Alkali-treated titanium dioxide promotes formation of proteoglycan layer and altered calcification and immunotolerance capacity in bone marrow stem cell.

Introduction: In this study, we report that a proteoglycans (PGs)-layer between the bone and titanium dioxide (TiO2) surface after osseointegration improved the calcification capacity and immunotolerance of human bone marrow mesenchymal stem cells (hBMSCs) on TiO2. Alkaline treatment of TiO2 is a method for promoting osteogenesis in hBMSCs. We hypothesized that promotion of osteogenesis due to alkaline treatment was caused by changing PGs-layer on TiO2. Objective: This study aimed to analyze whether alkaline treatment of TiO2 affects PGs-layer formation and immunotolerance in hBMSCs. Methods: The topology and wettability of the alkaline-treated titanium (Ti-Al) and unprocessed titanium (Ti-MS) surfaces were characterized. Initial cell attachment, cell proliferation, calcification capacity, alkaline phosphatase activity, PGs-layer formation, PGs function, and the expression of osteogenic and immunotolerance-related genes were analyzed. The conditioned medium (CM) from hBMSCs grown on Ti-Al and Ti-MS was added to macrophages (hMps) and Jurkat cells, and immunotolerance gene expression in these cells was analyzed. Results: hBMSCs cultured on Ti-Al showed increased initial cell attachment, cell proliferation, PG-layer formation, and osteogenic capacity compared with hBMSCs on Ti-MS. Gene expression of indoleamine 2,3-dioxygenase (IDO) in the hBMSCs cultured on Ti-Al was higher than that in the hBMSCs on Ti-MS. CM from hBMSCs did not affect markers of M1 and M2 macrophages in hMps. CM from hBMSCs cultured on Ti-Al altered the gene expression of Foxp3 in Jurkat cells compared to that of CM from hBMSCs on Ti-MS. Significance: These results suggest that alkaline treatment of TiO2 altered PGs-layer formation, and changed the osteogenesis and immunotolerance of hBMSCs.

Two cases of parapharyngeal space tumor resected by a double split mandibular osteotomy technique.

Parapharyngeal space tumors have poor subjective symptoms and often grow until diagnosed; therefore, mandibular transection may be needed to obtain a wider field of view during surgery. However, if a median lower lip incision is performed for the mandibular transection, esthetic problems occur after surgery. Here, we report two cases of parapharyngeal space tumors that were removed with a mandibular lateral segment-osteotomy technique without median lower lip incision to avoid esthetic problems. Case 1 was a 49-year-old woman. She was aware of a right tonsillar swelling, and an imaging test revealed a tumor lesion 60 mm in size in the right parapharyngeal space. Case 2 was a 40-year-old woman with an abnormal position of the uvula, and an imaging test showed the left parapharyngeal space tumor lesion 45 mm in size. Both cases were diagnosed as a pleomorphic adenoma, and surgery under general anesthesia was performed jointly with otolaryngology and oral surgery. The incision was performed from the lower part of the right auricle to the anterior part of the submandibular area. After the tumor resection, the mandible was repositioned, fixed by plates, and the intermaxillary fixation was performed with a surgical stent. In both cases, slight paralysis of the mandibular branch of the facial nerve and the mental nerve was observed after the operation, but they were improved immediately. One year after the operation, the plates were removed. There have been no recurrences until now.

Oral hygiene status and factors related to oral health in hospitalized patients with schizophrenia.

OBJECTIVE: This study aimed to elucidate the oral hygiene status and the factors associated with poor oral hygiene among patients with schizophrenia. METHODS: The relationships of oral hygiene status (calculus index [CI], debris index [DI]), the mean number of decayed-missing-filled teeth (mean DMFT), and Revised Oral Assessment Guide (ROAG) with related factors (hospitalization, chlorpromazine equivalents [CPZE], age, Barthel Index [BI], frequency of cleaning teeth, and self-oral hygiene ability) among 249 hospitalized schizophrenic patients were investigated. RESULTS: The results for oral hygiene status were as follows: median (range); CI 0.5 (0-6.0), DI 1.7 (0-6.0), ROAG 10.0 (7.0-15.0); and mean DMFT 21.7 ± 7.3. The average CPZE was 524.4 ± 353.6 mg (mean ± SD), and the BI was 76.4 ± 30.7. There was a negative correlation between BI and DI (r = -0.34), and a positive correlation between age and mean DMFT (r = 0.57). Male patients tended to have worse oral conditions (ROAG) than females. The least-squares multiple regression analysis revealed that BI for DI, age for mean DMFT, sex for ROAG, and self-oral hygiene ability for CI, DI, and mean DMFT were factors related to oral health status. CONCLUSION: Patients with schizophrenia tended to have poor oral hygiene. BI, being male, and low activities of daily living were associated with poor oral hygiene. Furthermore, advanced age was associated with an increased risk of dental caries.

