The Landscape of MYB/MYBL1- and Peri-MYB/MYBL1-Associated Rearrangements in Adenoid Cystic Carcinoma.

Approximately 60% of adenoid cystic carcinoma (AdCC) cases are positive for MYB::NFIB or MYBL1::NFIB, whereas MYB/MYBL1 oncoprotein, a key driver of AdCC, is overexpressed in most cases. Juxtaposition of superenhancer regions in NFIB and other genes into the MYB/MYBL1 locus is an attractive oncogenic hypothesis for AdCC cases, either negative or positive for MYB/MYBL1::NFIB. However, evidence supporting this hypothesis is insufficient. We examined 160 salivary AdCC cases for rearrangements in MYB/MYBL1 loci and peri-MYB/MYBL1 areas (centromeric and telomeric areas of 10 Mb each) using formalin-fixed, paraffin-embedded tumor sections. For the detection of the rearrangements, we employed conventional fluorescence in situ hybridization split and fusion assays and a 5 Mb fluorescence in situ hybridization split assay. The latter is a novel assay that enabled us to detect any possible splits within a 5 Mb distance of a chromosome. We found MYB/MYBL1- and peri-MYB/MYBL1-associated rearrangements in 149/160 patients (93%). AdCC cases positive for rearrangements in MYB, MYBL1, the peri-MYB area, and the peri-MYBL1 area numbered 105 (66%), 20 (13%), 19 (12%), and 5 (3%), respectively. In 24 peri-MYB/MYBL1 rearrangement-positive cases, 14 (58%) were found to have a juxtaposition of the NFIB or RAD51B locus into the MYB/MYBL1 loci. On comparing with a tumor group positive for MYB::NFIB, a hallmark of AdCC, other genetically classified tumor groups had similar features of overexpression of the MYB transcript and MYB oncoprotein as detected by semiquantitative RT-qPCR and immunohistochemistry, respectively. In addition, clinicopathological and prognostic features were similar among these groups. Our study suggests that peri-MYB/MYBL1 rearrangements may be a frequent event in AdCC and may result in biological and clinicopathological consequences comparable to MYB/MYBL1 rearrangements. The landscape of MYB/MYBL1 and peri-MYB/MYBL1 rearrangements shown here strongly suggests that juxtaposition of superenhancers into MYB/MYBL1 or peri-MYB/MYBL1 loci is an alteration that acts as a key driver for AdCC oncogenesis and may unify MYB/MYBL1 rearrangement-positive and negative cases.

Clinicopathological characteristics of four major histological types of high-grade parotid carcinoma.

OBJECTIVE: High-grade parotid carcinoma generally has a poor prognosis, and the histological type is mucoepidermoid carcinoma (MEC), salivary duct carcinoma (SDC), carcinoma ex pleomorphic adenoma (CEPA), or adenoid cystic carcinoma (AdCC) in the majority of cases. METHODS: During the 23-year period from September 1999 to December 2022, 250 patients with parotid carcinoma underwent initial treatment and had the histopathological type of their carcinoma. Retrospective study evaluated 111 MEC, SDC, CEPA, or AdCC cases among 134 patients with high-grade parotid carcinoma. We examined pathological and clinical features and prognosis, evaluated factors associated with recurrence, and performed immunohistological examinations. RESULTS: Pathological and clinical features and factors associated with recurrence were different for each histological type. The 10-year disease-free survival rates were as follows: MEC, 34.9%; SDC, 22.6%; CEPA, 47.1%; and AdCC, 56.3%. Human epidermal growth factor receptor type-2 and androgen receptor were positive in 48% and 56% of patients with SDC, respectively, 38% and 25% of those with CEPA. CONCLUSION: Each histological type has its own pathological and clinical features, recurrence types, and tumor activities, suggesting that differentiating between high-grade parotid carcinomas according to histological type will improve diagnosis, and thus prognosis.

Predicting postoperative facial nerve paralysis by using intraoperative nerve monitoring during parotid surgery.

