Novel decision tree models predict the overall survival of patients with submandibular gland cancer.

BACKGROUND: While the accurate prediction of the overall survival (OS) in patients with submandibular gland cancer (SGC) is paramount for informed therapeutic planning, the development of reliable survival prediction models has been hindered by the rarity of SGC cases. The purpose of this study is to identify key prognostic factors for OS in SGC patients using a large database and construct decision tree models to aid the prediction of survival probabilities in 12, 24, 60 and 120 months. MATERIALS AND METHODS: We performed a retrospective cohort study using the Surveillance, Epidemiology and End Result (SEER) program. Demographic and peri-operative predictor variables were identified. The outcome variables overall survival at 12-, 24-, 60, and 120 months. The C5.0 algorithm was utilized to establish the dichotomous decision tree models, with the depth of tree limited within 4 layers. To evaluate the performances of the novel models, the receiver operator characteristic (ROC) curves were generated, and the metrics such as accuracy rate, and area under ROC curve (AUC) were calculated. RESULTS: A total of 1,705, 1,666, 1,543, and 1,413 SGC patients with a follow up of 12, 24, 60 and 120 months and exact survival status were identified from the SEER database. Predictor variables of age, sex, surgery, radiation, chemotherapy, tumor histology, summary stage, metastasis to distant lymph node, and marital status exerted substantial influence on overall survival. Decision tree models were then developed, incorporating these vital prognostic indicators. Favorable consistency was presented between the predicted and actual survival statuses. For the training dataset, the accuracy rates for the 12-, 24-, 60- and 120-month survival models were 0.866, 0.767, 0.737 and 0.797. Correspondingly, the AUC values were 0.841, 0.756, 0.725, and 0.774 for the same time points. CONCLUSIONS: Based on the most important predictor variables identified using the large, SEER database, decision tree models were established that predict OS of SGC patients. The models offer a more exhaustive evaluation of mortality risk and may lead to more personalized treatment strategies.

Surgical treatment of liver and kidney metastasis from an adenoid cystic carcinoma of the submandibular gland: case report.

INTRODUCTION: Adenoid cystic carcinomas (ACCs) account for 10% of all malignant salivary tumours. They are slow-growing but locally aggressive. Reports of liver and renal metastases are rare. CASE DESCRIPTION: A 58-year-old woman who had undergone resection of a left submandibular ACC in 1995 was referred to our centre for follow-up in 2018. A computed tomography scan revealed two lesions: one on segment six of the liver and the other on a kidney. A hepatic wedge resection and right nephrectomy were performed. The postoperative course was uneventful. At 2-year follow-up, the patient was alive and well with no evidence of disease. CONCLUSION: Management of ACC is a therapeutic challenge because of its tendency for distant metastases. The literature recommends regular follow-up imaging and radical surgical treatment but specific guidelines for the approach to recurrence are lacking.

Paciente con xerostomía posradioterapia por cáncer de cabeza y cuello tratado con células madre mesenquimales autólogas expandidas de tejido adiposo: una nueva oportunidad terapéutica / Radiation-induced xerostomia in a patient with head and neck cancer treated with Injection of autologous expanded adipose tissue-derived mesenchymal stem cells: A new therapeutic opportunity

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Large cell neuroendocrine carcinoma of the submandibular gland: a case report and literature review.

Neuroendocrine tumors (NET) are a heterogeneous group of malignancies with a broad spectrum of histomorphologies, tissue origins, and clinical outcomes, which arise from neural crest cells with neuroendocrine differentiation. Salivary gland tumors account for 3-6% of all head and neck neoplasms, while large cell neuroendocrine carcinomas (LCNEC) of the salivary gland are extremely rare, with few cases reported in literature, and only 5 cases involving submandibular gland. The rarity of these tumors in salivary glands is probably related to the scarcity of neuroendocrine cells in this tissue, whose presence is still a matter of debate. Regardless of their low frequency, it is imperative to differentiate these tumors from the much more common squamous cell carcinomas and metastatic NETs, due to different therapeutic approach and prognosis. In this paper, we report the case of a 21-year-old man, with a LCNEC involving a submandibular gland followed by several recurrences over the years. In addition, we include a comprehensive review of the available literature on this topic.