Salivary gland polymorphous adenocarcinoma: Clinicopathological features and gene alterations in 36 Japanese patients.

BACKGROUND: Polymorphous adenocarcinoma is a common intraoral minor salivary gland carcinoma in Western countries but is extremely rare in Japan. The current study aimed to characterize the clinicopathological features and status of molecular alterations of polymorphous adenocarcinoma-associated genes, such as PRKD1/2/3, ARID1A, and DDX3X, in a large cohort of Japanese patients with polymorphous adenocarcinoma. METHODS: We examined the cases of 36 Japanese patients with salivary gland polymorphous adenocarcinoma and 26 cases involving histopathological mimics. To detect gene splits, fluorescence in situ hybridization was carried out for polymorphous adenocarcinoma-associated genes. Additionally, we applied a SNaPshot multiplex assay to identify PRKD1 hotspot mutations. RESULTS: This study revealed the indolent clinical course of polymorphous adenocarcinoma with a high 10-year overall survival rate (92.9%), accompanied by occasional local recurrences and cervical lymph node metastasis (23.3%). Twenty cases (55.6%) of polymorphous adenocarcinoma (but none of the mimics) exhibited alterations in at least one polymorphous adenocarcinoma-associated gene. Rearrangement of polymorphous adenocarcinoma-associated genes and PRKD1 E710D were identified in 17 (47.2%) and 4 (11.1%) cases, respectively; one case showed coexisting PRKD3 split and PRKD1 E710D. In the multivariate analysis, high clinical stage (p = 0.0005), the presence of prominent nucleoli (p = 0.0003), and ARID1A split positivity (p = 0.004) were independent risk factors for disease-free survival. CONCLUSION: Japanese patients with polymorphous adenocarcinoma showed clinicopathological features similar to those reported in Western countries. This study disclosed that polymorphous adenocarcinoma-associated genetic alterations were common and specific findings in polymorphous adenocarcinomas. The diagnostic role and possible prognostic significance of polymorphous adenocarcinoma-associated genetic alterations in polymorphous adenocarcinomas were suggested.

Efficacy of a deep leaning model created with the transfer learning method in detecting sialoliths of the submandibular gland on panoramic radiography.

OBJECTIVE: This study aimed to compare the performance of 3 deep learning models, including a model constructed with the transfer learning method, in detecting submandibular gland sialoliths on panoramic radiographs. STUDY DESIGN: We used data from 2 institutions (A and B) to create the models for use in institution B. In total, 224 panoramic radiographs with sialoliths were used. Model 1 was created using data from institution A only, model 2 was created using combined data from institutions A and B, and model 3 was created using the transfer learning method by having model 1 transferred and trained in various learning epochs using data from institution B. These models were tested and compared in their detection performance using testing data sets from institution B. RESULTS: Model 2 and model 3 with 300 epochs performed equally well and yielded the highest detection rates (recall: sensitivity of 85%, precision: positive predictive value of 100%, and F measure of 91.9%) for sialoliths on panoramic radiographs. CONCLUSION: The results of this study suggest that use of the transfer learning method with an appropriate number of epochs may be an alternative to sharing patient personal data among institutions.

Pleomorphic adenoma: detection of PLAG1 rearrangement-positive tumor components using whole-slide fluorescence in situ hybridization.

