Shintaro Beppu

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.

MYB, MYBL1, MYBL2 and NFIB gene alterations and MYC overexpression in salivary gland adenoid cystic carcinoma

Adenoid cystic carcinoma (AdCC) is one of the most common salivary gland malignancies and the long‐term prognosis is poor. In this study, we examined alterations of AdCC‐associated genes, MYB, MYBL1, MYBL2 and NFIB, and their target molecules, including MYC. The results were correlated to clinicopathological profile of the patients.

Lymph node density predicts lung metastases in oral squamous cell carcinoma.

The association between lymph node density and survival free of lung metastases in oral squamous cell carcinoma (SCC), has not been investigated so far to our knowledge. Lymph node density ≧ 0.07 has been reported by a multicentre international study to be a significant predictor of shorter survival in patients with oral SCC who have invaded nodes. We investigated whether a lymph node density of ≧ 0.07 correlates with shorter overall survival, survival free of distant metastases, and survival free of lung metastases, in patients with oral SCC and invaded lymph nodes. Thirty-five patients with histologically-confirmed invaded lymph nodes werestudied. Their density was calculated as the ratio of the number of invaded lymph nodes:total number of nodes. A density of ≧ 0.07 correlated significantly with shorter overall survival (p<0.02), survival free of distant metastases (p<0.01), and survival free of lung metastases (p<0.01) on log rank testing. On testing by Coxs proportional hazards model of multivariate survival analysis with adjustment for the pathological stage (pstage IV/pstage III), and invaded surgical margins or extracapsular spread, or both, we found that lymph node density ≧ 0.07 was associated with significantly shorter survival (p<0.02). We conclude that lymph node density predicts lung metastases in patients with oral SCC.

Impact of hematological inflammatory markers on clinical outcome in patients with salivary duct carcinoma: a multi-institutional study in Japan

The prognostic role of modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with salivary duct carcinoma (SDC) remains unclear. We conducted a multi-institutional retrospective cohort study of 140 SDC patients. The survival impact of these hematological markers was evaluated using multivariate proportional hazard models.High mGPS (≥1) was significantly associated with worse survival (3-year overall survival (OS): 16.7% vs 66.1%, p-value=0.003; 3-year progression-free survival (PFS): 0.0% vs 27.9%, p-value<0.001). Additionally, high C-reactive protein (CRP) (≥0.39 mg/dl) was significantly associated with worse survival (3-year OS: 32.1% vs 68.2%, p-value=0.001; 3-year PFS: 7.1% vs 31.1%, p-value<0.001). These associations were consistent with multivariate analysis adjusted for established prognostic factors. Although we also found significant association of high NLR (≥2.5) with OS (HR 1.80; 95% confidence interval, 1.05-3.08) in multivariate analysis, this association were inconsistent with the results of PFS. In addition, we found no significant associations of PLR with survival. In conclusion, we found that mGPS, CRP and NLR were identified as prognostic factors associated with survival in SDC patients.

Expression of cancer/testis antigens in salivary gland carcinomas with reference to MAGE ‐A and NY ‐ ESO ‐1 expression in adenoid cystic carcinoma

Cancer/testis antigens (CTAs) are detected in cancer cells but not in healthy normal tissues, with the exception of gametogenic tissues. CTAs are highly immunogenic proteins, and thus represent ideal targets for cytotoxic T‐lymphocyte‐mediated specific immune therapy. The aim of this study was to screen CTA expression in various types of salivary gland carcinoma and to clarify clinicopathological significance of MAGE‐A and NY‐ESO‐1 expression in adenoid cystic carcinomas (AdCCs) of the salivary gland, which is one of the most common salivary gland carcinomas, and usually has a fatal outcome.

