Treatment of lacrimal gland adenoid cystic carcinoma:a systematic review and Meta-analysis

AIM:To evaluate lacrimal gland adenoid cystic carcinoma(LGACC)of prognosis in patients who underwent different treatment regimens.METHODS:We searched PubMed,EMBASE,and the Cochrane Library for studies done on the treatment of LGACC,between January 1987 and April 2022.A Metaanalysis was conducted to pool the 5-year overall survival rate(OR),and the 5-year recurrence rate(RR)and 5-year metastasis rate(MR)were assessed.RESULTS:The 30 studies involved 585 patients were included in the Meta-analysis.The pooled 5-year OR with surgery alone was 50%,the 5-year RR was 63%,and the 5-year MR was 34%.The pooled 5-year OR with surgery and adjuvant radiotherapy combined was 67%(95%CI 61%,73%),the 5-year RR was 41%,and the 5-year MR was 35%.The pooled 5-year OR with surgery and adjuvant chemoradiotherapy combined was 72%(95%CI 59%,84%),the 5-year RR was 48%,and the 5-year MR was 36%.The pooled 5-year OR with surgery,intra-arterial cytoreductive chemotherapy,and adjuvant chemoradiotherapy combined was 78%(95%CI 68%,89%),the 5-year RR was 15%,and the 5-year MR was 27%.CONCLUSION:Comprehensive treatment is more effective than surgery alone.Surgery combined with intraarterial chemotherapy and adjuvant chemoradiotherapy seems to add value to the therapeutic effect of comprehensive treatment of LGACC but further high-quality research is required to validate this.

Comparison of biological behavior of lacrimal gland adenoid cystic carcinoma with high-grade transformation cells

AIM:To evaluate the differences between human lacrimal gland adenoid cystic carcinoma with high-grade transformation(LACC-HGT)primar y cells cultured by high-grade transformation tissue and non-high-grade transformation(non-HGT)primary cells cultured by non-highgrade transformation tissue in proliferation,metastasis,drug susceptibility,and genes.METHODS:LACC-HGT primary cells were established by tissue block culture,and the 4^(th)to 10^(th)generation primary cells were selected as research objects.The cells were preliminarily identified by immunofluorescent staining.The differences between non-HGT and LACC-HGT primary cells in terms of proliferation,metastasis,and drug susceptibility were compared by cell counting kit-8(CCK-8)assay,wound healing,and drug sensitivity experiments.Differentially expressed genes were screened using mRNA array.Gene expression was analyzed using real-time quantitative polymerase chain reaction(RT-qPCR).RESULTS:LACC-HGT primary cells were successfully cultured by tissue block culture.Immunofluorescence staining results showed that cytokeratin(CK)and CK7 expression levels were positive in LACC-HGT primary cells.CCK-8 results showed that the proliferation ability of LACCHGT cells was significantly higher than that of non-HGT cells.Wound healing experiment showed that the migration ability of LACC-HGT cells was significantly higher than that of non-HGT cells.LACC-HGT cells were also less sensitive to cisplatin and paclitaxel than non-HGT cells.Compared with non-HGT cells,9566 differentially expressed genes were found in LACC-HGT primary cells,of which 5162 were upregulated and 4404 were down-regulated.The expression of N-acetylneuraminate pyruvate lyase(NPL),MARVEL domain containing 3(MARVELD3),syntabulin(SYBU),and allograft inflammatory factor 1(AIF1)was higher in LACCHGT cells than in non-HGT cells,whereas that of periostin(POSTN)was lower.CONCLUSION:LACC-HGT primary cells have faster proliferation,stronger migration ability,and poorer sensitivity to chemotherapy drugs than non-HGT primary cells.The expression of mRNAs in non-HGT and LACC-HGT primary cells are significantly different.These features are speculated to be the reasons why high-grade transformation tissues exhibit higher malignant degree and poorer prognosis than their counterparts.

