Gland Carcinoma Research Articles

Clear cell carcinoma of the major salivary glands in an HIV-infected patient

Clear cell carcinoma is a rare type of salivary gland carcinoma. It has a low degree of malignancy and long-term prognosis is favourable after surgical removal. The authors describe the case of a human immunodeficiency virus (HIV) infected 43-year-old woman who presented with a tumour on the floor of the mouth. After biopsy, left suprahyoid lymph node dissection and removal of the submandibular and sublingual glands was performed, followed by radiotherapy. Histologically, the tumour presented the characteristic features of hyalinizing clear cell carcinoma, defined as a variant of clear cell carcinoma by the latest World Health Organization classification. Hyalinizing clear cell carcinoma has a characteristic histological pattern and, to date, there is insufficient information to determine whether both forms behave similarly or differently. The present case illustrates a highly uncommon tumour variant occurring in a HIV-infected patient. To date, this association has not been described in the medical literature. The low grade of malignancy reported for this tumour demands a precise diagnosis and complete tumoral excision.

Perineural Invasion in Adenoid Cystic Carcinoma of the Salivary Glands: Anatomical Influences on Oncological Management

The evidence as to the prognostic significance of perineural invasion in adenoid cystic carcinoma of the sali- vary glands is equivocal. Nevertheless, many head and neck surgeons and oncologists take account of histologically proven perineural invasion when planning treatment for adenoid cystic carcinoma. This review presents a digest of the data showing how neural involvement by adenoid cystic carcinoma of the salivary glands relates to local anatomy, and how this influences the extent of surgery and planning of radiotherapy.

Lymphoepithelial Carcinomystery: A Curious Case of a Rare Parotid Tumor

Lymphoepithelial Carcinomystery: A Curious Case of a Rare Parotid Tumor

Characteristics and Outcome of Radiation- and Chemotherapy-related Mucoepidermoid Carcinoma of the Salivary Glands

Background Mucoepidermoid carcinoma (MEC) of the salivary glands has been reported to occur in patients previously treated with chemotherapy and/or radiation. The purpose of our study is to review the patient, tumor, and treatment characteristics of patients who develop a treatment-related MEC. Procedure A PubMed search of English language articles was performed using the keywords and MeSH terms: mucoepidermoid, salivary gland, radiation-induced, second malignancy, radiotherapy, and chemotherapy. Results The search yielded 23 articles describing 58 patients who received chemotherapy and/or radiotherapy (RT) and subsequently developed MEC. The most common initial diagnoses were acute lymphoblastic leukemia (n = 18), acne (n = 9), and Hodgkin lymphoma (n = 6). Patients were divided into three groups according to chemotherapy and RT treatment: chemotherapy alone (n = 14), RT alone (n = 14), or chemotherapy and RT (n = 30). The parotid gland was the most common site for secondary MEC. Latent time (LT) to development of MEC from initial tumor treatment was significantly shorter in the patients treated with chemotherapy ± RT versus RT alone (7.9 years vs. 27.2 years, P < 0.01). The most common treatment for MEC was surgery alone followed by surgery and postoperative RT. The 2- and 5-year overall survival rates were 98% and 93.4% while the 2- and 5-year locoregional control rates were 97.7% and 92.5%, respectively. There was no difference in survival or locoregional control between groups exposed to RT alone, chemotherapy alone, or chemotherapy with RT for the initial tumor. Conclusion Radiation and chemotherapy-related MEC has an excellent prognosis. Pediatr Blood Cancer 2011; 57: 1137–1141. © 2011 Wiley Periodicals, Inc.

Abstract 351: Mutations of genes in the c-Kit receptor tyrosine kinase signaling pathway are inactive in adenoid cystic carcinoma of the salivary glands: Implications for c-Kit targeted therapy

