Carcinoma In Pleomorphic Adenoma Research Articles

Molecular characterization of a novel cancer cell line established from human carcinoma in pleomorphic adenoma (CaPA-4)

A cultured cell line (CaPA-4), derived from an undifferentiated carcinoma in a pleomorphic adenoma of the submandibular gland, was established through xenografted tumors in nude mice. Geneticin treatment eliminated surrounding mouse fibroblasts and yielded enriched tumor cells at an early stage of cell passage. In vitro, the line grew in a cobblestone pattern, revealing its epithelial origin. Chromosomal analysis by Giemsabanding confirmed its human origin, while electron microscopic examination showed its squamous-cell characteristics. CaPA-4 cells stained positive for the c-myc and Ha-ras antibodies. Molecular analysis showed over-expression of both c-myc and Ha-ras mRNA, with point mutation of p53 at codon 248 and of Ha-ras at codon 61. Amplification and rearrangement of the Ha-ras gene were observed; however, no loss of heterozygosity (LOH) of the p53 gene was detected by Southern blotting. This sequence of cancer-related gene activation may represent the malignant transformation from benign pleomorphic adenoma. This report describes the establishment and molecular characterization of this novel cell line from carcinoma in pleomorphic adenoma exhibiting squamous-cell differentiation. This could represent a useful model for investigating the cause of malignant transformation from human salivary-gland mixed tumors.

Molecular characterization of a novel cancer cell line established from human carcinoma in pleomorphic adenoma (CaPA‐4)

Molecular characterization of a novel cancer cell line established from human carcinoma in pleomorphic adenoma (CaPA‐4)

Coexpression of p53 and c-erbB-2 proteins is associated with histological type, tumour stage, and cell proliferation in malignant salivary gland tumours.

The development and progression of cancer are known to be regulated by various oncogenes and tumour suppressor genes. We analysed 63 primary malignant salivary gland tumours for the expression of p53 and c-erbB-2 proteins. Immunohistochemically, 7 of 63 tumours (11%) showed diffuse nuclear staining for p53 protein, and all 7 were also positive for c-erbB-2 protein. The overexpression of p53 protein correlated closely with the overexpression of c-erbB-2 protein (P<0.001). Overexpression of both p53 and c-erbB-2 proteins (coexpression) was found in tumours of certain histological types, such as adenocarcinoma, carcinoma in pleomorphic adenoma, and salivary duct carcinoma. Furthermore, it is noteworthy that coexpression was associated with high-grade carcinoma, advanced tumour stage, and a high Ki-67 labelling index (%) which is a marker of cell proliferation. In adenocarcinoma, we attempted to clarify the relationship between coexpression and histological grade. Coexpression was associated with histological grades showing high mitotic indices and necrotic areas, which reflected high cell-proliferative activity. These results suggest that the accumulation of genetic alterations, such as those involving p53 and c-erbB-2, plays an important part in the progression of malignant salivary gland tumours.

Carcinoma in Pleomorphic Adenoma of the Tongue; Report of a case

A carcinoma in pleomorphic adenoma occurring in the tongue of a 47-year-old Japanese woman is reported. The present report is the first to describe a carcinoma in pleomorphic adenoma derived from the posterior lingual glands.

多形性腺腫およびその悪性型（悪性多形性腺腫，多形性腺腫内癌）の臨床的特徴の比較検討

Pleomorphic adenoma is the most common tumor of the salivary gland. Usually, it grows slowly and has a good prognosis. However, some pleomorphic adenoma. generally referred to as malignant pleomorphic adenoma (carcinoma in pleomorphic adenoma) show invasive growth or distant metastasis. We examined clinical features in 69 patients who were given a diagnosis and treated at our clinic during the past 16 years. The 69 patients included 63 patients with pleomorphic adenoma and 6 patients with malignant pleomorphic adenoma. The 63 cases of pleomorphic adenoma occurred in 21 males and 42 females. The ratio of males to females was 1: 2, indicating a higher prevalence in females than males. The 6 cases of malignant pleomorphic adenoma occurred in 4 males and 2 females. The diagnosis was carcinoma in pleomorphic adenoma in 4 cases and so-calld malignant pleomorphic adenoma in the other 2 cases. Five of these patients were treated at our clinic; surgery was performed in all 5 patients. The 5 -year survial rate was 80%.