RNAi knockdown of C-erbB2 expression inhibits salivary gland adenoid cystic carcinoma SACC-83 cell growthin vitro

Objective：To knockdown the C-erbB2 gene in salivary gland adenoid cystic carcinoma SACC-83 cells using RNA interference,and determine the effect of silencing C-erbB2 on cell proliferation.Methods：C-erbB2-siRNA was transfected into SACC-83 cells.RT-PCR and immunohistochemistry were used to detect C-erbB2 expression in SACC-83 cells.Cell proliferation was measured by the MTT assay and gene knockdown was achieved by RNA interference.Apoptosis was analyzed by flow cytometry.Results：Compared with the control,C-erbB2 mRNA expression was decreased in the C-erbB2-siRNA transfection group,and immunohistochemical analysis indicated that C-erbB2 protein expression was decreased.After C-erbB2-siRNA was transfected for 48 h,absorbance at 570 nm （MTT）was 0.185±0.021 compared with 0.354±0.034,0.299±0.053,and 0.314±0.049 in the blank control,liposome control and negative control siRNA groups,respectively.The differences were statistically significant （P〈0.05）between the C-erbB2-siRNA group and the control groups.Following the C-erbB2 knockdown,the percentage of apoptotic cells was 5.63%compared with 2.04%,2.85%,and 2.98%in the three control groups,respectively.Proliferation of SACC-83 cells was inhibited,and early apoptotic cells were increased.Conclusion： RNA interference can effectively silence C-erbB2 gene expression and inhibit growth of SACC-83 cells,which indicates the potential of targeting this gene as a novel gene therapy approach for the treatment of salivary gland adenoid cystic carcinoma.

Inhibition of Salidroside on Salivary Gland Adenoid Cystic Carcinoma

To evaluate the role of salidroside on proliferation,apoptosis and invasiveness of salivary gland adenoid cystic carcinoma cells（SACC）,immunocytochemical staining was employed to detect proliferating cell nuclear antigen（PCNA）,caspase 3 and caspase 8 expression in SACC-2 cells.Modified Boyden chamber assay combined with laser confocal microscopy（LSCM） was used to evaluate the invasion and migration abilities of SACC-2 cells at different time point.Immunohistochemistry staining revealed that the expression of PCNA was significantly decreased（P0.01） after salidroside treatment.In contrast,salidroside treatment led to increased caspase 3 and caspase 8 in SACC-2 cells.Cell migration depth and number of cells that penetrated Boyden chamber were also decreased by salidroside.Salidroside potently inhibits the proliferation and simultaneously induces the apoptosis of SACC-2 cells.Migration and invasion of SACC-2 cells are also inhibited.Our data throw light on potential clinical application of salidroside to the patients with SACC.

Effects of Genistein on Proliferation and Cell Cycle of Salivary Adenoid Cystic Carcinoma Cells

Objective： To investigate the growth inhibiting effect of tyrosine protein kinase inhibitor, genistein, on human salivary adenoid cystic carcinoma SACC-83 cell line in vitro, and its effects on the expression of CyclinB1 protein and cell cycle. Methods： Effects of genistein on the growth of SACC-83 cells in vitro were measured with MTr assay. Cell cycle was detected with flow cytometry. The expressions of CyclinB1 and Cdkl proteins were measured with Western blot method, and the results of protein expression were quantitatively analyzed by FluorChem V2.0 software. The results were statistically analyzed by SPSSI 1.5 software. Results： Genistein inhibited the cell proliferation in a dose-dependant and time-dependant manner. The genistein-treated SACC-83 cells were arrested in the G2/M phase and had lower contents of CyclinB1 and Cdkl proteins compared with the control group. Conclusion： The growth inhibiting effect of genistein on SACC-83 cells may be associated with the regulations of genistein on the CyclinB1 and Cdk1 protein expressions and the cell cycle.

EXPRESSION OF EPIDERMAL GROWTH FACTOR RECEPTOR IN DIFFERENT SALIVARY ADENOID CYSTIC CARCINOMA CELL LINES

Objective： To investigate the expression of epidermal growth factor receptor, a receptor tyrosine protein kinase, in the subcellular fractions of human salivary adenoid cystic carcinoma cell lines SACC-83 and SACC-LM. Methods： Low metastatic and high metastatic cells of the adenoid cystic carcinoma, SACC-83 and SACC-LM, were cultured. Their subcellular fractions were extracted. The expression of epidermal growth factor receptor was detected with Western blot method, and the results of protein expression were quantitatively analyzed by FluorChem V2.0 software. Results： The results of Western blot analysis indicated that, EGFR expression on the membrane of SACC-83 cells was significantly higher than that of SACC-LM cells, but its expression in cytoplasm was significantly less in the former than the later （P〈0.01）. In SACC-83 cell line, EGFR was over-expressed in membrane （P〈0.01）, but in SACC-LM cell line, EGFR was over-expressed in cytoplasm （P〈0.01）. Conclusion： The results suggest that the obtaining of metastasis ability is related to the high expression of EGFR protein in cytoplasm, so the molecular targeting therapy to EGFR may be an ideal treatment for the invasion and metastasis of salivary adenoid cystic carcinoma.