Abstract Adenoid cystic carcinoma (ACC) is a malignant salivary gland tumor well-known for spreading in wide local area and invasion of vital structures of the head and neck. Unfortunately, conventional therapies have not improved longer-term survival, resulting in significant morbidity and a very low overall survival rate. Improved systemic therapies are clearly needed for this population. ACC tumors overexpress the receptor tyrosine kinase c-Kit, which is thought to be a therapeutic target. However, the role of c-Kit in the pathogenesis of ACC is not currently understood. We addressed this question through a functional genomic study with 17 sporadic ACC tumor specimens. We found heterogeneous missense mutations in three genes in the c-Kit signaling pathway, although mutations were identified at a low frequency. Two ACC tumors had distinct missense mutations in the gene KIT, resulting in G664R and R796G amino acid substitutions in the c-Kit kinase domain. Furthermore, two ACC tumors without KIT mutations had missense mutations in either KRAS or BRAF, causing S17N K-Ras and V590I B-Raf mutants. KRAS and BRAF are downstream effectors of c-Kit. We explored the functional consequences of these amino acid substitutions and found that all of c-Kit, K-Ras and B-Raf mutations in our ACC samples were inactive. These observations suggest that the c-Kit signaling pathway must be dispensable for maintaining established ACC. As a result, we believe that selective c-Kit inhibition is not a suitable treatment for the patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 351.

Reconstruction of eyelid after resection of carcinoma of meibomian glands:an observation of clinical outcomes

Reconstruction of eyelid after resection of carcinoma of meibomian glands:an observation of clinical outcomes

Loss of SFRP1 Expression is Associated with Aberrant β-Catenin Distribution and Tumor Progression in Mucoepidermoid Carcinoma of Salivary Glands

Cytoplasmic and nuclear accumulation of beta-catenin in mucoepidermoid carcinoma (MEC) is frequently noted, but the mechanism is unknown. The methylation status of adenomatous polyposis coli (APC) and secreted frizzled-related proteins (SFRPs) was examined by methylation-specific polymerase chain reaction (MSP) assay. The association of SFRP1, beta-catenin, and cyclin D1 expression in MEC was evaluated by immunohistochemical staining. A high percentage of methylation in APC and the SFRP genes was found in MEC compared with adjacent normal tissues, in which SFRP1 (58.6%) was the most frequent methylated gene. Moreover, abundant expression of SFRP1 was noted in normal tissues, whereas reduced SFRP1 expression was detected in 71.7% (33/46) of MECs. There was significant association between methylation and reduced expression of SFRP1. Cytoplasmic/nuclear (C/N) beta-catenin and high cyclin D1 expression were found in 13/55 (23.6%) and 36/55 (65.5%) of cases, respectively. There was significant correlation between C/N beta-catenin expression and reduced SFRP1 expression (P = 0.009). In addition, SFRP1 and beta-catenin expression correlated with tumor malignancy index such as tumor grade and stage. Overall patient survival was significantly worse in patients with reduced SFRP1 and C/N beta-catenin expression (P = 0.009 and P = 0.002, respectively). Methylation of the SFRP1 gene was the major cause of reduced SFRP1 expression. Reduced SFRP1 led to C/N accumulation of beta-catenin and was associated with tumor malignancy. Therefore, examination of SFRP1 expression and beta-catenin location could be useful predictors of tumor progression and prognosis in patients with MEC.

Expression of oestrogen and progesterone receptors in canine sebaceous gland tumours

Sebaceous gland oestrogen alpha (ERalpha) and progesterone (PR) receptor expression was examined immunohistochemically in 26 and 32 dogs respectively with sebaceous gland hyperplasia/adenomas, epitheliomas and carcinomas, and in the glands of 10 healthy controls. The mean percentage of ERalpha positive nuclei in control sebaceous glands was 21.31% compared with 11.5% in hyperplasia/adenoma-type lesions, although these values were not statistically different. In sebaceous gland epitheliomas and carcinomas, positive basal cells represented 7.86% and 3.53% of neoplastic cells respectively and these mean percentages were significantly lower in epitheliomas (P < 0.024) and carcinomas (P < 0.015) than in controls. The mean percentage of PR-positive nuclei in control sebaceous glands was 23.96%, similar to the 22.07% found in hyperplasia/adenoma-type lesions. In sebaceous gland epitheliomas and carcinomas, positive cells were scarce and represented 13.5% and 4.06% of neoplastic cells respectively. Differences in the percentage of positive cells between normal and pathological glands reached statistical significance for carcinomas (P < 0.043). In the control group there was greater PR (P < 0.001) and ERalpha expression (P < 0.014) in sebaceous glands in female dogs. The PR and ERalpha immunoreactivity in each category of neoplastic lesions could not be analysed because sample size was too small but when all the sebaceous gland tumours were grouped and analysed, no sex difference was found. The results suggest that oestrogen and progesterone receptor expression is reduced in some canine sebaceous gland tumours. These changes may represent a contributing factor for tumour growth or simply be a consequence of tumour progression.

