Toshiya Shinohara

Molecular pathologic study of human papillomavirus infection in inverted papilloma and squamous cell carcinoma of the nasal cavities and paranasal sinuses

Nasal inverted papilloma is a rare benign tumor occasionally associated with squamous cell carcinoma. To determine the etiological role of human papillomavirus in inverted papilloma, and to clarify the relationship between human papillomavirus and malignant transformation of this benign tumor, we retrospectively analyzed inverted papillomas from 26 patients, 7 of whom had squamous cell carcinoma.

Predictors of malignancy in intraductal papillary mucinous neoplasm of the pancreas: analysis of 310 pancreatic resection patients at multiple high-volume centers.

Objectives The present study was a retrospective investigation of predictors of malignancy in intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Methods The subjects were 310 patients who underwent pancreatic resection at 3 high-volume centers. Preoperative laboratory and imaging findings were analyzed in logistic regression analyses. Endoscopic ultrasonography measurements were essential for the size of mural nodules, and a central review was conducted for pathological diagnosis. Results Pathological diagnosis was benign IPMN in 150 cases and malignant in 160 (noninvasive carcinoma, n = 100; invasive, n = 60). In multivariate analysis, size of mural nodules, diameter of main pancreatic duct, and cyst size of branch pancreatic duct were independent predictors of malignancy, and areas under the receiver operating characteristic curve for these 3 factors were 0.798, 0.643, and 0.601, respectively. With 7 mm taken as the cutoff value for the size of mural nodules, the diagnosis of malignant IPMN had sensitivity of 74.3% and specificity of 72.7%. Carcinoma without nodules was present in 15 patients (15/160 [9.4%]). Conclusions The size of mural nodules measured with endoscopic ultrasonography showed high predictive ability. However, about 10% of carcinoma patients did not have nodules, and the handling of the diagnosis in such cases is a problem for the future.

Expression of the angiotensinogen gene and localization of its protein in the human heart.

BackgroundThere have been no reports on the presence of the tissue renin-angiotensin system in the human heart, although the presence of angiotensinogen has been described in the animal heart. Methods and ResultsTo determine whether angiotensinogen is synthesized in the human heart, we examined angiotensinogen messenger RNA (mRNA) synthesis in autopsy hearts by using ribonuclease protection assay. As a result, angiotensinogen mRNA was detected in the atrial muscle, muscles of the conduction system, and the left ventricular wall. In the left ventricular wall, mRNA expression was more prominent in the subendocardial muscles than in the midcardial or epicardial muscles. Using a monoclonal antibody to human angiotensinogen in immunoblotting experiments, we detected two closely spaced bands at approximately 70 kd in the heart, which was quite consistent with the human angiotensinogen molecule. Immunohistochemical studies with this monoclonal antibody demonstrated intense immunoreactivity in the atrial muscles, the muscles of the conduction system, and those of the subendocardial layers. ConclusionsWe conclude that angiotensinogen was synthesized in the human heart. It was evident that the localization of angiotensinogen was not ubiquitous in the cardiac muscles, showing its predilection for the atrial muscles, muscles of the conduction system, and subendocardial layer of the left ventricle.

High expression of tumor-associated antigen RCAS1 in pancreatic ductal adenocarcinoma is an unfavorable prognostic marker.

RCAS1 (receptor‐binding cancer antigen expressed on SiSo cells) is a recently identified human tumor‐associated antigen expressed on various cancer cells. It is thought that tumor cells evade immune surveillance by expression of RCAS1, which induces apoptotic cell death in receptor‐positive immune cells. The purpose of our study was to investigate the relation between RCAS1 expression and the clinicopathological variables and clinical outcome in patients with pancreatic adenocarcinoma. Immunohistochemical analysis for RCAS1 was performed on paraffin‐embedded specimens of 80 patients (mean age, 62 years) who underwent surgical resection for pancreatic adenocarcinoma. Of the 80 specimens, 77 (96%) were positive for RCAS1. No significant correlation was found between RCAS1 expression and age, gender, depth of invasion, tumor diameter, surgical margin, lymphatic invasion, venous invasion or histopathological grading. Borderline correlations between RCAS1 expression were noted for lymph node metastasis and stage (p = 0.0608 and 0.0934, respectively). RCAS1 expression was very frequently observed and the survival of patients with high RCAS1 expression was significantly shorter than that of those with low expression (p = 0.0012). Multivariate analysis using the Cox regression model indicated that high RCAS1 expression was an independent prognostic factor (risk ratio, 3.090; p = 0.0090). These results suggested that RCAS1 might be a significant tumor marker for pancreatic adenocarcinoma and an unfavorable predictor for prognosis of patients who have undergone surgical resection.

Expression of vascular endothelial growth factor in human myocardial infarction.

SummaryTo define mechanisms that may influence collateral circulation and angiogenesis, we investigated vascular endothelial growth factor (VEGF) mRNA expression in human hearts. In non-ischemic human hearts, VEGF mRNA was not detected in vessels, but was found in cardiomyocytes. In hearts with myocardial infarction, the intensity of the VEGF signal was much higher in smooth muscle cells of arterioles adjacent to necrosis and in infiltrating macrophages than in myocytes around the site of the necrosis. This study suggests that levels of VEGF expression are high in smooth muscle cells and macrophages around infarcted areas after myocardial infarction and that VEGF may play a role in promoting collateral circulation and angiogenesis in human ischemic hearts.

