Gland Adenoid Cystic Carcinoma Research Articles

Survival benefit added by adjuvant chemotherapy in adenoid cystic carcinoma of salivary gland

The aim of this study was to investigate the potential survival advantages associated with chemoradiotherapy (CRT) compared to radiotherapy (RT) as standalone modalities in the treatment of adenoid cystic carcinoma (ACC) of the salivary glands. Patients diagnosed with resected salivary gland ACC were retrospectively enrolled and categorized into two groups based on the type of adjuvant therapy received. The overall survival outcomes between the CRT and RT cohorts were evaluated using a multivariable Cox model. Post propensity score-matching, a total of 114 patients (57 in each treatment group) were included in the analysis. In the general patient population, CRT did not confer an additional survival benefit compared to RT alone. High-grade tumors, positive surgical margins, and the presence of five or more positive lymph nodes were identified as independent prognostic factors associated with poorer overall survival. Specifically, for patients with positive surgical margins, CRT was significantly associated with improved overall survival relative to RT, displaying a hazard ratio of 0.93 (95% CI: 0.81–0.99). Furthermore, in patients with more than four metastatic lymph nodes, CRT significantly reduced the risk of mortality by 6% (95% CI: 1-24%) when compared to RT alone. Conversely, in patients with high-grade tumors, the addition of adjuvant chemotherapy to RT did not yield significant alterations in survival outcomes compared to RT alone (p = 0.437, HR: 0.95, 95% CI: 0.75–2.07). CRT may offer an overall survival benefit for patients with salivary gland ACC, particularly those characterized by positive margin or the presence of five or more metastatic lymph nodes.

Molecular Analysis of Salivary and Lacrimal Adenoid Cystic Carcinoma.

Adenoid cystic carcinoma (ACC) of head and neck origin is associated with slow but relentless progression and systemic metastasis, resulting in poor long-term survival rates. ACC does not respond to conventional chemotherapy. Determination of molecular drivers may provide a rational basis for personalized therapy. Herein, we investigate the clinical and detailed molecular genomic features of a cohort of patients treated in Ireland and correlate the site of origin, molecular features, and outcomes. Clinical and genomic landscapes of all patients diagnosed with ACC over a twenty-year period (2002-2022) in a single unit in Ireland were examined and analyzed using fluorescence in situ hybridization, DNA sequencing, and bioinformatic analysis. Fourteen patients were included for analysis. Eleven patients had primary salivary gland ACC and three primary lacrimal gland ACC; 76.9% of the analyzed tumors displayed evidence of NFIB-MYB rearrangement at the 6q23.3 locus; 35% had mutations in NOTCH pathway genes; 7% of patients had a NOTCH1 mutation, 14.3% NOTCH2 mutation, and 14.3% NOTCH3 mutation. The presence of epigenetic modifications in ACC patients significantly correlated with worse overall survival. Our study identifies genetic mutations and signaling pathways that drive ACC pathogenesis, representing potential molecular and therapeutic targets.

Molecular characterization of the salivary adenoid cystic carcinoma immune landscape by anatomic subsites