STUDIES OF TISSUE CULTURE ON THE ADENOID CYSTIC CARCINOMA OF SALIVARY GLANDS

In this paper, the authors gave a synthetic report about sutdies of tissue culture on adenoid cystic carcinomas from human salivary glands. It includes the process of establishment of Acc-2 and Acc-3 cell lines, observations to the cellular morphostructures, chromosome analysis, proliferative kinetics and some cellular physiological functions. All of these observations confirm that two cell lines have obvious malignant natures, epithelial and glandulous cellular features as well as. Both of cell lines have provided the useful experimental models in vitro for research on histogenesis and biological behaviours at adenoid cystic carcinoma and seeking new methods of clinical treatment.

EXPRESSIONS OF P_(53), PROLIFERATING CELL NUCLEAR ANITIGEN,BCL-2 PROTEIN AND THEIR SIGNIFICANCE IN SALIVARY ADENOID CYSTIC CARCINOMA

Objective To study the effects of P53, PCNA, Bc1-2 protein and their relationship in salivary adenoid cystic carclnoma(SACC). Methods These protelns were examlned by lmmunohistochemistry. Results overexpressions of Ps, and PCNA were revealed in ACC samples, they were higher than those in (polymorphous adenomas) PA, but expression of Bc1-2 protein was not different between ACC and PA. In 3 subtypes of ACC, expressions of 3 proteins were different. Conciusion Mutations of P53, Bc1-2 may be involed in the occurrence of SACC, expression of PCNA and mutation of P53 may coexist in the development of the SACC.

Adenoid Cystic Carcinoma of Parotid Salivary Gland—A Case Study

Adenoid Cystic Carcinoma (ACC) is an infrequent slow growing epithelial tumour constituting for around less than 1% of all the oral and maxillo-facial malignancies and almost 10% of all the salivary gland tumors. Parotid gland is the second most common site to be involved in the head and neck region along with submandibular gland, Palate being the most common site involved in the oral cavity. Key feature of these tumors include its asymptomatic presentation, indolent nature, typically showing infiltrative growth and peri-neural invasion. Herein, we report a case of adenoid cystic carcinoma of right parotid gland of a 33-year-old male who presented with complaint of painless slow enlargement of left parotid gland and facial muscle weakness. On Examination firm mass in the region of the left parotid gland as well as left facial paralysis was seen. Biopsy results and further management is discussed here within.

Nerve Growth Factor and Vascular Endothelial Growth Factor: Retrospective Analysis of 63 Patients with Salivary Adenoid Cystic Carcinoma

Aim To detect the expression of nerve growth factor （NGF） and vascular endothelial growth factor （VEGF） in salivary adenoid cystic carcinoma （SACC） tissues, as well as to determine the correlation between growth factor expression and prognosis in SACC. Methodology Medical records of 63 patients surgically treated for SACC between January 1988 and October 2005 were reviewed. Immunohistochemistry was performed to examine the expression of NGF and VEGF in tumor tissues. Kaplan-Meier analysis and Cox＇s proportional hazard regression model were applied to assess predictors of survival. Results NGF and VEGF were overexpressed in SACC tissues, compared with those in normal salivary tissues （P〈0.05）, and the staining intensity of these two factors was stronger in groups of solid subtype, advanced TNM stage, perineural invasion and recurrence. Patients with high- expression of NGF and VEGF, solid subtype, advanced stage, perineural invasion, recurrence and extended resection alone had worse survival rates （P〈0.05）. Conclusion NGF and VEGF are expressed increasingly in the tissues of SACC cases with invasion and metastasis. NGF expression and VEGF expression are independent prognosis factors for survival.

