Extensive carcinoma cuniculatum of the mandible.

Carcinoma cuniculatum (CC) is a rare variant of squamous cell carcinoma first described in 1954. Cases of CC in the head and neck are exceedingly rare, with 66 cases reported since 1977. These tumors are generally low-grade, well-differentiated and locally aggressive malignancies. Patients are often subjected to a long period of misdiagnoses given the clinical similarity of these entities to odontogenic cysts and abscesses. We report a case of a carcinoma cuniculatum of the mandible with very advanced local involvement of disease, highlighting the unusual characteristics of this rare tumor that are important for clinicians to recognize. Clinical presentation, histology, risk factors, treatment options, and prognosis are also reviewed.

Rhabdomyosarcoma of the head and neck: impact of demographic and clinicopathologic factors on survival.

OBJECTIVE: To determine the survival factors for patients diagnosed with rhabdomyosarcoma of the head and neck. STUDY DESIGN: Data on patients diagnosed with rhabdomyosarcoma of the head and neck between 1973 and 2012 were extracted from the Surveillance, Epidemiology, and End Results database. Kaplan-Meier and Cox proportional hazard regression models were used to determine the demographic characteristics, prognostic factors, and treatment modalities that determine overall survival (OS) and disease-specific survival (DSS). RESULTS: Data on 503 patients diagnosed with rhabdomyosarcoma of the head and neck were analyzed; 51.3% were male and 48.7% were female, with a median OS of 4.9 years. Kaplan-Meier analysis determined 5-year survival rates of 30% for OS and 50% for DSS. Multivariate analysis found that age at diagnosis, tumor extent of disease, surgical resection, and radiation therapy were independent predictors of OS and DSS. CONCLUSIONS: To our knowledge, this is the largest year-span study to date to determine the factors of survival for rhabdomyosarcoma of the head and neck. Older age at diagnosis, histologic subtype of alveolar rhabdomyosarcoma, and further extent of disease were associated with decreased survival. Surgical resection improves survival in patients with localized or regional disease, and radiation therapy confers survival benefits in patients with distant extent.

Determining the epidemiologic, outcome, and prognostic factors of oral malignant melanoma by using the Surveillance, Epidemiology, and End Results database.

BACKGROUND: The authors conducted a retrospective analysis to determine the epidemiologic, outcome, and prognostic factors in patients with oral malignant melanoma (OMM). METHODS: The authors used the US National Cancer Institute's Surveillance, Epidemiology, and End Results database to analyze patients with OMM from 1973 to 2012. Study variables included age, sex, race, decade of diagnosis, extent of disease, tumor size, treatment modality, and socioeconomic status (SES). RESULTS: The search identified 232 patients with OMM. Overall survival (OS) and disease-specific survival (DSS) were 25% and 40%, respectively, at 5 years. Age (OS, P = .004; DSS, P = .294), surgical resection (OS, P = .046; DSS, P = .005), and extent of disease (OS, P < .001; DSS, P < .001) were independent survival determinants; tumor size was an independent predictor of OS (P = .085). For confined and locally invasive disease, surgery (OS, P = .001; DSS, P = .004) and size (OS, P = .154; DSS, P = .007) were independent determinants of OS and DSS. For metastatic disease, surgery (OS, P = .675; DSS, P = .518) was a survival determinant for both OS and DSS, whereas radiotherapy predicted improved OS (hazard ratio, 0.18; 95% confidence interval, 0.03 to 0.99; P = .049). CONCLUSIONS: Age at diagnosis, decade of diagnosis, extent of disease, tumor size, and SES are prognostic factors related to OMM survival. Surgical resection and radiation therapy both improve OMM survival. PRACTICAL IMPLICATIONS: Early and detailed examinations for OMM are critical to improving the survival rate in patients with OMM, especially in older patients and patients of lower SES.

Importance of tumor extent in adenosquamous carcinoma of the head and neck: a retrospective cohort study.

OBJECTIVE: The aim of this study was to determine the correlates of survival for patients diagnosed with adenosquamous carcinoma (ASC) of the head and neck. STUDY DESIGN: Patients diagnosed with ASC of the head and neck between 1973 and 2012 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier and Cox proportional hazard regression analyses were conducted to investigate the prognostic factors and treatment modalities that determine overall survival (OS) and disease-specific survival (DSS). RESULTS: In the analysis, of the 235 patients diagnosed with adenosquamous of the head and neck, 66.8% were male and 33.2% were female with a median age at diagnosis of 64 years. Kaplan-Meier analysis determined 5-year survival rates of 30% for OS and 50% for DSS. Univariate and multivariate analyses found that age at diagnosis, tumor size, tumor extent of disease, surgical resection, and radiation therapy were independent predictors of OS and DSS. CONCLUSIONS: This study, to our knowledge, is the largest study, to date, determining the correlates of survival for ASC of the head and neck. Older age at diagnosis, larger tumor size, and further extent of disease were correlated with decreased survival. Surgical resection improves survival in patients with localized or regional disease, whereas radiation therapy confers survival benefit in patients with distant extent.