Adenoid cystic carcinoma (AdCC) is a slow-growing salivary gland malignancy that relapses frequently. AdCCs of the submandibular gland exhibit unique differences in prognosis and treatment response to adjuvant radiotherapy compared to other sites, yet the role of tumor anatomic subsite on gene expression and tumor immune microenvironment (TIME) composition remains unclear. We used 87 samples, including 48 samples (27 AdCC and 21 normal salivary gland tissue samples) from 4 publicly available AdCC RNA sequencing datasets, a validation set of 33 minor gland AdCCs, and 39 samples from an in-house cohort (30 AdCC and 9 normal salivary gland samples). RNA sequencing data were used for single sample gene set enrichment analysis and TIME deconvolution. Quantitative PCR and multiplex immunofluorescence were performed on the in-house cohort. Wilcoxon rank-sum, nonparametric equality-of-medians tests and linear regression models were used to evaluate tumor subsite differences. AdCCs of different anatomic subsites including parotid, submandibular, sublingual, and minor salivary glands differed with respect to expression of several key tumorigenic pathways. Among the three major salivary glands, the reactive oxygen species (ROS)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway signature was significantly underexpressed in AdCC of submandibular compared to parotid and sublingual glands while this association was not observed among normal glands. Additionally, the NRF2 pathway, whose expression was associated with favorable overall survival, was overexpressed in AdCCs of parotid gland compared to minor and submandibular glands. The TIME deconvolution identified differences in CD4+ T cell populations between AdCC of major and minor glands and natural killer (NK) cells among AdCC of minor, submandibular, and parotid glands while plasma cells were enriched in normal submandibular glands compared to other normal gland controls. Our data reveal key molecular differences in AdCC of different anatomic subsites. The ROS and NRF2 pathways are underexpressed in submandibular and minor AdCCs compared to parotid gland AdCCs, and NRF2 pathway expression is associated with favorable overall survival. The CD4+ T, NK, and plasma cell populations also vary by tumor subsites, suggesting that the observed submandibular AdCC tumor-intrinsic pathway differences may be responsible for influencing the TIME composition and survival differences.

Abstract PO-092: Molecular characterization of the salivary adenoid cystic carcinoma tumor immune landscape by anatomic subsite

Abstract Introduction: Adenoid cystic carcinoma (AdCC) is typically indolent, however tends to behave more aggressively and present with perineural invasion and distant metastasis. Despite an improved understanding of AdCC pathobiology, the impact of anatomic tumor subsite (e.g., major versus minor salivary glands) on survival and response to treatment is relatively understudied. We recently discovered that submandibular AdCC’s exhibit unique differences in prognosis and treatment response to adjuvant radiotherapy. However, the impact of anatomic subsites on gene expression and immune cell composition, has not been investigated. Materials and methods: We used 4 publicly available AdCC molecular datasets (n = 37 AdCCs of different origin: 27 primary and 10 metastatic; 7 parotid (PG), 5 submandibular (SMG), 4 sublingual (SLG), 21 minor salivary gland (mG) and 21 normal salivary gland tissue samples). Data were harmonized between datasets using identical quantification procedures, followed by filtering and normalization performed simultaneously on the pooled data from all cohorts. Gene set enrichment analysis (GSEA) was performed Human Molecular Signatures Database (MSigDB) Hallmark and Oncologic signatures. Tumor immune microenvironment (TIME) decomposition was performed using a non-negative matrix factorization-based approach. GSEA and TIME differences between AdCC subsites were evaluated using Wilcoxon rank-sum and nonparametric equality-of-medians tests. Results: We identified different levels of enrichment for several key tumorigenic pathways between AdCCs arising within different anatomic subsites. Among AdCCs, major glands overexpressed the HALLMARK_SPERMATOGENESIS signature (parotid and sublingual glands), while the HALLMARK_REACTIVE_OXYGEN_SPECIES_PATHWAY (ROS) signature was significantly underexpressed in SMG AdCCs. In addition, the HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION (EMT) signature was significantly underexpressed in both SMG and PG AdCCs. These pathway signatures were not seen in control tissue comparison samples, indicating that these features are AdCC-specific. Additionally, TIME decomposition identified differences in CD4-T cell populations (minor > major gland AdCC) and natural killer (NK) cells (increased in PG and SLG). Meanwhile, normal control comparisons revealed a significant increase in plasma cells only within SM glands. Conclusions: AdCC subsites exhibit survival and treatment-response differences, and in this study demonstrate that these anatomical sites are associated with distinct molecular features. Specifically, these different anatomical sites vary in the expression of spermatogenesis, ROS, and EMT signature-related genes. Also, CD4-T and NK cell populations vary by anatomical site, suggesting that the SMG AdCC tumor-intrinsic pathway differences observed may be responsible for influencing the TIME composition and increased prognosis associated with these tumors following adjuvant radiotherapy. Validation with additional cohorts of primary AdCCs with accurate clinical annotation are required. Citation Format: Jason Tasoulas, Travis Schrank, Steven Johnson, Kimon Divaris, Stamatios Theocharis, Trevor Hackman, Siddharth Sheth, Kedar Kirtane, Juan Hernandez-Prera, Christine Chung, Wendell Gray Yarbrough, Natalia Issaeva, Antonio Amelio. Molecular characterization of the salivary adenoid cystic carcinoma tumor immune landscape by anatomic subsite [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-092.