Expressions of chemokine receptor CXCR4 and its ligand CXCL12 in salivary adenoid cystic carcinoma

Objective: To examine expressions of chemokine receptor CXCR4 and its ligand CXCL12 in primary focus and lymphogenous metastasis of salivary adenoid cystic carcinoma (ACC) with lung metastasis. Methods: Using immunohistochemical hypersensitivity catalyzed signal amplification (CSA), expressions of chemokine receptor CXCR4 and ligand CXCL12 were detected in tissue specimens from 20 cases of primary cancer focus and lymphogenous metastasis of salivary adenoid cystic carcinoma, of which 7 cases were associated with lung metastasis and 3 with lympogenous metastasis. Twenty cases of tongue carcinoma (including 10 cases with lymphogenous metastasis) and 15 cases of mucoepidermoid carcinoma (including 5 cases with lymphogenous metastasis) were used as the malignant control group;and salivary mixed tumor (n=10), tongue leukoceratosis (n=10) and cervical lymph node reactive hyperplasia (n=10) were used as the benign control group. Results: Expression of CXCR4 in the tissues and lymph metastases of oral and maxillofacial salivary ACC, mucoepidermoid carcinoma and tongue carcinoma was significantly higher than that of the benign control group (P<0.05); expression of CXCR4 in the primary focus of ACC was significantly higher than that of the malignant control group; and expression of CXCR4 in the ACC with lung metastasis was 87.1% (6/7), significantly higher than that without lung metastasis(P<0.01). There was evident positive expression of CXCL12 in endotheliocytes of microvessels within cancer and paracancer tissues and significantly high expression of CXCL12 in lymphogenous metastasis(P<0.05). Conclusion: Chemokine receptor CXCR4 and its ligand CXCL12 may be associated with local invasion and lymphogenous metastasis of oral and maxillofacial cancer, especially with lung metastasis of salivary ACC.

ANTIMETASTATIC EFFECT OF INTEGRIN IIb/IIIa INHIBITORSON SALIVARY ADENOID CYSTIC CARCINOMA

Objectives: To investigate the relation between metastatic potential of salivary adenoid cystic carcinoma (SACC) and tumor cell-platelet adhesion, and the antimetastatic effect of integrin IIb/IIIa inhibitor on SACC. Methods: Tumor cell-platelet adhesion of highly metastatic SACC-LM, non-highly metastatic SACC-83 and effect of aspirin, arginine-aspartate (RD), magnesium acetylsalicylate on adhesion were studiedin vitro. Antimetastafic effect of aspirin, RD, magnesium acetysalicylate on experimental metastasis of SACC was observedin vivo. Results: The tumor cell-platelet adhesion was stronger in SACC-LM than in SACC-83. Aspirin, RD and magnesium acetylsalicylate could inhibit the adhesion of SACC-LM at the concentration of 1, 5 and 25 μg/ml. RD can inhibit experimental metastasis of SACC. Conclusion: Metastasis of SACC is related to platelet-tumor cell adhesion, RD could inhibit metastasis of SACC.

Similar therapeutic effects of ^(125I) seed radiotherapy andγ-ray radiotherapy on lacrimal gland adenoid cystic carcinoma

AIM:To evaluate the survival outcomes of patients with lacrimal gland adenoid cystic carcinoma who underwent eye-sparing surgery combined with ^(125I)seed implantation radiotherapy or local externalγ-ray radiotherapy.METHODS:In this retrospective comparative case series,the clinical records of 27 primary and 8 recurrent patients were reviewed.Univariate and multivariate analyses were used to identify risk factors associated with distant metastasis(DM),and the overall survival(OS)after the initial surgery was analyzed.RESULTS:The median follow-up after radiotherapy was 36 mo(range 6-120 mo).At the last follow-up after radiotherapy,26(74.3%)patients had no evidence of disease,7(20%)patients had DM,2(5.9%)patients died of DM,and 1 patient with DM was lost to follow-up.Univariate analyses showed that duration of symptoms,bone destruction,T stage classification,and wide excision surgery were risk factors influencing DM(P<0.05).The 5-year and 10-year OS rates after the initial surgery were 95.8%and 79.9%,respectively.The 5-year DM-free survival and disease-free survival rates after radiotherapy were 66.4%and 52.7%,respectively.CONCLUSION:^(125I)seed radiotherapy and local externalγ-ray radiotherapy may have similar therapeutic effects in preventing DM.Patients with T1/T2 stage disease have a better prognosis than those with T3/T4 stage disease.

