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Malignant lymphoma involving the salivary glands is a rare entity that accounts for only 1 to 4% of all salivary gland tumors. We have analyzed the clinical features of MALT lymphoma of the salivary glands in 7 patients whom we have treated in the past 10 years, including data from 43 patients in the literature. The most common symptom was persistent or progressive swelling of the salivary glands without pain or facial palsy. The affected glands were the unilateral parotid in 62%, the unilateral submandibular gland in 6.8%, and the bilateral parotid or submandibular gland in 6.8%. The salivary gland swelling as evaluated by MRI or ultrasonography consisted of a localized solitary tumor in 68.9%, multiple tumors in 10.3%, and diffuse swelling of the gland in 26.1%. In 24 out of 50 patients, MALT lymphoma developed on the basis of Sjögren's syndrome. As for diagnosis, malignant lymphoma was suspected only in 4 cases out of 11 (36.7%) based on the fine needle aspiration cytology. In all patients, a definitive diagnosis was obtained based on histopathological study of the localized tumor or the biopsy specimens. When patients with Sjögren's syndrome have developed persistent swelling of the salivary glands, it is necessary to rule out malignant lymphomas, especially MALT lymphoma, by combination of ultrasonography, MRI, FNA, and biopsy or open surgery depending on image findings. The treatment of MALT lymphoma has not yet been standardized because MALT lymphoma is a rare entity. The choice of initial treatment is important because it is related to its prognosis. If MALT lymphoma remains in a local site, we should undertake an operation or radiotherapy. If MALT lymphoma has dissemineated systemically, we should choose chemotherapy.

Salivary duct carcinoma is a malignant salivary neoplasm with a poor prognosis. Effective treatment for remote metastases has not been recognized. We report herein on a case of this tumor overexpressing HER2 successfully treated with trastuzumab-based molecular targeted therapy. The patient was a 69-year-old man, who developed remote metastases into the liver and the thoracic vertebra six months after surgery and postoperative irradiation for the primary and nodal lesions. After targeted therapy including paclitaxel and trastuzumab, these metastatic lesions showed rapid and continued regression. After paclitaxel was discontinued due to peripheral neuropathy in the extremities, trastuzumab monotherapy followed without resulting in cardiotoxicity. After three years since development of remote metastases, the patient is doing well without re-progression of the disease.

The purpose of this retrospective study was to evaluate the prognostic factors in salivary gland cancer using a multivariate analysis. In total, 45 consecutive patients who underwent planned radical resection for salivary gland cancer between 1985 and 2010 were analyzed. Univariate and multivariate analyses were performed to analyze the clinical and pathological factors that influence patient survival in salivary gland cancer(tumor location, T and N classification, histological grade, excision margin status, postoperative radiotherapy, and postoperative adjuvant chemotherapy). The results of the multivariate analysis showed that T classification(odds ratio[OR]: 2.93, 95%confidence interval[CI]: 1.47-5.82), and excision margin status(OR: 4.86, 95% CI: 1.76-13.44)had a significant impact on tumor-free survival time, suggesting that both are important prognostic factors in salivary gland cancer. Moreover, postoperative adjuvant chemotherapy showed a tendency to improve tumor free survival time(OR: 0.28, 95% CI: 0.07-1.11), thereby indicating its potential in improving prognosis in patients with salivary gland cancer.

Background: Because of its low incidence, the clinical characteristics of the salivary duct carcinoma (SDC) based on a statistical analysis with a large number of patients remain to be elucidated, and thus it has been impossible to standardize the optimal treatments of SDC including adjuvant systemic therapy., Aims: The present study aimed to determine the prognostic factors along with the clinical outcomes of patients with SDC and to evaluate the expression of several receptor molecules as treatment targets., Methods: We performed a statistical analysis and immunohistochemical examination of 16 patients with SDC who had undergone initial treatment in the Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine from 1996 to 2010., Results: The 3-year disease-free survival (DFS) and cause-specific survival (CSS) rates were 29.2% and 72.7%, respectively. At the time of the analysis, 6 patients are alive without the disease, 2 patients are alive with distant metastasis, whereas 7 patients had died of distant metastasis, and 1 patient had died of another cause (pulmonary embolism). We examined the prognostic value of the clinico-pathological factors such as age, sex, T classification, N classification, clinical stage, primary site, histological pre-existence of pleomorphic adenoma. A univariate analysis revealed that DFS was significantly correlated with age (p = 0.049), T classification (p = 0.018), and clinical stage (p = 0.029), whereas no factor was found to be correlated with CSS. A multivariate analysis demonstrated that age (> or = 61 vs. < or = 60, risk ratio (RR) = 5.423, p = 0.042) and T classification (3, 4 vs. 1, 2, RR = 1.087, p = 0.020) were the independent prognostic factors for DFS. Positive expressions of HER2, ER (estrogen receptor), PR (progesterone receptor), AR (androgen receptor), and MIB-1 (index > 20%) were found in 50%, 6%, 13%, 100%, and 69%, respectively. However, none of them showed significant correlation with survival., Conclusion: Frequent expressions of HER-2 and AR in SDC suggest that these receptors can be suitable molecular targets of systemic therapy for patients with SDC in which distant metastasis seems to be the largest obstacle to improving survival. In order to assess the efficacy of anti-HER-2 therapy and anti-androgen therapy for each receptor-positive SDC, a multi-institutional joint research system should be organized.