Paediatric painless proptosis-not always benign: A case of adenoid cystic carcinoma of the lacrimal gland in a child treated with globe sparing surgery and proton beam radiation­

Adenoid cystic carcinoma (ACC) of the lacrimal gland is a rare aggressive malignant epithelial neoplasm. This tumor is rarely seen in children and adolescents. There is a paucity of studies describing the optimal treatment and prognosis of adenoid cystic carcinoma in the paediatric age group. Here, we report a case of lacrimal gland ACC in a 11-year-old girl treated with globe-sparing tumor resection and proton beam radiation therapy (PBRT).

Identification of MicroRNA Expression Profiles Related to the Aggressiveness of Salivary Gland Adenoid Cystic Carcinomas.

Adenoid cystic carcinoma (ACC) has been reported as the second most common carcinoma of the salivary glands. Few studies have associated miRNA expression with ACC aggressiveness. In this study, we evaluated the miRNA profile of formalin-fixed, paraffin-embedded (FFPE) samples of salivary gland ACC patients using the NanoString platform. We studied the miRNA expression levels associated with the solid growth pattern, the more aggressive histologic feature of ACCs, compared with the tubular and cribriform growth patterns. Moreover, the perineural invasion status, a common clinicopathological feature of the disease that is frequently associated with the clinical progression of ACC, was investigated. The miRNAs showing significant differences between the study groups were selected for target prediction and functional enrichment, which included associations with the disease according to dedicated databases. We observed decreased expression of miR-181d, miR-23b, miR-455, miR-154-5p, and miR-409 in the solid growth pattern compared with tubular and cribriform growth patterns. In contrast, miR-29c, miR-140, miR-195, miR-24, miR-143, and miR-21 were overexpressed in patients with perineural invasion. Several target genes of the miRNAs identified have been associated with molecular processes involved in cell proliferation, apoptosis, and tumor progression. Together, these findings allowed the characterization of miRNAs potentially associated with aggressiveness in salivary gland adenoid cystic carcinoma. Our results highlight important new miRNA expression profiles involved in ACC carcinogenesis that could be associated with the aggressive behavior of this tumor type.

Immunoexpression of Autophagy-Related Proteins in Salivary Gland Tumors: An Exploratory Study.

Autophagy is a cellular survival mechanism involved in several human diseases, but its participation in the development of salivary gland tumors is not fully understood. This study investigated the immunoexpression of autophagy-related proteins (autophagy-related 7 [Atg7], microtubule-associated protein 1 light chain 3A [LC3A], microtubule-associated protein 1 light chain 3B [LC3B], protein p62 [p62], and phosphorylated mammalian target of rapamycin [p-mTOR]) in pleomorphic adenoma (PA), polymorphous adenocarcinoma (PAC), mucoepidermoid carcinoma (MEC), and adenoid cystic carcinoma (ACC) of salivary glands. Twenty PAs, 20 PACs, 20 MECs, and 14 ACCs were selected. The percentages of cytoplasmic and nuclear positivity for autophagy-related proteins in neoplastic cells were assessed and correlated with histopathological parameters. Cytoplasmic immunoexpression of Atg7 was observed in all groups, with high median percentages of positivity. Regarding LC3A and LC3B, cytoplasmic immunoexpression was found in most PACs (95%) and in all cases of PA, MEC and ACC, with the highest percentages of positivity in PACs and PAs (p < 0.005). ACCs exhibited lower cytoplasmic immunoexpression of p-mTOR (p < 0.005) and lower nuclear expression of p62 (p < 0.05) when compared to PAs, PACs and MECs. Low nuclear immunoexpression of Atg7, LC3A and p-mTOR and absence of nuclear staining for LC3B were observed in all groups. Regarding histopathological parameters of PAs, MECs and ACCs, there were no significant differences in the expression of autophagy-related proteins. In all groups, positive correlations were observed between the immunoexpression of some autophagy-related proteins (p < 0.05). The results suggest the participation of autophagy in the pathogenesis of PA, PAC, MEC, and ACC of salivary glands. Upregulation of autophagy and reduced nuclear translocation of p62 may contribute to the aggressive biological behavior of salivary gland ACC.

