Clinicopathological characteristics and outcomes of 23 patients with secretory carcinoma of major salivary glands.

This retrospective study investigated the clinicopathological characteristics of secretory carcinoma of salivary glands (SCSG) in 23 patients with histopathologically confirmed SCSG between January 2010 and December 2020. In total, 13 males and 10 females (ratio, 1.3:1) aged 10 - 69 years (median, 45 years) were enrolled in this study; the average disease duration was 2.44 years (0.25-20 years). Twenty-one patients (91.3%) had SCSG in the parotid gland, and two (8.7%) in the submandibular gland. All patients had single nodules of diameters 0.8-4.8 cm (average 2.6 cm); five with lymph node metastases, and two with distant metastases. Immunohistochemically, tumors stained positive for S-100, mammaglobin, CK7, GATA3 and pan-Trk, and negative for DOG1, P63, and calponin, with Ki-67 positivity from 1 to 50%. ETV6 gene rearrangement was confirmed in 15 patients. All patients underwent oncological resection, four had radioactive particles implanted postoperatively, one received chemotherapy, and seven underwent chemoradiotherapy. Six patients had regional recurrences, two distant metastases, and one died before the last follow-up. SCSGs are typically indolent, with a low locoregional recurrence rate and excellent survival. Prognosis is correlated to clinical stage, pathological grade, and surgical procedures.

Patients with adenoid cystic carcinomas of the salivary glands treated with lenvatinib: Activity and quality of life.

BACKGROUND: The treatment of patients with recurrent and/or metastatic (R/M) salivary gland adenoid cystic carcinoma (ACC) remains an unmet need. METHODS: Patients with R/M disease with a history of clinical or symptomatic disease progression within 6 months and a maximum of 1 previous line of chemotherapy or a multiple kinase inhibitor received oral lenvatinib at a dose of 24 mg/day. The primary endpoint was the objective response rate; secondary endpoints included quality of life (QOL) (according to the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Items [EORTC QLQ-C30] and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Module Head and Neck Module [EORTC QLQ-H&N35]), progression-free survival and overall survival, duration of response, and toxicities. RESULTS: Twenty-eight patients with R/M ACC were enrolled. Among 26 evaluable patients, 3 partial responses (11.5%) were reported. Target lesion reductions between 23% to 28% were observed in 4 of 20 patients with stable disease. Treatment-related adverse events were frequent (all grades, 96%; grade≥3 in 50% of cases according to version 4.03 of the National Cancer Institute Common Terminology Criteria for Adverse Events). The dose of lenvatinib was reduced in 24 patients, whereas in 21 patients the dose was reduced within the first 12 weeks and 4 patients maintained the full dose throughout treatment. The QOL deteriorated between baseline and 6 months with regard to Fatigue and Dry Mouth. There was no evidence of changes in Swallowing and Physical Functioning. At a median follow-up of 29 months, 2 patients remained on treatment, 10 patients were off protocol for disease progression and were alive with disease, and 14 patients had died of disease progression. The median overall survival, progression-free survival, and duration of response were 27 months, 9.1 months, and 3.1 months, respectively. CONCLUSIONS: Lenvatinib appears to have modest activity in ACC. Toxicities are common but manageable and QOL was found to deteriorate in some domains.

The endocytic pathways of carbon dots in human adenoid cystic carcinoma cells.

OBJECTIVES: This study aimed at investigating cellular uptake pathways of carbon dots (CDs) in human adenoid cystic carcinoma cell line ACC-2. MATERIALS AND METHODS: We synthesized CDs using a hydrothermal method with citric acid and polyethylenimine (PEI, Mw = 25 000). The CDs incubated with the ACC-2 cells showed their bioimaging capabilities using a confocal microscopy test. Flow cytometry was used to analyse cellular uptake pathways of CDs in ACC-2 cells. RESULTS: Our findings indicated that CDs possessed good biocompatibility in ACC-2 cells. CDs were endocytosed mainly via micropinocytosis and energy-dependent pathways. CONCLUSIONS: In general, these findings suggested that CDs had excellent biomedical imaging properties for ACC-2 cells and there was a potential opportunity to develop biomedical applications.

Carcinoma ex pleomorphic adenoma: a case report and review of literature.