OBJECTIVES: To investigate a method for predicting postoperative facial nerve paralysis (POFNP) during parotid surgery using intraoperative nerve monitoring (IONM). METHODS: We assessed prediction for POFNP by using IONM, comparing between stimulation in the facial nerve trunk and each branch by using facial nerve monitoring. The amplitude response ratio (ARR) was calculated for the trunk/periphery. In addition, we then examined the correlation between ARR and time to recovery of paralyzed branches. RESULTS: 372 branches of 93 patients did not develop POFNP and were classified as group A. Among 20 patients who developed POFNP, 51 branches without POFNP were classified as group B, and 29 branches with POFNP were classified as group C. The ARR was approximately 1 in group A and B. but less than 0.5 in all branches in Group C. When the cut off value of ARR was set at 0.55, the sensitivity, specificity, and accuracy of POFNP diagnosis by ARR were 96.5%, 93.1%, and 96.8%, respectively. CONCLUSION: Using IONM during parotid surgery enables easy prediction of POFNP.

Increased Chymase-Positive Mast Cells in High-Grade Mucoepidermoid Carcinoma of the Parotid Gland.

It has long been known that high-grade mucoepidermoid carcinoma (MEC) has a poor prognosis, but the detailed molecular and biological mechanisms underlying this are not fully understood. In the present study, the pattern of chymase-positive mast cells, as well as chymase gene expression, in high-grade MEC was compared to that of low-grade and intermediate-grade MEC by using 44 resected tumor samples of MEC of the parotid gland. Chymase expression, as well as chymase-positive mast cells, was found to be markedly increased in high-grade MEC. Significant increases in PCNA-positive cells and VEGF gene expression, as well as lymphangiogenesis, were also confirmed in high-grade MEC. Chymase substrates, such as the latent transforming growth factor-beta (TGF-ß) 1 and pro-matrix metalloproteinase (MMP)-9, were also detected immunohistologically in high-grade MEC. These findings suggested that the increased chymase activity may increase proliferative activity, as well as metastasis in the malignant condition, and the inhibition of chymase may be a strategy to improve the poor prognosis of high-grade MEC of the parotid gland.

Salivary mucoepidermoid carcinoma: histological variants, grading systems, CRTC1/3-MAML2 fusions, and clinicopathological features.

AIMS: To investigate the histological diversity of salivary mucoepidermoid carcinoma (MEC), its clinicopathological features, and its associations with CRTC1/3-MAML2 fusions. METHODS AND RESULTS: Salivary MEC cases (n = 177) were examined for CRTC1/3-MAML2 fusions, histological variants were classified, and tumours were graded according to four different grading systems. Adverse histological features considered to be unusual in MEC were also investigated. Of the 177 MEC cases, 110 were positive for CRTC1/3-MAML2 fusions. The classical variant was the most frequent in the fusion-positive case group, the fusion-negative case group, and the total case group. The clear/oncocytic variant was the second most frequent in the fusion-positive and total case groups. Oncocytic, Warthin-like and spindle variants were seen in the fusion-positive case group only. Clear cell, sclerosing, mucinous and central variants were seen in both the fusion-positive case group and the fusion-negative case group. No case was classified as a ciliated variant, as a mucoacinar variant, or as a high-grade transformation. As compared with the classical variant, non-classical variants were characterised by frequent CRTC1/3-MAML2 fusions and a low clinical stage in all cases. Of the four histological features considered to be unusual in MEC, marked nuclear atypia, frequent mitoses (>10/10 high-power fields) and extensive necrosis were found independently of the fusion status, and were present in 3-5% of all cases. However, none of the cases showed overt keratinisation. On comparison, the Armed Forces Institute of Pathology and modified Healey grading systems downgraded tumours, the Brandwein system upgraded tumours, and the Memorial Sloan Kettering system provided a moderate means of assessment. CONCLUSION: Recognition of the histological diversity of MEC, its clinicopathological features and its associations with CRTC1/3-MAML2 fusions is helpful for an accurate diagnosis of this carcinoma.

Pathological evaluation of tumor grade for salivary adenoid cystic carcinoma: A proposal of an objective grading system.

Three pathological grading systems advocated by Perzin/Szanto, Spiro, and van Weert are currently used for adenoid cystic carcinoma (AdCC). In these systems, the amount or presence of the solid tumor component in AdCC specimens is an important index. However, the "solid tumor component" has not been well defined. Salivary AdCC cases (N = 195) were collected after a central pathology review. We introduced a novel criterion for solid tumor component, minAmax (minor axis maximum). The largest solid tumor nest in each AdCC case was histologically screened, the maximum oval fitting the solid nest was estimated, and the length of the minor axis of the oval (minAmax) was measured. The prognostic cutoff for the minAmax was determined using training and validation cohorts. All cases were evaluated for the four grading systems, and their prognostic impact and interobserver variability were examined. The cutoff value for the minAmax was set at 0.20 mm. Multivariate prognostic analyses showed the minAmax and van Weert systems to be independent prognostic tools for overall, disease-free, and distant metastasis-free survival while the Perzin/Szanto and Spiro systems were selected for overall survival but not for disease-free or distant metastasis-free survival. The highest hazard ratio for overall survival (11.9) was obtained with the minAmax system. The reproducibility of the minAmax system (kappa coefficient of 0.81) was scored as very good while those of the other three systems were scored as moderate. In conclusion, the minAmax is a simple, objective, and highly reproducible grading system useful for prognostic stratification for salivary AdCC.

