Cause-Specific Mortality in Patients with Mucoepidermoid Carcinoma of the Major Salivary Glands

Background

The objective of this study was to determine the incidence and cause of disease-specific death in patients with mucoepidermoid carcinoma (MEC) affecting the major salivary glands.

Methods

A total of 94 patients with MEC treated at Memorial Sloan-Kettering Cancer Center between 1985 and 2009 were identified from a preexisting database of 451 patients with major salivary gland cancer. Patient, tumor, and treatment characteristics were recorded from a retrospective analysis of patient charts. There were 49 males (52 %), and the median age was 57 years (range, 9–89 years). Of the 94 patients, 49 % had low, 22 % had intermediate, and 28 % had high-grade carcinoma. Overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were calculated using the Kaplan–Meier method. Cause of death was determined by chart review. Predictors of DSS were identified by univariate analysis.

Results

With a median follow-up of 59 months (range, 1–257), the 5-year OS, DSS, and RFS for all patients were 76 %, 83 %, and 79 %, respectively. DSS was significantly poorer for high-grade MEC compared with low/intermediate-grade MEC (5-year DSS 37 % vs 100 %, P < .001). There were 9 disease-specific deaths. The cause of death in 7 patients was distant metastatic disease with locoregional recurrence accounting for death in only 2 patients.

Conclusion

Outcome in patients with mucoepidermoid cancers of the major salivary glands is generally good. Mortality occurs almost exclusively in patients with high-grade tumors. The cause of death in the majority of patients is distant metastatic disease rather than locoregional recurrence.     

Expression of Mucins in Salivary Gland Mucoepidermoid Carcinoma

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumour in both adults and children. Histological grading of MEC is subjective, but plays an important role in predicting patient prognosis. Epithelial mucin (MUC) status may aid in establishing a more accurate grade. This study aimed to investigate the expression of various mucins (MUC1, MUC2, MUC4 and MUC5AC) in MECs to determine a possible correlation with tumour grade. Fifteen cases of each tumour grade (low-, intermediate-, and high-grade) were retrieved from the pathology archives of the Department of Oral Pathology and Oral Biology at the University of Pretoria. The patients included 23 men and 22 women, and ranged from 13 to 85 years (mean 49.8 years). Sections from formalin-fixed paraffin-embedded (FFPE) tissue were used for fluorescence in situ hybridization (FISH) for MAML2 rearrangements and MUC immunohistochemical analysis. The percentage immunohistochemical expression of the neoplastic mucous cells was evaluated first, followed by the overall percentage expression of all tumour cells. The results indicated that MUC1 overexpression may be a reliable marker of high-grade MECs, whereas MUC4 overexpression may be more indicative of low-grade tumours. MUC5AC expression was considered an unreliable marker in determining grade. MUC2 was only expressed in a single case of MEC and may be considered a useful marker to exclude MEC as a diagnostic possibility. This study demonstrates that MECs show an altered MUC expression pattern that can be used for diagnostic purposes and to aid in establishing a more accurate tumour grade.     

An Immunohistochemical Panel for Reliable Differentiation of Salivary Duct Carcinoma and Mucoepidermoid Carcinoma

Salivary duct carcinoma is a highly aggressive salivary gland malignancy that may be misdiagnosed as high-grade mucoepidermoid carcinoma. We utilized tissue microarrays with 78 examples of mucoepidermoid carcinoma and 47 salivary duct carcinomas to evaluate the utility of an immunohistochemical panel consisting of androgen receptor, Her2/neu, p63, and cytokeratin 5/6 in distinguishing these entities. Among all cases in the cohorts, androgen receptor was highly specific for salivary duct carcinoma, while cytokeratin 5/6 and p63 were specific for mucoepidermoid carcinoma. While the rate of unequivocal Her2/neu overexpression among the salivary duct carcinomas was low (8.9 %), discrimination of salivary duct carcinoma was enhanced when this marker was used in combination with androgen receptor due to profound sensitivity. The immunohistochemical panel was particularly efficacious at distinguishing the problematic subset of high-grade mucoepidermoid carcinomas from salivary duct carcinoma. Utilization of this set of immunohistochemical markers allows reliable differentiation of salivary duct and mucoepidermoid carcinoma, a distinction with important prognostic and therapeutic implications.     