Pleomorphic adenoma (PA) consists of heterogeneous histological architecture mixed with epithelioid and mesenchymal forms. Various types of epithelial or myoepithelial malignancies arise from PA, but sarcomas are extremely rare. A human androgen receptor gene (HUMARA) clonality assay has suggested that PA is clonal in nature. However, clonality of various tumor components of PA would be difficult to determine with this assay. In addition, the results obtained should be carefully interpreted. PLAG1 rearrangements are considered a good molecular marker for neoplasticity in PA. We aimed to clarify the neoplasticity of the various tumor components present in PA using whole-slide fluorescence in situ hybridization (FISH). Five PA cases positive for PLAG1 rearrangements were examined. Using an immunohistochemistry panel, cell components in PA were classified into eight cell types. To precisely localize PLAG1 rearrangement-positive cell components at the cellular level, sequential retrieval of whole-slide imaging (WSI) data of HE histology and FISH for PLAG1 rearrangement was carried out. PLAG1 rearrangements were detected in ductal cells, myoepithelial spindle cells, myoepithelial oncocytic cells, myoepithelial plasmacytoid cells, and mesenchymal chondroid cells, but not in mesenchymal lipid cells, mesenchymal fibrous cells, or vascular endothelial cells. Immunohistochemical PLAG1 expression was restricted to cell components harboring PLAG1 rearrangements.The results of the present study indicate that ductal and myoepithelial, chondroid cells are neoplastic but lipid, fibrous, and endothelial cells are not. PLAG1 immunohistochemistry is useful in discriminating neoplastic from non-neoplastic cell components. These findings may be important for elucidating tumorigenesis and the process of malignant transformation in PA.

Performance of deep learning models constructed using panoramic radiographs from two hospitals to diagnose fractures of the mandibular condyle.

OBJECTIVE: The present study aimed to verify the classification performance of deep learning (DL) models for diagnosing fractures of the mandibular condyle on panoramic radiographs using data sets from two hospitals and to compare their internal and external validities. METHODS: Panoramic radiographs of 100 condyles with and without fractures were collected from two hospitals and a fivefold cross-validation method was employed to construct and evaluate the DL models. The internal and external validities of classification performance were evaluated as accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). RESULTS: For internal validity, high classification performance was obtained, with AUC values of >0.85. Conversely, external validity for the data sets from the two hospitals exhibited low performance. Using combined data sets from both hospitals, the DL model exhibited high performance, which was slightly superior or equal to that of the internal validity but without a statistically significant difference. CONCLUSION: The constructed DL model can be clinically employed for diagnosing fractures of the mandibular condyle using panoramic radiographs. However, the domain shift phenomenon should be considered when generalizing DL systems.

Texture Analysis Using Preoperative Positron Emission Tomography Images May Predict the Prognosis of Patients With Resectable Oral Squamous Cell Carcinoma.

PURPOSE: Texture analysis is a computer-assisted technique used to measure intratumoral heterogeneity, which is known to have important roles in cancer research. This study aimed to assess the potential prognostic values of textural features extracted from preoperative 18F-fluorodeoxyglucose positron emission tomography images in patients with resectable oral squamous cell carcinoma. PATIENTS AND METHODS: This retrospective cohort study included patients with oral squamous cell carcinoma who underwent resection surgery. We extracted 31 textural indices from preoperative positron emission tomography images. Overall survival (OS) and disease-free survival (DFS) were chosen as the primary outcome variables, and the primary predictor variables were age, sex, primary tumor location, pathological T and N classification, histologic differentiation, resected margin, perineural and lymphovascular invasion, maximum standardized uptake value, and the 14 textural indices selected in the factor analysis. We analyzed OS and DFS using Kaplan-Meier curves, and the differences between survival curves were determined using a log-rank test. The independent prognostic factors were assessed using the Cox-proportional hazards model. RESULTS: We enrolled 81 patients (median age, 67.3 years; range, 32 to 88 years). The median follow-up duration was 50.1 months (range, 6.3 to 133.7 months). The univariable and multivariable analyses revealed that higher entropy values (≥1.91) were associated with worse OS (hazard ratio, 21.49; 95% confidence interval, 1.36 to 340.71; P = .03) and DFS (hazard ratio, 50.69; 95% confidence interval, 5.23 to 491.18; P = .001). CONCLUSIONS: This study showed that entropy is a statistically significant prognostic factor of both OS and DFS. Texture analysis using preoperative positron emission tomography images may contribute to risk stratification.

