[An autopsy case of ulcerative colitis with disseminated aspergillosis, complicated by brain hemorrhage].

An 80-year-old Japanese woman suffered multiple brain infarctions of unknown etiology during maintenance therapy of prednisolone and azathioprine for ulcerative colitis. Although a small cavity in the left lung spontaneously regressed, the patient suddenly died of massive brain hemorrhage due to disseminated aspergillosis, which was not identified until autopsy.

A juvenile case of pulmonary lymphangitic carcinomatosis caused by sigmoid colon cancer with a component of micropapillary carcinoma.

Micropapillary carcinoma is known to be associated with a poor prognosis and high propensity for lymphovascular invasion and lymph node metastasis. Case reports on colorectal micropapillary carcinoma are relatively rare. We report here a 26-year-old woman who had sigmoid colon cancer with a micropapillary component. We made the diagnosis of pulmonary lymphangitic carcinomatosis but could not identify the primary lesion. We gave her chemotherapy as an occult primary cancer. But her respiratory condition did not improve and she died of respiratory failure. Autopsy was performed after her death. The final diagnosis was pulmonary lymphangitic carcinomatosis and multiple lymph node metastases of sigmoid colon cancer with a component of micropapillary carcinoma.

[Bacillus cereus bacteremia in Crohn's disease with multiple ileal stricture on maintenance azathioprine therapy].

We describe a case of 36-year-old Japanese man with Crohn's disease, complicated by Bacillus cereus bacteremia on maintenance azathioprine therapy. Although anti-microbial agents were ineffective, the patient became well immediately after a partial resection of the ileum with multiple severe stenosis.

Multifocal metanephric adenoma in childhood.

Metanephric adenoma is the most commonly occurring member of the metanephric tumor family, which also includes metanephric adenofibroma and metanephric stromal tumor. According to the World Health Organization classification, however, it is not commonly multifocal. Reported herein is the case of a 9-year-old boy with multifocal metanephric adenoma. Histologically, surgical sections showed multifocal proliferation of small rounded and uniform cells with smooth nuclear contours, scant pale-staining cytoplasm, dark-staining nuclei, and inconspicuous nucleoli: the cells were arranged in sheets and acinal, ductal, glomeruloid, and papillary structures. On immunohistochemistry the tumor cells were positive for vimentin, cytokeratins (CAM5.2, AE1/AE3, and CK18), and WT1, but negative for cytokeratin 7 (CK7) and epithelial membrane antigen (EMA). The Ki-67 labeling index was <1%. In addition, cytogenetic analysis indicated a normal karyotype (46XY). Other histologically similar tumors are papillary renal cell carcinoma and nephroblastoma, and it is necessary to distinguish metanephric adenoma from those tumors because of malignancy. In contrast to those tumors, metanephric adenoma has inconspicuous nucleoli, loss of CK7 and EMA expression, and no mitotic figures. Thus, the histological and immunohistochemical features of the present case were compatible with metanephric adenoma.

Neurofibromatosis type 1-related gastrointestinal stromal tumors: a special reference to loss of heterozygosity at 14q and 22q.

PURPOSE: Multiple gastrointestinal stromal tumors (GISTs) rarely occur in patients with neurofibromatosis type 1 (NF-1). In contrast to sporadic GISTs characterized by frequent allelic losses of 1p, 14q and 22q and mutations of KIT or PDGFRA gene with the activation of the downstream RAS-MAPK pathway, the molecular pathogenetic mechanisms of NF-1-related GISTs (NF-1 GISTs) remain unclear. METHODS: Thirty-one GISTs and two foci of Cajal cell hyperplasia (CCH) were obtained from five patients with NF-1. Phospho-MAPK p44/42 expression was examined by immunohistochemical stain. KIT and PDGFRA mutations were analyzed by PCR and direct sequencing methods. Loss of heterozygosity (LOH) was analyzed by PCR-based method with microsatellite markers on 14q and 22q. RESULTS: Immunohistochemical expression of phospho-MAPK p44/42 was frequently found in NF-1 GISTs (23/25 cases, 92%). Neither the KIT nor PDGFRA mutation was detected in 25 NF-1 GISTs and 2 CCH. Among the informative cases, LOH was seen at 14q and 22q in 7/8 (87.5%) and 5/12 (41.7%) NF-1 GISTs, respectively. Such LOH was not detected in CCH, whereas it was detected in small GIST less than 1 cm in diameter. CONCLUSIONS: Our results support that KIT and PDGFRA mutations are very rare events in NF-1 GIST. Rather, activation of the Ras-MAPK pathway associated with the inactivation of the NF1 gene may play an important role in the cell proliferation of NF-1 GIST. Additionally, LOH at 14q and 22q may contribute to the relatively early phase of tumor development of NF-1 GIST.

Correlation between beta-catenin widespread nuclear expression and matrix metalloproteinase-7 overexpression in sporadic desmoid tumors.