[A case of paraneoplastic limbic encephalitis associated with neck neuroendocrine carcinoma].

A 69-year-old man presented with a history of personality change for several years. He was admitted to our hospital due to partial seizure. A cerebrospinal fluid test and an electroencephalogram showed no specific abnormalities, but brain magnetic resonance imaging revealed abnormal findings in the right temporal pole, bilateral amygdala to hippocampus, and insular cortex. He was diagnosed with limbic encephalitis accompanied by partial seizure, and received infusion of an antiepileptic agent and acyclovir. Additional examinations for malignancy and autoimmune disease were performed, and neck CT and MRI revealed a neck tumor. Neck lymph node biopsy suggested lymph node metastasis of a neuroendocrine neoplasm derived from other organs. He did not want aggressive treatment involving surgical resection and chemotherapy, and thus, conservative treatment was chosen by an otorhinolaryngologist and immunotherapy was not used. After discharge, the neck tumor grew gradually. To manage the focal mass effect, chemotherapy and surgical resection followed by chemoradiotherapy were performed by the otorhinolaryngologist on days 244 and 325 of the disease course, respectively. Histology of resected tissues disclosed neck neuroendocrine carcinoma derived from a submandibular gland. His personality change improved temporarily after surgical resection, but then worsened again with regrowth of the tumor. He died on day 723. After death, a blood test revealed the presence of anti-amphiphysin antibody. This case suggests that neck neuroendocrine carcinoma can induce paraneoplastic limbic encephalitis, and in such cases, early surgical resection of the neck tumor with suspected lymph node metastasis is necessary both to control symptoms associated with encephalitis and to exclude carcinoma derived from the neck itself.

Genomic Alterations in Undifferentiated Malignant Tumors with Rhabdoid Phenotype and Loss of BRG1 Immunoexpression Identified by Fine Needle Aspirates.

OBJECTIVE: Evidence shows that the switch/sucrose nonfermenting chromatin remodeling complex plays a critical role in DNA repair, cancer progression and dedifferentiation. BRG1 is one of its key catalytic subunits. While the loss of BRG1 expression by immunocytochemistry has been identified in a subset of malignancies arising in various sites with undifferentiated/rhabdoid morphology and poor prognosis, the underlying basis for its loss is unclear. METHODS: A retrospective search was conducted in our cytopathology archive for undifferentiated malignant tumors with rhabdoid phenotype and BRG1 loss. Clinical information was obtained from electronic medical records. Next-generation sequencing was performed following macro-dissection of paraffin-embedded cellblock tissue. RESULTS: Three cases were identified; all presented with widely metastatic disease with no previously diagnosed primary malignancy, and subsequently died within 6 months of initial presentation. Cytologically, the aspirates showed dyshesive and undifferentiated cells with rhabdoid features. Extensive immunocytochemical workup demonstrated immunoreactivity with vimentin only and could not establish a specific lineage. BRG1 expression was absent, while INI1 expression was retained. Two cases harbored deleterious mutations in BRG1/SMARCA4. Pathogenic mutations in TP53 were identified in all tumors. CONCLUSIONS: BRG1 deficiency reflects underlying mutation in SMARCA4 gene in some but not all cases, suggesting that additional mechanisms may be causing BRG1 silencing. Pathogenic mutations in TP53 in all tumors are consistent with their highly aggressive nature. Recognizing the cytomorphology of this group of neoplasms and confirming their BRG1-deficient status by immunocytochemistry not only has prognostic implications, but may also impart potentially therapeutic value in the near future.

The number and ratio of positive lymph nodes are independent prognostic factors for patients with major salivary gland cancer: Results from the surveillance, epidemiology, and End Results dataset.