Sublingual immunotherapy for 4 years increased the number of Foxp3+ Treg cells, which correlated with clinical effects.

OBJECTIVE: At least 3 years of sublingual immunotherapy (SLIT) is required to achieve long-term clinical tolerance for allergens. However, immunological changes with more than 3 years of SLIT have not yet been elucidated in detail. The present study investigated whether the numbers of regulatory T (Treg) cells and regulatory B (Breg) cells increased with 4 years of SLIT and if these increases correlated with clinical effects for pollinosis. METHODS: Seven Japanese cedar pollinosis patients received SLIT in 2014 or 2015 and continued treatment until May 2019. In May 2017 and May 2019, peripheral blood mononuclear cells (PBMCs) were collected from the patients, and analyzed by flow cytometer. RESULTS: (1) The visual analogue scale (VAS) was significantly higher in 2019 than in 2017. (2) The percentages of Foxp3+ Treg cells, type 1 regulatory T (Tr1) cells, and Breg cells in PBMCs were significantly higher in 2019 than in 2017. (3) The percentage of Foxp3+ Treg cells in PBMCs positively correlated with VAS, whereas those of Tr1 cells and Breg cells did not. CONCLUSIONS: These results suggest that 4 years of SLIT is needed to achieve sustained increases in Foxp3+ Treg cells, which are closely associated with the efficacy of SLIT.

Symptoms and signs of parotid tumors and their value for diagnosis and prognosis: a 20-year review at a single institution.

BACKGROUND: Detailed clinical features other than parotid mass have not been investigated in detail for parotid tumors. Symptoms and signs are useful for the differentiation of benign versus malignant, and may also be of value to determine the grade of malignancy and histological type as well as the assessment of prognosis. METHODS: We reviewed symptoms and signs of 965 patients with benign tumors and 200 patients with malignant tumors. Symptoms and signs included pain/tenderness, adhesion to surrounding tissues, and facial nerve palsy. We reviewed the incidence in benign and malignant tumors, in histological type of benign tumors, and in grade and histology of malignant tumors. For each symptom or sign, covariates were analyzed, and their correlation with the prognosis was investigated. RESULTS: The incidence of symptoms and signs was significantly higher in malignant than benign tumors, and more frequent in higher grade of malignancy. Facial nerve palsy was observed in 18.0% of malignant tumor cases, while none occurred in benign tumor cases. Pain/tenderness was more commonly observed in adenoid cystic carcinoma, while adhesion to surrounding tissues and facial nerve palsy were most frequently noted in salivary duct carcinoma. The prognosis of patients with these symptoms and signs was significantly poor. CONCLUSION: A detailed investigation of symptoms and signs in parotid gland tumors is the first step that leads to the diagnosis of malignant tumors. Symptoms and signs are also useful for estimating the grade of malignancy and histological type, and they are important information for predicting prognosis.

A novel clinically-oriented classification of fine-needle aspiration cytology for salivary gland tumors: a 20-year retrospective analysis of 1175 patients.

BACKGROUND: When determining treatment strategy for a salivary gland tumor, assessing histology and malignancy grade before surgery is essential. Several new diagnostic classification systems for salivary gland cytology have recently been proposed. However, none incorporate histology and grade of malignancy. METHODS: We developed a new cytology classification system that incorporates histology and grade of malignancy of salivary gland tumors (OMC classification), consisting of 11 categories. Our OMC classification was applied to 1175 patients who had preoperative cytology and confirmed final pathological diagnosis available from the past 20 years at our hospital (benign tumor: 981 patients, malignant tumor: 194 patients). RESULTS: Based on the cytology, 729 patients (62.0%) had benign histology (Category 4-1), and 87 patients (7.4%) were diagnosed with grade of malignancy (Category 6-3 + 6-4). Based on the final pathological diagnosis, the accuracy rate of Category 4-1 and Category 6-3 + 6-4 of our classification system was 93.4% and 88.5%, respectively. CONCLUSION: Based on the correct diagnosis rate, the inclusion of histology and grade of malignancy in the salivary gland cytology classification was considered feasible. Thus, the OMC classification system is considered a useful tool when determining the treatment strategy for a salivary gland tumor.