Comparative Cytokeratin Expression in the Different Cell Types of Salivary Gland Mucoepidermoid Carcinoma

Mucoepidermoid carcinoma is the most common malignant salivary gland tumor, composed of several different cell types, with controversial histogenesis. The aim of this study was to assess the expression of cytokeratins in mucoepidermoid carcinoma, comparing to cytokeratin expression in normal salivary glands, in order to establish a possible correlation between tumor cells immunostaining and mucoepidermoid carcinoma histogenesis and differentiation. Eighty cases of salivary gland mucoepidermoid carcinoma were immunohistochemically examined with the use of antibodies against cytokeratins 6, 7, 8, 13, 14, 18, and 19. Cytokeratin expression varied according to the cellular type: squamous cells presented high expression of cytokeratins 6, 7, 8, 14, 18, and 19; intermediate and mucous cells of cytokeratin 7; clear and columnar cells of cytokeratins 6, 7, 8 and the latter also expressed cytokeratin 18. Cytokeratin 13 expression was low in all cell types. Cytokeratin immunoexpression in mucoepidermoid carcinoma was variable according to the cellular type; but regardless of the cellular type studied, cytokeratins 7 and 13 were, respectively, constantly high and low expressed. The immunoprofile of the normal salivary glands was variable according to the component but, in general, cytokeratin profile in mucoepidermoid carcinoma showed similarity to the immunoexpression on the excretory duct unit of normal salivary glands.     

Multiple Malignant Salivary Gland Neoplasms: Mucoepidermoid Carcinoma of Palate and Adenoid Cystic Carcinoma of Floor of Mouth

Salivary gland tumors usually occur as single lesions. To have more than one tumor is unusual. We report a case of an adult male who presented with a mucoepidermoid carcinoma involving the minor salivary glands of the palate at age 57 years, followed by an adenoid cystic carcinoma of the floor of mouth at age 63 years. The patient later succumbed to non-Hodgkin lymphoma at age 72 years. There are 31 acceptable cases of multiple malignant salivary gland neoplasms reported in the world literature. Multiple malignant tumors of the same histologic type are more common than those of different histologic type. Bilateral acinic cell adenocarcinoma was the most frequent combination of multiple salivary gland malignancy, accounting for 14 cases (10 synchronous and four metachronous). All involved the parotid glands bilaterally with the exception of one case that involved parotid and submandibular gland. Polymorphous low-grade adenocarcinoma accounted for three of the four cases of multiple malignant tumors involving minor salivary glands. Individuals with a history of malignancy are at risk for the development of additional malignant tumors and should receive appropriate clinical follow-up.

Expression of the Vascular Endothelial Growth Factor and Angiopoietins in Mucoepidermoid Carcinoma of Salivary Gland

Disrupted coordination of angiogenesis regulating signals, among them the vascular endothelial growth factor (VEGF) and angiopoietins (Angs), has been associated with abnormal angiogenesis and tumor progression. While VEGF induces endothelial cell proliferation, thereby initiating vessel formation, Angs are subsequently required for mural cell attachment, thus influencing remodeling and maturation of this vasculature. In addition to tumor cell, endothelial and mural cells, as well as myofibroblasts may also contribute to the secretion of these factors. In this study, we have analyzed by immunohistochemistry the expression of VEGF, Ang-1, Ang-2 and the Angs receptor Tie2 in both the stroma and tumor cells of mucoepidermoid carcinoma (MEC) of salivary gland. We have demonstrated that when myofibroblasts were detected adjacent to the cancer cells, they were frequently associated with intense positive staining for Ang-1 and Ang-2, and no reactivity to VEGF and Tie2. These myofibroblast-rich Ang-1 and Ang-2-stained areas were more commonly found in high-grade MEC cases than in low-grade ones. As for the malignant cells, they frequently expressed all proteins studied, but Ang-2 and VEGF were detected at higher levels compared to Ang-1 and Tie2. Our results indicate that the MEC environment favors cooperative activity between Angs and VEGF in modulating vascular growth and tumor aggressiveness.     

