Michio Shimizu

Cyclin E Expression, a Potential Prognostic Marker for Non-Small Cell Lung Cancers

BackgroundCD133 is a membrane glycoprotein containing five transmembrane loops. Previous reports suggest that a CD133-positive subpopulation of multipotent cells with extensive proliferative and self-renewal characteristics has biological features of a cancer stem cell. In addition, the presence of CD133-positive cells was associated with a significantly poorer prognosis for some solid tumors, compared to those with CD133-negative cells. However, the clinicopathological significance of CD133 in non-small cell lung cancer (NSCLC) remains controversial.MethodsWe conducted immunohistochemical assessment of 161 NSCLCs surgically resected at Hokkaido University Hospital between 1982 and 1994 to evaluate correlations between CD133 expression and various clinicopathological features.ResultsCD133 expression was significantly correlated with pathological stages (pStages) II, III, and IV for the various NSCLC types analyzed and was an independent factor for unfavorable prognosis in this population (hazard ratioxa0=xa03.157, Pxa0=xa00.015).ConclusionCD133 expression was correlated with pStage and was predictive of unfavorable prognosis in patients with pStages II, III, and IV NSCLC. These results suggest the possibility of using CD133 as a novel prognostic marker in these patients.

Histopathological prognostic factors of adult granulosa cell tumors of the ovary

Background. The prognostic factors of adult granulosa cell tumor (AGCT) have not been well defined.

Increased expression of β-catenin predicts better prognosis in nonsmall cell lung carcinomas

β‐Catenin has been shown to function as a Wnt signaling molecule to stimulate cyclin D1 expression and cell growth in several kinds of tumors.

Molecular and immunohistochemical analysis of signaling adaptor protein Crk in human cancers.

Crk is a signaling adaptor protein which is mostly composed of SH2 and SH3 domains, and has been shown to play a pivotal role in cell proliferation, differentiation, and migration. Because Crk was originally isolated as an avian sarcoma virus CT10 encoding oncoprotein v-Crk, we examined a potential role for c-Crk in the carcinogenesis of human cancers. First, to analyze gene mutations of c-Crk, we isolated a human bacterial artificial chromosome clone containing Crk genome and exon/intron structures. However, polymerase chain reaction-single strand conformation polymorphism methods failed to show any genomic mutations in the Crk exon which could be related to carcinogenesis. Second, immunohistochemical analysis of c-Crk-II demonstrated that the levels of c-Crk-II were significantly elevated in most of the tumors, particularly in the colon and lung cancers. Furthermore, immunoblot analysis using human lung cancer cell lines revealed that the expression levels of c-Crk-II were correlated to growth rates of cells. The elevated expression levels of c-Crk-II might be related to the development of human cancers.

Primary extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type in the CNS.

Extranodal marginal zone B‐cell lymphoma of the mucosa‐associated lymphoid tissue (MALT) type has been reported in various internal organs. Here a case is reported of MALT lymphoma developing in the cerebellopontine (CP) angle in a patient with Sjögren syndrome, and the concept of MALT lymphoma of the CNS is introduced. Pathologically, the tumor showed inflammatory features of reactive lymphocytic infiltration with follicle formation, but there were slightly atypical lymphocytes and plasmacytes with B‐cell markers. These cells invaded reactive follicles, showing follicular colonization, and showed aberrant expression indicating their neoplastic nature. A review of the literature revealed eight cases of MALT lymphoma originating from the dura mater and one from the CP angle. The average age of patients was 50 years (range 28–66 years), and all patients were female. The tumors were slow to develop and the patients were cured after surgical removal and/or additional therapies. It is proposed that MALT lymphoma should be considered as a differential diagnosis of inflammatory pseudotumor of the CNS.