Effective surgical management of anterior tumors of the parotid gland: Main trunk method vs. peripheral Smethod.

OBJECTIVE: Several surgical procedures have been proposed for tumors in the anterior parotid gland. Although the standard approach to other parotid tumors is generally also used for anterior tumors, handling of the facial nerve has not been addressed in any previous reports. METHODS: A total of 654 patients with benign parotid tumors who underwent surgery in our department were classified into anterior (AT), middle (MT), and posterior tumor (PT) groups according to tumor location. Clinical characteristics, histopathological types, and frequency of postoperative transient facial palsy were examined. In the AT group, two surgical methods were compared, which were the main trunk method (MTM) and the peripheral method (PM). RESULTS: 172 patients were included in the AT group, 175 in the MT group, and 307 in the PT group. The AT group showed significant female predominance and a higher percentage of deep lobe tumors than the PT group. There was no significant difference in the rate of postoperative transient facial palsy among the AT (MTM), MT, and PT groups. The PM had a significantly shorter operating time and lower rate of transient facial palsy than the MTM. CONCLUSION: The PM for AT was considered a useful surgical method from the standpoints of postoperative complications and operating time. In the PM, a wide operating field made identification of the facial nerve easier.

Increase in Chymase-Positive Mast Cells in Recurrent Pleomorphic Adenoma and Carcinoma Ex Pleomorphic Adenoma of the Parotid Gland.

Incomplete excision of pleomorphic adenoma (PA) may result in recurrent pleomorphic adenoma (RPA). Furthermore, long-term neglected PA may become carcinoma ex pleomorphic adenoma (CXPA). In the present study, the relationships between mast cell-derived chymase and these tumors were examined. The tumor tissues of PA consisted of either or both glandular and fibrotic structures. Histological features of RPA were almost similar to those of PA, except that they showed multinodular structures. CXPA is composed of a mixture of PA and carcinoma. The main stromal cells in PA were myofibroblasts, whereas fibroblasts constituted the main cellular portion in the stromal tissue of RPA. Cancer-associated fibroblasts (CAFs) were present abundantly in CXPA. With increased VEGF expression, neovascularization tended to increase in RPA or CXPA. Compared with PA, chymase-positive mast cells, as well as chymase gene expression, were increased in the tumor tissues from patients with RPA or CXPA. SCF, TGFß1, and PCNA-positive staining was widely observed in these tumor tissues. The above results suggest that mast cell-derived chymase through its direct or cooperative effects with other mediators may participate in the pathophysiology of RPA and CXPA.

Prognostic impact of CRTC1/3-MAML2 fusions in salivary gland mucoepidermoid carcinoma: A multiinstitutional retrospective study.

Mucoepidermoid carcinoma (MEC) is rare, but the most common primary malignancy of the salivary gland and not infrequent in young individuals. CRTC1/3-MAML2 fusions are frequently detected in MEC and are useful as a diagnostic biomarker. However, there has been debate as to whether the fusions have prognostic significance. In this study, we retrospectively collected 153 salivary gland MEC cases from 11 tertiary hospitals in Japan. As inclusion criteria, the MEC patients in this study had curative surgery as the initial treatment, received no preoperative treatment, and had no distant metastasis at the time of the initial surgery. The MEC diagnosis was validated by a central pathology review by five expert salivary gland pathologists. The CRTC1/3-MAML2 fusions were detected using FISH and RT-PCR. In 153 MEC cases, 90 (58.8%) were positive for CRTC1/3-MAML2 fusions. During the follow-up period, 28 (18.3%) patients showed tumor recurrence and 12 (7.8%) patients died. The presence of the fusions was associated with favorable tumor features. Of note, none of the fusion-positive patients died during the follow-up period. Statistical analysis showed that the presence of the fusions was a prognostic indicator of a better overall survival in the total and advanced-stage MEC cohorts, but not in the early-stage MEC cohort. In conclusion, CRTC1/3-MAML2 fusions are an excellent biomarker for favorable overall survival of patients with salivary gland MEC.