Salivary ductcarcinoma (SDC)is a high-grade malignant tumor arising predominantly in the parotid gland. Androgen receptor(AR)expression was mainly restricted to SDC in salivary cancer. We report successful treatment of a patient with advanced SDC using an endocrine chemotherapy. A 76-year-old man was hospitalized with lumbalgia and swelling of left submandibular region. Radiological examination indicated a tumor in left submandibular gland and metastatic tumors in lumbar vertebra, accompanied by swollen lymph nodes of the neck, mediastinum. Needle biopsies of both vertebral tumor and cervical lymph node revealed SDC. Positive nuclear staining was observed against AR in tumor cells of our patient by immunohistochemical analysis. He obtained a partial response after 1 course of treatment with both anti-androgen therapy and palliative chemotherapy using paclitaxel. In contrast to previous reports of poor response to chemotherapy alone and short-term survival of patients with SDC, our patient has demonstrated that chemotherapy combined with anti-androgen therapy may be an effective modality as a therapeutic regimen for SDC.

We proceeded with intratumoral injection therapy of dendritic cells (DC) in combination with hyperthermia for 41 cancer patients in the past two years. We confirmed a total of two CR cases (one of them already reported). We report two successful cases in this paper. Case 1: A uterine cervical cancer patient with metastases in cervical and abdominal lymphnodes was treated with intratumoral DC injection therapy combined with hyperthermia in cervical. She showed a CR not only in cervical but also in abdominal lymph nodes. Case 2: A sialyl grand cancer patient with metastases in cervical and axillary lymphnodes was treated with intratumoral DC injection therapy combined with hyperthermia in cervical. She showed a PR.

In the 22 years between March 1979 and February 2001, we treated 16 patients--10 men and 6 women aged 10-80 years (mean: 44 years)--with mucoepidermoid carcinoma (MEC) of the salivary gland, evaluating them clinically and histopathologically. Tumor sites included 12 at the parotid gland, 3 at the submandibular gland, and 1 at the minor salivary gland. All tumors were graded histopathologically based on the criteria of Goode et al. as follows: low grade (n = 10), intermediate grade (n = 1), and high grade (n = 5). Female gender was associated with low grade MEC and male gender with high grade MEC (P < 0.05). The age at onset in high grade MEC was older than that in low grade MEC (P < 0.005). Lymph-node metastasis was detected in 7 out of the 16 patients (44%) associated significantly with high grade MEC (P < 0.05). Distant metastasis was detected in 4 of 16 patients (25%). Distant metastasis was significantly associated with high grade MEC (P < 0.05). Local recurrence was detected in 3 of 15 patients undergoing surgery (20%). No difference was seen in local recurrence frequency between low and high grade MEC. Survival was calculated with Kaplan-Meier's method. In all 16, 5-year survival was 86% and 10-year survival 75%. Five-year survival in low grade MEC was 100%, whereas that in high grade MEC was 67% (P < 0.05). In MEC of the salivary gland, it was suggested that the histopathological MEC grade evaluated by Goode's criteria significantly correlated with gender, age, lymph-node metastasis, distant metastasis, and 5-year survival.