Cytology of the Salivary Glands

Common usage of fine-needle aspirate (FNA) for salivary gland lesions is the preoperative determination of whether a lesion is neoplastic, its lineage, and if neoplastic, whether it is low grade/benign, or high grade. Immunohistochemical stains can be performed on cell blocks to determine lineage and help refine diagnosis, although their performance is not always equivalent to that seen in surgical specimens. Several characteristic translocations have been described in various entities in these categories, and these can be evaluated using fluorescence in situ hybridization. In the future, high-throughput next-generation sequencing panels may further refine cytologic diagnosis in salivary tumors.     

碱性成纤维细胞生长因子和血管生成与胃癌发展的关系

目的:探讨碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)和血管生成与胃癌发展的关系.方法:应用免疫组织化学方法检测56例人胃癌组织碱性成纤维细胞生长因子表达和微血管密度(microvasculardensity,MVD),分析bFGF和MVD及其与胃癌组织学分型、浸润深度、生长方式、淋巴结转移、远处转移和预后的关系.结果:bFGF阳性者MVD值显著高于bFGF阴性者(P<0.01),MVD值和bFGF表达与胃癌浸润深度(P<0.05)、淋巴结转移(P<0.01)和远处转移(P<0.05)密切相关;MVD≥43或bFGF表达阳性的胃癌患者5年生存率较低.结论:血管生成在胃癌发展中具有重要作用,bFGF不仅与胃癌的血管生成有关,而且与胃癌的生长和浸润转移也有关,MVD或bFGF可作为判断胃癌患者预后的指标.     

Lysozyme Expression Can be Useful to Distinguish Mammary Analog Secretory Carcinoma from Acinic Cell Carcinoma of Salivary Glands

Lysozyme is an enzymatic marker of acinar and intercalated duct cells of normal salivary glands. The aim of this study was to verify whether lysozyme expression could be useful to distinguish acinic cell carcinoma (ACC) from its main mimic, mammary analog secretory carcinoma (MASC). For comparison, DOG1 expression was analyzed as well. Seventeen cases of ACC, 15 MASC, and 125 other salivary tumors were studied. Lysozyme expression was found in tumor cells as well as in secreted material of MASC (86.6 % of cases) and in ductal cells of epithelial–myoepithelial carcinoma (EMC-53.8 %), pleomorphic adenoma (PA-29.1 %) and polymorphous low-grade adenocarcinoma (PLGA-23.8 %). However, in ACC, lysozyme was not expressed. Three patterns of DOG1 staining were seen: apical–luminal, cytoplasmic, and mixed cytoplasmic/membranous. The apical–luminal pattern was detected in ductal cells of ACC (58.8 % of cases), EMC (38.4 %), adenoid-cystic carcinoma (AdCC-35.3 %), PA (8.3 %), and PLGA (4.8 %). These tumors also showed mixed membranous/cytoplasmic staining for DOG1. MASC, mucoepidermoid, and salivary duct carcinomas exhibited only DOG1 cytoplasmic staining. In conclusion, lysozyme cannot be used as a marker of acinar differentiation in salivary tumors. However, lysozyme expression can be helpful to distinguish MASC from ACC due to its high frequency in the former and absence in ACC. It is likely that in MASC, lysozyme expression may reflect a lactational-like secretory differentiation since lysozyme belongs to breast milk proteins. Regarding DOG1 expression, the apical–luminal pattern is related to acinar and intercalated duct differentiation whereas the cytoplasmic staining does not seem to be associated with a specific cellular phenotype.     

Outcomes of Pediatric Patients with Malignancies of the Major Salivary Glands

Background  

To report the outcomes and early to long term treatment complications among pediatric patients with major salivary gland malignancies treated at a single institution.