P1.04. Hyalinizing clear cell carcinoma of salivary glands: Experiencein the National Institute of Cancer of México

P1.04. Hyalinizing clear cell carcinoma of salivary glands: Experiencein the National Institute of Cancer of México

P1.14. Metallothionein expression is associated to metastatic behavior of adenoid cystic carcinoma of the salivary glands

P1.14. Metallothionein expression is associated to metastatic behavior of adenoid cystic carcinoma of the salivary glands

P1.01. Tumor-associated macrophage correlated with angiogenesis and progression of mucoepidermoid carcinoma of salivary glands

P1.01. Tumor-associated macrophage correlated with angiogenesis and progression of mucoepidermoid carcinoma of salivary glands

P1.24. Mucoepidermoid carcinoma of palatal salivary glands: Clinicopathological experience with 10 patients

P1.24. Mucoepidermoid carcinoma of palatal salivary glands: Clinicopathological experience with 10 patients

Immunotherapy for adenoid cystic carcinoma of salivary glands: Cancer/testis antigens and 5-aza-2′-deoxycytidine

Adenoid cystic carcinoma of salivary glands is the epithelial tumor. There are amount of malignant occurrences of adenoid cystic carcinoma of salivary glands in the head and neck area. Cancer/testis antigens can be found in various malignant tumors, normal adult testis and occasionally placenta, but not in the other normal adult tissues. This characteristic makes Cancer/testis antigens as potential markers to be applied in immunotherapeutic strategies against cancer. It has been shown that in different tumors, the expression of certain Cancer/testis antigens is activated treated with 5-aza-CdR via the demethylation of their promoter CpG islands. It is logical that multiple Cancer/testis antigens may correlate with the clinicopathologic factors of adenoid cystic carcinoma of salivary glands and be the potential markers of prognosis treated with 5-aza-CdR. So the hypothesis will provide the new direction that we can use Cancer/testis antigens as candidate antigens for adenoid cystic carcinoma of salivary glands immunotherapy due to the high expression rate activated with 5-aza-CdR.

Is maspin immunolocalization a tool to differentiate central low-grade mucoepidermoid carcinoma from glandular odontogenic cyst?

Mucoepidermoid carcinoma (MEC) of the salivary glands has a low-grade variant (LGMEC), which may be found within the jawbones. LGMEC shares a number of histopathological similarities with glandular odontogenic cysts (GOC) of the jawbones. Maspin has been identified in several benign and malignant salivary gland neoplasms. We investigated the immunolocalization of maspin in LGMEC and GOC and evaluated its potential to distinguish between these two entities. Cases of LGMEC (n=6), GOC (n=8) and various odontogenic cysts with marked mucous metaplasia (OCMM, n=7), which served as controls, were immunohistochemically labeled for the binding of an antibody directed against maspin. Immunomorphometry was performed separately for maspin-immunopositive epithelial cells and epithelial-mucous cells in either their nuclear or cytoplasmic compartments. Results were presented as the volume fraction (Vv) of each element. The Vv of the maspin-immunopositive epithelial-mucous cytoplasm and nuclei was significantly higher in LGMEC than in GOC and OCMM (p<0.001 and p=0.026, respectively). In the epithelial cells, no significant differences were observed among the lesions (p>0.05). It is suggested that the high levels of maspin in the epithelial-mucous cells (in both cytoplasm and nuclei) in LGMEC may serve as a tool to distinguish it from GOC. This may be useful especially in equivocal cases and in small incisional biopsy samples.

