %). The study results demonstrate the lack of particular statistically substantiated symptoms or clinical factors — predictors, individually and independently affecting the unfavorable results of the surgical treatment of the patients with disseminated malignant skull base tumors. On the contrary, the syndromological combination of local, general and organizational problems definitely influences the surgery result significantly, while not all mathematically predicted combinations can be formalized into some clinical equivalent.

CD138 Is Expressed in Different Entities of Salivary Gland Cancer and Their Lymph Node Metastases and Therefore Represents a Potential Therapeutic Target.

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.

Frequency and malignancy rate of incidental focal salivary gland lesions identified by 18F-fluorodeoxyglucose-positron emission tomography.

We aimed to evaluate the frequency and malignancy rate of incidental salivary gland lesions (ISGLs) in patients undergoing 18F-fluorodeoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT). Using a predefined algorithm, all descriptions of FDG-PET/CT scans performed in the North Denmark Region at the Department of Nuclear Medicine, Aalborg University Hospital from 1.12 2009 to 31.12 2019 were electronically searched for focal uptake in one or more salivary glands. In total, 28,362 FDG-PET/CT scans were performed in the study period. ISGLs were found in 197 (0.7%). A total of 193 (98%) had parotid gland ISGL, and four (2%) had submandibular ISGL. No sublingual lesions were found. Ultimately, 117 patients (60%) were referred to the Department of Otorhinolaryngology-Head and Neck Surgery for evaluation. Fine needle aspiration biopsy was performed in 97 patients, and the most frequent cytopathology was Warthin's tumour (n = 62). Two patients had verified malignancy: one with histopathologically proven acinic cell carcinoma and one with cytopathologically proven metastasis from an oral squamous cell carcinoma. Incidental salivary gland findings on FDG-PET/CT are rare, and the risk of malignancy is low. Patients with ISGL may be evaluated secondary to the primary disease, but special attention should be given to patients with prior or known head-and-neck malignancies and patients with symptoms from the salivary glands, including swelling.

Utility of NR4A3 on FNA cytology smears and liquid-based preparations of salivary gland.

Fine-needle aspiration cytology (FNAC) is generally the initial sampling method for salivary gland neoplasms. The cytomorphologic features of acinic cell carcinoma (AciCC) of salivary gland can overlap with other neoplastic and nonneoplastic entities. AciCCs harbor a recurrent t(4;9) rearrangement with upregulation of nuclear receptor subfamily 4 group A member 3 (NR4A3). NR4A3 protein overexpression has been shown to be highly sensitive and specific for the diagnosis of AciCC in histologic specimens and cell block preparations. However, data on NR4A3 immunocytochemistry (ICC) on conventional smears or liquid-based cytology are limited. The authors identified 18 FNAC of histologically proven AciCC cases between 2013 and 2019. FNAC samples of diagnostic mimickers were likewise retrieved and included in the study cohort for comparison. The NOR1/NR4A3 mouse monoclonal antibody was applied directly to FNAC slides using a standard ICC technique. The cohort included ethanol-fixed Papanicolaou-stained cytologic smears and liquid-based preparations from 18 AciCC, one secretory carcinoma, four mucoepidermoid carcinomas, four salivary duct carcinomas, five pleomorphic adenomas (PA), five Warthin tumors, five oncocytomas, one oncocytic hyperplasia, and five nonneoplastic salivary gland cases. Strong nuclear staining for NR4A3 was present in all AciCC, weak nuclear staining was present in one PA, and all other non-AciCC were negative (sensitivity, 100%; specificity, 97%). NR4A3 ICC can be used directly on FNAC conventional smears and liquid-based cytology to reliably distinguish AciCC from its mimickers. This marker may be useful in cases where a cell block preparation is unavailable or inadequate.