We compared preoperative evaluations of 93 fine-needle aspiration biopsies (FNAB) of major salivary gland tumors done over a 5 year period with pathologic diagnoses of surgically resected specimens. The overall accuracy was 88.5%. Eight of 15 aspirates from malignant tumors were correctly diagnosed by FNAB, for a sensitivity of 53.3%, while 69 of 72 aspirates from benign tumors were correctly diagnosed by FNAB, for a specificity of 95.8%. Five malignant tumors diagnosed as benign by FNAB were squamous cell carcinoma, carcinoma in pleiomorphic adenoma, malignant lymphoma, low-grade mucoepidermoid carcinoma, and acinic cell carcinoma. The false negatives in the first 2 cases appeared to be due to inaccurate placement of the aspiration site. The other 3 cases showed lack of atypia, leading to a benign diagnosis. Malignant lymphoma is difficult to diagnose as malignant, even in properly aspirated specimens, so we recommend open biopsy when malignant lymphoma is suspected from physical and radiological examinations. A case confirmed pathologically as benign myoepithelioma was diagnosed as adenoid cystic carcinoma preoperatively, based on the finding of a cribriform pattern containing mucin. It should be borne in mind that myoepithelioma and adenoid cystic carcinoma are difficult to distinguish by FNAB. Although FNAB is useful in diagnosing major salivary gland tumors, its low sensitivity (high percentage of false negatives) is undesirable. It may thus be helpful in intraoperative decision-making when combined with frozen sectioning.

Salivary duct carcinoma (SDC) was first described by Kleinsesser in 1968 and was classified as an independent entity by the 1991 Revised World Health Organization. It is a rare but highly malignant tumor. We reviewed pathology in 49 cases of salivary adenocarcinoma, and diagnosed 6 cases as SDC. All had a rapidly enlarged mass in the parotid gland. All were men, and 4 involved facial palsy and metastasis to cervical lymph nodes. Fine needle aspiration biopsy was conducted in 3 cases, but none was diagnosed as SDC. Two had chemotherapy, but showed no effect. All underwent surgery, but only 1 survived more than 4 years. Immunohistochemically, none showed s-100 protein. Four showed PCNA and p53 protein. Highly positive cells of PCNA and p53 were found around comedo necrosis.

Pleomorphic adenoma (PA) of the salivary gland has diverse biological behavior in spite of its being a benign tumor. So the nuclear DNA content of 36 PAs was measured by flow cytometry to determine the relationship between proliferative activity and histopathological variable. DNA histograms were evaluated according to the rate of S and G2+ M phase cells (S + G2M%). We assumed that the DNA histogram measured algebraically, S + G2 M% < or = 0%, is the near diploid pattern and calculated its ratio to the near diploid pattern. A statistically significant difference between PA and normal salivary gland was found by the ratio to the near diploid pattern (P < 0.05), which confirmed the usefulness of the ratio to the near diploid pattern for measuring low proliferative activity. The tumors were divided into 3 groups: epitheloid type, intermediate type and myxochondroid type. In the 3 groups no differences were found by S + G2M% and the ratio to the near diploid pattern. The areas of the tumor were divided into 5 groups according to the ratio in the epitheloid region and the myxochondroid region. In the 5 groups, the area which consists partly of epitheloid components and mostly of myxochondroid components had the lowest ratio to the near diploid pattern and the highest S + G2M%, and the area which consists of only myxochondroid components had the highest ratio to the near diploid pattern and the lowest S + G2M%. Between only these two areas a statistically significant difference was found by the ratio to the near diploid pattern (P < 0.05). We considered that the area which consists partly of epitheloid components, and mostly of myxochondroid components has the highest proliferative activity in PA. Neither aneuploid or polyploid cells were found in any tumor, but the S + G2M% is more than 20% in 4 tumors. None of these high S + G2M% tumors except one recurrent tumor had clinical and histopathological features. A differences between PAs of the parotid glands and PAs of the submandibular glands was not found in S + G2M%.

We correlated the histopathology of 32 cases of salivary gland tumors with MR imaging and flow cytometric DNA analysis. All malignant tumors were invasive and/or had an ill-defined margin. Fifty-seven percent of the pleomorphic adenomas were shown as a high signal intensity area on T2 weighted images. Fifty-six percent of Warthin tumors were shown as a low or iso signal intensity area on T2 weighted images associated with the cystic portion. Sixty-seven percent of malignant tumors were characterized by DNA aneuploidy and/or a total percentage of the S-phase fraction plus the G2 + M fraction higher than 10%. It was less than 10% and the Ki-67 positive fraction was higher than 20% in all pleomorphic adenomas. The Ki-67 positive fraction was less than 20% in 78% of Warthin tumors. The histopathology of all malignant tumors, 86% of the pleomorphic adenomas, and 89% of Warthin tumors was correctly predicted by the combination of MR images and flow cytometry. We suggest that the MR images combined with flow cytometric analysis of fine needle aspiration-derived materials is useful in the pre-operative histopathologic diagnosis of salivary gland tumors.

