• Korean Journal of Head & Neck Oncology
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• v.18 no.2
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• pp.157-162
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• 2002

Background and Objectives: Adenoid cystic carcinoma (ACC) is a unique tumor characterized by frequent and delayed distant metastasis (DM) with uncommon regional lymph node metastasis. We evaluated the factors affecting DM of ACC and survival after appearance of DM. Materials and Methods: Medical records, radiographs and pathologic slides were reviewed for 94 patients from 1979 through 2001. Results: DM of ACC occurred in 46 patients, and developed more frequently in patients with tumors of the solid histologic subtype than in patients with tubular or cribriform subtypes. DM occurred less frequently in the sinonasal tract, and development of DM was not affected by tumor stage. Disease-specific 5- and 10-year survival rates were 88% and 72% for patients without DM, respectively and 76% and 48% for those with DM(p=0.02). Regarding the site of DM and its impact on outcomes, 30 patients had lung metastasis alone, 5 patients bone metastasis alone and 6 patients developed both lung and bone metastasis. Median survivals after appearance of DM among patients with isolated lung metastases and those with bone metastases with or without lung involvement were 54 and 21 months, respectively (p=0.04). Conclusions: Development of DM in ACC is predicted by solid histologic subtype, and major salivary gland or oral/pharyngeal rather than sinonasal primary site. Those patients with bone involvement with our without lung metastases had worse outcomes than those with pulmonary metastasis only.

• Korean Journal of Head & Neck Oncology
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• v.9 no.1
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• pp.74-87
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• 1993

Immunohistochemical studies on S-100 protein and lactoferrin were carried out to evaluate the existence and distribution pattern of S-100 protein and lactoferrin positive cells in salivary gland tumors. The specimens used were 25 cases of pleomorphic adenoma, 2 cases of monomorphic adenoma, 2 cases of mucoepidermoid tumor, 2 cases of acinic cell tumor, 3 cases of adenoid cystic carcinoma and 2 cases of adenocarcinoma occured in parotid and submandibular salivary gland. ABC kits(Dako corp. Copenhagen. Denmark) for S-100 protein and lactoferrin were used. The results obtained were summarized as follows: In the normal salivary gland. positive immunoreaction for S-100 protein was observed in myoepithelial cells of acini and intercalated ducts. Positive immunoreaction for lactoferrin was observed in serous acinic cells, epithelial cells of intercalated ducts, and excretory material in the ductal lumina. In the pleomorphic and monomorphic adenomas. most of tumor cells were positive for S-100 protein, while luminal tumor cells in gland-like or duct-like structures were rarely positive for lactoferrin. In mucoepidermoid tumor, most of squamous cells and a few of intermediate cells were positive for S-100 protein, but all of tumor cells were negative for lactoferrin. In acinic cell tumor, most of tumor cells were positive for lactoferrin, but all of tumor cells were negative for S-100 protein. In adenoid cystic carcinoma, basaloid tumor cells in trabecular structure were focally positive for S-100 protein. and in adenocarcinoma, many of tumor cells were posivive for both S-100 protein and lactoferrin. Thus, according to the embryonic stage of the development of the tumor cell origin, it was possible to classify the salivary gland tumor as followings: mucoepidermoid carcinoma which originated from the earliest stage, acinic cell tumor which originated from the end stage. Between these two extremes, there were pleomorphic adenoma, adenoid cystic carcinoma and adenocarcinoma which originated in the middle stage of the development of .the salivary glands. Based on the above results, it can be stated that S-100 protein is demonstrated in tumor cells orginated from myoepithelial cells and lactoferrin in glandular differentiated tumor cells.

• Radiation Oncology Journal
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• v.17 no.4
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• pp.293-298
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• 1999

Intracranial involvement by adenoid cystic carcinoma (ACC) is very rare and there is no report of intracranial extension from the palate ACC in Korea. Intracranial involvement can occur in one of three ways: direct extension, perineural spread, and hematogenous spread. A case report of a 35-year-old woman with intracranial ACC is presented. Initially she had ACC of the right palate and was treated by surgery and postoperative radiation therapy. Three years and 10 months later, the paresthesia in the distribution of ophthalmic and maxillary branch of right trigeminal none developed without evidence of recurrence in CT scan. Ptosis and total ophthalmoplegia developed sequentially and the second operation was peformed. It was suggested that the tumor was spread perineurally along the trigeminal news into the Gasserian ganglion and then cavernous sinus and orbit. Seven years and 6 months after the first operation, direct intracranial extension into the right temporal lobe developed via sphenoid bone, sphenoid sinus and temporal bone and the third operation was done. And then lung metastasis was diagnosed. She is alive for 9 years 5 months after first operation.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.31 no.4
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• pp.339-342
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• 2009