Dominant Gene Expression Profiles Define Adenoid Cystic Carcinoma (ACC) from Different Tissues: Validation of a Gene Signature Classifier for Poor Survival in Salivary Gland ACC.

Adenoid cystic carcinoma (ACC) is an aggressive malignancy that most often arises in salivary or lacrimal glands but can also occur in other tissues. We used optimized RNA-sequencing to analyze the transcriptomes of 113 ACC tumor samples from salivary gland, lacrimal gland, breast or skin. ACC tumors from different organs displayed remarkedly similar transcription profiles, and most harbored translocations in the MYB or MYBL1 genes, which encode oncogenic transcription factors that may induce dramatic genetic and epigenetic changes leading to a dominant 'ACC phenotype'. Further analysis of the 56 salivary gland ACC tumors led to the identification of three distinct groups of patients, based on gene expression profiles, including one group with worse survival. We tested whether this new cohort could be used to validate a biomarker developed previously with a different set of 68 ACC tumor samples. Indeed, a 49-gene classifier developed with the earlier cohort correctly identified 98% of the poor survival patients from the new set, and a 14-gene classifier was almost as accurate. These validated biomarkers form a platform to identify and stratify high-risk ACC patients into clinical trials of targeted therapies for sustained clinical response.

Vulvar Adenoid Cystic Carcinoma with Squamous Cell Carcinoma Component.

Adenoid cystic carcinoma (ACC) is a major histological type of salivary gland cancer but an uncommon form of vulvar cancer. Salivary gland ACC occasionally dedifferentiates into high-grade carcinoma, resulting in poor prognoses. The dedifferentiated component is usually a poorly differentiated cribriform or solid carcinoma, whereas squamous cell carcinoma (SCC) is exceptional. Herein, we report the case of a 78-year-old woman with vulvar ACC, including an SCC component. She presented with a vulvar nodule that had been present for 30 years and increased in size over the past few years. Magnetic resonance imaging showed a ball-like mass with high intensity on T1-weighted images and high intensity with non-uniformity on T2-weighted images. Considering the systemic and social conditions, the tumor was maximally resected without lymphadenectomy. Histologically, the tumor was composed of a marginal ACC component with a central SCC component. Stage IB vulvar cancer, which was assumed to originate from the Bartholin's gland, was diagnosed. She has survived over 2 years without additional treatments after the surgery. In this case, we assumed that slowly progressive indolent ACC could be dedifferentiated to high- grade SCC. According to our review of available literature, dedifferentiation of vulvar ACC with a high-grade SCC component has not been specifically documented. Although the nature of dedifferentiated vulvar cancer is unclear, it should be noted that high-grade dedifferentiation can occur in long-lasting vulvar masses.

Metastasis of Sublingual Gland Adenoid Cystic Carcinoma to the Upper Gingiva.

Adenoid cystic carcinoma (ACC) of the sublingual gland is rare. There are no previous reports of the metastasis of sublingual gland ACC to the upper gingiva. Herein, we report the first case of a patient with metastasis of sublingual gland ACC to the upper gingiva. It should be recognized that although metastasis of sublingual gland ACC to the upper gingiva is very rare, it can occur.

MYB RNA In Situ Hybridization Is a Useful Diagnostic Tool to Distinguish Breast Adenoid Cystic Carcinoma From Other Triple-negative Breast Carcinomas.