Purpose: To evaluate the efficiency of dynamic contrast-enhanced magnetic resonance imaging (MRI) for the diagnosis of salivary gland masses., Materials and Methods: We retrospectively examined 19 salivary gland masses that were pathologically diagnosed by surgical operation or biopsy. We obtained T1- and T2-weighted images on MRI, performed dynamic studies on each mass and examined the correlation between enhancement patterns and pathological findings., Results: Four enhancement patterns were recognized on contrast-enhanced MRI: type 1 showed marked, homogeneous enhancement; type 2 slight, homogeneous enhancement; type 3 marginal enhancement; and type 4 poor enhancement of the mass. Most pleomorphic adenomas had a type 1 enhancement pattern, but two had a type 2 pattern. Pathologically, each mass enhancement pattern had different tumor cell and matrix components. Warthin's tumor generally showed the type 4 pattern. Primary malignant tumors of the salivary gland all showed the type 3 pattern, and pathological specimens showed many tumor cells along the marginal portion of the tumor. One inflammatory cyst and one Warthin's tumor also showed the type 3 pattern. Except for metastatic renal cell carcinoma, the enhancement patterns of late phase images and dynamic study images were the same., Conclusions: Dynamic MRI added little diagnostic information about salivary gland masses, but the contrast-enhanced MR features correlated well with the pathological findings.

The proliferative activity of tumors and the expression of c-erbB-2 oncoprotein were investigated in 86 salivary neoplasms (54 pleomorphic adenomas and 32 malignant tumors), and in 17 normal salivary glands. Numbers of cells that stained positive to anti-proliferating cell nuclear antigen (PCNA) antibody and the nucleolar organizer region associated protein (AgNOR) were used as an index of the proliferative activity. The results obtained in this study were as follows: 1) PCNA-positive and AgNOR-positive cells were elevated in malignant tumors relative to pleomorphic adenomas and normal salivary glands. 2) Salivary gland tissue around the pleomorphic adenoma with high proliferative activity demonstrated higher activity than normal gland tissue. 3) The proliferation of pleomorphic adenoma was not affected by the age or size of the tumors. 4) Expression of c-erbB-2 oncoprotein was not observed in pleomorphic adenoma and normal gland but was observed in malignant tumors. 5) In one case of a carcinoma in pleomorphic adenoma, the pleomorphic adenoma region also revealed c-erbB-2 positive cells.

The adenocarcinoma cell line derived from an intercalated ductal epithelium of a human salivary gland (HSG) proliferates autonomously mediated by an epidermal growth factor-(EGF)-like molecule with a molecular weight of 46 kDa and an EGF receptor (EGFR). The c-erbB2 protein, a member of EGFR family was also expressed in HSG cells and was involved in the growth signal pathway of HSG cells as well as EGFR. The autocrine growth is regulated by glucocorticoid and retinoic acid (RA) via their receptors. Retinoic acid receptor (RAR) of HSG cells revealed a transcriptional activity in vivo, and the heterodimerization between RAR and 9-cis retinoic acid receptor (RXR) is requisite for the binding with a specific DNA element termed RA response element in vitro. RXR alpha and RXR beta were cloned from HSG cells, and these RXRs, together with RAR, seemed to play a physiological role in RA signaling in vivo.

A 70-year-old woman complained of a dry mouth and swelling in the area of the left parotid gland for 6 years, and was admitted for evaluation of an abnormal shadow on chest X-ray film. She underwent a lip biopsy and a 99mTcO4- scintigram of the salivary gland, and Sjögren's syndrome was diagnosed. Histopathological examination of the percutaneous lung biopsy specimen showed pseudolymphoma, and examination of a specimen of the left parotid gland tumor showed myoepithelial sialadenitis. The patient died of respiratory failure due to a right pleural effusion 4 years later. Autopsy revealed pulmonary non-Hodgkin's lymphoma (diffuse, large, B cell, IgG) with monotonous infiltration of centrocyte-like cells. A retrospectively resected specimen of the left parotid gland tumor showed non-Hodgkin's lymphoma similar to that found in the autopsied lung. This patient probably had pulmonary non-Hodgkin's lymphoma that arose in mucosa-associated lymphoid tissue of the salivary gland and was associated with Sjögren's syndrome.