Ultrastructural assessment of adenoid cystic carcinoma with emphasis on tumour infiltration periphery

Summary Background There is a wide variety of morphological and clinical types of tumours of the salivary glands. Almost 30 histological types of these neoplasms are known. Adenoid cystic carcinoma is a rarely occurring malignant epithelial neoplasm. It occurs in major salivary glands, but may also originate in the salivary glands of the respiratory tract. Aim The aim of the present study was the ultrastructural assessment of the infiltration periphery of different histological types of adenoid cystic carcinoma of the salivary glands. Materials and Methods Tissue samples from patients with adenoid cystic carcinoma of the salivary glands were studied. The study group consisted of 30 pts. 21 pts with tumour of parotid, 8 with submandibular and 1 with tumour of sublingual salivary glands. All patients were surgically treated and undergone supplementary treatment using radiotherapy in the Greater Poland Cancer Centre. Assessment of tissue samples was performed using morphological diagnoses and ultrastructural evaluation. Results Ultrastructural electron microscopy assessment of adenoid cystic carcinoma revealed differentiation of the tumour cells towards ductal salivary, myoepithelial and pluripotential cells. Epithelial cells showed an increased nucleus-cytoplasm ratio, and their nucleoli were characteristic for actively proliferating cells. The analysis showed histological and structural differences between the central and peripheral parts of the tumour. Conclusions The ultrastructural assessment of adenoid cystic carcinoma revealed that the cells in the peripheral parts of the tumour show a lower degree of maturation than the ones in its centre, peripheral stroma contains fewer collagen fibres, and dominant elements at the periphery of the tumour are proteoglycans and glycosaminoglycans, no histoformative features typical of the principal (central) part of the tumour were found at its periphery.

Cliniconathologic diagnosis of oncocytic moeoepidermoid carcinoma in salivary glands

Objective To investigate the elinicopathologic features, diagnosis and differential diagnosis of oncocytic mucoepidermoid carcinoma of the salivary glands. Methods One case of oncocytic mucoepidermoid carci-noma was observed by clinicopathology and immunohistochemistry, followed by discussion through review of the litera-ture. Results The tumor was consisted of acidophilic cells, mucous cells,epidermoid cells and intermediate cells. The neoplastic cells arranged in a sheet, nest and glandular pattern, that were segregated by fibrous tissue. Some area the tumaor was composed of the same types of acidophilie cells,which had abundant finely granular eosinophilic cytoplasm, showed moderate unclear atypia. Histochemistry staining: the mucous secretory cells and some epidermoid cells were positive for PAS. IHC staining, the tumor cells were positive for CK7 and CK20 ,focal positive reaction to CEA, negative for NSE and CgA. Conclusion Oncocytic mucoepidermoid carcinoma is an extremely rare subtype of mucoepidar-moid carcinoma of the salivary glands. Histological examination plays an important role in diagnosis of this tumor. More attention should be paid on the daily practice in order to differentiate this tumor from oncocytic adenoma, pleomorphic adenoma and mucinous cystadenoma. Key words: Salivary neoplasms; Carcinoma, muccepidermoid; Oncocytic cells; Clinicopathology

Recurrence after Treatment of Salivary Gland Adenoid Cystic Carcinoma

Background and Objectives：Adenoid cystic carcinoma of salivary glands has distinct characteristics of indolent but persistent growth, late onset of metastasis and eventual death of patients. We performed this study to find parameters affecting the recurrence and survival of patients with adenoid cystic carcinoma in salivary glands. Subjects and Method：A retrospective study was done on 55 patients who underwent surgery between 1990 and 2006. We analyzed the effect of patient’s factors, characteristics of tumor and treatment modalities to local recurrence, distant metastasis and survival. Results：There were 20 males and 35 females, with the median age of 50.2 years. The mean follow-up duration after treatment was 70.9 months. Patients who received surgery alone were 12 (22%), with radiation therapy were 34 (62%) and with concurrent chemoradiation therapy were 9 (16%). There were 7 patients who had local recurrence alone, 8 who had distant metastasis alone and 3 who had local recurrence with distant metastasis. There was no correlation between the above parameters and local recurrence. Distant metastasis was influenced by old age (p= 0.018), lymph node involvement (p=0.005) and treatment with concurrent chemoradiation therapy (p<0.001). Eight patients died during the follow up period. Five-year overall survival rate was 88.2% and the disease-free survival was 72.9%. The multivariate analysis found that only lymph node involvement was associated with survival (p=0.043). Conclusion：Lymph node involvement was predictive of poor prognosis in salivary adenoid cystic carcinoma. Therefore, it is necessary to establish highly sensitive diagnostic tools with which surgeons can find lymph node involvement. (Korean J Otorhinolaryngol-Head Neck Surg 2009;52:154-60)