Breast adenoid cystic carcinoma (AdCC) has overlapping features with basal-like triple-negative breast carcinoma (TNBC), yet carries a more favorable prognosis, and accurate diagnosis is critical. Like salivary gland AdCC, breast AdCC demonstrates recurrent alterations in the MYB gene. Novel chromogenic RNA in situ hybridization (ISH) for MYB has emerged as sensitive and specific for salivary gland AdCC. Here, we evaluate MYB RNA ISH in invasive ductal carcinomas (IDCs) including basal-like TNBC, and in the histologic mimics ductal carcinoma in situ (DCIS) and collagenous spherulosis. MYB RNA ISH was also performed on previously constructed tissue microarrays containing 78 evaluable IDC, including 30 basal-like TNBC (EGFR+ and/or CK5/6+), 19 luminal A (ER+/HER-2-), 12 HER-2+ (ER-/HER-2+), 11 non-basal-like TNBC, and 6 luminal B (ER+/HER-2+). MYB RNA ISH overexpression was seen in 100% (n=18/18) of primary breast AdCC and 10% (n=8/78) of IDC (P<0.0001). MYB RNA ISH was overexpressed in 37% (n=7/19) of luminal A and 8% (n=1/12) of HER-2+ IDC, and in no cases of TNBC or luminal B IDC. The majority (67%, n=8/12) of DCIS and all (n=7) cases of collagenous spherulosis demonstrated overexpression of MYB RNA. MYB gene rearrangement was detected in 67% (n=4/6) evaluable AdCC. Although MYB RNA ISH overexpression cannot be used to distinguish between cribriform DCIS or collagenous spherulosis and AdCC, MYB RNA ISH is absent in basal-like TNBC and rare in ER+ or HER-2+ IDC. MYB RNA ISH could be a useful, sensitive, and rapid diagnostic adjunct in the workup of a triple-negative carcinoma in the breast.

Clinicoepidemiological profile of adenoid cystic carcinoma: Experience from a tertiary care oncology center in Kashmir, India

Background: Adenoid cystic carcinoma (ACC) is a relatively rare tumor mostly involving head and neck region of the body. Due to lack of high-quality evidence, optimal treatment is still controversial and continues to evolve over time. Aim and Objectives: To analyze the clinicoepidemiological profile of ACC in Kashmir. Materials and Methods: Data of 30 patients, who were treated in the Regional Cancer Center at She-i-Kashmir Institute of Medical Sciences (Deemed University, Srinagar) between January 2015 and December 2019, were reviewed with respect to their demographic and clinical profile. Results: The study included 30 patients with ACC. The mean age at presentation was 55 ± 12.15 years. There were 10 (33.3%) males and 20 (66.6%) females. Among salivary gland ACC s, sublingual gland (06/30, 20%) was the most common site followed by parotid gland (05/30, 16.7%). Nonhead and neck primary ACC cases were reported from lung (6.7%) and breast (6.7%). Majority of the patients presented in stage-III (43.3). Only 5 patients presented with distant metastasis. All patients were subjected to surgery. Adjuvant radiotherapy was given in 18 patients (60%). Three patients received all three modalities (surgery, radiotherapy, and chemotherapy). The overall one year survival was 96%. However, the mean & median survivals reported were 24 & 18 months respectively. Surgery with negative surgical margin is the first choice of treatment for the patients with ACC. Our findings show that the prognosis of patients with ACC in our center is comparable to other parts of country. Conclusion: ACC has locally aggressive behavior. Adjuvant radiotherapy improves local control in locally advanced disease. Longer follow-up is mandatory in view of incidence of late metastasis.

Vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 alpha (HIF-1ɑ) in lacrimal gland Adenoid cystic carcinoma: Correlation with clinical outcome