INTRODUCTION: To investigate whether the positive lymph node number (PLNN) and positive lymph node ratio (PLNR) could predict the prognosis of patients with major salivary gland cancer (MSGC) and to identify the optimal cutoff points for these variables that stratify patients according to their risk of survival. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify all patients with MSGC between 1988 and 2014. A logistic regression analysis was carried out to evaluate the risk factors for lymph node metastasis (LNM) in MSGC. The X-tile program was used to identify the cutoff values for the PLNN and PLNR in MSGC patients with LNM. Cox proportional hazards regression models were performed to identify the predictors of cancer-specific survival (CSS). RESULTS: In the SEER database, 8668 eligible patients were identified and 3046 of them had LNM. The logistic regression analysis indicated that older age, male sex, larger tumor size, higher grade, tumor extension and high-risk pathology were associated with LNM. The X-tile program showed that a PLNN>4 and a PLNR>0.15 were prognostic indicators of CSS. A multivariable analysis indicated that, after the factors that might potentially affect the prognosis were adjusted for, the PLNN and PLNR were still associated with CSS. CONCLUSIONS: Our Results demonstrated that the PLNN and PLNR were independent prognostic indicators for MSGC patients with lymph node metastasis.

Autoimmune Granulomatous Inflammation of Lacrimal Glands and Axonal Neuritis Following Treatment With Ipilimumab and Radiation Therapy.

Immune checkpoint inhibitors such as anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), anti PD-1 (programmed cell death protein 1) and PD-L1 (programmed cell death protein-ligand 1) monoclonal antibodies are emerging as standard oncology treatments in various tumor types. The indications will expand as immunotherapies are being investigated in various tumors with promising results. Currently, there is inadequate identification of predictive biomarkers of response or toxicity. Unique response patterns include pseudoprogression and delayed response. The use of immune checkpoint inhibitors exhibit an unique toxicity profile, the immune-related adverse events (irAEs). The most notable immune reactions are noted in skin (rash), gastrointestinal track (colitis, hepatitis, pancreatitis), lung (pneumonitis), heart (myocarditis), and endocrine system (thyroiditis, hypophysitis). We present a patient with metastatic adenoid cystic carcinoma of the left submandibular gland with granulomatous inflammation of the lacrimal glands and axonal neuritis of the cervical and paraspinal nerves following treatment with ipilimumab and radiation therapy.

A gland of diverse pathology and unpredictable behaviour: our experience of primary submandibular gland malignancies.

Submandibular gland tumours are relatively uncommon tumours and demonstrate diverse histological types and a variable prognosis. The aim of this study was to analyze our experience with submandibular malignancies over a period of 6 years (January 2009 to December 2015). Patient data from the 6-year period were reviewed retrospectively and 51 patients with submandibular malignancies were identified. Demographic data, clinicopathological details, treatment received, complications, and follow-up were recorded. The mean age of the 51 patients at presentation was 49.1 years. They were followed up for a mean 20.3 months. Nine of 47 patients (19.1%) developed distant metastasis during follow-up, while only three (6.4%) developed local recurrence. Disease-free survival at 2 years was 69.7% and overall survival at the end of 2 years was 77.8%. Actuarial 5-year survival was 57.8% when all subtypes were considered. The overall mean time to recurrence was 10 months (6-24 months). Nodal positivity was the only prognostic factor that was significant on multivariate analysis, while age, sex, perineural invasion, and grade were not. With advances in surgical and radiotherapy techniques, loco-regional control rates have improved greatly; however, effective adjuvant treatment to prevent systemic relapse is still lacking.

Adenoid cystic carcinoma of head and neck: A retrospective clinical analysis of a single institution.

Objective: In this study, patients with head and neck adenoid cystic carcinoma were investigated with respect to disease characteristics, treatments, and potentially prognostic variables. Materials and Methods: Between January 1995 and December 2010, 29 patients with ACC of the head and neck treated at our institution were retrospectively reviewed. Results: The 29 patients had a mean age of 54.7 years. Of the 29 patients, 4 (13.8%) underwent surgical resection only, 21 (72.4%) underwent surgery with radiotherapy, and 4 (13.8%) received postoperative chemoradiotherapy. Of 9 patients (31.0%) who experienced a recurrence within the follow-up period, 3 (10.3%) had local recurrence and 5 (17.2%) had distant metastasis; 1 (3.4%) patient had both local recurrence and distant metastatic spread. Conclusion: ACC is a relatively rare tumor associated with long survival, even in metastatic settings. Despite aggressive therapy with surgery, radiotherapy, and chemo- therapy, a marked potential for local and distant recurrence still remains.

