No abstract

Some patients with gastrointestinal schwannoma (GIS) have been previously reported in the literature. However, GIS of the colon is quite rare. In addition, it is sometimes difficult to differentiate neurogenic tumors from other soft tissue tumors. We herein describe two cases of schwannoma of the colon, while also reviewing the relevant Japanese literature. The first case, a 73-year-old woman underwent a sigmoidectomy with lymph node dissection following the diagnosis of submucosal tumor. In the second case, a submucosal tumor was located in the cecum of a 44-year-old man. An endoscopic tumor resection was performed in the second case. The resected tumors measured 3.6 and 1.0 cm in maximal diameter, respectively. Microscopically, the tumors consisted predominantly of spindle-shaped cells that proliferated in an interlaced fashion. Mitosis was rarely seen in these tumors. Immunohistochemically, the tumor cells were strongly positive for S-100 protein, weakly positive for glial fibrillary acidic protein, and negative for CD34, alpha-smooth-muscle actin, and cytokeratin (CAM 5.2) in both cases. The tumors in the two cases were both diagnosed to be benign schwannoma of the colon. In general, schwannoma of the gastrointestinal tract is considered to be benign and should therefore be distinguished from other spindle-cell tumors or malignancies. Once diagnosed as schwannoma, extensive surgery should be avoided. Actually, such patients tend to show a good postoperative course with no evidence of recurrence.

To evaluate the significance of murine double minute 2 (MDM2) oncoprotein in human breast cancer as a nuclear-cytoplasmic shuttling protein, an estrogen receptor (ER) alpha regulator, and a prognostic marker and to study how MDM2 is overexpressed, we investigated its status in tissue samples and examined the correlation between overexpression and MDM2 gene abnormalities, status, and clinicopathological parameters. We detected MDM2 oncoprotein in both nucleus and cytoplasm by frozen-section immunohistochemistry. There was a significant correlation between MDM2 overexpression and low-grade nuclear atypia, absence of lymph node involvement, and increased levels of ER alpha protein. Our molecular assays found no point mutations in Ser17, but there was a correlation between MDM2 overexpression and the lack of splice variant mRNAs. These results suggest that the distribution of MDM2 reflects its nuclear-cytoplasmic shuttling ability; that interaction between p53 and MDM2 for tumor progression is not enhanced by point mutations at codon 17; and that the expression of MDM2 splice variants is a reason for the lack of its overexpression. MDM2 overexpression correlates with favorable prognostic parameters. A decreased level of MDM2 will lead to a deviation from the ER alpha signaling pathway.

In the peripheral blood leukocytes (PBLs) from the carriers of the human T-lymphotropic virus type-1 (HTLV-1) or the patients with adult T-cell leukemia (ATL), nuclear factor kappaB (NF-κB)-mediated antiapoptotic signals are constitutively activated primarily by the HTLV-1-encoded oncoprotein Tax. Tax interacts with the I κB kinase regulatory subunit NEMO (NF-κB essential modulator) to activate NF-κB, and this interaction is maintained in part by a molecular chaperone, heat-shock protein 90 (HSP90), and its co-chaperone cell division cycle 37 (CDC37). The antibiotic geldanamycin (GA) inhibits HSP90's ATP binding for its proper interaction with client proteins. Administration of a novel water-soluble and less toxic GA derivative, 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride (17-DMAG), to Tax-expressing ATL-transformed cell lines, C8166 and MT4, induced significant degradation of Tax. 17-DMAG also facilitated growth arrest and cellular apoptosis to C8166 and MT4 and other ATL cell lines, although this treatment has no apparent effects on normal PBLs. 17-DMAG also downregulated Tax-mediated intracellular signals including the activation of NF-κB, activator protein 1 or HTLV-1 long terminal repeat in Tax-transfected HEK293 cells. Oral administration of 17-DMAG to ATL model mice xenografted with lymphomatous transgenic Lck-Tax (Lck proximal promoter-driven Tax transgene) cells or HTLV-1-producing tumor cells dramatically attenuated aggressive infiltration into multiple organs, inhibited de novo viral production and improved survival period. These observations identified 17-DMAG as a promising candidate for the prevention of ATL progression.

We report an unusual case of mucinous adenocarcinoma of the anus associated with a chronic anal fistula, treated successfully by abdominoperineal resection (APR). Although multiple biopsies failed to reveal any histological evidence of malignancy, cancer was diagnosed from the mucin obtained for cytology. Subsequent histological examination of the resected specimen revealed clusters of cancer cells floating in a mucous lake, suggesting that it would have been difficult to acquire the cells in a biopsy sample. Conversely, the presence of mucin lakes and globules in specimens drained from the region of perianal sepsis may have been histologically informative for diagnosis. Thus, although biopsy of the lesion is undoubtedly essential for diagnosis, it often fails to provide enough information to make a definite diagnosis of mucinous carcinoma. This case illustrates that clinicians should base their decision on whether to perform surgery on clinical manifestations, imaging findings, and cytology of mucin obtained by drainage when it is difficult to obtain malignant cells by biopsy.