Recent studies have shown that inactivation of tumor suppressor p53 gene is a key point in the development of human carcinomas and that normal p53 protein acts as a "molecular policeman" monitoring the integrity of the genome. In the present study, a series of 22 primary human salivary gland carcinomas were examined for alterations and expression of the p53 gene by a combined molecular and immunohistochemical approach, polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP), direct gene sequencing and p53 protein immunostaining. In addition, in order to identify correlations between p53 abnormalities and genetic instability, DNA aneuploidy and tumor growth characteristics were analyzed by cytofluorometry and the AgNOR technique. Seven of the 22 cases displayed nuclear p53 overexpression as revealed by immunostaining with p53 monoclonal antibody (Do-7), and 2 of these 7 cases were associated with the presence of point mutations [codon 140: ACC (Thr)-->ATC (Ile), codon 175: CGC (Arg)-->CAC (His)] of the p53 gene. Twelve of the 22 cases were aneuploid on the DNA histogram, and this phenomenon was statistically correlated with the 7 cases exhibiting p53 nuclear accumulation. AgNOR staining, on the other hand, was not statistically correlated with p53 abnormalities. These findings support the view that abnormal nuclear accumulation of the p53 protein is correlated with genetic instability of human salivary gland carcinoma cells.

A neoplastic human salivary intercalated duct cell line, HSG and its derivative HSG-AZA1 cells with a myoepithelial cell phenotype and HSG-AZA3 cells with an acinar cell phenotype, which were induced by treatment of HSG cells with 5-azacytidine, have been used in our laboratory as models for studying mechanisms regulating cytodifferentiation in salivary glands as well as for developing differentiation therapy for salivary gland tumors. Consequently, it has been shown that the treatment of HSG, HSG-AZA1 and HSG-AZA3 cells with various differentiation agents results in cellular differentiation into myoepithelial, acinar or neuronal cells as well as keratinizing squamous cells, chondrocytes, and osteoblast, with a concomitant decrease of anchorage-independent and anchorage-dependent growths in addition to decreased tumorigenicity in nude mice. It was also found that the treatment of an adenoid cystic carcinoma of the maxillary sinus with adoptive immunotherapy involving intra-arterial injection of LAK cells and IL-2 in combination with radiotherapy, resulted in bone formation in the treated tumor, which was then replaced completely by lamellar bone tissue with myxomatous stroma. These findings may suggest the potential usefulness of differentiation therapy in human salivary gland tumors.

Twenty-five pleomorphic adenomas and 10 normal salivary glands were immunohistochemically studied with respect to cytoskeletal proteins and extracellular matrix components to observe the relationship between these components and the differentiation of tumor cells in pleomorphic adenomas. For immunohistochemical observation, keratin (AE1), vimentin (V9), alpha-smooth muscle actin (1A4) and type IV collagen (JK-199) were studied by means of monoclonal antibodies, and laminin (LM) and fibronectin (FN) were analysed with polyclonal antibodies. AE1 was localized in inner tubular cells, and 1A4 was identified in spindle and leiomyomatous cells. These observations may provide evidence of differentiation into ductal epithelia and myoepithelial cells, respectively. Positive staining for V9 in cuboidal cells suggests dedifferentiation. The extracellular matrix components, JK-199, LM and FN, were localized in surrounding areas of cells stained by V9 and/or 1A4. This suggests that expression of these cytoskeletal proteins and extracellular matrix components may affect each other, and ther by contribute to cellular differentiation and production of extracellular matrix.

In 43 cases of adenoid cystic carcinomas of the salivary glands (ACC), expressions of the oncogene products such as epidermal growth factor receptor (EGF-R), erbB-2 product, c-myc product and N-myc product were investigated immunohistochemically. First, we confirmed the specificity of the antibodies used with the 13 cell lines. Of the anti-EGF-R antibodies, clone 29. 1. 1 reacted only with A431 but not with the other cell lines overexpressing EGF-R, so that it was most likely to cross-react with the blood type A antigen. Also, the anti-N-myc product antibody revealed the presence of a certain cross-reacting antigen in Lu65. Overexpression of EGF-R was observed in only one case. Nine cases (20.9%) showing tubular and cribriform patterns overexpressed the erbB-2 product, but the signals were mainly localized in the cytoplasm as a granular appearance. Eighteen cases (41.9%) with slight cellular atypia showed an overexpression of the c-myc product. The immunolocalization of the c-myc product was at the nuclei in most cases, or both the nuclei and the cytoplasm in some cases. None of the ACC expressed the N-myc product. It is speculated that the multiple oncogene expressions might be partly related to the acquirement of the differentiated or malignant phenotype in the ACC.