Adenoid cystic carcinoma of the Bartholin's gland:a case report and review of the literature

Adenoid cystic carcinoma(ACC) of the Bartholin's gland is a rare malignant tumor of vulvar which is characterized by slow growth,local invasion and perineural infiltration.The survival rates for 10 years range from 50% to 100%.The disease free interval for 10 years range from 33% to 38%.Currently,there is no consensus on the treatment of ACC of the Bartholin's gland.Primary surgery includes wide local excision or radical vulvectomy with or without lymph node dissection.Adjuvant radiotherapy and chemotherapy are advocated for the treatment of this cancer.Work is still needed to identify an effective systemic therapy.

Pleomorphic Adenoma with Exuberant Squamous Metaplasia and Keratin Cysts Mimicking Squamous Cell Carcinoma in Minor Salivary Gland

Salivary gland tumors, the second most common neoplasm of the mouth after squamous cell carcinoma, account for a significant proportion of tumors of the oral and perioral regions. An unusual case of adenoma presented as a solitary intraoral palatine mass in a 32-year-old woman is reported here. The tumor was interpreted as an unusual pleomorphic adenoma because of the presence of exuberant squamous metaplasia, clinically mimicking squamous cell carcinoma. Moreover, the presence of cystic structures filled with keratinized material was also salient feature. Pleomorphic adenomas may occasionally display focal squamous metaplastic changes;when extensive, it presents the potential for misinterpretation of the histology as indicative of well-differentiated squamous cell carcinoma.

Effect of Exogenous bFGF on the Proliferation of Human Adenoid Cystic Carcinoma ACC-2 Cells

To observe the effects of basic fibroblast growth factor （bFGF） on human adenoid cystic carcinoma ACC-2 cell line proliferation and ERK, cyclin D1/p21^waf/cip1 signaling pathways, human adenoid cystic carcinoma cells （ACC-2） were cultured and the influence of bFGF of different concentrations on cell proliferation was determined by MTT. Protein was detected by immuno-precipitation and ERK activity by using ERK agent kit. p-ERK1/2 and down-stream cyclin D1, p21^waf/cip1 expression were detected by Western blotting and the interfering role of mitogen protein-activated kinase （MEK） suppressor U0126 in the afore-mentioned indicators was examined. MTT demonstrated ACC-2 cell proliferation was substantially enhanced by bFGF, immuo-precipitation displayed ERK activity was up-regulated by bFGF, and immuno-imprinting also showed p-ERK1/2, cyclin D1 expression was greatly enhanced and p21^waf/cip1 expression was inhibited by bFGE U0126 suppressed the effect of bFGF. It is concluded that bFGF can promote the proliferation of human adenoid cystic carcinoma ACC-2 cells, and its pathways are associated with the up-regulated activity and expression of p-ERK1/2, inhibited p21waf/cip1 expression and enhanced cyclin D1 expression.

Liver metastasis as the initial clinical manifestation of sublingual gland adenoid cystic carcinoma: A case report

BACKGROUND Adenoid cystic carcinoma(ACC)is a common malignant tumor of salivary gland.The lung and liver are frequent sites of distant metastasis.Liver metastasis as the initial clinical manifestation of sublingual gland ACC is very rare.CASE SUMMARY A 51-year-old Chinese woman presented with a painless mass in the right lobe of liver.The tumor was composed of ductal cells and myoepithelial cells with a morphology including tubiform and cribriform structures.Immunostaining results showed ductal cells positive for CK7,CK14,CK19,CD117,and 34βE12,and negative for MYB,vimentin,ER,PR,and CEA.The myoepithelial cells were positive for p63,calponin and CK5/6.Metastatic salivary ACC was considered,and a sublingual gland mass was revealed by computed tomography.Histological evaluation confirmed primary sublingual gland ACC.Fluorescence in situ hybridization(FISH)did not find an MYB-NFIB fusion gene in specimens from either the primary or metastatic ACC tumors.The sublingual gland ACC relapsed in 20 mo.The recurrent lesion disappeared following local radiation therapy and computed tomography-guided radioactive seed implantation.The patient remains in good condition until now.CONCLUSION Metastatic sublingual gland ACC with initial clinical manifestation as a liver mass is very rare,and was pathologically confirmed in this patient by its histological appearance.Primary hepatic tumors and metastatic carcinomas should be included in the differential diagnosis.Immunohistochemical detection of MYB protein and MYB-NFIB fusion gene detection by FISH can be helpful,but occasional negative results confuse the diagnosis.