Application of multimodal combined surgical strategy in children with intractable laryngeal airway obstruction

Objective:To explore the selection of surgical methods and intraoperative strategies for the treatment of children with intractable laryngeal airway obstruction, and to provide new options for the diagnosis and treatment of children with intractable laryngeal airway obstruction. Methods:The clinical data of 12 children with intractable laryngeal airway obstruction treated by our team from January 2005 to December 2021 were retrospective analyzed. All the children were treated with minimally invasive surgery under rigid bronchoscope or suspension laryngoscope combined with electronic endoscope. The surgical methods included laryngeal microsurgery, plasma ablation, balloon dilatation, drug-eluting stents, laser ablation, endoscopic snare, etc. The patients were followed up after operation. Results:All patients completed the operation under general anesthesia, and there were no intraoperative or postoperative complications. Except for one patient with bilateral vocal cord paralysis who failed to extubation due to restenosis, the others were successfully extubated after operation. Among them, 9 cases of benign space-occupying obstruction were followed up for 5-60 months without recurrence, and 2 cases of malignant tumor-induced obstruction were followed up for 24 months（acinar cell carcinoma） and 36 months（mucoepidermoid carcinoma） without recurrence. Conclusion:Endoscopic multi-operation is effective for children with intractable obstruction. Compared with traditional thoracotomy, endoscopic multi-operation strategies has the advantages of less trauma, faster and safer. For different sizes, locations and pathological types of obstruction, different surgical equipment and methods should be combined.

The expression of the adenosine pathway markers CD39 and CD73 in salivary gland carcinomas harbors the potential for novel immune checkpoint inhibition

BackgroundIn salivary gland carcinomas (SGC), there is only a small fraction of entities that appears to profit from immune checkpoint inhibition (ICI). Recent findings connected the activation of adenosine-signaling with a tolerogenic microenvironment. Therefore, the inhibition of adenosine pathway markers (CD39 and/or CD73) can augment ICI and/or display a novel immunotherapeutic strategy beyond ICI. Here, we assessed the immuno-histochemical expression of CD39 and CD73 across a wide spectrum of SGCs.MethodsIn total, 114 patients with SGCs consecutively diagnosed between 2001 and 2021 were assessed for clinicopathological baseline characteristics and underwent confirmatory histopathological review. Immunohistochemical expression levels of CD39 and CD73 were assessed by applying the tumor proportion score (TPS) and the immune proportional score (IPS) comparable to PD-L1 expression analysis in routine clinical practice. Additionally, findings were correlated with PD-L1 expression levels.ResultsThe median age was 60.6 and 51.8% patients were female. The cohort covered a spectrum of eight distinct entities. Advanced-stage disease (UICC/AJCC III/IVA-IVC) at initial diagnosis was present in the majority of patients (64/114). Immunohistochemical staining revealed positivity for CD39 and CD73 in 48.2% and 21.1% on tumor cells (TPS ≥ 1%) as well as 46.4% and 42.9% within the immune cell infiltrate (IPS ≥ 1%), respectively. Further comparative analyses revealed immune-cold entities such adenoid cystic carcinoma (AdCC), immune-hot tumors such as adenocarcinoma, not otherwise specified (AC (NOS)) and entities with intermediate immunologic features such as acinic cell carcinoma (ACC).ConclusionCurrent results indicate entity-specific adenosine signaling signatures. These findings suggest that the adenosine pathway plays a decisive role in tumor immunity among the major spectrum of SGCs. Targeting the adenosine pathway might pose a promising therapeutic option for selected entities.

Evaluation of survival outcomes and prognostic factors in acinic cell carcinomas of the parotid gland receiving adjuvant radiotherapy