Optimization of therapeutic strategy for p16-positive oropharyngeal squamous cell carcinoma: Multi-institutional observational study based on the national Head and Neck Cancer Registry of Japan.

BACKGROUND: Although the American Joint Committee on Cancer TNM classification has been amended to include human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) as an independent entity, to the authors' knowledge the optimized de-escalating treatment modality has not been established to date. METHODS: The authors conducted a retrospective, nationwide, observational study in patients with HPV-related OPSCC who were treated from 2011 to 2014 in Japan to determine the best treatment modality. RESULTS: A total of 688 patients who were newly diagnosed with HPV-related OPSCC who were treated with curative intent at 35 institutions and had coherent clinical information and follow-up data available were included in the current study. In patients with T1-T2N0 disease (79 patients), both the 3-year recurrence-free survival and overall survival (OS) rates were 100% in the group treated with radiotherapy (RT) as well as the group receiving concurrent chemoradiotherapy (CCRT). The 3-year OS rates were 94.4% (for patients with T1N0 disease) and 92.9% (for patients with T2N0 disease) among the patients treated with upfront surgery. In patients with stage I to stage II HPV-related OPSCC, the 5-year recurrence-free survival and OS rates were 91.4% and 92%, respectively, in the patients treated with CCRT with relatively high-dose cisplatin (≥160 mg/m2 ; 114 patients) and 74.3% and 69.5%, respectively, in the patients treated with low-dose cisplatin (<160 mg/m2 ; 17 patients). CONCLUSIONS: Despite it being a retrospective observational trial with a lack of information regarding toxicity and morbidity, the results of the current study demonstrated that patients with T1-T2N0 HPV-related OPSCC could be treated with RT alone because of the equivalent outcomes of RT and CCRT, and patients with stage I to stage II HPV-related OPSCC other than those with T1-T2N0 disease could be treated with CCRT with cisplatin at a dose of ≥160 mg/m2 .

The impact of clinicopathological factors on clinical outcomes in patients with salivary gland adenoid cystic carcinoma: a multi-institutional analysis in Japan.

BACKGROUND: Owing to the low incidence of adenoid cystic carcinoma (AdCC), reliable survival estimates and prognostic factors remained unclarified. METHODS: In this multi-institutional retrospective analysis, we collected 192 AdCC cases, and investigated the impact of clinicopathological factors on clinical outcomes of the patients. All AdCC cases were of salivary gland origin and were surgically treated with curative intent. Diagnoses of AdCC were validated by a central pathology review by expert pathologists. RESULTS: The 5-year overall survival (OS) and disease-free survival (DFS) rates were 92.5 and 50.0%, respectively. Treatment failure occurred in 89 patients (46%) with the distant failures in 65 (34%). Multivariate analysis indicated that pN2 and a pathologically positive surgical margin were independent prognostic factors for both OS and DFS. Histological grade III was an independent prognostic factor for OS. A primary site in the submandibular gland, pT3/4, pN1, and histological grade II were independent prognostic factors for DFS. Postoperative radiation therapy (PORT) improved the locoregional control (LRC) rate. Prophylactic neck dissection was not associated with a better OS or better LRC among patients with cN0. Facial nerve dissection did not improve clinical outcomes in parotid AdCC cases without facial nerve palsy. CONCLUSIONS: A higher TN classification, a pathologically positive surgical margin, and a higher histological grade were associated with a lower OS. PORT improved LRC rates but neck dissection failed to improve clinical outcomes in patients with cN0. As the distant metastasis was frequent, effective systemic therapy is imperative to improve the survival of AdCC patients.

Challenges with preoperative diagnosis of low/intermediate-grade carcinoma of the parotid gland: single-center study of 112 patients.

BACKGROUND: The malignancy of parotid carcinoma varies, and accurate preoperative assessment of malignancy is important for selecting the appropriate treatment. However, the preoperative diagnosis of low/intermediate-grade carcinoma is difficult, and surgery may sometimes be performed without any prior knowledge of malignancy. METHODS: The results of fine-needle aspiration cytology (FNA), imaging studies (MRI and US), physical examination, and frozen section biopsy (FSB) were evaluated in 112 patients with low/intermediate-grade parotid carcinoma. RESULTS: The result of FNA was benign/inadequate specimen in 44.6% of the patients. In addition, the tumor was diagnosed as benign by MRI/US in 21.4% of the patients and 37.5% had no symptoms/signs of malignancy on physical examination. The rate of misdiagnosis as benign decreased when FNA was combined with imaging and physical findings. However, malignancy could not be diagnosed by FNA and FSB in 12.5% of the patients who were only found to have malignant tumors by the final pathological examination. CONCLUSION: FNA shows a high misdiagnosis rate of malignancy in patients with low/intermediate-grade cancer. Therefore, it is necessary to carefully evaluate the findings of imaging studies and physical examination, and FSB should be conducted if such findings suggest the possibility of malignancy.

