• The Korean Journal of Cytopathology
• /
• v.1 no.2
• /
• pp.175-178
• /
• 1990

A case of metastatic adenoid cystic carcinoma of the lung, originated from the trachea, was diagnosed by fine needle aspiration. Although the cytologic features of adenoid cystic carcinoma have been well described, it is easy to confuse adenoid cystic carcinoma with more common primary small cell neoplasms of the lung, i.e., small cell carcinoma, well differentiated adenocarcinoma, and carcinoid tumor of the lung. The features distinguishing adenoid cystic carcinoma from these neoplasms include 1) tight, globular, honeycomb pattern of cells, 2) acellualr basement membrane material in the lumen, and 3) cells lacking true nuclear melding and having bland chromatin pattern. The morphologic feature of metastatic adenoid cystic carcinoma in this case was so distinctive as to permit a definite diagnosis by aspiration cytology.

• The Korean Journal of Cytopathology
• /
• v.9 no.2
• /
• pp.207-211
• /
• 1998

Adenoid cystic carcinoma of the uterine cervix is a rare tumor accounting for less than 1% of all cervical adenocarcinoma. This tumor is characterized by aggressive biological behavior with frequent local recurrence or metastatic spread, postmenopausal onset, and occasional association with conventional squamous cell carcinoma. The cytologic diagnosis of adenoid cystic carcinoma in the uterine cervix is often difficult because of negative smear due to intact overlying mucosa, cytologic findings mimicking endometrial cells, and masquerade as squamous ceil carcinoma. Recently we have experienced a case of adenoid cystic carcinoma arising in the uterine cervix, which was identified on the routine Papanicolaou smear and was histologically confirmed by the consequent biopsy. The smear showed abundant cellularity composed of relatively uniform cells. The tumor cells were arranged in small clusters, acini, naked cells, and loose sheets with abortive cribriform pattern. There were scattered globoid basement membrane-like materials and tumor diathesis. The nuclei were pleomorphic and showed hyperchromatic and coarsely granular choromatin with inconspicuous nucleoli. The punch biopsy of the uterine cervix showed typical histologic findings of adenoid cystic carcinoma characterized by tumor nests composed of hyperchromatic uniform basaloid cells, cribriform pattern, and cylindrical hyaline bodies.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.33 no.2
• /
• pp.81-93
• /
• 2007

Purpose: Adenoid cystic carcinoma (ACC) is a relatively rare tumor that arises in glandular tissues of the head and neck region and sometimes has a protracted clinical course with perineural invasion and delayed onset of distant lung metastasis. Treatment failure of salivary ACC is most often associated with perineural and hematogenous tumor spread. However, very little has been known about the cellular and molecular mechanisms of perineural invasion and hematogenous distant metastasis of parotid ACC. This study was designed to develop an orthotopic tumor model of parotid adenoid cystic carcinoma in athymic nude mice. Experimental Design: A melanoma cell line was injected into the parotid gland of athymic mice to determine whether such implantation was technically feasible. A parotid ACC cell line was then injected into the parotid gland or the subcutaneous tissue of athymic mice at various concentrations of tumor cells, and the mice were thereafter followed for development of tumor nodule. The tumors were examined histopathologically for perineural invasion or regional or distant lung metastasis. We used an oral squmous cell carcinoma cell line as control. Results: Implantation of tumor(melanoma) cell suspension into the parotid gland of nude mice was technically feasible and resulted in the formation of parotid tumors. A parotid ACC cell line, ACC3 showed no significantly higher tumorigenicity, but showed significantly higher lung metastatic potential in the parotid gland than in the subcutis. In contrast, mucosal squmous cell carcinoma cell line doesn’t show significantly higher lung metastatic potential in the parotid gland than in the subcutis. The ACC tumor established in the parotid gland seemed to demonstrate perineural invasion of facial nerve, needs further study. Conclusion: An orthotopic tumor model of salivary ACC in athymic nude mice was successfully developed that closely recapitulates the clinical situations of human salivary ACC. This model should facilitate the understanding of the cellular and molecular mechanisms of tumorigenisis and metastasis of salivary ACC and aid in the development of targeted molecular therapies of salivary ACC.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.27 no.2
• /
• pp.110-122
• /
• 2005

Adenoid cystic carcinoma (ACC) of salivary glands has a protracted clinical course with perineural invasion, delayed onset of hematogenous metastasis, and poor responses to classical cytotoxic chemotherapic agents. Most deaths from salivary ACC are caused by lung metastases that are resistant to conventional therapy. Therefore, knowledge of cellular properties and tumor-host interactions that influence the dissemination of metastatic cells is important for the design of more effective therapy of salivary cancer. I determined in vitro expression of epidermal growth factor receptor (EGFR) and its downstream effectors and vascular endothelial growth factor receptor (VEGFR)-2 on a human salivary ACC cell line (ACC2). I also evaluated the expression of EGF and VEGF signaling molecules and metastasis-related proteins on human salivary ACC cells orthotopically growing in nude mice. In Western blot and immunohistochemical analyses, EGFR and VEGFR-2 were presented and phosphorylated in ACC2 cells. In human parotid cancer xenografts in nude mice, EGF and VEGF signaling molecules, IL-8, and MMP-9 were expressed at markedly higher levels than in normal parotid tissues. Moreover, tumor-associated endothelial cells of this orthotopic parotid tumor expressed phosphorylated VEGFR-2 and phosphorylated Akt, which is a cell-survival protein. These data show that those biomarkers can be molecular targets for therapy of salivary ACC, which has a propensity for delayed lung metastasis.