Aim: To evaluate the survival outcomes and prognostic factors in acinic cell carcinoma of the parotid gland, a retrospective study was designed. Material and Method: Consecutive patients diagnosed with parotid acinic cell carcinoma and treated with surgery and adjuvant radiotherapy were retrospectively reviewed. Data regarding age, sex, TNM stage, pathologic characteristics, treatment details, and follow-up examinations were collected and analysed. The primary end-point was overall survival; the distant metastasis free survival was calculated from the date of surgery to the date of death or the latest follow-up examination and analysed by the Kaplan-Meier method. Independent prognostic factors were evaluated by the Cox proportional hazards method. Results: Between years of 2010-2020, two radiotherapy centers’ database were reviewed. A total of 32 patients were included. The median age was 55 years (35-80 years). Four-teen (43.75%) were male and 18 (56.25%) were female. Median follow-up was 44 months (8-120). Seven (21.9%) were in T1, 7 (21.9%) in T2, 6 (18.8%) in T3 and 12 (37.5%) in T4 at the time of diagnosis. In all cohort, 6 (18.8%) of them had lymph node metastasis. The 2-year and 5-year OS rates were 92.6% and 78.5%, locoregional recurrence-free survival rates were 100% and 89.1%, distant metastasis free survival rates were 85.9% and 85.9%, respectively. Locoregional recurrence detected in 2 (6.25%), distant metastases detected in 4 (12.5%) patients. All distant metastases detected in the lungs. Univariate analysis showed that age, gender, margin status, T stage, facial nerve involvement, lymphovascular invasion, and perineural invasion were not significantly related to overall survival (all p&amp;gt;0.05). Lymph node involvement (p&amp;lt;0.013) and grade (p&amp;lt;0.006) were the only significant prognostic factors for OS. In multivariate analysis, both lymph node involvement (p&amp;lt;0.050) and grade (p&amp;lt;0.028) remained the significant prognostic factors. Conclusion: In acinic cell carcinoma of the parotid gland, high-grade histology and node positivity are independent variables that affect OS. Since survival is lower in these patient groups, it is imperative to explore other treatment options in addition to adjuvant radiotherapy.

Pancreatoblastomas and mixed and pure acinar cell carcinomas share epigenetic signatures distinct from other neoplasms of the pancreas

AbstractPancreatic neoplasms are heterogenous and have traditionally been classified by assessing their lines of cellular differentiation using histopathologic methods, particularly morphologic and immunohistochemical evaluation. These methods frequently identify overlapping differentiation along ductal, acinar, and neuroendocrine lines, raising diagnostic challenges as well as questions regarding the relationship of these neoplasms. Neoplasms with acinar differentiation, in particular, frequently show more than one line of differentiation based on immunolabeling. Genome methylation signatures, in contrast, are better conserved within cellular lineages, and are increasingly used to support the classification of neoplasms. We characterized the epigenetic relationships between pancreatoblastomas, acinar cell carcinomas (including mixed variants), pancreatic neuroendocrine tumors, solid pseudopapillary neoplasms, and pancreatic ductal adenocarcinomas using a genome-wide array platform. Using unsupervised learning approaches, pancreatic neuroendocrine tumors, solid pseudopapillary neoplasms, ductal adenocarcinomas, and normal pancreatic tissue samples all localized to distinct clusters based on their methylation profiles, whereas all neoplasms with acinar differentiation occupied a broad overlapping region located between the predominantly acinar normal pancreatic tissue and ductal adenocarcinoma clusters. Our data provide evidence to suggest that acinar cell carcinomas and pancreatoblastomas are similar at the epigenetic level. These findings are consistent with genomic and clinical observations that mixed acinar neoplasms are closely related to pure acinar cell carcinomas rather than to neuroendocrine tumors or ductal adenocarcinomas.

Salivary gland-like breast tumors: A review of diagnostic features and prognosis

Salivary gland-like breast tumors are rare and diagnostic challenging tumors. The tumors show similar histological features and molecular diagnostic alterations to their counterpart in the salivary glands, except for acinic cell carcinomas. Some tumors show a complex epithelial and myoepithelial composition (pleomorphic adenoma, basal cell adenoma, adenomyoepithelioma, and adenoid cystic carcinoma). In contrast, others are predominantly epithelial (polymorphous adenocarcinoma, mucoepidermoid carcinoma, secretory carcinoma, and acinic cell carcinoma). Some tumors are benign, while others are carcinomas of low malignant potential. Occasional cases show high-grade transformation and aggressive behavior, with distant metastases.Despite being triple-negative tumors, they do not require conventional chemotherapy in most instances, except for cases with high-grade histology and metastases. Limited experience exists in metastatic secretory carcinomas with pan-NTRK inhibitor therapy, which is promising.