BACKGROUND: Carcinoma ex pleomorphic adenoma (CA-ex-PA) is extremely unusual in minor salivary glands of oral cavity. CAex-PA is a carcinomatous change as a primary or as a recurrence of pleomorphic adenoma. OBJECTIVE: Due to resemblance of clinical symptoms of Ca ex PA and benign pleomorphic adenoma, it is mandatory for surgeons to keep high degree of clinical alertness, considering the peculiarity of this tumor. CASE REPORT: 54-year-old male presented with swelling on left side in the pre-auricular region from the middle of zygomatic arch to mastoid process and from tragus of the ear up to angle of mandible. Fine needle aspiration cytology revealed a mixture of benign and malignant components. Total left parotidectomy with left radical neck dissection followed by reconstruction with cervicodeltopectoral flap was performed. Combination of chemotherapy and radiotherapy were given to patient. Histologic examination and pre-operative fine needle aspiration cytology confirmed the diagnosis of Carcinoma ex pleomorphic adenoma (CA-ex-PA). Two-year follow-up of patient showed no recurrence of the lesion. CONCLUSION: Due to the similarity in the clinical symptoms of CA-ex-PA and benign pleomorphic adenoma, it is vital that clinicians maintain a high degree of clinical vigilance, considering the oddity of this malignancy.

Salivary duct carcinoma of the supraglottis with a distinct presentation: A case report and literature review.

RATIONALE: Salivary duct carcinoma (SDC) is a rare and aggressive subtype of salivary gland carcinoma that histologically resembles in situ and invasive ductal carcinoma of the breast. We present the first case of advanced SDC of the minor salivary gland arising from the supraglottis and review the literature on the clinicopathologic characteristics and prognosis of SDC. PATIENT CONCERNS: A 59-year-old male patient with progressive difficulty in swallowing and a muffled voice for 2 months. DIAGNOSES: The patient was diagnosed with SDC arising from the supraglottis with extensive tumor invasion into the subsites of the larynx and pharynx. INTERVENTIONS: Due to impending airway obstruction, the patient underwent CO2 laser debulking surgery. In addition to local disease, lymph node and distant metastases were also noted at diagnosis and concurrent chemoradiation therapy was arranged. OUTCOMES: Laryngeal function was preserved and tracheostomy was avoided. The patient has survived for >1 year after the initial diagnosis. LESSONS: SDC is a rare and aggressive subtype of salivary gland carcinoma that histologically resembles in situ and invasive ductal carcinoma of the breast. Here we presented the first case of advanced SDC of the minor salivary gland arising from the supraglottis that was treated with CO2 laser debulking surgery followed by concurrent chemoradiation therapy. Due to their rarity, further studies are required to establish the most effective treatment protocol for advanced SDC.

Liquid-based cytology versus conventional cytology in fine-needle aspirates of salivary gland neoplasms.

BACKGROUND: Liquid-based cytology (LBC) is a method of retrieving and processing of cytological material for the assessment of both gynecological and nongynecological cases introduced in 1996. Mostly conventional smears (CS) are prepared in Indian scenario; however, due to increasing popularity of LBC in nongynecology specimens, LBC is also used in few centers for diagnosing salivary gland neoplasm. AIM: The aim of this study is to compare CS and LBC in fine-needle aspiration cytology (FNAC) of the salivary gland neoplasms in terms of cytomorphological details, adequacy, ease of interpretation, pitfalls, and diagnostic efficiency. MATERIALS AND METHODS: We conducted a prospective, observational, comparative study which included 64 salivary gland neoplasms. Both CS and LBC (SurePath) were prepared as per standard protocols and examined. RESULTS AND CONCLUSION: In our study, specificity and positive predictive value of both the techniques (conventional and LBC) were found to be 100%. Sensitivity of both the techniques was found to be similar (66.7%). Negative predictive value and diagnostic accuracy of conventional technique were found to be almost similar to that of LBC technique (97.6% vs. 97.2% and 97.7% vs. 97.4%). In terms of adequacy and cellularity, CSs were better than LBC. Ease of interpretation was better with CSs due to abundant chondromyxoid stroma, an important clue in the diagnosis of pleomorphic adenoma. Nuclear details and background were better in LBC as compared to CS. Hence, we conclude that in salivary gland FNAC, both CS and LBC have similar diagnostic efficiency. however, interpretation of conventional smears is easier than Liquid Based Cytology especially in cases of pleomorphic adenoma. However, some advantages of LBC in respect to conventional cytology, with better-preserved morphology obtained from LBC becomes furthermore obligatory.

[Laryngeal pleomorphic adenoma]. / Pleomorfnaia adenoma gortani.