Automatic detection of cervical lymph nodes in patients with oral squamous cell carcinoma using a deep learning technique: a preliminary study.

OBJECTIVE: To apply a deep learning object detection technique to CT images for detecting cervical lymph nodes metastasis in patients with oral cancers, and to clarify the detection performance. METHODS: One hundred and fifty-nine metastatic and 517 non-metastatic lymph nodes on 365 CT images in 56 patients with oral squamous cell carcinoma were examined. The images were arbitrarily assigned to training, validation, and testing datasets. Using the neural network, 'DetectNet' for object detection, the training procedure was conducted for 1000 epochs. Testing image datasets were applied to the learning model, and the detection performance was calculated. RESULTS: The learning curve indicated that the recall (sensitivity) for detecting metastatic and non-metastatic lymph nodes reached 90% and 80%, respectively, while the model performance recall by applying the test dataset was 73.0% and 52.5%, respectively. The recall for detecting level IB and Level II metastatic lymph nodes was relatively high. CONCLUSIONS: A system that has the potential to automatically detect cervical lymph nodes was constructed.

Case report of API2-MALT1 fusion-positive MALT lymphoma arising from bilateral submandibular glands with no evidence of autoimmune syndromes.

Mucosa-associated lymphoid tissue (MALT) lymphoma arising from the salivary glands is usually associated with chronic infection or autoimmune syndromes, such as primary Sjogren syndrome. The occurrence of t(11;18)/API2-MALT1 is rare in salivary MALT lymphoma. Here we describe a case of API2-MALT1 fusion-positive MALT lymphoma of the bilateral submandibular glands with no evidence of autoimmune syndromes. A 70-year-old man complained of a painless swelling in the bilateral submandibular gland. Serology examination results were negative for anti-SSA and anti-SSB. His right submandibular gland was dissected, and he was diagnosed with MALT lymphoma with the API2-MALT1 fusion gene. Positron emission tomography/computed tomography scanning indicated mild fluorine-18-fluorodeoxyglucose uptake in the left submandibular gland and liver. He was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. After 6 years, the patient is alive and disease free. In the present case, the patient with API2-MALT1 fusion-positive MALT lymphoma had a good outcome despite the advanced clinical stage.

The prognostic significance of intratumoral heterogeneity of 18F-FDG uptake in patients with oral cavity squamous cell carcinoma.

PURPOSE: This study aimed to evaluate the prognostic significance of two major indices of intratumoral heterogeneity of 18F-fluorodeoxyglucose uptake by positron emission tomography (PET)/computed tomography (CT), namely heterogeneity index (HI) and heterogeneity factor (HF), in patients with oral squamous cell carcinoma. METHODS: We performed a retrospective analysis of 62 patients who underwent resective surgery. HI, HF, maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were obtained from pretreatment PET. HI was obtained by dividing SUVmax by SUVmean for the primary lesion; HF was obtained by taking the derivative (dV/dT) of the volume-threshold function from 30 to 70%. Univariate and multivariate analyses for the overall survival (OS) and disease-free survival (DFS) were performed using PET and clinicopathological parameters. RESULTS: Univariate and multivariate analyses of OS revealed that higher HI levels (threshold for the SUVmean is 30% of the SUVmax) were associated with poorer OS [hazard ratio (HR) = 11.57; 95% confidence interval (CI) = 1.45-92.28; P = 0.021]. Moreover, univariate and multivariate analyses of DFS revealed that higher TLG levels (threshold for the MTV and SUVmean is 4.0 of the SUV) were associated with poorer DFS (HR = 14.48; 95% CI = 1.27-164.78; P = 0.031). CONCLUSIONS: HI and TLG may be statistically significant prognostic factors for OS and DFS, respectively.

Adenoid Cystic Carcinoma With Sialolithiasis of the Left Submandibular Gland: A Case Report and Literature Review.