A Clinicopathological study of salivary gland neoplasms in a tertiary care hospital: A three year study

Background: The tumors of the salivary glands are uncommon head and neck neoplasms. The aim of this study was to observe the clinical occurrence of salivary gland neoplasms and to study the various histo-morphological features of salivary gland tumours, their frequency, age and sex distribution. Materials and Methods: The cases which have arrived to the Dental OP at Drs Sudha and Nageswara Rao Sidhhartha Institute of Dental Sciences with swellings in the head and neck region were identified and sent to pathology department from June 2013 to May 2016 and cases which were diagnosed as salivary gland neoplasms (96 cases) were taken into consideration and Histopathological examination was done. Results: Out of 96 cases, 51 (53.1 %) were benign and 45(46.9 %) were malignant with M:F ratio of 1.74:1. Age range of patients was from 10 to 80 years. Pleomorphic adenoma was found to be the commonest benign tumor (74.5 %), followed by Warthin’s tumor (19.6%), monomorphic adenoma (3.9 %) and basal cell adenoma (3.9 %). The mucoepidermoid carcinoma was the most common malignant tumor (48.8%) followed by adenoid cystic carcinoma (33.3%), acinic cell carcinoma (13.3%), adenocarcinoma NOS (2.2%) polymorphous adenocarcinoma (2.2%) Conclusion: Males were more affected than females and pleomorphic adenoma was the most frequent lesion followed by warthin’s tumor among benign neoplasms. Mucoepidermoid carcinoma is the most common malignant neoplasm followed by adenoid cystic carcinoma.

Expression of matrix metalloproteinase-2 and survivin in pancreatic carcinoma

Background and Aim Matrix metalloproteinase (MMP) is a member of the MMP family, which is a zinc-dependent endopeptidase that degrades all extracellular matrix components and vascular basement membrane. Survivin plays a leading role in the process of apoptosis regulation. Survivin is unique for its expression in human malignancies but not in normal adult cells. This study aimed to assess immunoexpression of MMP-2 and survivin in pancreatic carcinoma. Patients and methods A total of 25 pancreatic carcinomas were evaluated for immunohistochemical expression of MMP-2 and survivin. The expression was evaluated by immunoreactive score that combines the intensity of immunoreactions with the percentage of positive cells. Results In this study, 24/25 of the cases were pancreatic ductal adenocarcinoma (PDAC) and 1/25 was acinar cell carcinoma. Regarding tumor differentiation, PDAC included five cases of adenocarcinoma that were well differentiated, 16 cases were moderately differentiated, and three cases were poorly differentiated. Pancreatic carcinoma specimens showed positive cytoplasmic MMP-2 staining with high expression in 22/25 (88%) studied specimens ranging from 6/9 to 9/9 with high extent and intensity. Survivin staining with high expression was seen in 23/25 (92%) studied specimens, ranging from 9/12 to 12/12 with high extent and intensity. Conclusion MMP-2 and survivin expressions were positive in pancreatic carcinoma with various grades but negative in non-neoplastic parenchymal, acinar, and pancreatic ductal epithelium. There were significant positive relationships between MMP-2 and survivin expression and poor histological grade in PDAC (P&lt;0.024 and 0.021, respectively).

Potential role of hybrid positron emission tomography in pre-operative assessment of primary salivary gland carcinomas.

The added value of hybrid positron emission tomography is increasingly recognised in head and neck cancer. However, its potential role in salivary gland carcinomas has been scarcely investigated. A consecutive cohort of 45 salivary gland carcinoma patients who underwent pre-therapeutic hybrid positron emission tomography and surgical resection was reviewed. This study investigated whether maximum standardised uptake value correlated with tumour phenotype. Tumours of high-grade disease on histology (salivary duct carcinoma, carcinoma ex pleomorphic adenoma) had higher maximum standardised uptake value (Kruskal-Wallis test, p = 0.011) than low-grade tumours (adenoid cystic carcinoma and acinic cell carcinoma). Patients with pathologically confirmed node-positive disease had significantly higher maximum standardised uptake value of the primary tumour than patients with pathologically confirmed node-negative disease (Kruskal-Wallis test, p = 0.012). Maximum standardised uptake value of the primary tumour may guide clinical decision-making in patients with salivary gland carcinomas, as a high maximum standardised uptake value is associated with high-grade tumour histology and the presence of lymph node metastases. Clinicians may consider more aggressive surgery for these patients.