Natural history, clinicopathologic classification and prognosis of gastric ECL cell tumors.

A series of 50 gastric endocrine tumors classified according to Rindi et al. [1] comprised 12 small cell neuroendocrine carcinomas (NEC) and 38 ECL cell carcinoids, of which 22 associated with type A chronic atrophic gastritis (A-CAG), eight with hypertrophic gastropathy due to combined Multiple Endocrine Neoplasia and Zollinger/Ellison syndrome (MEN/ZES), and eight sporadic. Variables found to predict tumor malignancy were: size > 2 cm, > 2 mitoses and > 130 Ki67 positive cells/10 high power fields (HPF), grade 2 or 3 histology, angioinvasion, p53 protein nuclear accumulation, and the presence of a single tumor. None of these factors increased significantly the predicting ability of tumor classification itself, although grade 2 + 3 shows 100 percent negative predictive value and Ki67 and angioinvasion 100 percent positive predictive value. When the mostly non-malignant A-CAG and MEN-ZES tumors were analysed against the mostly malignant sporadic and NEC tumors, a positive predictive value of 90 percent and a negative predictive value of 93 percent was obtained. Investigation of a larger tumor series is under way with the aim to develop an optimal model for prognostic evaluation of gastric endocrine tumors

The significance of duodenal mucosal atrophy in patients with common variable immunodeficiency: a clinical and histopathological study

Gastrointestinal manifestations and villous atrophy can be seen in patients with common variable immunodeficiency (CVID). In some patients, infectious agents may be responsible, whereas in Others, celiac diseases (CD) may be the cause. In this study, we investigate the causes and th ehistopathologic festures seen in patients with CVID. Eleven patients with CVID and villous atrophy underwent duodenal biopsies, human leukocyte antien (HLA) typing, and testing for all celiac antibodies. Fifteen patients with CVID and normal villi and 6 patients with CD but without CVID served as controls. Histologic response to a gluten-free diet (GFD) allowed a diagnosis of CD in 3 of 11 patients. In the remaining 8, the lack of a histologic response to a GFD or HLA typing excluded CD. Celiac antibodies gave conflicting results and were of no help. Polymorphonuclear infiltrates and lesions like graft-versus-host disease are seen more ofter in flat mucos aunresponsive to a GFD. However, the specificity of these findings remains to be determined and response to a GFD remains the only diagnostic criteria for CD in these patients. Villous atrophy was gluten-sensitive in 3 of 11 patients with CVID. It was not related to gluten-responsive CD in most patients

Increase in chromogranin A- and serotonin-positive cells in pouch mucosa of patients with ulcerative colitis undergoing proctocolectomy

Background: Inflammatory bowel disease (IBD) is associated with neuroendocrine cell hyperplasia. Aims: We investigated neuroendocrine cells in J-pouches of patients with ulcerative colitis undergoing restorative proctocolectomy and ileal pouch-anal anastomosis. Methods: Sections from pouch biopsies of 17 patients and ileal biopsies of 17 active IBD patients and 16 controls were processed by immunohistochemistry for chromogranin A (CgA) and serotonin. Mucosal tryptophan hydroxylase (TpH)-1 and serotonin-selective reuptake transporter (SERT) transcripts were measured by quantitative RT-PCR. TpH-1 and SERT transcripts were detected in pouch biopsies cultured with infliximab or its isotype control, while interleukin (IL)-6 and IL-8 were measured in biopsy supernatants. Results: A significant increase in CgA-positive cells and serotonin-positive cells was observed in both pouch and IBD ileum compared to control ileum. Significantly raised transcripts of TpH-1, but not SERT, were found in IBD ileum in comparison to control ileum, with no significant difference between pouch and IBD ileum. Infliximab had no influence on ex vivo pouch expression of TpH-1 and SERT, nor on the production of IL-6 and IL-8. Conclusion: We here demonstrated neuroendocrine cell hyperplasia in pouch mucosa. Further studies are needed to clarify the pathophysiological implication of this finding

Prognostic relevance and putative histogenetic role of cytokeratin 7 and MUC5AC expression in Crohn\u2019s disease-associated small bowel carcinoma