Adenoid cystic carcinoma(ACC) is the second most common malignant neoplasm in the salivary gland. In spite of ACC shows slowly growing nature, it is sometimes highly detrimental that it readily invades adjacent tissues and metastasize to distant organs at the early stage of disease. Hence, treatment outcome may be misfortunate due to wide regional infiltration, pathognomonic perineural spread and the tendency of hematogenous metastasis. We present a unusal case of ACC of the scalp in which the patient initially presented with bumpy mass of the scalp who had been diagnosed as the primarily developed ACC of the right hard palate that extended to infratemporal fossa, nasal cavity, and paranasal sinuses and had been treated by total excision and post-operative chemotherapy and radiation therapy for 10 years ago. Although this lesion occured at the scalp, which is a frequent site of primary dermatologic ACC, its histomorphology was the same with that of previous tumor. Complete clinical examination showed no recurrence sign at the primary site and suggested the scalp as a sole treatment failure site. Accordingly, it would be reasonable to consider the present case as either a scalp metastasis or a second primary lesion of salivary gland ACC.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.4
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• pp.427-434
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• 2000

The authors analyzed retrospectively the 36 patients with malignant salivary gland tumors who were treated at Department of Oral and Maxillofacial Surgery, Pusan National University Hospital from February, 1989 to September, 1997. The results obtained were as follows: 1. There were 14 males(38.9%) and 22 females(61.1%). The peak age of patients with major salivary gland tumors was the 6th decade, but with minor salivary gland was the 5th decade. 2. Of all salivary gland tumors, 5 cases arose in the parotid glands, 2 cases in the submanibular glands, 1 case in the sublingual gland and 28 cases in the minor salivary glands. 3. The incidence according to the anatomic primary site for minor salivary glands was 15 cases in the palate, 5 in the floor of mouth and 2 cases each arising in the tongue, lip, retromolar area and buccal mucosa. 4. Of all salivary gland tumors, adenoid cystic carcinoma was 5 cases in the major salivary glands and 8 in the minor salivary glands. mucoepidermoid carcinoma was 2 cases in the major salivary glands and 14 in the minor salivary glands and others were 2 cases of adenocarcinoma, 4 malignant mixed tumors and 1 undifferentiated carcinoma. 5. The incidence of cervical lymph node metastasis was 100%(2/2) in the submandibular glands, 80%(4/5) in the floor of mouth, 50%(1/2) in the tongue and 20%(1/5) in the parotid glands. The highest incidence of lymph node metastasis according to histopathological classfication was found in the high grade of mucoepidermoid carcinoma and tubular type of adenoid cystic carcinoma. 6. Nerve invasion was common in the adenoid cystic carcinoma. 7. The lung was the commonest site for distant metastasis comprising 7 cases among 7 cases in which distant spread occurred.

• Radiation Oncology Journal
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• v.2 no.2
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• pp.191-202
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• 1984

Biological behavior and treatment results of 33 patients with Adenoid Cystic Carcinoma (ACC) in the Head and Neck at Yonsei Cancer Confer for 10 years between 1971 and 1980 were retrospectively analysed. Most common, primary site was minor salivary glands such as maxillary sinus, nasal cavity and base of tongue. The typical biological behavior of these tumors was very slowly in growth with long time of duration(mean 19 months) from 1 month to 10 years and more frequent of nerve invasion but rare invasion of neck nodes. Local control and failure pattern in the results of treatment, 16 of 17 patients with irradiation alone were seen complete or partial response but 5 cases of locoregional recurrence, 2 cases of failure of neck node and 4 cases of distant metastasis as lung and brain. On the other hand, among 10 cases of surgery and postoperative irradiation, 2 cases of locoregional failure and 3 cases of distant metastasis as lung and bone. 2 of 4 cases with surgery alone were recurred within primary site. Actuarial overall NED survival at 3 ana 10 years were $52.6\%$ and $42.8\%$, respectively. Survival rate of 10 Patients with surgery and Postoperative irradiation was more high than 17 Patients of radiation alone. Therefore, we have known that surgery with postoperative adjunctive irradiation is most effective treatment modality of adenoid cystic carcinoma in the head and neck. Primary site, treatment modality and with or without nerve ana bone invasion have influenced on prognosis.

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

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.1
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• pp.59-70
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• 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 Oral Medicine and Pain
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• v.41 no.1
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• pp.30-33
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• 2016

Malignant tumors located in the head and neck areas intermittently show symptoms similar to a temporomandibular disorder (TMD). In our case, a patient who first visited us complaining of TMD-like symptoms, such as trismus and temporomandibular joint (TMJ) pain on the left side, was identified as a sufferer of adenoid cystic carcinoma (ACC) that arose from the left maxillary sinus. The patient may have a TMD symptom, but we are skeptical because the patient also complained of a spontaneously developed numbness on the same side of his upper lip. We observed the panoramic radiograph closely and found the blurred maxillary sinus inferior wall. Dental cone-beam computed tomography confirmed the tentative diagnosis of malignancy on the maxillary sinus. After he had been referred to the Department of Otolaryngology, the diagnosis of the ACC was confirmed. Adequate diagnosis is vital for a quick treatment of the malignancy. There are some keys for differential diagnosis of TMD-like symptoms.

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