Adenoid cystic carcinoma is one of the most common salivary gland malignancies with poor long-term prognosis, but the coexistence of sialoliths is extraordinarily rare. In this article, we report a case of 30-year-old woman with a history of submandibular area swelling with intermittent pain increasing during mealtimes that had led her attending physician to diagnose a sialolith in the left submandibular gland on a radiograph 10 years before. However, the surgical specimen proved to be an adenoid cystic carcinoma accompanied with a sialolith. Histopathologically, the submandibular gland was displaced with a fibrous granulation tissue containing a small cribriform carcinoma invading the extracapsular region of the gland. We performed fluorescence in situ hybridization examination with an MYB-NFIB fusion probe of the lesion, with positive results. The patient underwent a supraomohyoid neck dissection as additional procedure because of the possibility of the extracapsular cancer nest remaining around the submandibular gland, but she remains well and disease free 11 years after the first operation.

Remarkable Short-Term Regression of a Posterior Mediastinum Metastasis From Primary Intraosseous Carcinoma Treated With Nivolumab: A Case Report.

Primary intraosseous carcinoma (PIOC; not otherwise specified) is a rare odontogenic malignancy that is believed to arise from the odontogenic epithelium. In addition, some cases arise in odontogenic cysts or other benign precursors. There are no established treatment protocols for PIOC because of its rarity. In particular, no standard therapy has been established for patients with recurrent or metastatic PIOC. This report describes a case in which the use of nivolumab showed a marked treatment response in metastatic PIOC. The patient was a 71-year-old man with PIOC. The patient underwent segmental mandibulectomy with modified radical neck dissection after neoadjuvant chemotherapy, including 2 cycles of paclitaxel, cetuximab, and carboplatin and 1 cycle of docetaxel, cisplatin, and 5-fluorouracil. The lesion rapidly enlarged during neoadjuvant chemotherapy, and surgical specimens showed no histologic therapeutic effects of chemotherapy. Three months after the surgery, contrast-enhanced computed tomograms showed posterior mediastinal lymph node metastasis. Treatment with nivolumab was initiated, and notable clinical improvement was noted after 2 cycles. Although it was a short-term treatment, remarkable effects were observed and no adverse events were noted during and after nivolumab treatment. Nivolumab could be an attractive treatment option for metastatic PIOC that is resistant to traditional chemotherapy and target therapy, including cetuximab. Further investigation of this treatment is warranted.

Idiopathic Isolated Unilateral Hypoglossal Nerve Palsy: A Report of 2 Cases and Review of the Literature.

Hypoglossal nerve palsy (HNP) is a common finding in neurologic diseases when associated with other cranial nerve palsies or further pathology and exhibits characteristic clinical manifestations, including unilateral atrophy of the musculature of the tongue. It occasionally appears as the initial or solitary sign of an intracranial or extracranial space-occupying lesion, head or neck injury, or vascular abnormality of the internal carotid artery. There are few cases of idiopathic isolated unilateral HNP, which should be diagnosed through exclusion. This report describes 2 patients who had different outcomes and presents a literature review of idiopathic isolated unilateral HNP. Case 1 was a 71-year-old man who was referred with a 1-month history of dysphagia and speech impairment. Intraoral examination disclosed marked left-side hemiatrophy of the tongue and deviation toward the left on protrusion. At coronal Tl-weighted magnetic resonance imaging, left-side hemiatrophy of the tongue was clearly visible through deviation of the median septum to the left. The patient was diagnosed with idiopathic isolated unilateral HNP through exclusion and was treated with steroids and mecobalamin, but he did not recover. Case 2 was a 32-year-old man complaining of tongue weakness for 2 days. On examination, left HNP was evident, with deviation of the tongue to the left on protrusion. He was diagnosed with idiopathic isolated unilateral HNP through exclusion and was treated with steroids. After 3 weeks, the patient had completely recovered. To the best of the authors' knowledge, this is the first detailed literature review on idiopathic isolated unilateral HNP. This condition is very rare but should be considered for diagnosis. It warrants a thorough and stepwise approach for etiologic diagnosis.

Quantitative analysis of chronological changes in the volume of flaps used for reconstruction of oral cavity defects.