In order to clarify the neoplastic-mesenchymal cell interaction, tumor structures were histologically classified into duct, solid and scattered types, and stromal changes were observed in each type with histochemical techniques. The quantitative and qualitative differences of the stromal components as proteoglycan and collagen were histochemically differed in these morphological features. Ca++ ATPase was ultrastructurally localized on the plasma membrane of myoepithelial cell in salivary glands. The activity of Ca++ ATPase changes in tumor cell differentiation of pleomorphic adenoma and adenoid cystic carcinoma. These results suggest that the stromal components and Ca++ ATPase play an important role on the tumor cell proliferation and differentiation in these tumors.

Till 1985, UICC had not developed the TNM-classification system of salivary gland cancer because of insufficiency of the number of cases. In this study, influences of various parameters such as age, sex, histological type, mobility of the tumors and facial nerve involvement were analyzed in a total of 354 cases of parotid gland cancer obtained by nationwide research. Furthermore, UICC classification system made in 1985 was assessed by application to these 354 cases.

Four kinds of cultured human tumor cell lines sensitive or resistant to bleomycin (BLM) were examined for the effect of filipin, a polyene antibiotic, on peplomycin (PEP)-induced cell killing. Although PEP was more effective than BLM against BLM-resistant HeLa cells (HeLa-BLMr), neoplastic cells derived from salivary gland (HSG) and melanoma cells (MEC), these three cell lines were still at least ten times more resistant to PEP than epidermoid carcinoma cell lines including HeLa cells by comparison of IC50, and showed lower cellular accumulation of 3H-PEP as compared with HeLa cells. When these lines were pretreated with filipin, 3H-PEP accumulation by the cells was increased 1.33-, 2.34-, 1.91- and 1.14-fold in HeLa, HeLa-BLMr, HSG and MEC cells, respectively. Combination use of PEP and filipin resulted in a remarkable enhancement of cytocidal effect in HeLa-BLMr and HSG cells (100- and 25-fold decrease of IC50, respectively), and a slight enhancement in HeLa cells, but not in MEC cells. It is therefore suggested that there are differences among cell types in the potentiation of PEP-induced cell killing by filipin.

A rare case of clear cell carcinoma of the palatal salivary gland in a 69-year-old man is reported. Histopathologically, nests and cords of tumor cells, which showed predominantly clear cytoplasms, and occasionally eosinophilic cytoplasms, proliferated on the overlying epithelium and capsules of the fibrous connective tissue. The clear cell cytoplasms were found to be PAS positive, diastase soluble, and Alcian-blue negative, indicating the presence of glycogen. Ultrastructurally, the tumor cells were found to contain glycogen and cytoplasmic filaments in various proportions. These observations suggest that clear cell carcinoma is myoepithelial in origin.

A human salivary adenocarcinoma cell line, HSGc, was tested for the chemosensitivity and compared with a human squamous cell carcinoma cell line, KB. From IC50 values of anti-cancer drugs on the cells, it was found that HSGc was sensitive to CDDP, 5-FU and DTIC but resistant to ADM, MTX, VCR, PEP and MMC as compared to KB. The chemosensitivity of HSGc was in agreement with previously reported clinical data on the therapeutic results of salivary gland tumors. This suggests that HSGc may be an useful model for understanding the biological response of salivary adenocarcinoma cells to anti-cancer drugs. We further examined the combined effects of filipin and verapamil with these anti-cancer drugs. Filipin was found to enhance cell-killing effect of 5-FU and PEP on HSGc, while the combination of filipin with either DTIC or PEP was also effective on KB. Verapamil was effective in combination with 5-FU, VCR or PEP on HSGc and with DTIC, VCR or PEP on KB. Especially the most predominant enhancement on HSGc was observed in combination of filipin or verapamil with PEP. These findings suggest that even low-sensitive drug, PEP, is also useful when combined with either filipin or verapamil.

Forty-four salivary gland tumors were seen at The Center for Adult Diseases, Osaka, between 1979 and 1981; 30 were benign and 14 malignant. Of the latter, 7 (50%) were adenoid cystic carcinoma (ACC). Six of 7 ACC were reviewed with special attention to their histologic pattern, atypism, connective tissue around the cell nest, tumor cell nest, tumor cell invasion into lymphatics(ly) and blood vessels(v), and mitosis. ACC was divided into 3 histological groups. Patients with ly and/or v develop cervical and/or distant metastases at the early stage or during the follow-up period. Ly and v were closely correlated with metastasis.