Functional Nerve Preservation in Extracranial Head and Neck Schwannoma Surgery

IMPORTANCE A schwannoma is an uncommon, benign neurogenic tumor of Schwann cells. Tumor enucleation is the recommended surgical method to preserve function of the original nerve, although enucleation does not guarantee completely intact nerve function after the operation. OBJECTIVE To establish a strategy for functional preservation in extracranial head and neck schwannoma treatment by using an electromyographic (EMG) system during tumor resection. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study was conducted of 15 patients who underwent surgery for removal of schwannoma tumors between April 1, 2006, and March 31, 2015, at an academic tertiary referral center. Data analysis was conducted from April 3, 2006, to September 15, 2015. Neurogenic tumors were diagnosed according to preoperative findings, and during surgery tumors were exposed and given EMG-controlled electrical stimulation to analyze their origins. In motor nerve cases, the electrical activity of the muscle was measured and recorded by EMG. The tumor was then enucleated by incision along tumor fibers mapped using EMG stimulation. If a nerve bundle was visible, we incised along there and enucleated the tumor. INTERVENTIONS A strategy using electrical stimulation to improve preservation of nerve function in extracranial head and neck schwannoma operations. MAIN OUTCOMES AND MEASURES Frequency and duration of postoperative neurologic complications associated with functional preservation surgery with tumor enucleation was evaluated using EMG monitoring according to tumor origin. RESULTS Of the 15 patients with extracranial schwannoma, 9 (60%) were women (mean [SD] age, 36.3 [15.3] years). All 15 patients underwent surgery using a transcervical approach. The most common nerves of origin were the vagus nerve and the sympathetic chain. In sensory or sympathetic nerve cases, the EMG response was absent. Two of 5 patients with vagus schwannoma had postoperative temporary vocal nerve palsy. These symptoms showed improvement after 1 year. There was no tumor recurrence during the follow-up period in any patient. CONCLUSIONS AND RELEVANCE The strategy used here demonstrated a method of diagnosis and nerve preservation surgery for extracranial schwannomas. Nerve functionality was preserved in all vagus schwannoma cases. However, preservation of nerve function in sympathetic nerve schwannoma cases remains problematic and needs further investigation.

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.

Peak of Standardized Uptake Value in Oral Cancer Predicts Survival Adjusting for Pathological Stage

Background/Aim: To predict survival outcomes of different patients with the same stage of disease is difficult. The possible correlation between 18F-fluorodeoxyglucose (18F-FDG) uptake parameters and survival outcomes was investigated in oral squamous cell carcinoma patients by multivariate analysis adjusted for the pathological stage according to the 8th edition of the tumor-node-metastasis (TNM) classification of the Union for International Cancer Contro. Patients and Methods: 18F-FDG-uptake parameters of 28 patients were assessed by positron emission tomography with computed tomography (PET/CT). Results: A peak of standardized uptake value of primary tumor (p-SUVpeak) of ≥14.1 was significantly correlated with shorter overall survival by univariate and multivariate analyses adjusted for the pathological TNM stage. A p-SUVpeak of ≥14.1 was significantly associated with shorter local recurrence-free survival and disease-free survival. Conclusion: A higher p-SUVpeak on pretreatment 18F-FDG-PET/CT is a prognostic parameter of identifying lower survival outcomes.

Lymph node density in papillary thyroid carcinoma is a prognostic factor after adjusting for pathological stage

We investigated the possible association between the lymph node density and survival outcomes in differentiated papillary thyroid carcinoma, and examined whether the lymph node density was a predictor in a multivariate analysis adjusted for the pathological stage in the eighth edition of the Union for International Cancer Control Tumor-Node Metastasis Classification of Malignant Tumors. A total of 543 patients with papillary thyroid carcinoma were enrolled. We performed restaging according to the eighth edition. The lymph node density was the ratio between number of positive lymph nodes and total number of excised lymph nodes. A log-rank test and Coxs proportional hazards model were used for univariate and multivariate analysis with adjustment for the pathological stage in the eighth edition, respectively. In both the univariate and multivariate analyses of 150 patients with pN1bM0, the presence of a lymph node density of ≥ 0.3 with pN1b was significantly associated with shorter disease-specific survival. In both the univariate and multivariate analyses of all 543 patients, a lymph node density of ≥ 0.3 with pN1b were also significantly associated with shorter overall and disease-specific survival. In conclusion, these results suggest that the lymph node density can be used as a predictor for the survival outcomes after adjustment for the pathological stage in the eighth edition.

The Impact of Skeletal Muscle Depletion on Head and Neck Squamous Cell Carcinoma

Background: Skeletal muscle depletion and sarcopenia have been reported as poor prognostic factors for several types of cancer. The aim of this study was to investigate the prognostic impact of skeletal muscle depletion and sarcopenia on the outcomes in head and neck cancer patients. Methods: Patients with head and neck squamous cell carcinoma (HNSCC) treated from January 2013 to June 2014 were included in this study. The pretreatment cross-sectional area of skeletal muscle at the third lumbar vertebra (L3) was measured by computed tomography image analysis using the ImageJ software. L3 skeletal muscle index (SMI) and fat-free mass (FFM) were calculated. Results: Eighty-five patients with HNSCC were included. The cut-off value of sarcopenia was set at SMI <46.7 cm2/m2 (males) and 30.3 cm2/m2 (females). The cut-off value of FFM was set at 42.3 kg (males) and 30.6 kg (females). Patients with a low SMI (sarcopenia) and low FFM had a significantly poorer prognosis than others, especially those who received definitive radiotherapy. Sarcopenia and low FFM are independent factors for poor prognosis in patients with HNSCC. Conclusion: The skeletal muscle area at L3 should be calculated when considering treatment options for head and neck cancer.