MOLECULAR DETECTION OF MECT1-MAML2 FUSION GENE IN MUCOEPIDERMOID CARCINOMA WITH ORDINARY AND VARIANT HISTOLOGY: A STUDY USING ARCHIVAL PARAFFIN EMBEDDED TISSUE

Mucoepidermoid carcinoma (MEC) has been characterized by t (11; 19)(q21; p13). This chromosomal translocation has been recently shown to generate a MECT1- MAML2 fusion gene. MEC can pose diagnostic challenges when they are of high-grade, of variant histologic appearance and occurring in an unusual site. The aim of this study was to evaluate the frequency of the MECT1-MAML2 fusion gene among primary salivary gland MECs and extrasalivary gland MECs, together with some histological variants and its role as a possible diagnostic adjunct, comparing the salivary gland tumors including Warthin's tumor(WT)，pleomorphic adenoma(PA)，and adenoid cystic carcinoma(ACC). Using a reverse transcription-polymerase chain (RT-PCR)-based approach, we assayed for the MECT1-MAML2 transcript in 39 cases for which paraffin- embedded tumor tissue with adequate RNA was available. These included 19 MECs，10 WTs， five PAs， and five ACCs. The MECT1-MAML2 fusion gene transcript was detected in 16 (84.2%) of 19 MECs. These positive cases included two cases of MEC with WT-like areas，a sclerosing MEC and a clear cell MEC. Three negative cases were high- grade MECs. Two of them were not easy to distinguish from squamous cell carcinoma. The MECT1-MAML2 fusion gene was negative in all cases of WT，PA and ACC. The potential usefulness of MECT1-MAML2 fusion gene expression as a molecular marker in the diagnosis of MEC is supported

薬剤性過敏症症候群(DIHS)の皮疹部においてCD3陽性T細胞数に対するFoxP3陽性制御性T細胞数の割合は増加している

博士（医学）・甲第604号・平成25年11月27日© 2014 British Association of Dermatologists / The definitive version is available at http://onlinelibrary.wiley.com

Hibernoma of the axillary region: a rare benign adipocytic tumor

Hibernoma is a rare benign tumor considered to arise from remnants of fetal brown adipose tissue. It tends to occur in sites where brown fat persists beyond fetal life, such as the interscapular region, but can occur in sites where brown fat is usually absent in adults. Clinicallywell, hibernomas are slow-growing, asymptomatic tumors. However, unlike lipomas, MRI findings sometimes mislead clinicians to diagnose a malignant neoplasm. We describe a 63-year-old male with an axillary hibernoma involving the brachial neurovascular bundles and mimicking a well-differentiated liposarcoma, from which it should be distinguished

腹膜および胸膜悪性中皮腫におけるEGFR発現の比較

An evaluation of epidermal growth factor receptor (EGFR) phenotypic expression in malignant pleural and peritoneal mesothelioma was undertaken, using immunohistochemical (IHC) and fluorescence in situ hybridization (FISH) analysis. Thirty-eight malignant mesothelioma (MM) specimens were subjected to IHC staining and FISH to evaluate the expression of EGFR protein and gene status. Overall positive IHC reaction was detected in 20/38 (53%) cases, in 11/22 (50%) pleural MM, and in 9/16 (56%) peritoneal MM. Our study confirmed that EGFR membranous expression is a common feature in MM, but not in benign mesothelial lesion. Thirty-seven cases did not show a gene copy number gain. Only one case showed a copy number gain. The protein overexpression of EGFR was not related to a gene copy number gain.博士（医学）・乙第1299号・平成24年5月28日© 2012 The Authors. Pathology International© 2012 Japanese Society of Pathology and Blackwell Publishing Asia Pty Ltd

原発性シェーグレン症候群患者における再生因子REG(regenerating gene)に対する自己免疫の関与

The regenerating gene (Reg) was isolated originally as a gene specifically over-expressed in regenerating pancreatic islets and constitute a growth factor family. Reg gene product (Reg) is important in the pathophysiology of various human inflammatory diseases. Recently, the possible involvement of human REG in the regeneration of salivary ductal epithelial cells of patients with primary Sjögren's syndrome (SS) was reported. However, the expression of the REG family genes in minor salivary glands (MSG) and the occurrence of anti-REG Iα autoantibodies in SS patients were obscured. In this study, we examined the expression of REG family genes in the MSG of SS and screened anti-REG Iα autoantibodies in SS. The mRNA levels of REG family genes in MSG were quantified using real-time reverse transcription-polymerase chain reaction (RT-PCR) and REG Iα expression in the MSG was analysed by immunohistochemistry. The mRNA level of REG Iα in the MSG of SS patients was significantly higher than that of control. REG Iα protein was expressed highly in SS ductal epithelial cells. Anti-REG Iα autoantibodies in the sera were found in 11% of SS. All the MSG in the anti-REG Iα autoantibody-positive group showed REG Iα expression, whereas only 40% showed REG Iα expression in the anti-REG Iα autoantibody-negative group. The anti-REG Iα autoantibody-positive group showed significantly lower saliva secretion and a higher ratio of grade 4 (by Rubin-Holt) in sialography. These data suggest strongly that autoimmunity to REG Iα might play a role in the degeneration of MSG ductal epithelial cells in primary SS.博士（医学）・乙第1319号・平成25年11月27日The definitive version is available at " http://dx.doi.org/10.1111/cei.12142