Immunohistological study on proliferative activities and expression of c-erbB-2 oncoprotein in salivary gland tumors

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.

Adenocarcinoma Arising from the Submandibular Gland; A case report with its relationship to carcinoma in pleomorphic adenoma

Adenocarcinoma Arising from the Submandibular Gland; A case report with its relationship to carcinoma in pleomorphic adenoma

Immunohistochemical pattern of Bcl-2- and PTHrP-positive cells in primary, in recurrent and in carcinoma in pleomorphic adenomas

Forty-seven samples of paraffin-embedded formalin-fixed (and 25 related frozen) sections of 27 primary pleomorphic adenomas, 15 recurrent pleomorphic adenomas and 5 carcinomas in pleomorphic adenomas were studied to analyse their immunohistologic patterns with respect to the ratio of the expression of 'normally' and 'aberrantly' differentiated cell types. In primary pleomorphic adenoma PTHrP-positive cells are seen in the inner layer of tubulo-ductal structures, in part of the cells in the mucoid, chondroid, or myxochondroid matrix, and in the squamous metaplastic areas. Bcl-2-positive cells are found in the outer layer of tubulo-ductal structures, in part of the cells in the mucoid, chondroid, or myxochondroid matrix, and around the squamous metaplastic areas. In one case of primary pleomorphic adenoma, which recurred later, the positivity for Bcl-2 is more intense and seen in the periphery of this tumour with a predominantly myxoid pattern. In recurrent pleomorphic adenomas, which also mostly showed a predominantly myxoid pattern, the positivity for Bcl-2 showed a pattern similar to the primary-to-recur tumour. PTHrP-positive cells are found less frequently than Bcl-2-positive cells. In carcinoma in pleomorphic adenoma, the benign part shows the features of primary pleomorphic adenoma with its Bcl-2 and PTHrP-positivity patterns. The malignant part strongly shows Bcl-2-positive cells in the periphery of the tumour. We conclude that the maintained presence of Bcl-2 and PTHrP-positive cells in the tumours we studied shows the variable capacity of tumour cells to differentiate.

The Thomsen-Friedenreich (T) simple mucin-type carbohydrate antigen in salivary gland carcinomas.

The simple mucin-type T (Thomsen-Friedenreich) antigen is a marker of carcinomas, and has been related to aggressiveness of malignant tumours. We studied the expression of T, sialosyl-T, A and H blood group antigens in salivary gland carcinomas. The aim was to study whether the tumours, based on the expression of these structures, could be divided into new diagnostic groups that may later show prognostic significance. Formalin fixed paraffin-embedded tissue sections from 77 salivary gland carcinomas of different histological types were studied using immunohistology and monoclonal antibodies (MAbs). Fresh frozen tissue was examined in 30 of the cases. Frozen sections were superior to paraffin sections in demonstrating T and H antigens. Aberrant glycosylation with accumulation of T (in cytoplasm) and sialosyl-T antigens (in cytoplasm, membrane and mucin) was found in all tumour types except acinic cell carcinomas. In carcinomas in pleomorphic adenomas (CinPA) the effect of fixation was minimal and T antigen location was different. In carcinomas with myoepithelial cell (MEC) participation, the MECs had retained a normal glycosylation pattern. H antigen was expressed in all tumour types, except acinic cell carcinomas and CinPA. A antigen was expressed in all tumour types from blood group A patients, except in CinPA. The expression of T, sialosyl-T, H and A antigens in relation to differentiation grade varied with tumour type in poorly differentiated areas. High and moderate differentiated areas were always stained, whereas poorly differentiated areas in some tumour types expressed T and sialosyl-T antigens and others did not. The accumulation versus lack of expression of the investigated structures in poorly differentiated areas of the tumours may be of prognostic significance.