Reconstruction of oral defects using flaps following resection of oral cancer has become a standard approach for restoration of oral function. The purpose of this study was to investigate chronological changes in the volume of such flaps used for reconstruction and the factors affecting flap volume. We performed a retrospective analysis of 17 patients who had undergone oral cancer resection and reconstruction with flaps. Measurements were performed using data from computed tomography, and the flaps were selected semi-automatically using a computer-operated region-of-interest system. The data indicated that the change in total flap volume at 1 year after surgery was 30.6%, and that body weight loss was a risk factor for volume reduction. Our results suggested that flaps should be at least 30% larger than the defects they are intended to repair. However, as large flaps have the potential to cause upper airway obstruction, flap volume should be determined on an individual basis according to defect size and location.

Cellular-level characterization of B cells infiltrating pulmonary MALT lymphoma tissues.

Mucosa-associated lymphoid tissue (MALT) lymphoma mainly consists of three types of tumor B cells, small (centrocyte-like), scattered large transformed, and intraepithelial. However, it is difficult to differentiate tumor B cells from reactive B cells at the cellular level. We examined five cases of API2-MALT1 fusion-positive MALT lymphoma of the lung. A single paraffin section for each case was subjected to sequential retrieval of whole-slide imaging (WSI) data of hematoxylin and eosin (HE) staining, immunofluorescence staining for CD79a, and fluorescence in situ hybridization (FISH) for the MALT1 split. We counted the number of MALT1 split-positive or MALT1 split-negative cells among CD79a-positive cells. The MALT1 split was detected in 59, 46, and 76 % of small, large, and intraepithelial B cells, respectively. A review of the HE-WSI data showed that cytomorphological distinction between the MALT1 split-positive and MALT1 split-negative B cells was virtually impossible. None of CD79a-negative lymphoid cells, epithelial cells, and microvascular endothelial cells was positive for MALT1 splits. As API2-MALT1 fusion is an early and critical event in the lymphomatogenesis, our findings are best interpreted as that a considerable number of B cells, either small, large, or intraepithelial, are reactive cells and that it is difficult to distinguish cytomorphologically between tumor B cells and reactive B cells. These findings suggest that the tumor architecture may be the central factor for making a correct histopathological diagnosis of MALT lymphoma. The sequential WSI of HE staining, immunofluorescence staining, and FISH as described here is a useful tool for pathological analysis at the cellular level.

Warthin-like Mucoepidermoid Carcinoma: A Combined Study of Fluorescence In Situ Hybridization and Whole-slide Imaging.

There has been some debate as to whether a subset of metaplastic Warthin tumors (mWTs) harbor the mucoepidermoid carcinoma (MEC)-associated CRTC1-MAML2 fusion. We analyzed 15 tumors originally diagnosed as mWT (mWT-like tumors), 2 of which had concurrent MECs. We looked for the CRTC1/3-MAML2 fusion transcripts and performed immunohistochemistry for p63 and fluorescence in situ hybridization (FISH) for the MAML2 split. To localize MAML2 split-positive cells at the cellular level, whole tumor tissue sections were digitalized (whole-slide imaging [WSI]). The CRTC1-MAML2, but not CRTC3-MAML2 was detected in 5/15 mWT-like tumors. FISH-WSI results showed that all epithelial cells harbored the MAML2 split in fusion-positive mWT-like tumors and were totally negative in fusion-negative mWT-like tumors. A review of the hematoxylin and eosin-stained slides showed that morphology of the "metaplastic" epithelium was virtually indistinguishable between fusion-positive and fusion-negative tumors. However, oncocytic bilayered tumor epithelium, characteristic to typical WT, was always found somewhere in the fusion-negative tumors but not in the fusion-positive tumors. This distinguishing histologic finding enabled 5 pathologists to easily differentiate the 2 tumor groups with 100% accuracy. The age and sex distribution of fusion-positive mWT-like tumor cases was similar to that of fusion-positive MEC cases and significantly different from those of fusion-negative mWT-like tumor and typical WT cases. In addition, only fusion-positive mWT-like tumors possessed concurrent low-grade MECs. In conclusion, a subset of mWT-like tumors were positive for the CRTC1-MAML2 fusion and had many features that are more in accord with MEC than with WT. The term Warthin-like MEC should be considered for fusion-positive mWT-like tumors.

Mammary analogue secretory carcinoma of salivary glands: a clinicopathologic and molecular study including 2 cases harboring ETV6-X fusion.