PurposeVEGF and HIF-1α are important regulators of angiogenesis, overexpressed in various tumors. Lacrimal gland Adenoid cystic carcinoma (ACC) is a malignant tumor whose angiogenic properties remain unexplored. This study was designed to evaluate the expression of HIF-1α and VEGF in lacrimal gland ACC. MethodsVEGF and HIF-1α immunoexpression was undertaken in 30 lacrimal gland ACC cases. mRNA expression of VEGF and HIF-1α was analysed in 17 cases by quantitative real time PCR. The results obtained were correlated with clinicopathological features and survival of the patients to determine the prognostic significance. ResultsImmunoexpression of HIF-1α and VEGF was seen in 36.6% and 46.6% ACC cases. HIF-1α expression showed significant association with advanced T-stage (P = 0.001) and VEGF with intracranial extension (P = 0.014) and solid histological pattern (P = 0.045). HIF-1α mRNA expression was seen in 29.4% cases and showed significant association with perineural invasion (P = 0.027). Recurrence occurred in 60%, distant metastasis in 20% and death in 20% cases. Survival analysis revealed that patients with HIF-1α, VEGF immunoexpression, solid histological pattern, perineural invasion, bone erosion, intracranial extension, metastasis, advanced T-stage, and exenteration had poor survival. On multivariate analysis VEGF immunoexpression (hazard ratio, 16.785; 95% confidence interval, 1.872–150.495; P = 0.012) was the most significant poor prognostic factor. ConclusionsThis study demonstrates that VEGF is a potential predictor for poor clinical outcome in lacrimal gland Adenoid cystic carcinoma.

Antizyme inhibitor 2 (AZIN2) associates with better prognosis of head and neck minor salivary gland adenoid cystic carcinoma.

The key regulator of the polyamine biosynthetic pathway is ornithine decarboxylase (ODC). ODC is activated by antizyme inhibitor 1 (AZIN1) and 2 (AZIN2). AZIN1 and recently AZIN2 have been related to cancer; however, their functions in adenoid cystic carcinoma (ACC) have not been studied. We performed immunohistochemical study on minor salivary and mucous gland ACC tissue samples of patients treated at the Helsinki University Hospital (Helsinki, Finland) during 1974-2012. We scored AZIN1 and 2 immunoexpression in 42 and 45 tumor tissue samples, respectively, and correlated them with clinicopathological factors and survival. Enhanced AZIN2 expression was associated with better survival. In addition, both AZINs were seen more commonly in cribriform and tubular than in solid growth patterns. AZIN1 expression did not correlate with the studied clinicopathological factors. It seems that AZIN2 expression is higher in cancer tissue with secretory functions. In ACC tissue, high AZIN2 expression could be related to well-differentiated histological type which still has a functioning vesicle transportation system. Thus, AZIN2 could be a prognostic factor for better survival of ACC patients.

Genomic profiling by cell-free circulating tumor DNA in patients with recurrent adenoid cystic carcinoma (ACC) and the potential activity of selective fibroblast growth factor receptor (FGFR) inhibitors.

e15018 Background: Few effective systemic therapies are available for adenoid cystic carcinoma (ACC). Multitargeted Tyrosine Kinase inhibitors (TKIs) as Lenvatinib and Rivoceranib can provide disease control and limited radiographic response in unselected ACC patients. Next-generation sequencing in tissue (tNGS) has identified MYB gene fusions in [patients with ACC but currently, only Notch1 mutations have an available targeted agent. The fibroblast growth factor receptor (FGFR) pathway is a downstream target of MYB. Methods: We retrospectively reviewed adult patients with a diagnosis of recurrent ACC seen at the University of Miami Sylvester Comprehensive Cancer Center between January 1, 2019 and October 31, 2020. Commercially available cell free DNA panel of 73 genes was used for analyzing circulating tumor DNA (ctDNA). Patients included had radiographically measurable disease and both tNGS and ctDNA data available. Results: Twelve patients were included. Median age at diagnosis was 54 years (28 - 68), and 69% were males. 83% of the patients had genomic abnormalities reported by tNGS, with the same number by ctDNA sequencing. Seven patients (58%) had genomic abnormalities in ctDNA of potentially therapeutic significance which were not found on tNGS, including FGFR1 amplification as well as FGFR2, BRAF, KRAS and JAK2 mutations. Three patients with FGFR genomic abnormalities only seen by ctDNA had been previously treated with Lenvatinib. One patient with primary lacrimal gland ACC metastatic to the liver and tNGS positive for NOTCH 1 had disease progression despite treatment with Lenvatinib and a NOTCH γ-secretase inhibitor. The patient’s ctDNA reported a FGFR2 mutation. The patient was started on Erdafitinib, an oral selective FGFR inhibitor, achieving a partial response at the primary site and metastatic liver lesions and remained on therapy for 7 months. Follow-up ctDNA after 3 months of therapy noted resolution of both FGFR and NOTCH abnormalities. Conclusions: Patients treated with lenvantinib or other TKIs may develop acquired resistance mutations and other genomic abnormalities. ctDNA can reveal additional therapeutic targets not present on tNGS and can be repeated serially. FGFR genomic abnormalities can be a driver mutation in patients with refractory advanced ACC and the activity of Erdafinib should be evaluated in this subset of patients with few therapeutic options.