• Tuberculosis and Respiratory Diseases
• /
• v.41 no.5
• /
• pp.579-583
• /
• 1994

A 22-year old female visited CNUH due to palpable neck mass. Cytologic examination of a fine needle aspiration was performed and the result was Pap class II. Routine chest x-ray shows solitary pulmonary nodule. For rule-out malignancy, FNA at neck mass was repeated and pathologic finding was dysplasia. She was admitted to MI department for evaluation of solitary pulmonary nodule and percutaneous needle aspiration was done. Pathologic diagnosis was adenoid cystic carcinoma. Thereafter, the lesions were treated by excisional biopsy of submandibular gland mass with left supraomohyoid neck dissection and wedge resection of right lower lobe at ENT department and thoracic and cardiovascular surgery department, respectively. Final diagnosis was adenoid cystic carcinoma arising in submandibular gland with solitary lung metastasis. According to TMN staging system, surgical staging is stage IV of T2N0M1. Clinical follow-up to postoperative 13 months in this case showed that she is alive and well without evidence of recurrence.

• The Korean Journal of Cytopathology
• /
• v.4 no.2
• /
• pp.111-120
• /
• 1993

Fine needle aspiration cytology has become a frequently used technique for the diagnosis of lesions in the head and neck. Fine needle aspiration cytology of the salivary glands were performed on 66 patients. In 59 patients with satisfactory samples, cytologic diagnoses were as follows; there were 47 benign lesions, including pleomorphic adenoma(20), Warthin's tumor(3), benign cystic lesion(4), Inflammatory lesion(4), lymphoid lesion(3), myoepithelioma(1), unspecified benign neoplasm (5), and unclassified benign lesion(7). There were 6 cases of undetermined malignancy and 6 malignant lesions including mucoepidermoid carcinoma(3), adenoid cystic carcinoma(1), carcinoma ex pleomorphic adenoma(1), and metastatic carcinoma(1) in cytologic diagnosis. In 25 patients, the cytologic diagnosis was correlated with histologic findings. The sensitivity of the benign lesion was 96% and the specificity was 82%. There was no false-positive diagnosis. The sensitivity and the specificity of pleomorphic adenoma were 75% and 95%, respectively. Some of Warthin's tumors were confused with benign cystic lesion due to frequent cystic change of the tumor. The sensitivity and specificity of the malignant lesions were 56% and 88%, respectively. There were three false negative diagnoses. Two mucoepidermoid carcinomas were correctly diagnosed by cytology. Two of three adenoid cystic carcinomas were misdiagnosed as benign tumors.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.34 no.1
• /
• pp.59-70
• /
• 2008

Purpose: We evaluated the therapeutic effect of AEE788, a dual inhibitor of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) receptor tyrosine kinases on human salivary adenoid cystic carcinoma (ACC) cells growing in nude mice. Experimental Design: We examined the effects of AEE788 on salivary ACC cell growth and apoptosis. To determine the in vivo effects of AEE788, nude mice with orthotopic parotid tumors were randomized to receive oral AEE788 (50 mg/kg) three times per week, injected paclitaxel ($200{\mu}g$) once per week, AEE788 plus paclitaxel, or placebo. Mechanisms of in vivo AEE788 activity were determined by immunohistochemical analysis. Results: Treatment of salivary ACC cells with AEE788 led to growth inhibition and induction of apoptosis. AEE788 inhibited tumor growth and prevented lung metastasis in nude mice. Furthermore, AEE788 potentiated growth inhibition and apoptosis of ACC tumor cells mediated by paclitaxel. Tumors of mice treated with AEE788 and AEE788 plus paclitaxel exhibited down-regulation of activated EGFR and its downstream mediators (Akt and MAPK), increased tumor and endothelial cell apoptosis, and decreased microvessel den-sity, which correlated with a decrease in the level of MMP-9, MMP-2 and bFGF expression and a decrease in the incidence of vascular metastasis. Conclusions: These data show that tumor-associated endothelial cells are important in the process of tumor-metastasis. And VEGFR can be a molecular target for therapy of metastatic lung lesion of salivary ACC.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.36 no.3
• /
• pp.177-185
• /
• 2010