Adoptive transfer of type 1 regulatory T cells suppressed the development of airway hyperresponsiveness in ovalbumin-induced airway inflammation model mice.

Type 1 regulatory T (Tr1) cells are CD4+ T cells that produce a large amount of IL-10, an anti-inflammatory cytokine. However, it has not been fully elucidated whether Tr1 cells suppress allergic asthma. In this study, the effects of adoptive transfer of in vitro-induced Tr1 cells on allergic asthma were evaluated. Splenocytes from ovalbumin (OVA)-sensitized BALB/c mice were cultured with OVA, IL-21, IL-27, and TGF-ß. After culture, IL-10-producing CD4+ T cells were isolated by Dynabeads mouse CD4 and IL-10 secretion assay, and analyzed by flow cytometry. Purified Tr1 cells (IL-10+ CD4+ T cells) were intravenously injected into OVA-sensitized BALB/c mice. The recipient mice were intratracheally challenged with OVA. Airway hyperresponsiveness to methacholine was assessed by the forced oscillation technique, followed by bronchoalveolar lavage (BAL). Almost all of the induced IL-10-producing CD4+ T cells were negative for interferon-γ, IL-4, IL-17A, and forkhead box P3, suggesting that the cells were Tr1 cells. The adoptive transfer of Tr1 cells significantly suppressed the development of airway hyperresponsiveness, and increases in IL-5, eosinophils, and neutrophils in BAL fluid. In conclusion, we demonstrated that Tr1 cells suppressed allergic asthma in mice.

Patterns of lymph node metastasis and the management of neck dissection for parotid carcinomas: a single-institute experience.

BACKGROUND: There is no consensus about the indications and range of neck dissection in patients who have parotid carcinoma, with elective neck dissection for cN0 disease being particularly controversial. METHODS: This study retrospectively reviewed 185 patients with newly diagnosed parotid carcinoma who were treated at our department between September 1999 and August 2018. RESULTS: 50 of the 185 patients had lymph node metastasis, including 7.7%, 12.2%, 36.0%, and 55.8% of patients with T1, T2, T3, and T4 disease, respectively. When classified by histological grade, 5.7% of patients with low/intermediate-grade disease had lymph node metastasis versus 55.0% of patients with high-grade disease. Multivariate analysis revealed that the histological grade and T classification were independent predictors of lymph node metastasis. Occult metastasis was found in 8 out of 73 clinically node negative patients undergoing neck dissection. The most common site of cervical metastasis was level 2, followed by the periparotid nodes, level 3, and level 4. CONCLUSION: Elective neck dissection may be most appropriate for parotid carcinoma patients with high grade disease and/or an advanced T classification. Because preoperative evaluation of the histological grade of parotid carcinoma has limited reliability, it is important to decide the indications and range of neck dissection from the results of frozen section biopsy.

Clinical characteristics of acinic cell carcinoma and secretory carcinoma of the parotid gland.

PURPOSE: Mammary analogue secretory carcinoma (SC) of the parotid gland is a relatively uncommon cancer associated with the ETV6-NTRK3 fusion product similar to breast cancer. The clinical characteristics and outcome of treatment were reviewed for patients with this tumor at our hospital. METHODS: In this retrospective case series, 24 patients with a diagnosis of acinic cell carcinoma (AcCC) of the parotid gland were classified as having either SC or AcCC based on analysis of the ETV6-NTRK3 fusion gene. These two groups were compared with respect to their clinical and imaging characteristics (MRI/US), cytologic findings, accuracy of fine-needle aspiration cytology and frozen section, treatment outcomes, and immunohistochemical findings. RESULTS: Based on re-classification by ETV6-NTRK3 fusion gene analysis, the diagnosis was SC in 14 patients and AcCC in 10 patients. The SC group had a significantly higher proportion of male patients and was also significantly younger than the AcCC group. Imaging studies revealed that SC was significantly more likely to show internal heterogeneity. Correct grading of both tumors was comparable by fine needle aspiration, with the rate being 60% for AcCC and 50% for SC. Diagnosis by frozen section biopsy diagnosis obtained the correct grade in 90% of the AcCC group and 93% of the SC group. CONCLUSIONS: In 24 patients previously diagnosed with AcCC, re-analysis of the ETV6-NTRK3 fusion product indicated that 14 patients actually had SC. Although AcCC and SC show similarities of their biological aggressiveness and prognosis, patients with SC were significantly more likely to be male and younger.