Submandibular gland cancer: Specific features and treatment considerations.

BACKGROUND: In the absence of unified treatment protocol, we evaluated the management and outcomes of submandibular gland cancers in an unselected patient series. METHODS: We included all patients with resected submandibular gland cancer treated at the Helsinki University Hospital from 2000 to 2010 with a 5-year minimum follow-up. RESULTS: Twenty-five patients with cancer represented 30% of submandibular gland neoplasms, and most were adenoid cystic carcinomas (ACCs; 56%). At presentation, 3 patients showed clinical signs of probable malignancy. Of 22 neck dissection specimens, 5 patients (20%) had metastases with an occult metastasis rate of 4%. Cancer recurred in 11 patients (44%), of which 7 (28%) were only at a distant site. The 5-year disease-specific survival (DSS) and overall survival (OS) rates were 76%, and disease-free survival (DFS) was 68%. CONCLUSION: Most tumors were ACCs differing from the histological pattern of parotid gland cancers. Occult metastases were rare. The rarity of submandibular gland cancer, its variable histological pattern, and varying biological behavior warrant centralized management.

Oncocytic carcinoma of the salivary glands: A Danish national study.

OBJECTIVES: To present a Danish national series of oncocytic carcinoma (OC) patients, including data on treatment, recurrence and survival. METHODS: From the national Danish database of salivary gland carcinomas, all patients diagnosed with OC from 1990 to 2005 were identified and data concerning demographics, tumor site, clinical stage and treatment profiles were extracted. A follow-up was carried out. RESULTS: Of the 15 cases of salivary gland OC, eight were female. The incidence was 0.02/100.000 inhabitants per year in Denmark, 13 patients presented with OC in the parotid gland and two patients with OC in the submandibular gland. Eight patients had nodal involvement at the time of diagnosis. None of the patients had distant metastases at the time of diagnosis. All patients were treated with primary surgery and seven patients received adjuvant radiotherapy. Half of the patients had recurrence. Six patients were alive at 5 years follow up and one patient was alive without recurrence at 10 years follow up. CONCLUSIONS: This study is the first to report a national incidence of oncocytic carcinoma in the salivary glands. The results confirm oncocytic carcinoma to be a salivary gland carcinoma with a poor prognosis. All patients experiencing recurrence died of the disease. Treatment must be aggressive. National registries are necessary to achieve further knowledge for future treatment recommendations.

Coexistence of Lymphoepithelial Carcinoma of the Parotid Gland and Submandibular Gland Pleomorphic Adenoma.

Lymphoepithelial carcinoma is a variant of undifferentiated carcinoma with characteristic dense lymphoid stroma in which nasopharynx is site of predilection. Racial and geographic association and Epstein-Barr virus positivity in endemic areas are other characteristics of this rare neoplasm. Lymphoepithelial carcinoma accounts for only 0.4% of malignant salivary gland tumors. The authors present a patient with Epstein-Barr virus positive lymphoepithelial carcinoma of the parotid gland in a nonendemic region. Besides this, synchronous pleomorphic adenoma in the contralateral submandibular gland caused a challenge in making initial therapeutic decision.

Salivary Duct Carcinoma with Invasive Micropapillary and Rhabdoid Feature Arising in the Submandibular Gland.

Salivary duct carcinoma (SDC) is a high-grade malignant salivary gland tumor associated with poor prognosis, frequent recurrence, and metastasis. An 82-year-old man presented at the department of oral and maxillofacial surgery at Tokai University Hospital with a painless swelling in the right submandibular region that had been there for 20 years. On presentation, an elastic hard tumor, 50 × 50 mm in size, was observed in the submandibular region. Diagnostic imaging was performed, and a malignant tumor in the submandibular gland was suspected. The suspected tumor was excised and postoperative radiotherapy and adjuvant-chemotherapy were performed. Despite this treatment, the patient died of multiple metastases 12 months postoperatively. SDCs are often diagnosed as carcinoma ex pleomorphic adenomas and multiple variants and subtypes exist. This case was histopathologically rare in terms of the coexistence of invasive micropapillary and rhabdoid features.