Introduction: Epidermal growth factor receptor (EGFR) is expressed in human epithelial tumors including salivary cancers, and known to be correlated with tumor progression and poor clinical courses in some epithelial tumors. In this study, we determined the therapeutic effect of the anti-EGFR monoclonal antibody Erbitux (C225, cetuximab) in combination with the DNA topoisomerase I inhibitor irinotecan (CPT-11) on human salivary adenoid cystic carcinoma (SACC) cells growing in nude mice. Materials and Methods: At first, immunocytochemical analysis for the expression of EGFR and phosphorylated EGFR (pEGFR) on a human salivary ACC cell line (ACC3). To determine the in vivo effects of Erbitux and CPT-11, nude mice with orthotopic parotid tumors were randomized to receive intraperitoneal Erbitux (1 mg) two times per week, intraperitoneal Irinotecan (50 mg/kg) once per week, Erbitux plus CPT-11, or placebo. (control) Tumor volume and weight were measured. And mechanisms of in vivo activity of Erbitux and/or CPT-11 were determined by immunohistochemical/ immunofluorescent analyses. Results: Immunocytochemical staining of ACC3 demonstrated that EGFR was expressed and phosphorylated. CPT-11 inhibited ACC tumor growth in nude mice. Tumors of mice treated with CPT-11 and CPT-11 plus Erbitux exhibited increased tumor cell apoptosis and decreased microvessel density, which correlated with a decrease in the tumor volume in nude mice. But, CPT-11 seems not to be synergistic with Erbitux in our ACC3 model system. Conclusion: These results suggest that anti-EGFR monoclonal antibody and the DNA topoisomerase I inhibitor will be effective in the treatment of recurred or metastatic lesions of salivary ACC.

• The Korean Journal of Cytopathology
• /
• v.2 no.2
• /
• pp.90-97
• /
• 1991

Liver is generally known as an organ which is most commonly involved by the metastic tumors. According to the tendency of using fine needle aspiration in the diagnosis of hepatic tumors, the differentital diagnosis between hepatocellular carcinoma and metastatic carcinoma frequently has been a main issue in the poorly differentitated cases, especially to the pathologists of Korea, an endemic area of hepatocellular carcinoma. Until now the problem has been usually solved by the comparison of cytologic characteristics of their tumor cells but not by background cytologic features which rarely have been studied. We observed the background cytologic features helpful for the differential diagnosis through the analysis of 20 cases who had confirmed primary cancer and were diagnosed as metastatic carcinomas in the liver by fine needle aspiration cytology. Twenty cases included 9 adenocarcinomas, 7 spuamous cell carcinomas, 1 small cell carcinoma, 1 carcinoid, 1 adenoid cystic carcinoma, and 1 renal cell cacinoma. Analysis of background cytologic features revealed that 77% of adenocacinoma cases showed benign mesenchymal components and hepatocytes and spuamous cell carcinoma cases disclosed benign mesenchymal tissue (71%) and necrosis (57%), Remaining cases showed variable combinations of benign mesenchymal component, necrosis, hepatocytes, and bile duct epithelial cells. No case revealed atypical hepatocytic naked nuclei, a useful cytologic finding of hepatocellular carcinoma. In summary, the background cytologic features more commonly observed in metastatic carcinomas than in the hepatocellular carcinoma were benign mesenchymal components, hepatocytes, necrosis, and bile duct epithelium. The endothelial cells and hepatocytic naked nuclei, two relatively specific findings of hepatocellular carcinoma were not observed except for renal ceil carcinoma. Above background cytologic features are thought to be helpful for the differential diagnosis between the hepatocellular carcinoma and various metastatic carcinomas in the poorly differentiated cases.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.32 no.6
• /
• pp.530-543
• /
• 2006

Adeonoid cystic carcinoma (ACC) is one of the most common malignant tumors of salivary glands. It is characterized by a relentless regrowth especially around nerve tissues and a high rate of hematogenous distant metastasis. Clinically most deaths from salivary ACC are caused by delayed lung metastases that are resistant to conventional chemotherapy. So, knowledge of cellular and molecular properties that influence the dissemination of metastatic tumor cells, is important for new treatment strategies of metastatic lesions. We determined expressions of angiogenic signaling molecules microvessel density (MVD) using surgical specimens of human salivary ACC. Protein expressions of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR)-2, activated VEGFR-2, and human CD31 were assessed in 20 cases of salivary ACC by immunohistochemical staining. Most of the tumors, especially ACC with a tubulocribriform pattern, were positive for antibodies of VEGF, VEGFR-2, and activated VEGFR-2. The overall percentages of the 20 specimens expressing VEGF, VEGFR-2, activated VEGFR-2 were 90, 95, and 95%, respectively. Immunoreactivities of the biomarkers in salivary ACC were higher than those in normal salivary gland. Furthermore, immune-related cells as well as tumor cells expressed VEGF/VEGFR-2. Microvessel density of salivary ACC was higher than that of normal salivary gland (P<0.05). Taken together, angiogenic signaling molecules are actively expressed in salivary ACC. And we suggest that these molecules may have critical role in the hematogenous spread of salivay ACC, which has a propensity for delayed lung metastasis. Therefore, these biomarkers can be molecular targets for therapy of metastasis of salivary ACC.