Mammary analogue secretory carcinoma (MASC) is a recently described low-grade carcinoma with morphologic and genetic similarity, including ETV6-NTRK3 fusion, to secretory carcinoma of the breast. ETV6 is frequently involved in other epithelial and nonepithelial tumors, and many fusion partners of ETV6 have been reported. In the present study, 14 Japanese MASC cases were clinicopathologically and molecularly analyzed. The median age of the patients was 39 years, and the male:female ratio was 6:8. All cases showed histopathologic findings compatible with those previously described for MASC and harbored an ETV6 split as visualized by fluorescence in situ hybridization. Two cases showed thick fibrous septa and invasive features including vascular or perineural tumor involvement, findings that are rare in MASC. In addition, in these 2 cases, non-NTRK3 genes appeared to fuse with ETV6 (ETV6-X fusion). NTRK1 and NTRK2, both members of the NTRK family, were not involved. Of the 14 MASC cases, the ETV6-NTRK3 fusion transcript was positive in 6 cases, and the relative expression level of the ETV6-NTRK3 fusion transcript was variable, ranging from 1 to 5.8. Results of the present study of MASC suggest that (1) ETV6 occasionally fuses with unknown non-NTRK3 genes, (2) ETV6-X cases might have an invasive histology, (3) for molecular diagnosis of MASC, fluorescence in situ hybridization to detect ETV6 splits is the method of choice, and (4) the expression level of the ETV6-NTRK3 fusion transcript is considerably variable. These findings provide a novel insight into the oncogenesis, histopathology, diagnosis, treatment, and prognosis of this newly recognized carcinoma.

Androgen receptor-positive mucoepidermoid carcinoma: case report and literature review.

Androgen receptor (AR) is usually expressed in salivary duct carcinoma (SDC), but only infrequently in other carcinoma types including mucoepidermoid carcinoma (MEC). The clinicopathological characteristics of AR-positive MEC remain to be clarified. Here we report a case of AR-positive MEC. A 76-year-old man presented with a growing painless tumor of the right parotid. The resected tumor was a high-grade tumor with necroses. Since the tumor was positive for AR, GCDFP-15, and HER2, SDC was first suspected, but it was also positive for CK5/6 and P63, and negative for S-100 protein and α-smooth muscle actin. In addition, scattered mucous secreting tumor cells were found in the tumor nests, and they were positive for Alcian blue. A diagnosis of AR-positive MEC was finally made. The patient died of the tumor 5 years after the surgery. The present case may expand the histopathological spectrum of high-grade MEC.

Characterization of mammary analogue secretory carcinoma of the salivary gland: discrimination from its mimics by the presence of the ETV6-NTRK3 translocation and novel surrogate markers.

Mammary analogue secretory carcinoma (MASC) is a recently recognized salivary gland tumor harboring an ETV6-NTRK3 translocation similar to secretory carcinoma of the breast. Histologically, MASC mimics papillary-cystic, microcystic, and follicular-type acinic cell carcinoma (AciCC) and low-grade cribriform cystadenocarcinoma (LGCCC) of the salivary gland. Using histology, immunohistochemistry (IHC), and molecular genetic techniques, we reevaluated 18 cases originally diagnosed as AciCC between 1993 and 2012. The last of these methods was used to detect the ETV6-NTRK3 translocation. The results reconfirmed 6 cases as AciCC (3 men; average age, 63 years) and helped us reclassify 10 cases as MASC (6 men; mean age, 46 years) and 2 as LGCCC (2 women; mean age, 48 years). Using IHC, we identified the 3 histologic types according to the expression patterns of vimentin, high-molecular-weight cytokeratin, cytokeratin 19, S-100, mammaglobin, MUC1, GATA-binding protein 3, adipophilin, α-amylase, DOG-1, SOX-10, and p63. The number of tumors diagnosed as MASC indicates that AciCC includes bona fide MASC cases. Because differential diagnosis among zymogen granule-poor AciCC, MASC, and LGCCC tumors is challenging, we recommend using molecular genetic tests for ETV6-NTRK3 for accurate diagnosis. Furthermore, detailed analyses of hematoxylin and eosin-stained tissues and IHC studies using the markers described here should be incorporated into routine practices.