Evidence of a Threshold-Effect for 2-Amino-3,8-dimethylimidazo-[4,5-f]quinoxaline Liver Carcinogenicity in F344/DuCrj Rats

To estimate potential human risk of exposure to a food-derived, genotoxic hepatocarcinogen, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), a 2-year carcinogenicity test was conducted using male F344 rats administered MeIQx-containing diet at doses of 0 (control), 0.001, 1, and 100 ppm. The lowest dose 0.001 ppm was established as equivalent to the daily intake of this carcinogen in humans (0.2 to 2.6 microg/man/day). Significant decreases of survival rate and body weight gain were observed in rats treated with 100 ppm MeIQx. Histopathological examination revealed significant induction of hepatocellular carcinomas, adenomas, and development of glutathione S-transferase placental form-positive foci with MeIQx at 100 ppm. Moreover, the incidences of Zymbal's glands carcinoma, mammary fibroadenoma, and subcutaneous fibroma were found significantly increased in a 100 ppm MeIQx group. However, no significant induction of altered preneoplastic hepatocellular foci was observed in 0.001 and 1 ppm groups as compared to the controls. 8-Hydroxy-2'-deoxyguanosine levels in the rat liver DNA of the 100 ppm-treated group were not elevated, but MeIQx-DNA adduct formation increased as compared with the 1 ppm case, albeit without significance. No significant induction of any other neoplastic lesions related to the carcinogen administration was found in MeIQx-administered groups except for 100 ppm. These results imply that 1 ppm may be a no-effect level for MeIQx carcinogenesis.

Gefitinib prevents cancer progression in mice expressing the activated rat HER2/neu

We tested the efficacy of gefitinib in the prevention of HER2/neu-mediated breast cancer development in BALB-NeuT transgenic mice. Oral administration of gefitinib to female transgenic mice from 5 to 14 weeks of age reduced tumor multiplicity from 9.6 +/- 0.82 to 0.58 +/- 1.1 (83%). We observed a decrease in the number and size of lobules and lobular nodules in treated mice with a reduction in the overall disease burden per gland. Normal duct development in the mammary glands was not affected by gefitinib. The development of acinic cell carcinoma in the parotid glands of these animals was also reduced coincident with decreased stromal involvement during progression. Gefitinib eliminated phosphorylation of HER2 and HER3 and signaling through MAPK and Akt in lobular hyperplasias and carcinomas. At the same time MAPK activity and cytokine production in splenocytes and lymph nodes was increased in gefitinib-treated animals coincident with an increase in lymph node size. Delaying gefitinib treatment until mammary glands exhibited atypical lobular hyperplasias reduced efficacy. These studies demonstrate the critical role of HER2 signal transduction in the onset and progression of HER2/neu-dependent breast cancer and suggest a role for specific inhibitors to prevent the outgrowth of early hyperplastic disease.

Receptores de progesterona y grado histológico del cáncer ductal de glándula mamaria

El presente estudio buscó determinar la frecuencia porcentual que existe en la expresión para receptores hormonales de progestágenos y estrógenos según el grado de diferenciación histológica del carcinoma de glándula mamaria (GM). Se revisaron 56 pacientes con cáncer de GM en el Hospital de San José en el período comprendido entre enero 1 de 2004 a enero 31 de 2006, a quienes en la biopsia se les practicó análisis de inmunohistoquímica para receptores de estrógenos y progestágenos. La información se recolectó en una base de datos y se analizó en el programa estadístico EN INFO 6.0. De los 56 casos estudiados 16 fueron diagnosticados como grado 1 (28.6%), 26 grado 2 (46.4%) y 14 grado 3 (25%). De la totalidad de casos marcados para receptores de estrógenos 40 expresaron positividad y para progestágenos 36. Este estudio demostró que la frecuencia del porcentaje de positividad para receptores de estrógenos y progestágenos está relacionada con el grado de diferenciación histológica del tumor. Abreviaturas: GM, glándula mamaria.