Most Crohn\u2019s disease-associated small bowel carcinomas (CrD-SBCs) are diagnosed in advanced stage and have poor prognosis. To improve diagnosis and therapy, a better knowledge of tumour precancerous lesions, histotypes and prognostic factors is needed. We investigated histologically and immunohistochemically 52 CrD-SBCs and 51 small bowel carcinomas unrelated to inflammatory disease, together with their tumour-associated mucosa, looking for Crohn-selective changes. Histologic patterns and phenotypic markers potentially predictive of CrD-SBC histogenesis and prognosis were analysed. Cytokeratin 7 or MUC5AC-positive metaplastic changes were found in about half of investigated CrD-SBCs, significantly more frequently than in CrD-unrelated SBCs. They correlated with metaplastic changes of their associated mucosa, while being absent in normal ileal mucosa. Histologic patterns suggestive for progression of some cytokeratin 7 and/or MUC5AC-positive metaplastic lesions into cancer of the same phenotype were also observed. Patient survival analyses showed that tumour cytokeratin 7 or MUC5AC expression and non-cohesive histotype were adverse prognostic factors at univariable analysis, while cytokeratin 7 and non-cohesive histotype were also found to predict worse survival in stage- and age-inclusive multivariable analyses. Besides conventional dysplasia, hyperplasia-like non-conventional lesions were observed in CrD-SBC-associated mucosa, with patterns suggestive for a histogenetic link with adjacent cancer. In conclusion the cytokeratin 7 and/or MUC5AC-positive metaplastic foci and the non-conventional growths may have a role in cancer histogenesis, while tumour cytokeratin 7 and non-cohesive histotype may also predict poor patient survival. Present findings are worth being considered in future prospective histogenetic and clinical studies

Small bowel carcinomas in celiac or Crohn's disease: Distinctive histophenotypic, molecular and histogenetic patterns

Non-familial small bowel carcinomas are relatively rare and have a poor prognosis. Two small bowel carcinoma subsets may arise in distinct immune-inflammatory diseases (celiac disease and Crohn's disease) and have been recently suggested to differ in prognosis, celiac disease-associated carcinoma cases showing a better outcome, possibly due to their higher DNA microsatellite instability and tumor-infiltrating T lymphocytes. In this study, we investigated the histological structure (glandular vs diffuse/poorly cohesive, mixed or solid), cell phenotype (intestinal vs gastric/pancreatobiliary duct type) and Wnt signaling activation (β-catenin and/or SOX-9 nuclear expression) in a series of 26 celiac disease-associated small bowel carcinoma, 25 Crohn's disease-associated small bowel carcinoma and 25 sporadic small bowel carcinoma cases, searching for new prognostic parameters. In addition, non-tumor mucosa of celiac and Crohn's disease patients was investigated for epithelial precursor changes (hyperplastic, metaplastic or dysplastic) to help clarify carcinoma histogenesis. When compared with non-glandular structure and non-intestinal phenotype, both glandular structure and intestinal phenotype were associated with a more favorable outcome at univariable or stage- and microsatellite instability/tumor-infiltrating lymphocyte-inclusive multivariable analysis. The prognostic power of histological structure was independent of the clinical groups while the non-intestinal phenotype, associated with poor outcome, was dominant among Crohn's disease-associated carcinoma. Both nuclear β-catenin and SOX-9 were preferably expressed among celiac disease-associated carcinomas; however, they were devoid, per se, of prognostic value. We obtained findings supporting an origin of celiac disease-associated carcinoma in SOX-9-positive immature hyperplastic crypts, partly through flat β-catenin-positive dysplasia, and of Crohn's disease-associated carcinoma in a metaplastic (gastric and/or pancreatobiliary-type) mucosa, often through dysplastic polypoid growths of metaplastic phenotype. In conclusion, despite their common origin in a chronically inflamed mucosa, celiac disease-associated and Crohn's disease-associated small bowel carcinomas differ substantially in histological structure, phenotype, microsatellite instability/tumor-infiltrating lymphocyte status, Wnt pathway activation, mucosal precursor lesions and prognosis

Nasal paraganglioma. A case report

Nonchromaffin paragangliomas or chemodectomas arise in paraganglia distributed in various parts of the body. The jugular bulb, the vagal body and the bifurcation of the carotid artery are the most common sites of origin of paraganglioma in the head and neck region. Paragangliomas in the nose and paranasal sinuses are extremely rare and very few cases of definite paraganglioma arising primarily in the nose or paranasal sinuses have been reported. The paraganglioma is a slow-growing tumour that produces nasal obstruction, profuse epistaxis and facial swelling. Complete excision of the glomus tumour is normally curative. We report a case of nasal paraganglioma and discuss the diagnosis and therapy