A case of Mikulicz's disease complicated by malignant lymphoma: a postmortem histopathological finding.

A 66-year-old Japanese man with an 11-year history of Mikulicz's disease (MD) received continuous corticosteroid administration. At age 58, a left renal pelvic mass was identified and diagnosed as an IgG4-related inflammatory pseudotumor. The patient underwent an operation to remove the tumor. Subsequently, he contracted repeated pulmonary infections and eventually died of severe gastrointestinal bleeding. Autopsy revealed systemic lymph node swelling and infiltration in some organs, and diffuse large B-cell lymphoma (DLBCL) was diagnosed. These findings suggest that an IgG4-related disease can be causally related to the development of malignant lymphoma through the occurrence of mucosa-associated lymphoid tissue lymphoma.

Primary gastric diffuse large B-cell lymphoma with orbital involvement: diagnostic usefulness of 18F-fluorodeoxyglucose positron emission tomography.

A 38-year-old man presented to our hospital with abdominal pain and melena. Gastrointestinal endoscopy revealed a large gastric ulcer, and the pathological diagnosis of diffuse large B-cell lymphoma (DLBCL) was made based on immunohistochemical findings. Left diplopia developed soon after commencement of chemotherapy. Despite normal findings from head MRI, orbital involvement in DLBCL was detected with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). The patient was treated with salvage chemotherapy with success. Treatment analysis using FDG-PET for patients with DLBCL, especially for those with clinical symptoms and negative findings on conventional modalities, may be useful for assessing disease status and adjusting treatments.

Usefulness of double balloon enteroscopy and video capsule endoscopy for the diagnosis and management of primary follicular lymphoma of the gastrointestinal tract in its early stages.

AIM: The aim of this study is to evaluate the usefulness of double balloon enteroscopy (DBE) and video capsule endoscopy (VCE) in patients with primary follicular lymphoma (FL) of the gastrointestinal (GI) tract. Furthermore, we estimate the effectiveness of chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) including rituximab for them. METHODS: Thirteen consecutive patients who were diagnosed of having FL in the duodenum between July 2005 and September 2008 were studied. All patients were given the conventional staging examinations, including total enteroscopy using DBE and/or VCE procedures. Chemotherapy was performed after written informed consent. Response assessment was performed every 6-12 months. The median follow-up period was 30.2 months. RESULTS: FL was diagnosed in each patient as low grade (grade 1, n = 7; 2, n = 6) and, in all but 4 patients, localized lymphoma (stage I, n = 8; II(1), n = 1; II(2), n = 4). DBE revealed multifocal lesions in the jejunum in 10 of the patients, and in the ileum in 6. VCE showed similar findings in the jejunum in the recent 2 patients. Eleven of 13 patients finally received chemotherapy, and all of them achieved complete regression. They showed no evidence of recurrence after that. CONCLUSION: Total examination of the small intestine using DBE should be performed before treatment to choose a suitable treatment procedure for primary FL of the GI tract. On the other hand, VCE is useful for screening and following the small intestine in the patients with it. Chemotherapy is effective to achieve complete regression of primary FL of the GI tract.

Altered expression of CDX-2, PDX-1 and mucin core proteins in "Ulcer-associated cell lineage (UACL)" in Crohn's disease.

The ulcer-associated cell lineage (UACL) induced at the site of ileac chronic ulceration in Crohn's disease has been reported to show histological differentiation resembling gastric pyloric mucosa. To clarify the significance of homeobox gene-encoded transcription factors in the formation of the UACL in Crohn's disease, we investigated the immunohistochemical expression of gastrointestinal mucins (MUC5AC for gastric surface mucous cells; MUC6 for gastric gland mucous cells, and MUC2 for intestinal goblet cells) and homeobox gene-encoded transcription factors (CDX-2 for intestinal mucosa and PDX-1 for pyloric mucosa) in the UACL. The analysis was undertaken on ileal mucosa obtained from ileal resections performed in 19 patients with active Crohn's disease of the small bowel. The UACL was observed in nine patients. In the UACL, expression of mucous cells with a foveolar-structure showed immunoreactivity to MUC5AC, and the mucous cells with a glandular structure showed immunoreactivity to MUC6, and the expression of MUC2 was decreased. In addition, we detected the decreased expression of CDX-2 along with the increased expression of PDX-1 in the UACL. The UACL showed histological differentiation simulating gastric pylori mucosa. The down-regulation of CDX-2 and the up-regulation of PDX-1 could be an important mechanism in the induction of the UACL.

Ultrastructure of Helicobacter pylori in human gastric mucosa and H. pylori-infected human gastric mucosa using transmission electron microscopy and the high-pressure freezing-freeze substitution technique.

BACKGROUND: Conventional ultrastructural analyses of Helicobacter pylori and H. pylori-infected gastric mucosa by transmission electron microscopy (TEM) have limitations because of structural artifacts introduced during fixation. METHODS: We used high-pressure freezing (HPF) followed by freeze substitution for TEM to investigate the ultrastructure of H. pylori and H. pylori-infected gastric mucosa. For HPF-freeze substitution, human gastric biopsy specimens were placed in the HPF instrument at a pressure of approximately 2,000 atm at the temperature of liquid nitrogen. Specimens were then transferred to an instrument for freeze substitution. Specimens were first placed in acetone containing 2% OsO4 at -85 degrees C. The temperature was increased to -3 degrees C, followed by embedding in Quetol 812. Ultrathin sections were double-stained by uranium acetate/lead nitrate. HPF and conventionally prepared samples were examined by TEM. RESULTS: The H. pylori envelope was clearly seen to consist of an outer membrane, periplasmic space, and plasma membrane. The periplasmic space was filled with electron-dense materials. A peptidoglycan layer was only occasionally visible. A thick, very fine filamentous or reticular fringe corresponding to the bacterial glycocalyx was seen surrounding the H. pylori cells. At the adhesion loci of H. pylori to gastric epithelial cells, H. pylori was connected to the epithelial cells by very fine, thickly arranged filaments or more closely, with a contact zone. The epithelial cells showed indentations or pedestals. CONCLUSIONS: The well-developed, thick bacterial glycocalyx of H. pylori appears to strongly interact with external cellular components and may play an important role in the adhesion of H. pylori to epithelial cells.

Regulation of the ASC expression in response to LPS stimulation is related to IL-8 secretion in the human intestinal mucosa.

Expression of the caspase-activating adaptor ASC was reported to be associated with the production of IL-8, a primary mediator of mucosal inflammation, in vitro. However, the significance of the ASC-mediated IL-8 production in primary tissues has remained poorly understood. Primary intestinal mucosa isolated from surgically resected ileum or colon was incubated with several concentrations of LPS or left untreated. ASC expression was up-regulated at 2 h after stimulation with low doses of LPS (1-10 ng/ml), and was associated with IL-8 secretion, and then was down-regulated later. In contrast, ASC expression remained at the basal level in mucosal tissue treated with a high dose of LPS (1000 ng/ml). Interestingly, in mucosa from several cases of Crohn's disease, ASC was highly expressed without stimulation, and IL-8 was stably secreted with no regulation by LPS. These findings revealed that ASC expression correlates with IL-8 secretion and may play an important role in maintaining mucosal homeostasis.