口蓋部腫りゅうの臨床的検討

To determine what conditions should be considered in the diagnosis of palatal tumors which were indolent, well circumscribed, and hemispherical, 83 cases of palatal tumors were clinically studied. The pathological diagnosis was pleomorphic adenoma in 73 cases, carcinoma in pleomorphic adenoma in 2 cases, schwannoma in 2 cases, and adenoid cystic carcinoma, neurofibroma, chronic sialoadenitis, hyperplasia of the salivary gland, myxofibroma and granular cell tumor, in one case each. Thus, approximately 10% of the cases had other pathological conditions, among which one-third had malignant salivary gland tumors. As to sex, age, tumor location, size, and duration of symptoms, there were no obvious differences between pleomorphic adenoma and other conditions, including malignant salivary gland tumor. The tumor consistency was elastic hard in about half of the pleomorphic adenomas, and most of the other lesions were soft or elastic soft.

顎下腺多形性腺腫内癌手術後に発症したエレースによる薬剤性肺臓炎の１例

We report a case of drug-induced pneumonitis caused by inhalation therapy with fibrinolytic enzyme after supraomohyoid neck dissection of a submandibular gland tumor. The patient was a 54-year-old man who had a diagnosis of carcinoma in pleomorphic adenoma. Two days before operation, inhalation therapy was started with two drugs and Elase®, containing fibrinolysin and deoxyribonuclease, to avoid postoperative respiratory complications. Three days after operation, he developed a high fever and severe cough, and the chest roentgenogram showed diffuse shadows in bilateral lung-fields. Although bacterial pneumonitis was suspected, intravenous antibiotics were not effective and no causative organism was detected in his sputum and arterial blood. However, as the administration of corticosteroids and the cessation of inhalation therapy remarkably improved clinical symptoms, we suspected drug-induced pneumonitis. The drug lymphocyte stimulation test demonstrated that Elase® was responsible for this pneumonitis. Although previous clinical reports of drug-induced pneumonitis could not be found, the possibility of side effects with any kind of drug should always be borne in mind.

Characteristic karyotypic features in lacrimal and salivary gland carcinomas.

Short-term cultures from 12 non-squamous cell carcinomas (NSCCs) of the head and neck were cytogenetically investigated. Three tumours were acinic cell carcinomas, two adenoid cystic carcinomas, three mucoepidermoid carcinomas, two carcinomas in pleomorphic adenoma, and two adenocarcinomas. Clonal chromosome aberrations were detected in all but one adenocarcinoma. Including our data, a total of 40 head and neck NSCCs with clonal aberrations have been described. Deletions of the long arm of chromosome 6 are the most common aberrations (11/40 cases); they have been detected in all types of NSCC except carcinoma in pleomorphic adenoma. Two aberrations seem to be closely associated with tumour type: t(6;9)(q21-24;p13-23), which has been seen in three of 11 adenoid cystic carcinomas (in two as the sole aberration), and structural rearrangements of 8q12-13, which have been detected in three of four carcinomas in pleomorphic adenoma.

Evaluation of malignant grade of salivary gland tumors: studies by cytofluorometric nuclear DNA analysis, histochemistry for nucleolar organizer regions and immunohistochemistry for p53.

Investigations were carried out in 109 surgically resected salivary gland tumors, 46 adenomas and 63 carcinomas for nuclear DNA content by cytofluorometry, nucleolar organizer regions (AgNOR) by histochemistry and nuclear p53 accumulation by immunohistochemistry. The mean nuclear DNA content and the incidence of aneuploidy as well as the mean number of the AgNOR in carcinomas were significantly higher than those in adenomas. In the DNA histogram pattern, the aneuploidy frequently appeared in high grade carcinoma groups (adenocarcinoma, salivary duct carcinoma, carcinoma in pleomorphic adenoma and oncocytic carcinoma). Immunohistochemical nuclear p53 accumulation was observed in 15 tumors, of which ten showed DNA aneuploidy. In high grade carcinomas, DNA aneuploidy was closely related to p53 immunoreactivity. This study revealed that combined cytofluorometric nuclear DNA analysis, histochemical AgNOR count and immunoreactivity for p53 might be quite useful for evaluating the malignant grade of salivary gland tumors.