GATA 3 Reactivity in Adenoid Cystic Carcinoma and Pleomorphic Adenoma of Salivary Glands

Objectives: The main targets is evaluate clinicopathological distribution and comparison of immunohistochemical (IHC) expression of GATA 3 between in adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA) of salivary . Design and Methods: This retrospective analysis, open surgical specimens of salivary gland that were done , and consisting of 150 cases that divided into three groups: normal salivary gland tissues (n=50), adenoid cystic carcinoma(n=50), and pleomorphic adenoma(n=50). Clinical data (age, sex, previous diseases ), physical examination, and investigations are done for all patients. In addition. These 150 cases of paraffin embedding blocks of salivary tissue were stained by ordinary stained (hematoxylin and eosin staining ). Manual IHC staining of GATA 3 was done. Results: Age groups is younger for normal salivary gland tissues than PA, and ACC . Sex distribution was slightly increase in male in comparison to female in normal salivary gland tissues and PA. GATA 3 staining was showing more positivity in normal salivary gland tissues (43/50 patients) than PA (27/50 patients) and ACC (14/50 patients). This positivity in GATA 3 IHC staining were more in male sex, regarding 55.8% in normal salivary gland tissues than ACC 50% and PA 51.9% . Age group 31-40, 40-50 and 61-70 years were showing more positive GATA 3 IHC staining in normal salivary gland tissues, PA, and ACC respectively. there was insignificant association between GATA 3 IHC staining with either age groups or sex groups distribution . Conclusion: GATA3 IHC is good marker and can used for searching salivary gland tumor origin, assisting in diagnosis Salivary gland tumors subtypes but GATA3 IHC staining has no association to specific sex or age groups in Salivary gland tumors. Usage of surgical operations for histopathological specimens preparation are better and give good efficiency for IHC markers staining.

GATA 3 Reactivity in Adenoid Cystic Carcinoma and Pleomorphic Adenoma of Salivary Glands

Objectives:The main targets is evaluate clinicopathological distribution and comparison of immunohistochemical (IHC) expression of GATA 3 between in adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA) of salivary . Design and Methods: This retrospective analysis, open surgical specimens of salivary gland that were done , and consisting of 150 cases that divided into three groups: normal salivary gland tissues (n=50), adenoid cystic carcinoma(n=50), and pleomorphic adenoma(n=50). Clinical data (age, sex, previous diseases ), physical examination, and investigations are done for all patients. In addition.These 150 cases of paraffin embedding blocks of salivary tissue were stained by ordinary stained (hematoxylin and eosin staining ). Manual IHC staining of GATA 3 was done. Results: Age groups is younger for normal salivary gland tissues than PA, and ACC . Sex distribution was slightly increase in male in comparison to female in normal salivary gland tissues and PA. GATA 3 staining was showing more positivity in normal salivary gland tissues (43/50 patients) than PA (27/50 patients) and ACC (14/50 patients). This positivity in GATA 3 IHC staining were more in male sex, regarding 55.8% in normal salivary gland tissues than ACC50% and PA 51.9% . Age group 31-40, 40-50 and 61-70 years were showing more positive GATA 3 IHC staining in normal salivary gland tissues, PA, and ACC respectively. there was insignificant association between GATA 3 IHC staining with either age groups or sex groups distribution .Conclusion: GATA3 IHC is good marker and can used for searching salivary gland tumor origin, assisting in diagnosis Salivary gland tumors subtypes but GATA3 IHC staining has no association to specific sex or age groups in Salivary gland tumors. Usage of surgical operations for histopathological specimens preparation are better and give good efficiency for IHC markers staining.