Malignant sublingual gland tumors: demographics, prognostic factors, and treatment outcomes.

OBJECTIVE: To determine the demographic characteristics, prognostic factors, and optimal treatment modalities of patients diagnosed with malignant primary tumors of the sublingual gland. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) registry contains 210 patients diagnosed with sublingual gland tumors in the SEER database. Kaplan-Meier and multivariate Cox regression analysis were performed on age, sex, race, histologic subtype, stage, and treatment modality. RESULTS: Kaplan-Meier analysis found an overall survival and disease-specific survival at 5 years of 69% and 83%, respectively. Multivariate analysis demonstrated that age, sex, stage, and surgery were predictors of overall survival, whereas stage was a predictor of disease-specific survival. CONCLUSIONS: Here we report, to our knowledge, the largest study to date investigating demographic characteristics, prognostic factors, and treatment modalities of patients diagnosed with primary malignant tumors of the sublingual gland. Increased age and stage correlated with decreased survival, whereas female gender and surgical therapy correlated with increased survival in the overall population. Radiation therapy for patients diagnosed with adenoid cystic carcinoma in the sublingual gland was correlated with increased survival.

Characteristics and prognostic factors of osteosarcoma of the jaws: a retrospective cohort study.

IMPORTANCE: Osteosarcoma of the jaws is rare and clinically distinct from osteosarcoma of the long bones of the body with different treatment and outcomes. The literature on these tumors is limited to case reports and small case series mostly from single institutions. We used data from the population-based national Surveillance, Epidemiology and End Results (SEER) cancer registry to determine the epidemiology and prognostic factors associated with osteosarcoma of the jaws. OBJECTIVE: To investigate the epidemiologic characteristics and prognostic factors for survival in patients diagnosed with osteosarcoma of the jaws. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, population-based cohort study of 541 patients in the SEER tumor registry diagnosed with osteosarcoma of the jaws from 1973 through 2011 were reviewed. EXPOSURES: Patients had been treated with surgery, radiation, both, or neither. MAIN OUTCOMES AND MEASURES: Overall and disease-specific survival. RESULTS: A total of 541 patients diagnosed with osteosarcoma of the jaws were identified (49.9% male and 50.1% female, with a mean age of 41.3 years). Kaplan-Meier analysis demonstrated an overall survival (OS) and disease-specific survival (DSS) of 53% and 62%, respectively, at 5 years and 35% and 54%, respectively, at 10 years. Multivariate Cox regression analysis revealed that independent predictors of OS and DSS included age at diagnosis (hazard ratio [HR], 1.03; 95% CI, 1.02-1.04 [P < .001] for OS; and HR, 1.03; 95% CI, 1.02-1.05 [P < .001] for DSS); stage at presentation (HR, 1.37; 95% CI, 1.10-1.71 [P = .006] for OS; and HR, 1.34; 95% CI, 1.01-1.76 [P = .04] for DSS); and surgical resection (HR, 0.31; 95% CI, 0.16-0.60 [P < .001] for OS; and HR, 0.22; 95% CI, 0.09-0.56 [P = .001] for DSS). Tumor size was not significant for OS (HR, 1.00; 95% CI, 1.00-1.01 [P = .11] but significant for DSS (HR, 1.01; 95% CI, 1.00-1.01 [P = .003]). CONCLUSIONS AND RELEVANCE: To our knowledge, this is the largest study to date investigating prognostic factors for survival in patients diagnosed with osteosarcoma of the jaws. Determinants of survival include age at diagnosis, stage at presentation, tumor size, and surgical therapy. Radiation therapy was not associated with improved survival, reflecting the controversy surrounding its use in clinical literature.

Epidemiology, prognostic factors, and management of malignant odontogenic tumors: an analysis of 295 cases.

OBJECTIVE: To determine the demographic characteristics, prognostic factors, and management for patients diagnosed with a malignant odontogenic tumor (MOT). STUDY DESIGN: The Surveillance, Epidemiology, and End Results (SEER) registry was reviewed for patients diagnosed with MOT from 1973 to 2011. Kaplan-Meier and multivariate Cox regression analyses were performed on patient demographic characteristics and pathologic variables. RESULTS: The SEER database identified 295 MOT patients. The mean age at diagnosis was 50.5 years (range 5-89 years). Of these patients, 61.7% were male and 38.3% were female. The racial composition was 66.4% White, 22% Black, 6.1% Asian, 3.1% Pacific Islander, 0.3% Native American, and 2.1% Other/Unknown. Kaplan-Meier analysis found an overall survival (OS) and disease-specific survival (DSS) at 5 years of 54% and 67%, respectively. Multivariate analysis of the entire cohort found that age and stage were predictors of OS and that age was a predictor for DSS. For stage I/II MOTs, age and surgical therapy were predictors of OS and DSS, respectively. CONCLUSIONS: Here we report the largest study to date investigating demographic characteristics, prognostic factors, and management of MOT patients. Determinants of survival for OS and DSS include age, stage, and surgical therapy.

