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

AN AUTOPSY CASE OF PORTOPULMONARY HYPERTENSION ASSOCIATED WITH ALCOHOLIC LIVER CIRRHOSIS

We report an autopsy case of pulmonary pexogenic arteriopathy associated with portal hypertension due to alcoholic liver cirrhosis, termed portopulmonary hypertension (PPHT). A 49-year-old man who has had alcoholic liver cirrhosis for 10 years complained of severe dyspnea (Fletcher-Hugh-Jones V). Chest CT revealed marked enlargement of bilateral hilar pulmonary arteries and cardiomegaly associated with right ventricular hypertrophy. The patient died from hepatic. encephalopathy and respiratory failure. Autopsy c1early revealed the wall thickness of pulmonary small vessels diffusely in peripheral fields on cut surfaces and marked dilatation of the main pulmonary artery, together with liver cirrhosis. Microscopically, the pulmonary small arteries demonstrated grade 5 pulmonary plexogenic arteriopathy inc1uding plexiform lesions and a micronodule resembling an arachnoid granulation or meningioma throughout the lungs. This case suggested that a typical plexogenic arteriopathy morphologically and definitely contributed to confirm PPHT, although the patient was c1inically suspected of hepatopulmonary syndrome (HPS)

Expression of ADAM15 in rheumatoid synovium: up-regulation by vascular endothelial growth factor and possible implications for angiogenesis

ADAMs (a disintegrin and metalloproteinases) comprise a new gene family of metalloproteinases, and may play roles in cell-cell interaction, cell migration, signal transduction, shedding of membrane-anchored proteins and degradation of extracellular matrix. We screened the mRNA expression of 10 different ADAMs with a putative metalloproteinase motif in synovial tissues from patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Reverse transcription PCR and real-time quantitative PCR analyses indicated that among the ADAMs, ADAM15 mRNA was more frequently expressed in the RA samples and its expression level was significantly 3.8-fold higher in RA than in OA (p < 0.01). In situ hybridization, immunohistochemistry and immunoblotting demonstrated that ADAM15 is expressed in active and precursor forms in the synovial lining cells, endothelial cells of blood vessels and macrophage-like cells in the sublining layer of RA synovium. There was a direct correlation between ADAM15 mRNA expression levels and vascular density in the synovial tissues (r = 0.907, p < 0.001; n = 20). ADAM15 was constitutively expressed in RA synovial fibroblasts and human umbilical vein endothelial cells (HUVECs), and the expression level was increased in HUVECs by treatment with vascular endothelial growth factor (VEGF)(165). On the other hand, ADAM15 expression in RA synovial fibroblasts was enhanced with VEGF(165 )only if vascular endothelial growth factor receptor (VEGFR)-2 expression was induced by treatment with tumor necrosis factor-α, and the expression was blocked with SU1498, a specific inhibitor of VEGFR-2. These data demonstrate that ADAM15 is overexpressed in RA synovium and its expression is up-regulated by the action of VEGF(165 )through VEGFR-2, and suggest the possibility that ADAM15 is involved in angiogenesis in RA synovium

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

CYTOLOGICAL APPROACH TO DIAGNOSISFOR LARGE CELL NEUROENDOCRINE CARCINOMA

Clinical data or investigation of large cell neuroendocrine carcinoma (LCNEC) have accumulated, some of which however, can be flawed by erroneous cytological diagnosis. In this report, we present a case of LCNEC suspected of originating in the lung, and discuss cytological features Qr differential diagnosis. Aspiration cytology showed clusters of tumor cells with large and polymorphic nuclei and distinct nucleoli. The cytoplasm was positive for some markers for neuroendocrines, is similarly as demonstrated in histological findings of metastasis in the cervical lymph node. LCNEC rapidly develops and often reaches an advanced stage, and we have sometirnes found that fine needle biopsy or cytology is the only tool for pathological suggestion or diagnosis. Therefore, it is necessary to accumulate case reports as presented here and confirm cytological features, which might help us to make an accurate diagnosis of LCNEC and to distinguish it from other neuroendocrine neoplasms including small cell carcinoma or poorly differentiated tumors

A modified Larson’s method of posterolateral corner reconstruction of the knee reproducing the physiological tensioning pattern of the lateral collateral and popliteofibular ligaments

<p>Abstract</p> <p>Background</p> <p>Consensus has been lacking as to how to reconstruct the posterolateral corner (PLC) of the knee in patients with posterolateral instability. We describe a new reconstructive technique for PLC based on Larson's method, which reflects the physiological load-sharing pattern of the lateral collateral ligament (LCL) and popliteofibular ligament (PFL).</p> <p>Findings</p> <p>Semitendinosus graft is harvested, and one limb of the graft comprises PFL and the other comprises LCL. Femoral bone tunnels for the LCL and popliteus tendon are made at their anatomical insertions. Fibular bone tunnel is prepared from the anatomical insertion of the LCL to the proximal posteromedial portion of the fibular head, which corresponds to the insertion of the PFL. The graft end for popliteus tendon is delivered into the femoral bone tunnel and secured on the medial femoral condyle. The other end for LCL is passed through the fibular tunnel from posterior to anterior. While the knee is held in 90 of flexion, the graft is secured in the fibular tunnel using a 5 mm interference screw. Then, the LCL end is passed into the femoral bone tunnel and secured at the knee in extension.</p> <p>Conclusions</p> <p>Differential tension patterns between LCL and PFL is critical when securing these graft limbs. Intrafibular fixation of the graft using a small interference screw allows us to secure these two graft limbs independently with intended tension at the intended flexion angle of the knee.</p