血清TARC/CCL17値は薬剤性過敏症症候群(DIHS) の早期診断および病勢の指標となりうる。

BACKGROUND:Drug-induced hypersensitivity syndrome (DIHS)/drug rash with eosinophilia and systemic symptoms (DRESS) is a serious acute drug reaction with fever, cutaneous eruption, lymphadenopathy, and several visceral dysfunctions. Eosinophilia is a common hematological abnormality in DIHS/DRESS suggesting that the Th2-type immune response is involved. Thymus and activation-regulated chemokine (TARC/CCL17) is a family of CC chemokines known to play an important role in Th2-mediated immune-inflammatory processes. OBJECTIVE:We investigated the pathogenic role of TARC in patients with DIHS. METHODS:Sera were obtained from 8 patients with DIHS, 7 patients with Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN), and 14 patients with drug-induced maculopapular exanthema (MPE). Serum TARC levels were measured by ELISA. TARC levels were then compared with clinical symptoms and various hematological parameters. In addition, a biopsy was taken from the lesional skin of patients with DIHS and stained with anti-TARC Ab and anti-CD11c Ab. RESULTS:Serum TARC levels in patients with DIHS were significantly higher than those in patients with SJS/TEN and MPE during the acute phase. Serum TARC levels in DIHS patients correlated with skin eruptions, serum sIL-2R levels, eosinophil counts, and serum IL-5 levels. Immunohistochemical staining revealed that TARC was mainly expressed on CD11c+ dermal dendritic cells in patients with DIHS. CONCLUSION:Serum TARC levels may be associated with the initial presentation of DIHS as well as disease activity during the course. Thus, they could be useful as an indicator for early diagnosis and assessment of disease activity in DIHS. CD11c+ dendritic cells may be the main source of TARC in patients with DIHS.博士（医学）・甲第597号・平成25年3月15日Copyright © 2012 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved

Combined use of CSF NfL and CSF TDP-43 improves diagnostic performance in ALS:A comprehensive analysis on diagnostic and prognostic significance of plasma and CSF NfL, TDP-43, and tau

Objective To determine the diagnostic and prognostic significance of neurofilament light chain (NfL), TAR DNA-binding protein 43 (TDP-43), and total tau (t-tau) in cerebrospinal fluid (CSF) and plasma of patients with amyotrophic lateral sclerosis (ALS) and to investigate whether the combined use of those biomarker candidates can improve their diagnostic performance. Methods This was a single-center, prospective, longitudinal study. CSF and plasma samples were collected at the time of enrollment from a discovery cohort of 29 patients with ALS and 29 age-matched controls without neurodegenerative disease. In a validation cohort, there were 46 patients with ALS, and 46 control (not age-matched) patients with motor weakness resulting from neuromuscular diseases. NfL, TDP-43, and t-tau levels in CSF and plasma were measured using ultrasensitive single molecule assay (Simoa) technology. Results The following findings were reproducibly observed among the discovery and validation cohorts: increased levels of CSF NfL, plasma NfL, and CSF TDP-43 in ALS compared with control groups; shorter survival associated with higher levels of CSF and plasma NfL. When the CSF NfL and CSF TDP-43 levels were combined, the areas under the ROC curves (AUC) were slightly improved relative to AUCs for each biomarker alone. Interpretation CSF and plasma NfL may not only serve as diagnostic biomarkers but also provide a measure of disease progression. CSF TDP-43 is also useful as a diagnostic biomarker of ALS, but has no prognostic value. The combined use of CSF NfL and CSF TDP-43 may be a useful biomarker for the diagnosis of ALS

Clinicopathological significance of antinuclear antibodies in non-alcoholic steatohepatitis

金沢大学大学院医学系研究科がん細胞学Aim: Serum antinuclear antibodies (ANA) are occasionally noted in patients with non-alcoholic steatohepatitis (NASH). We examined the significance of ANA in NASH. Methods: We compared clinicopathological features in patients with ANA-positive NASH (n = 35) and ANA-negative NASH (n = 36). Inflammatory cell profiles and the distribution of oxidative stress markers were also examined immunohistochemically. Results: ANA-positive NASH was significantly associated with female gender (P = 0.005), high degree of portal inflammation (P = 0.039), interface activity (P = 0.036) and hepatocellular ballooning (P = 0.0008). In addition, ANA of high titer (320-fold or more) was significantly associated with the histological grade and stage of NASH (P = 0.02). The degree of steatosis wais rather mild in the high-titer ANA group(P = 0.01). The analysis of inflammatory cell profiles revealed that CD3-positive T cells were predominant and plasma cells were rather few in the portal area and hepatic lobules in both ANA-positive and ANA-negative groups. There was no difference in the distribution of oxidative stress markers between ANA-positive and ANA-negative groups. Conclusion: These findings suggest that the presence of ANA may be related to the progression of NASH and that a different type of autoimmune mechanism may be involved in the pathogenesis of NASH with ANA, compared to the pathogenesis of autoimmune hepatitis. © 2007 The Japan Society of Hepatology