Mucin-Secreting Bile Duct Adenoma – Clinicopathological Resemblance to Intraductal Papillary Mucinous Tumor of the Pancreas

We describe a case of mucin-secreting biliary adenoma associated with obstructive jaundice due to mucin production. Duodenal endoscopy revealed mucin secretion through an enlarged papilla of Vater. On the cholangiogram, large filling defects caused by mucin were observed in the dilated bile duct. Granular and/or papillary mucosa was noted from the hilar to the common bile duct by using percutaneous transhepatic cholangioscopy. Biopsy specimens taken from the papillary mucosa revealed slightly papillary projection without any evidence of malignancy. This lesion was diagnosed as mucin-secreting superficial adenoma and pancreatoduodenectomy was performed according to the malignant behavior. Using a histologic examination of the specimen, pure adenoma was documented. Since the surgical margin was positive, radiation was added for the residual adenoma in the intrahepatic bile ducts. The patient has been well without any evidence of recurrence for 21 months since her operation. It is only recently that the term ‘intraductal papillary mucinous tumor (IPMT)’, which is accepted as a distinct disease entity of pancreas, has begun to be used for mucin-secreting bile duct tumor. This case also seemed to clinicopathologically resemble an IPMT of the pancreas.

Detection of human papillomavirus DNA in carcinomas of the nasal cavities and paranasal sinuses by polymerase chain reaction

The authors retrospectively searched for human papillomavirus (HPV) types 16 and 18 in 60 cases of carcinoma arising from the nasal cavities (NC) and paranasal sinuses (PS) by using the polymerase chain reaction (PCR) on DNA extracted from formalin‐fixed, paraffin‐embedded tissues. In cases of SCC (n = 49), the authors also compared the clinical features of patients with HPV‐positive and HPV‐negative results to determine the clinical significance of HPV. HPV 16 and 18 were detected in 7 of the 49 cases (14%) of SCC. In the other histologic types of carcinoma (n = 11), neither HPV 16 nor HPV 18 was detected. No significant differences in the clinical features were observed between patients with SCC with HPV‐positive and HPV‐negative results. The results suggest that HPV 16 and 18 are implicated in the pathogenesis of SCC arising from the NC and PS. However, the presence of HPV is not related to local progression, occurrence of metastases, or the prognosis of the patients.

Clinicopathological studies of peripheral neuropathy in Churg-Strauss syndrome.

Clinicopathological studies were performed on the visceral organs and the sural nerve of a male patient with Churg–Strauss syndrome (CSS) in order to understand the mechanisms of peripheral nervous system damage. A 67‐year‐old man, with a 2‐year history of bronchial asthma, developed acutely painful paraplegia and dyspnea. Laboratory data showed a leukocytosis, an elevated serum creatinine kinase (CK) and marked eosionophilia. Autoantibodies including p‐ and c‐ANCA were negative. Electrophysiological studies revealed a severe sensory‐motor neuropathy of multiple mononeuritis type. Steroid pulse therapy performed a day after biopsy of skin, muscle and sural nerve was effective in resolving his respiratory and neurological dysfunction but a perforation of an intestinal ulcer occurred which required surgical intervention. In the biopsied sural nerve and the surgically resected intestine and mesentery there was vasculitis with fibrinoid necrosis accompanied by numerous eosinophils and macrophages containing eosinophil cationic protein (ECP). These findings suggest that in addition to ischemic changes due to vasculitis some neurotoxic substances generated by the eosinophils may be involved in the development of neuropathy in CSS.

RCAS1 expression as a prognostic factor after curative surgery for extrahepatic bile duct carcinoma

BackgroundRCAS1 (receptor-binding cancer antigen expressed on SiSo cells) is a cancer cell-surface antigen and has been identified as a prognostic factor in several cancers. It is thought that tumor cells escape from immune attack by expressing RCAS1, which induces apoptosis in receptor-positive immune cells. We investigated the relationship between RCAS1 expression and clinicopathologic features and clinical outcome in patients with extrahepatic bile duct carcinoma (EBDC) who underwent curative resection.MethodsRCAS1 expression was determined by immunohistochemistry in 60 patients with EBDC who underwent curative resection from 1992 to 1999. The patients were divided into two groups on the basis of the extent of RCAS1 expression: a low-expression group (immunoreactivity in <25% of cells) and a high-expression group. Expression was correlated with clinicopathologic features and prognosis.ResultsRCAS1 was expressed in 52 (86.7%) of 60 tumors and at a high frequency in all histopathologic stages. High expression of RCAS1 was detected in 46 (76.7%) of 60 cases. No correlation existed between the pattern of RCAS1 expression and any clinicopathologic feature, although high expression did correlate with poor prognosis. High RCAS1 expression was an independent negative predictor for survival.ConclusionsRCAS1 expression predicts poor outcome in resectable EBDC.

Pathology of pure hippocampal sclerosis in a patient with dementia and Hodgkin's disease: The Ophelia syndrome

An archive autopsy case of a 50‐year‐old man who died of Hodgkins lymphoma had a 4‐year, 4‐month history of dementia. After radiochemotherapy, the lymphoma subsided except for involvement of the spleen, but the dementia remained. Neuropathological examination revealed that the pathology was confined to the hippocampus, both hippocampi showing sclerosis without inflammation. Neurons of sector cornu ammonis (CA) 1 were completely lost whereas moderate neuron loss was also observed in sectors CA3 and 4, and the dentate gyrus. Neurons of sector CA2 were relatively well preserved and the subiculum was intact. There was no evidence of global hypoxia, or of neurodegenerative disorders with pathological changes affecting the hippocampus. Although there was a long preneoplastic history, and no inflammatory changes were found at autopsy, the present case of hippocampal sclerosis could be included in the category of paraneoplastic limbic encephalitis associated with Hodgkins lymphoma or the Ophelia syndrome.