Prognostic impact of Notch1 receptor and clinicopathological High-Risk Predictors in lacrimal gland adenoid cystic carcinoma.

Adenoid Cystic Carcinoma (ACC) is an aggressive malignant lacrimal gland tumour associated with poor prognosis. Aberrant Notch signalling has been investigated in various tumours. However, very few studies on Notch signalling in lacrimal gland ACC are reported. The aim of the present study was to evaluate the status of Notch1 receptor and activated Notch1 (NICD1) in lacrimal gland ACC and to correlate it with high-risk clinicopathological features. A total of 23 cases of histopathologically proven lacrimal gland ACC, who underwent surgical treatment, were included in this study. Expression of Notch1 receptor and NICD1 was evaluated by immunohistochemistry on formalin fixed paraffin embedded tissues. The results obtained were correlated with clinicopathological high-risk features and survival of the patients. Kaplan-Meier survival and multivariate analysis was performed to determine the prognostic significance. Overexpression of Notch1 receptor and NICD1 was observed in 65% and 39% of lacrimal gland ACC cases, respectively. On Kaplan-Meier survival analysis, patients with Notch1 receptor overexpression had reduced disease free survival. On univariate analysis, male gender, bone erosion, perineural invasion, solid histologic pattern, intracranial extension and advanced tumour stage were also indicators of poor prognosis. On multivariate analysis bone erosion was the most significant poor prognostic indicator. Our study demonstrates that overexpression of Notch1 receptor plays a critical role in the biology and aggressive behaviour of lacrimal gland ACC. Bone erosion, solid histologic pattern, advanced T stage, perineural invasion and intracranial extension are other high-risk clinicopathological predictors of lacrimal gland ACC.

Liver Resection for Metastasis of Adenoid Cystic Carcinoma of the Lacrymal Gland : A Case Report and Literature Review

Adenoid cystic carcinoma (ACC) is a rare malignant tumor. The first description of the ACC dates back to 1856 by Billroth. The ACC of the lacrimal glands are very rare. They are known for their locally aggressive character. Liver metastases are almost exceptional. We report the case of a patient with hepatic metastasis ACC. After eye enucleation of the primitive lacrimal gland ACC, the patient received external adjuvant radiotherapy. Three years later, she presented an upper abdominal pain. CT scan and MRI showed a liver tumor and the diagnosis of intrahepatic cholangiocarcinoma was made regarding imaging features. A left hepatectomy was performed; histology concluded to a liver metastasis of ACC. The immediate post-operative course was uneventful and no adjuvant treatment was decided. Thirty four months later, the patient presented with lung metastasis. Liver metastasis of ACC are very rare. Extended liver surgery is recommended especially for isolated liver metastasis with a long free gap between primary tumor and the liver metastasis. Keywords: Adenoid cystic carcinoma, Hepatic metastasis, Lacrymal gland

Adenoid cystic carcinoma of Bartholin's gland diagnosed after lung lobectomy: Review of the literature and a case presentation.

Bartholin’s gland was first identified in human female in 1675 by Caspar Bartholin. The Bartholin gland is composed of several epithelial types: The body is mucinous acini, the duct is predominantly transitional epithelium, and the orifice is the squamous epithelium. Primary carcinoma of the bartholin’s gland is an uncommon neoplasm. Adenoid cystic carcinoma (ACC) of bartholin gland carcinom is a rare variant of bartholin gland carcinoma, comprising 15% of all bartholin gland malignancies. ACC of the Bartholin’s gland is characterized by slow growth so recurrence and distant metastases can take a long period. So distant metastasis has been found in only a few cases to the lungs, liver, bone and brain. Here, we present the case of Bartholin’s gland ACC after four years follow up and presented with a lung metastasis.