Atypical Cystic Parotid Gland Acinic Cell Carcinoma in a Child

Purpose: To describe the extremely rare occurrence of acinic cell carcinoma of the parotid in a young child. Materials & Methods: A 14-year-old boy presented with a left sided facial mass. It was initially thought to be a bug bite or perhaps a wrestling injury. However, it progressed rapidly overall several weeks. CT revealed a well-circumscribed, cystic, 3.9 × 2.8 × 3.2 cmmass centered in the deep lobe of the left parotid gland, also involving the superficial lobe and extending medially through the stylomandibular tunnel with a component extending to the stylomastoid foramen. There was no solid enhancing portion. There were several enlarged level II lymph nodes suspicious for nodal metastases. Results: The mass was biopsied and pathology was consistent with acinic cell carcinoma. Complete left parotidectomy and left selective neck dissection was performed, confirming the diagnosis. Conclusions: Salivary gland neoplasms are rare in children. Less than 5% of salivary gland tumors occur in children. Salivary gland neoplasms account for less than 8% of pediatric head and neck tumors. Approximately 1/3 of salivary gland tumors arising in childhood are malignant;most being mucoepidermoid. Acinic cell carcinoma of the parotid gland in children is extremely rare, especially in those under age 16, with only a few available case reports. This case was also unusual in that the lesion was predominantly cystic.

Clear cell carcinoma of salivary gland type presenting as an endotracheal polypoid tumor

A 66-year-old woman presented with a 2-year history of asthma has progression of dyspnea within a week, and a computed tomography (CT) revealed an endotracheal tumor at level of aortic arch. The resected tumor, measured by 18 × 12 × 10 mm, has histologically malignant features including frank invasion with desmoplastic stroma and foci of necrosis. Presence of glycogen and mucin was confirmed by periodic acid-Schiff (PAS) and diastase PAS staining. Immunohistochemically, the tumor cells were diffusely positive for cytokeratin (CK) 7 and AE1/3, focally positive for CK5/6 and CK14, but negative for CK20. Thyroid transcription factor-1 (TTF-1), Napsin A, and SP-A, indicating lung parenchymal origin were all negative. Other muscular markers, neuroendocrine markers, renal cell carcinoma markers, and markers related to perivascular epithelioid cell tumors were all negative. Postoperative systemic examination suggests no primary tumor outside the lung. The follow up was excellent being recurrence free for 14 months in spite of the positive surgical margin by the tumor cells. This is a first report ?of rare neoplasm, clear cell carcinoma of salivary gland type, presenting as an endotracheal mass.

Prognostic factors for lacrimal gland adenoid cystic carcinoma:a retrospective study in Chinese patients

AIM:To explore the prognostic factors for lacrimal gland adenoid cystic carcinoma(LGACC)in Chinese patients.METHODS:Clinical and histopathological data were reviewed in patients with pathologically confirmed LGACC.Local recurrence,metastasis,and disease-specific death were the main outcome measures.Univariate and multivariate analyses were performed by the Kaplan-Meier method and a Cox proportional hazard model.RESULTS:This retrospective cohort study included 45 patients with pathologically confirmed LGACC between January 2008 and June 2022.Tumor(T)classification(P=0.005),nodal metastasis(N)classification(P=0.018)and positive margin(P=0.008)were independent risk factors of recurrence;T(P=0.013)and N(P=0.003)classification and the basaloid tumor type(P=0.032)were independent risk factors for metastasis;T classification(P<0.001)was an independent factor of death of disease.In the further analysis,the durations from first surgery to radiotherapy is correlated with metastatic risk in LGACC patients with basaloid component(P=0.022).CONCLUSION:Histological subtype should be emphasized when evaluating prognosis and guiding treatment.Timely radiotherapy may reduce the risk of metastasis in patients with basaloid component.