Cytogenetic subtyping of salivary gland pleomorphic adenoma and carcinoma in pleomorphic adenoma

Current research on salivary gland pleomorphic adenoma is aimed at grouping the cases by cytogenetical aberrations into several subtypes. In this report, 21 cases of pleomorphic adenomas were analysed cytogenetically and divided into 4 subtypes following Bullediek's method; normal karyotype (6 cases), 8q12 rearrangement (8 cases), 12q13-15 rearrangement (5 cases) and other aberrations (2 cases). The average occurrence age of each group was examined. The 8q12 rearrangement group (37.2 y.o.) was younger than the normal karyotype (49.2 y.o.) and 12q13-15 rearrangement groups (52.4 y.o.). Histological subtyping based on Seifert's classification was made and its relationship with the above cytogenetic subtypes was studied. In the 8q12 rearrangement group, Seifert's type-1 was predominant (88%), while in the normal karyotype and 12r13-15 rearrangement groups, Seifert's type-2 was the most common (50% and 80% respectively). We also examined 2 cases of carcinoma in pleomorphic adenoma. Although both showed some cytogenetic abnormalities, no aberrations specific to pleomorphic adenoma (8q12 or 12q13-15 rearrangement) were found. This suggests that original adenomas of these carcinomas showed a normal karyotype or other types of aberrations.

当科における多形性腺腫症例の検討

We reviewed and clinically analyzed 31 cases of pleomorphic adenoma treated at our hospital between 1978 and 1992. These cases (9 males and 22 females) ranged in age from 19 to 80 years old with a mean age of 44.7 years. There were 20 cases with adenoma in the parotid gland (64.5%),7 cases in the submandibular gland (22.6%), and 4 cases in the minor salivary glands (12.9%). The chief complaint was tumor palpation.Spontaneous pain and tenderness were found in a few cases. Ultrasonics, scintigraphy, computed tomography and magnetic resonance imaging were useful for preoperative diagnosis, with ultrasonography, in particular, showing more characteristic findings than other methods.The adenoma in 30 cases was surgically removed. One case was diagnosed as a malignant mixed tumor by aspiration biopsy and only radiotherapy was performed. All cases were followed by histopathologic examinations, but there were no case diagnosed as carcinoma in pleomorphic adenoma. There were no cases of recurrence or malignant change. In conclusion, complete removal in the initial surgery, precise histopathologic examination and long-term follow-up are required in the treatment of pleomorphic adenoma.

多形腺腫内癌腫の臨床と組織像

多形腺腫内癌腫の臨床と組織像

Dysplastic pleomorphic adenoma of the sublingual salivary gland

All tumours of the sublingual gland are rare and paradoxically the large majority are malignant. A case of pleomorphic adenoma in the sublingual gland is described. The tumour showed areas of dysplasia and the difficulties in distinguishing this from benign pleomorphic adenoma or carcinoma in pleomorphic adenoma are considered, and the literature is reviewed.

Simple mucin-type Tn and sialosyl-Tn carbohydrate antigens in salivary gland carcinomas

Neoplastic transformation is associated frequently with changes in the glycosylation process. Simple mucin-type glycosylation in cancer cells has been found to be characterized by incomplete synthesis with precursor accumulation, leading to the exposure of the structures Tn and sialosyl-Tn, which are normally cryptic in human cells and secretions, including saliva and salivary glands. Paraffin sections from 50 salivary gland carcinomas of different histologic types were investigated with immunohistologic studies and a panel of monoclonal antibodies with well-defined specificity for Tn and sialosyl-Tn. Tn and sialosyl-Tn antigens were expressed in the cytoplasm of glandular differentiated cells; in the luminal membranes and mucinous content of the glandular differentiated areas in almost all mucoepidermoid carcinomas and adenocarcinomas; and in carcinoma in pleomorphic adenoma, when the malignant component was an adenocarcinoma. In contrast, acinic cell carcinomas and adenoid cystic carcinomas expressed only minimal amounts of Tn and sialosyl-Tn, and the staining was seen only in relation to the luminal membrane and mucin of a few glandular structures. Mucin-type Tn and sialosyl-Tn may be regarded as markers of a glandular differentiation pattern in salivary gland carcinomas. The cellular location of the antigen-antibody complex indicates that they are synthesized and secreted from the tumor cells into saliva or serum.