Pleomorphic adenomas are the most widespread epithelial tumours originating from the salivary glands. In almost 90% of the cases, they are localized in the parotid salivary glands. Pleomorphic adenomas only rarely affect the larynx. To the best of our knowledge, as many as 27 cases of laryngeal pleomorphic adenoma have thus far been described in the special literature. The present article was designed to report a case of pleomorphic adenoma in the larynx of a 76 year-old male patient. The surgical treatment of this condition proved beneficial for the patient whose condition remains uncomplicated by the relapse of the tumour during the 5 year-long postoperative follow-up.

Cytokeratin-14 contributes to collective invasion of salivary adenoid cystic carcinoma.

Collective invasion of cells plays a fundamental role in tissue growth, wound healing, immune response and cancer metastasis. This paper aimed to investigate cytokeratin-14 (CK14) expression and analyze its association with collective invasion in the invasive front of salivary adenoid cystic carcinoma (SACC) to uncover the role of collective invasion in SACC. Here, in the clinical data of 121 patients with SACC, the positive expression of CK14 was observed in 35/121(28.93%) of the invasive front of SACC. CK14 expression in the invasive front, local regional recurrence and distant metastasis were independent and significant prognostic factors in SACC patients. Then, we found that in an ex vivo 3D culture assay, CK14 siRNA receded the collective invasion, and in 2D monolayer culture, CK14 overexpression induced a collective SACC cell migration. These data indicated that the presence of characterized CK14+ cells in the invasive front of SACC promoted collective cell invasion of SACC and may be a biomarker of SACC with a worse prognosis.

Downregulation of nucleophosmin expression inhibited proliferation and induced apoptosis in salivary gland adenoid cystic carcinoma.

BACKGROUND: This study aimed to explore the relationship between nucleophosmin (NPM1) and patient clinical characteristics. Moreover, we investigated the effect of NPM1 in tumor proliferation and apoptosis of salivary gland adenoid cystic carcinoma (SACC). MATERIALS AND METHODS: NPM1 expression was examined in 74 specimens of SACC and 31 non-cancerous epithelium adjacent to carcinoma (NCEAC) by immunohistochemistry (IHC). RNA interference technology was used to silence NPM1 expression in SACC cells. We used transwell culture assay, cell counting kit-8 tests, and colony formation assay to test the proliferation, cisplatin resistance, migration, and invasiveness of SACC cells. RESULTS: The nuclear and cytoplasmic expression of NPM1 in SACC tissue was overexpressed and was tightly linked to perineural invasion and lymph node metastasis. The downregulation of NPM1 inhibited proliferation and induced apoptosis in SACC cells. Knockdown of NPM1 expression had no effect on chemoresistance migration, or invasiveness. CONCLUSIONS: NPM1 may play an important role in tumor progress in SACC and is a potential biomarker for SACC.

Subglottic Basal Cell Adenocarcinoma.

OBJECTIVES: To discuss the presentation and management of a rare neoplasm in a previously unreported laryngeal subsite. METHODS: Case report and literature review. RESULTS: An 89-year-old woman presented with a subglottic mass, biopsy of which was consistent with basal cell adenocarcinoma. She was successfully treated with surgical intervention and remains disease free 29 months postoperatively. CONCLUSIONS: Basal cell adenocarcinoma is a rare salivary gland tumor, the laryngeal variant of which is even scarcer. Herein we describe the presentation and successful surgical management of the first reported case of subglottic basal cell adenocarcinoma. We additionally provide a histologic review followed by approaches to treatment.

Survival benefit for adjuvant radiation therapy in minor salivary gland cancers.

OBJECTIVES: The goal of the current study is to investigate the role of adjuvant radiation therapy (adjuvant RT) in minor salivary gland tumors (mSGT) using an established national database. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients treated with or without adjuvant RT for mSGT from 1988 to 2008. Regression analyses were performed to identify factors associated with improved overall survival (OS). RESULTS: Most tumors were located within the oral cavity (75%) followed by nasal cavity/paranasal sinuses (15%). Multivariate Cox analysis showed that adjuvant RT was associated with better OS compared to surgery alone. Using logistic regression analysis, we provide a novel web based tool for predicting survival impact of adjuvant RT in patients with mSGT. CONCLUSIONS: Adjuvant RT is associated with improved survival in patients with mSGT and adverse clinicopathologic factors such as advanced T/N category, adenoid cystic histology, high grade, and nasopharynx location.

[A difficult case of the differential diagnosis of focal infiltrative lung changes in phthisiatric practice].