Solid-pseudopapillary carcinoma of the pancreas

A case of solid‐pseudopapillary carcinoma (SPC) of the pancreas in a 34‐year‐old Japanese woman is presented. An abdominal ultrasonography revealed a mass, which measured 10 cm in diameter, in the body and tail of the pancreas. The tumor was resected and it was originally diagnosed as a non‐functioning islet cell tumor. One year and five months later, the patient was re‐admitted to hospital, and liver metastasis was confirmed by ultrasonography. The patient died 6 days after the second transcatheter arterial embolization (TAE) required for the metastasis. The autopsy showed small foci of liver metastasis. A retrospective examination of the tumor suggested the diagnosis of SPC because of its characteristic solid and pseudopapillary structures, immunohistochemical findings, and liver metastasis. This case suggests that capsular invasion, specifically found at the surgical margin of the peritoneal side, may be an important pathological finding that is suggestive of malignant potential in solid‐pseudopapillary tumor. If there is such a finding in a surgical specimen, an intensive follow up should be advised to the clinician.

HHV8-negative primary effusion lymphoma of the peritoneal cavity presenting with a distinct immunohistochemical phenotype

Primary effusion lymphoma (PEL) has been recognized as a body‐cavity‐based lymphoma that was originally reported to be associated with human herpes virus 8 (HHV8) infection, and was frequently found in human immunodeficiency virus‐positive (HIV) patients. Here we describe an autopsy case of PEL of the peritoneal cavity in an immunocompetent patient. Cytological analysis of tumor cells within ascites revealed immunocytochemical features of keratin positivity and CD45 negativity. At autopsy, the presence of a massive volume of ascites as well as diffuse tumor cell infiltrates within the serosa of the intestine and mesenterium were observed. Tumor cells were morphologically similar to anaplastic large‐cell lymphoma, but were immunohistochemically positive for keratin and epithelial membrane antigen (EMA). They also showed no reactivity to representative lymphocyte surface markers including CD45, in addition to being negative for CD30 and p80NPM/ALK. Molecular analysis of the tumor cells revealed monoclonality of the immunoglobulin heavy‐chain gene rearrangement which demonstrated a lymphoma of the B‐cell lineage. Furthermore, HHV8 was not detected by immunohistochemical analysis, PCR or nested PCR technique. Based on these results, we consider the present case to be an HHV8‐negative PEL with keratin and EMA positivity.

Cytologic findings in noninvasive intraductal papillary-mucinous carcinoma of the pancreas: A report of two cases

BACKGROUNDnIntraductal papillary-mucinous carcinoma of the pancreas is a new diagnostic term proposed by the 1996 World Health Organization classification of the exocrine pancreas. So far, there have been only a few reports concerning its cytologic findings, especially in noninvasive cases.nnnCASESnThe clinical and cytohistologic findings in two cases of noninvasive intraductal papillary-mucinous carcinoma of the pancreas were reviewed. Cytologic specimens were obtained from pure pancreatic juice in the dilated main pancreatic duct during the operation (case 1) and during endoscopic retrograde pancreatography (ERP) (case 2). Both cases showed three-dimensionally or individually scattered tumor cells with an increased nuclear/cytoplasmic ratio and prominent nucleoli.nnnCONCLUSIONnOur cases suggest that pancreatic juice cytology during ERP or surgery is useful in diagnosing pancreatic cancers and that it may detect noninvasive intraductal papillary-mucinous carcinoma of the pancreas.

A rare case of bronchial glomus tumor

A 48-year-old man was admitted because of bloody sputum in whom a chest computed tomography (CT) scan and fiberoptic bronchoscopy demonstrated a polypoid tumor in the left main bronchus. The tumor was surgically resected, and the pathological and immunohistochemical findings led to diagnosis of the tumor as a bronchial glomus tumor.

Application of laser capture microdissection to cytologic specimens for the detection of immunoglobulin heavy chain gene rearrangement in patients with malignant lymphoma.

The demonstration of the monoclonality of immunoglobulin heavy chain (IgH) gene rearrangement is an indispensable method for the diagnosis of B‐cell lymphoma as well as histocytochemical analysis. For the detection of IgH gene rearrangement, the extraction of DNA from a homogenous cell population is necessary. Recently, the laser capture microdissection (LCM) technique was shown to isolate specific cells from histopathologic specimens for molecular analysis. However, to the authors knowledge the applicability of LCM to cytologic specimens has not yet been well established.