Desmoid tumors (desmoid-type fibromatoses) are locally aggressive soft tissue tumors associated with the Wnt/beta-catenin signaling pathway (APC-beta-catenin-Tcf pathway). Matrix metalloproteinase-7, which is one of the target genes of the Wnt/beta-catenin signaling pathway, has been reported to play an important role in tumor progression. We examined the immunohistochemical expression of beta-catenin and matrix metalloproteinase-7 in 72 samples (63 primary and 9 recurrent samples, 63 patients) of sporadic desmoid tumors without familial adenomatous polyposis, and the genetic alteration of the beta-catenin gene in 33 frozen materials (22 primary and 11 recurrent samples, 22 patients). We further examined messenger RNA expression of matrix metalloproteinase 7 by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and compared the results with those of normal skeletal muscles. Immunohistochemically, there was a statistically significant correlation between widespread nuclear expression of beta-catenin and overexpression of matrix metalloproteinase-7 (P < .01 in extra-abdominal desmoid, Fisher test). There were 7 missense point mutations in the 22 primary frozen samples (32%). In the beta-catenin mutated group, matrix metalloproteinase-7 messenger RNA expression was significantly higher than that of the beta-catenin wild-type group (P = .0018, Mann-Whitney U test). Our results suggest that the matrix metalloproteinase-7 gene may be up-regulated by mutated or continuously elevated beta-catenin protein and that the matrix metalloproteinase-7 gene may also be targeted in the Wnt/beta-catenin signaling pathway in sporadic desmoid tumors.

[Case of gastric cancer with isolated brain metastasis successfully managed by gamma knife radiotherapy and chemotherapy].

We describe a 51-year-old man case of a huge gastric cancer with an initial presentation of isolated brain metastasis. The patient was successfully managed by gamma knife radiotherapy, followed by chemotherapy using 5-fluorouracil and cisplatin. He has continued oral administration of TS-1 on an outpatient basis with disease free survival for more than one year.

Clinicopathological and immunohistochemical study of extrapleural and pleural solitary fibrous tumors: A special emphasis on the comparison between ordinary tumors and their malignant variant.

Solitary fibrous tumors (SFTs) are rare spindle cell tumors that usually arise in the pleura, although they also occur in extrapleural sites. SFTs usually have a favorable clinical course; however, a small number of metastasizing cases have been reported. We evaluated the detailed clinicopathological findings of 20 extrapleural and 16 pleural SFTs. Among them, 6 cases of the histologically malignant variant (4 extrapleural and 2 pleural tumors) were identified. According to the follow-up data, none of the cases, including the 6 malignant tumors, developed metastases in this series. There were no significant differences in the histologic findings between the extrapleural and pleural SFTs. Tumor necrosis was frequently associated with the malignant variant. Immunohistochemically, malignant SFTs revealed more frequent p53 expression (4/6) compared with ordinary SFTs (2/30) (P=0.0027). The MIB-1 labeling index (LI) was significantly higher in malignant SFTs (mean 13.48) than in ordinary SFTs (mean 7.27) (P=0.0023). Our results indicate that tumor necrosis, p53 expression and a high MIB-1 LI are additional parameters of the malignant variant of SFTs, although they do not necessarily have predictive value for biological behavior. Further studies are required to find reliable molecular biomarkers for predicting the clinical outcome of patients with this unique tumor.

[Crohn's ileocolitis with initially superimposed cytomegalovirus infection, resembling intestinal tuberculosis].

We describe a case of 41-year-old Japanese man with Crohn's ileocolitis and cytomegalovirus infection, confirmed by histology of ileal ulcers. Although his colonoscopic and radiological features resembled those of intestinal tuberculosis, granulomas of typical Crohn's disease were evident on histology of biopsy specimens taken from the duodenum and colon. The lesions remain unchanged even after 1.5 years by oral administration of salazosulphapyridine 3g daily.

An autopsy case of Merkel cell carcinoma presenting aggressive intraabdominal metastasis and duodenal obstruction.

A 85-year-old Japanese woman was urgently admitted to our hospital complaining of vomiting 20 months after the initial diagnosis of Merkel cell carcinoma on the right eyelid. The patient died of a huge intra-abdominal mass with complete obstruction of the distal duodenum two months later. On autopsy, the mass measuring 18 x 12 x 5 cm in size was histologically diagnosed as metastatic Merkel cell carcinoma and directly invaded the stomach, pancreas, and distal duodenum.

Late-onset life threatening hemorrhage of omeprazole-resistant duodenal ulcer managed by interventional radiology: report of a case.

A 67-year-old diabetic man was emergently hospitalized in our department because of a huge duodenal ulcer without visible vessels. Despite of intravenous administration of 40 mg omeprazole and fasting with intravenous nutritional support, endoscopically unmanageable massive bleeding occurred on the 8th hospital day. Emergent angiography showed extravasation of contrast media from a duodenal branch of the proper hepatic artery, and superselective arterial embolization was successfully achieved. The patient recovered from the hemorrhagic shock and underwent subsequent successful surgery. Analysis of CYP2C19 enzyme genotype indicated the patient was a homozygous extensive metabolizer, considered a poor responder for omeprazole treatment.