Errors occur rather commonly in the differential diagnosis of respiratory diseases accompanied by X-ray lung tissue changes as foci and infiltration. Infiltrative and disseminated pulmonary tuberculosis, lung cancer, and pneumonia constitute a high proportion among the detected concurrent lung diseases. The rate of diagnostic discordance for these lung abnormalities accounts for more than 30%; and the diagnosis period for an infiltrative lung process lasts 2­3 weeks in 20% of cases and above 1­3 months in 80%. In particular, clinicians are faced with great difficulties in diagnosing aspiration pneumonia; this is due to that its X-ray manifestations are not purely specific and they are characterized by the parenchymal (alveolar) infiltration of lung tissue with a varying extent of lung inflammation. This paper describes a clinical case of a patient with salivary gland adenocarcinoma and focal infiltrative lung changes. Diagnostic difficulties have emerged in establishing the genesis of the changes in the lung.

RBE and OER within the spread-out Bragg peak for proton beam therapy: in vitro study at the Proton Medical Research Center at the University of Tsukuba.

There are few reports on the biological homogeneity within the spread-out Bragg peak (SOBP) of proton beams. Therefore, to evaluate the relative biological effectiveness (RBE) and the oxygen enhancement ratio (OER), human salivary gland tumor (HSG) cells were irradiated at the plateau position (position A) and three different positions within a 6-cm-wide SOBP (position B, 26 mm proximal to the middle; position C, middle; position D, 26 mm distal to the middle) using 155-MeV/n proton beams under both normoxic and hypoxic conditions at the Proton Medical Research Center, University of Tsukuba, Japan. The RBE to the plateau region (RBE(plateau)) and the OER value were calculated from the doses corresponding to 10% survival data. Under the normoxic condition, the RBE(plateau) was 1.00, 0.99 and 1.09 for positions B, C and D, respectively. Under the hypoxic condition, the RBE(plateau) was 1.10, 1.06 and 1.12 for positions B, C and D, respectively. The OER was 2.84, 2.60, 2.63 and 2.76 for positions A, B, C and D, respectively. There were no significant differences in either the RBE(plateau) or the OER between these three positions within the SOBP. In conclusion, biological homogeneity need not necessarily be taken into account for treatment planning for proton beam therapy at the University of Tsukuba.

Carcinoma epitelial-mioepitelial de glándula salival menor. Diagnóstico inesperado ante sospecha de patología benigna / No disponible

No disponible

Mammalian target of rapamycin regulates isoliquiritigenin-induced autophagic and apoptotic cell death in adenoid cystic carcinoma cells.

Previous studies, including those from our laboratory, have demonstrated that isoliquiritigenin (ISL), a flavonoid isolated from licorice, is a promising cancer chemotherapeutic agent. However the mechanisms underlying its anticancer effects are still far from clear. We now show, for the first time, that ISL triggers the mammalian target of rapamycin (mTOR)-dependent autophagic and apoptotic cell death in adenoid cystic carcinoma (ACC). Exposure of both ACC-2 and ACC-M cells to ISL resulted in several specific features for autophagy, including the appearance of membranous vacuoles, formation of acidic vesicular organelles, punctate pattern of LC3 immunostaining, and an increase in autophagic flux. Moreover, ISL treatment also resulted in significantly increased apoptosis in ACC cells. The ISL-mediated autophagic and apoptotic cell death were obviously attenuated by transfection with dominant negative Atg5 (DN-Atg5(K130R)) plasmids or treatment with 3-methyladenine(3-MA). In additon, the data also revealed that the autophagic and apoptotic cell death induced by ISL occurred through a mTOR-dependent pathway. More importantly, the xenograft model using ACC-M cells provided further evidence of the occurrence of ISL-induced autophagy and apoptosis in vivo, correlating with the suppresson of mTOR activation as well as up-regulation of Atg5 expression. Taken together, these findings in our study suggest that induction of mTOR-dependent autophagic and apoptotic cell death may be an important mechanism in cancer chemotherapy by ISL.

Toll-like receptor 5 activation promotes migration and invasion of salivary gland adenocarcinoma.