Latency shift in compound muscle action potentials during electroneurography in facial palsy.

OBJECTIVE: Electroneurography (ENoG) reliably predicts the prognosis of facial palsy. However, the results of ENoG are dependent on the location, where the wave is detected, as a compound muscle action potential (CMAP) arising from the facial muscles. To minimize errors in prognostic prediction, we analysed the latencies of facial CMAPs. MATERIALS AND METHODS: Fifty-seven patients with unilateral peripheral facial palsy and 24 healthy volunteers were enrolled. Amplitudes, negative peak latencies (NPL), and rise latencies (RL) of CMAPs were measured on the paralysed and healthy sides in patients and in healthy volunteers. The relationships of these latencies with ENoG values and the lowest House-Brackmann (H-B) scores were also analysed. RESULTS: The amplitude of CMAP on the paralysed side was smaller, and NPL and RL were longer, than those on the healthy side in patients and healthy volunteers (p < 0.01). In patients, there was no difference in NPL between the ENoG < 40% group and the ENoG ≥ 40% group. Conversely, there was a significant difference in RL between the ENoG < 40% group and ENoG ≥ 40% group (p = 0.03). No relationships were observed between NPL or RL and the lowest H-B score. CONCLUSIONS: NPL and RL of CMAP on the paralysed side were equivalent or longer than those on the healthy side. During ENoG for facial palsy, CMAP should be measured on the healthy side first, and then detected (and the amplitude measured) on the paralysed side with reference to CMAP latency on the healthy side, to reduce errors in detecting facial CMAPs.

Microsurgical mandibular reconstruction using a resin surgical guide combined with a metal reconstructive plate.

INTRODUCTION: In mandibular reconstruction, repositioning the mandibular position is still challenging and time consuming. We invented a new re-positioning technique using a resin plate combined with a reconstructive plate in reconstructing the mandible with an osteocutaneous free flap. The purpose of this report is to introduce this technique and evaluate the accuracy of mandibular reconstruction using free flaps. We hypothesized that this technique is precise and can reduce intraoperative plate bending at a low cost and short preparation period. METHODS: Mandibular reconstruction was successfully performed in a total of 10 cases without any complications. In this technique, a pre-bent reconstructive plate was prepared in accordance with a three-dimensional model, and then coated with resin. Intraoperatively, the mandibles were secured by fitting these plates snugly and fixing them using a reconstructive plate. Then the resin was removed and free osteocutaneous free flaps were transfer to the defect. Ten patients with a mean age of 68.2 who underwent mandibular resection for aggressive benign (n = 1) or malignant disease (n = 9) were reconstructed using this technique. Seven cases were reconstructed using fibular osteocutaneous free flaps, while scapular osteocutaneous free flaps were used in the remaining cases. The resections entailed: unilateral symphysis and lateral body in four cases, angle to ipsilateral angle in two, ramus to symphysis in two, and lateral body plus angle to symphysis in one case. The deviation of the mandible was evaluated by measuring the preoperative versus postoperative differences in the distances between six bilateral landmarks. RESULTS: There were no complications and flap failure in any of the 10 cases. No further intraoperative plate bending was required. One case underwent additional mucosal resection due to recurrence of cancer. Three cases were referred to postoperative chemoradiotherapy. Two patients expired during follow-up due to recurrence of cancer. Six cases were put back on a normal diet. The other cases who lacked opposing teeth had to remain on a soft diet. The mean follow-up period was 46.2 months. The average of the absolute deviation values was 1.45 mm. This value was 0.94 mm in six cases with mandibular body defects and 2.26 mm in four cases with mandibular defects involving the ramus. CONCLUSIONS: The present novel technique is simple, quick to prepare, and accurate. This technique can be a viable option for microsurgical mandibular reconstruction.