Epidemiology, Prognostic Factors, and Treatment of Malignant Submandibular Gland Tumors: A Population-Based Cohort Analysis.

IMPORTANCE: Malignant tumors of the submandibular gland are uncommon, leading to limited information regarding prognostic factors and difficulty in evaluating treatment modalities. OBJECTIVE: To investigate the correlates of survival in patients with primary malignant tumors of the submandibular gland. DESIGN, SETTING, AND PARTICIPANTS: Data from 2626 patients with a diagnosis of primary tumors of the submandibular gland between 1973 and 2011 in the Surveillance, Epidemiology, and End Results database were used in a retrospective population-based cohort analysis. Kaplan-Meier analysis along with multivariate Cox regression analysis was performed to determine prognostic factors in overall survival (OS) and disease-specific survival (DSS). INTERVENTIONS: Patients were treated with surgery, radiation therapy, both, or neither. MAIN OUTCOMES AND MEASURES: Overall and disease-specific survival. RESULTS: We identified 2626 patients with a diagnosis of primary malignant tumors of the submandibular gland, 52.9% male and 47.1% female, with a mean (range) age of 61.3 (7-101) years. Adenoid cystic carcinoma (36.0%) was the most prevalent histologic subtype, followed by squamous cell carcinoma (18.1%), mucoepidermoid carcinoma (16.9%), and adenocarcinoma (13.7%). Kaplan-Meier analysis demonstrated an OS and DSS of 65% and 74%at 2 years, 54% and 67% at 5 years, and 40% and 60% at 10 years, respectively. Multivariate Cox regression analysis revealed independent predictors of OS and DSS to be age (HR, 1.04 [95% CI, 1.03-1.04], P < .001; HR, 1.02 [95% CI, 1.01-1.03], P < .001), sex (HR, 0.69 [95% CI, 0.57-0.84], P < .001; HR, 0.73 [95% CI, 0.56-0.96], P = .02), tumor grade (HR, 1.47 [95% CI, 1.19-1.81], P < .001; HR, 1.67 [95% CI, 1.25-2.25], P = .001), stage at presentation (HR, 1.56 [95% CI, 1.41-1.72], P < .001; HR, 1.96 [95% CI, 1.69-2.28], P < .001), and surgical resection (HR, 0.55 [95% CI, 0.41-0.74], P < .001; HR, 0.51 [95% CI, 0.35-0.75], P = .001). CONCLUSIONS AND RELEVANCE: We report, to our knowledge, the largest study to date focused on correlates of survival in submandibular gland malignant neoplasms. Multivariate analysis found that older age at diagnosis, high tumor grade, and later stage at presentation were correlated with decreased survival whereas female sex and surgical resection were correlated with increased survival. In addition, a 3-cm tumor cutoff size was demonstrated above which was associated with a significantly less favorable prognosis. Radiation therapy had mixed association with survival, dependent on tumor size and subtype.

Natural killer cells preferentially target cancer stem cells; role of monocytes in protection against NK cell mediated lysis of cancer stem cells.

Mounting effective anti-tumor immune responses by cytotoxic effectors is important for the clearance of tumors. However, accumulated evidence suggests that the cytotoxic function of immune effectors is largely suppressed in the tumor microenvironment by a number of distinct effectors and their secreted factors. The aims of this review are to provide a rationale and potential mechanism for immunosuppression in cancer, and to demonstrate the significance of such immunosuppression in cellular differentiation and tissue regeneration in pathological conditions, and progression of cancer. We have recently shown that increased NK cell function was seen when they were cultured with primary oral squamous carcinoma stem cells (OSCSCs) as compared to their more differentiated oral squamous carcinoma cells (OSCCs). In addition, human embryonic stem cells (hESCs), Mesenchymal Stem Cells (hMSCs), dental pulp stem cells (hDPSCs) and induced pluripotent stem cells (hiPSCs) were significantly more susceptible to NK cell mediated cytotoxicity than their differentiated counterparts or parental cells from which they were derived. We have also reported that inhibition of differentiation or reversion of cells to a less-differentiated phenotype by blocking NFκB or targeted knock down of COX2 augmented NK cell function significantly. Total population of monocytes and those depleted of CD16(+) subsets were able to substantially prevent NK cell mediated lysis of OSCSCs, MSCs and DPSCs. Taken together, our results suggest that stem cells are significant targets of the NK cell cytotoxicity. The concept of split anergy in NK cells and its contribution to tissue repair and regeneration and in tumor resistance and progression will be discussed in this review. Therefore, patients with cancer may benefit from repeated allogeneic NK cell transplantation at the site of the tumor for specific elimination of cancer stem cells.