BACKGROUND: Toll-like receptor (TLR) signaling has been found to be closely associated with tumor development. The aim of this study was to examine whether activation of TLRs promote migration and invasion of salivary gland adenocarcinoma. MATERIALS AND METHODS: TLR expression in SGT and HSG cells was examined by RT-PCR. Wound scratch and chemotaxis cell migration assay were performed. Invasiveness was determined by Matrigel invasion assay. RESULTS: All the tested TLRs including TLR1, TLR2, TLR4, and TLR5 and myeloid differentiation factor-2 (MD-2) were expressed on SGT and HSG cells. Treatment of flagellin, but not Pam(3) CSK(4) and LPS, led to the production of IL-6 and IL-8, suggesting TLR5 is functional in both cells. Stimulation by flagellin also accelerated wound closure of SGT and HSG cells in a dose-dependent manner. In addition, flagellin promoted migration and invasion ability of SGT cells. Blocking of TLR5 using antibody restored the promoting effect of flagellin on migration and invasion of SGT cells. CONCLUSION: These findings suggest that TLR5 activation by flagellin can promote migration and invasion of salivary gland adenocarcinoma.

Spectrum of malignancy in mixed tumors of salivary gland: a morphological and immunohistochemical review of 23 cases.

Malignancy arising in mixed tumors of the salivary gland is a distinct entity that can occur sporadically or in association with a background of pleomorphic adenoma. Carcinoma arising with a background of pleomorphic adenoma is well documented. However, there are rare occurrences of aggressive de novo carcinosarcomas of the parotid that have been reported. Various cell lineages such as the epithelial glandular cells and the stromal spindle cells are involved. We report 23 cases of tumors of the salivary gland comprising 18 cases of carcinoma ex pleomorphic adenoma, four cases of carcinosarcoma of the parotid and one case of benign metastasizing pleomorphic adenoma. The occurrence of various malignancies suggests that this phenomenon is not very uncommon and should be looked for when reporting a mixed tumor.

Parotidectomía: experiencia en 3 años / Parotidectomy: experience in 3 years

Este trabajo descriptivo observacional expone la casuística de parotidectomías realizadas en el Hospital Universitario de Los Andes entre los años 2004 y 2007. De 23 pacientes con tumor de parótida 18 fueron mujeres. A todos se les practicó parotidectomías. El 64,3 por ciento eran mayores de 45 años, el aumento de volumen postoperatorio prevaleció en 22 pacientes. La PAAF fue benigna en 60,86 por ciento. La variedad histológica mas frecuente fue el Adenoma Pleoformórfico. La complicación mas frecuente fue lesión del nervio facial. El 80 por ciento de tumores de glándulas salivales afecta a la parótida. Aparecen en promedio a los 50 años de edad. La PAAF ofrece un diagnóstico preoperatorio cercano al definitivo, lo que evita una cirugía innecesaria. En este estudio existió concordancia del 100 por ciento entre PAAF e histopatología. La cirugía es el tratamiento indicado, preservando el nervio facial.

Cimetidine inhibits salivary gland tumor cell adhesion to neural cells and induces apoptosis by blocking NCAM expression.

BACKGROUND: Cimetidine, a histamine type-2 receptor antagonist, has been reported to inhibit the growth of glandular tumors such as colorectal cancer, however the mechanism of action underlying this effect is unknown. Adenoid cystic carcinoma is well known as a malignant salivary gland tumor which preferentially invades neural tissues. We demonstrated previously that human salivary gland tumor (HSG) cells spontaneously express neural cell adhesion molecule (NCAM), that HSG cell proliferation may be controlled via a homophilic (NCAM-NCAM) binding mechanism and that NCAM may be associated with perineural invasion by malignant salivary gland tumors. We further demonstrated that cimetidine inhibited NCAM expression and induced apoptosis in HSG cells. Here, we investigated the effects of cimetidine on growth and perineural/neural invasion of salivary gland tumor cells. METHODS: In this study, we have examined the effect of cimetidine on cancer cell adhesion to neural cells in vitro, one of the critical steps of cancer invasion and metastasis. We have also used an in vivo carcinogenesis model to confirm the effect of cimetidine. RESULTS: We have demonstrated for the first time that cimetidine can block the adhesion of HSG cells to neural cell monolayers and that it can also induce significant apoptosis in the tumor mass in a nude mouse model. We also demonstrated that these apoptotic effects of cimetidine might occur through down-regulation of the cell surface expression of NCAM on HSG cells. Cimetidine-mediated down-regulation of NCAM involved suppression of the nuclear translocation of NF-kappaB, a transcriptional activator of NCAM gene expression. CONCLUSION: These findings suggest that growth and perineural/neural invasion of salivary gland tumors can be blocked by administration of cimetidine via induction of apoptosis and in which NCAM plays a role.