C-myc, ras p21 and p53 expression in pleomorphic adenoma and its malignant form of the human salivary glands.

Using an immunohistochemical study and an immunoblot analysis, the expression of cellular oncogenes of the human salivary glands such as c-myc, ras p21, and p53 tumor-suppressor gene in pleomorphic adenomas and its malignant form, carcinoma in pleomorphic adenomas was examined to evaluate a differential biological significance, in comparison with that in normal salivary gland tissues. Immunohistochemically, the c-myc product was detected in 42% of the pleomorphic adenomas and in 56% of the carcinomas in pleomorphic adenoma. The ras p21 expression was observed in 24% of pleomorphic adenomas, and in 50% of carcinomas in pleomorphic adenoma. The p53 protein was detected in 18% of the pleomorphic adenomas and in 67% of the carcinomas in pleomorphic adenoma. Although there was no significant difference between the benign and malignant forms for the expression of c-myc, a statistical significance in ras p21 and p53 expression was found between the pleomorphic adenoma and its malignant form (P < 0.05) and P < 0.001, respectively). An immunoblotting assay clearly demonstrated the expression of c-myc and p53 gene products in both the benign and malignant forms of the pleomorphic adenoma, and that of ras p21 in the malignant form. These results indicate that activation of c-myc and ras p21 proto-oncogenes and the involvement of p53 mutation may play important roles in the malignant transformation of salivary gland pleomorphic adenoma.

唾液腺腫よう１０５例の検討

A total of 105 salivary gland tumors treated and followed up by our department from 1965 to 1987 were clinically studied. The results were as follows:1. There were 65 benign tumors (61.9%) and 40 malignant tumors (38.1%).2. Histologically, the tumors occurred in the following order of frequency: adenomaspleomorphic adenoma (52 cases), Warthin tumor (7 cases), oncocytoma (2 cases), basal cell adenoma (1 case) and cystadenoma (1 case); carcinomas-mucoepidermoid carcinoma (15 cases), adenoid cystic carcinoma (12 cases), carcinoma in pleomorphic adenoma (5 cases), adenocarcinoma (4 cases), squamous cell carcinoma (2 cases), acinic cell carcinoma (1 case) and epithelial-myoepithelial carcinoma (1 case); non-epithelial tumors-angioma (2 cases).3. The tumors originated from the major salivary glands in 32 cases and from the minor salivary glands in 73 cases. Among the cases that developed in the minor salivary glands, the most frequently affected site was the palate (45 cases), followed by the oral base (8 cases) and the buccal mucosa (7 cases).4. Clinical findings associated with a high incidence of malignancy were symptoms of pain and ulcers in addition to swelling at the first medical examination (75%). With respect to the primary site, the minor salivary glands except for the palate and lips had a high incidence of malignancy.5. Surgical treatment was performed for all benign tumors and 90% of the malignant tumors. In 70% of operated malignant tumors, radiotherapy and/or chemotherapy used concomitantly.6. The cumulative survival rate for all malignant cases was 78.9% at 5 years and 61.9% at 10 years. Histologically, mucoepidermoid carcinoma and carcinoma in pleomorphic adenoma had good prognoses, but adenoid cystic carcinoma, adenocarcinoma and squamous cell carcinoma had poor prognoses.7. Misdiagnoses were made before surgery in 3% of the benign tumors (2 cases) and in 30% of the malignant tumors (12 cases). Among the misdiagnosed malignant tumors 10 had no clinical findings indicative of malignancy and their prognoses were good. Two cases misdiagnosed as benign tumors had clinical findings of malignancy and their prognoses were poor.