A Case of Nuclear Protein in Testis Midline Carcinoma Arising From the Submandibular Gland Duct in a Pregnant Patient.

This report describes the first reported case of a nuclear protein in testis midline carcinoma (NMC) arising from the submandibular gland (SMG) duct in a pregnant woman. A 29-year-old pregnant woman presented with a left-side mass in the floor of the mouth. An NMC arising from the SMG duct was confirmed by excisional biopsy examination. Intensive treatment, including surgery and chemotherapy, was provided without termination of the pregnancy. Additional chemotherapy and radiotherapy were provided after delivery. The treatment was successful. Neither the patient nor her infant had any complications and the patient remained disease free 20 months after her initial surgery. This report describes the successful diagnosis and treatment of a rare presentation of an NMC of the SMG duct in a pregnant woman.

Predictors of outcomes in large cell undifferentiated carcinoma of the major salivary glands.

OBJECTIVE: Major salivary gland large-cell undifferentiated carcinoma (LCUC) is rare and has a poor prognosis. Characterization of patient demographics, tumor characteristics, and predictors of outcome have been limited by low case numbers, as well as grouped analysis with other salivary malignancies. The objective of this study was to address these issues using large-scale national data. STUDY DESIGN: Retrospective case series. METHODS: Data from the National Cancer Database, including cases diagnosed from 1998 to 2012, was analyzed, identifying 247 records of LCUC. Tumor, demographic, and survival information was extracted and analyzed retrospectively. RESULTS: Large-cell undifferentiated carcinoma comprised < 1% of all major salivary gland cancers. Seventy percent of patients presented with advanced-stage disease. The incidence of occult nodal disease was 39%. Surgery followed by radiation was the most common treatment. Five-year overall survival was 36%. Comorbidity, distant metastasis, and positive surgical margins were found to be predictors of overall survival. CONCLUSION: To our knowledge, this represents the largest reported case series of LCUC. The survival analysis demonstrates poorer survival in patients with positive surgical margins; therefore, efforts to complete resection are reasonable. Reported high rates of occult nodal disease also strongly support elective treatment of the neck. LEVEL OF EVIDENCE: 4. Laryngoscope, 2016 127:372-376, 2017.

Risk Factors and Survival Associated with Distant Metastasis in Patients with Carcinoma of the Salivary Gland.

BACKGROUND: Salivary gland cancer (SGC) is rare and has various pathologies and metastatic potentials. Because distant metastasis can be observed after treatment, as well as at initial presentation, this study aimed to investigate the rates, risk factors, and survivals associated with distant metastasis in patients with SGC. METHODS: This study involved 454 consecutive patients with previously untreated SGC who were treated at our tertiary referral center. Clinical factors, operative and pathologic findings, and treatment outcomes were carefully reviewed. Univariate and multivariate analyses were performed to identify factors associated with distant metastasis and their associations with distant metastasis-free survival (DMFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: Of 454 patients, 95 (20.9 %) presented with distant metastases; of these, 7 (7.4 %) were at the initial stage, while 88 (92.6 %) were detected during a median follow-up of 100 months (range 24-282). Distant metastases to single and multiple organs were found in 64 (67.4 %) and 31 (32.6 %) patients, respectively, with the most common site being the lung (77.9 %). In multivariate analysis, a non-parotid tumor site, high histological grade, perineural invasion, and T3-4 and N2-3 classifications were independent variables of DMFS, while distant metastasis was an independent variable of CSS and OS (p < 0.005 each). The median survival duration after distant metastasis development was 15 months (range 2-103). CONCLUSIONS: Distant metastasis frequently develops after treatment for SGC and is associated with poor survival outcomes; thus, close surveillance may be required for patients with SGC and risk factors.

Salivary gland malignancies - an update on current management for oral healthcare practitioners.

Salivary gland tumours represent a diverse range of tumours with many histological subtypes which occur in major and minor salivary glands. The management of these tumours is complex owing to their heterogeneity. Surgery together with radiotherapy and/or chemotherapy remains the treatment strategy for these tumours. The aim of this review is to examine the current management of these tumours.