Adult autoimmune enteropathy in autoimmune hepatitis patient. Case report and literature review.

Autoimmune enteropathy (AIE) is a rare disease characterized by prolonged diarrhea, vomiting and weight loss; although it is mainly a rare pediatric disease, over the years a number of adults have also been found to be affected. In this study, we present a case report of a 73-year-old woman with a history of autoimmune hepatitis, antinuclear (ANA) and positive anti-enterocyte antibodies (AEA), who has suffered two months of intractable diarrhea, nausea, anorexia and severe weight loss. The histological examination of the endoscopic duodenal mucosa biopsies revealed severe shortening and flattening of the villi, resulting in mucosal atrophy. The immunohistochemical study revealed a polymorphic lymphoid population, exhibiting a B cell (CD20+) phenotype in follicles and a T cell phenotype (CD3+) in the diffuse component within the lamina propria. Our patient had a complete recovery after two weeks of taking prednisone and following a gluten-rich diet. To our knowledge this is the first case of autoimmune enteropathy in adults with ANA and AEA 7 years after a diagnosis of autoimmune hepatitis. To date, the patient is still in clinical remission on a low dose of orally administered predinisone without any additional immunosuppression.

PATZ1 expression correlates positively with BAX and negatively with BCL6 and survival in human diffuse large B cell lymphomas.

Non-Hodgkin lymphomas (NHLs) include a heterogeneous group of diseases, which differ in both cellular origin and clinical behavior. Among the aggressive malignancies of this group, the diffuse large B-cell lymphomas (DLBCLs) are the most frequently observed. They are themselves clinically and molecularly heterogeneous and have been further sub-divided in three sub-types according to different cell of origin, mechanisms of oncogenesis and clinical outcome. Among them, the germinal center B-cell-like (GCB) derives from the germinal center and expresses the BCL6 oncogene. We have previously shown that Patz1-knockout mice develop B-cell neoplasias, suggesting a tumor suppressor role for PATZ1 in human NHLs. Here, by immunohistochemical analysis of a tissue-microarray including 170 NHLs, we found that PATZ1 nuclear expression is down-regulated in follicular lymphomas and DLBCLs. Moreover, consistent with our previous results showing a PATZ1-dependent regulation of BCL6 and BAX transcription, we show that low PATZ1 nuclear expression significantly correlates with high BCL6 expression, mainly in DLBCLs, and with low BAX expression, also considering separately follicular lymphomas and DLBCLs. Finally, by analyzing overall and progression-free survival in DLBCL patients that underwent rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, low levels of PATZ1 were significantly associated to a worst outcome and demonstrated an independent prognostic factor in multivariate analysis, including known prognostic factors of DLBCL, IPI score and cell of origin (GCB/non-GCB). Therefore, we propose PATZ1 as a new prognostic marker of DLBCLs, which may act as a tumor suppressor by enhancing apoptosis through inhibiting and enhancing transcription of BCL6 and BAX, respectively.

High CD20+ background cells predict a favorable outcome in classical Hodgkin lymphoma and antagonize CD68+ macrophages.

We studied by immunohistochemistry the background CD20 + cells in 131 cases of classical Hodgkin lymphoma (cHL). High CD20 + dispersed cells (CD20BG) showed a significant correlation with longer overall survival (OS) and a trend toward improved progression-free survival (PFS). At multivariate analysis high CD20BG was also an independent prognostic factor of improved PFS and OS. The prognostic role of CD20BG seems to be opposite with respect to tumor associated macrophages (TAMs) we studied previously in most cases of the series. We scored patients on the basis of the respective CD20BG and TAM count and found that the combination of low CD20BG and high TAMs was related to a significantly reduced PFS and OS at univariate and multivariate analysis. Microenvironment CD20 + cells seem to play a favorable prognostic role in cHL. Depletion of CD20 + cells together with an increase of TAMs identifies a group of patients with high-risk disease.

Prognostic role of tumor-associated macrophages and angiogenesis in classical Hodgkin lymphoma.

We studied by immunohistochemistry CD68 + tumor-associated macrophages (TAMs) and angiogenesis in 121 consecutive cases of uniformly treated classical Hodgkin lymphoma (cHL). High TAM count showed a significant correlation with age ≥ 45, mixed cellularity subtype and high ß2-microglobulin level. Vessel density (VD) was unrelated to clinicopathological features, while a significant correlation was found between TAM count and VD. Patients with high TAMs showed a trend toward reduced progression-free survival and significantly shorter overall survival (OS). No correlation was found between VD and survival. At multivariate analysis, bulky disease was an independent predictor of reduced progression-free survival, while independent adverse prognostic factors for OS were male sex, age ≥ 45, advanced stage and bulky disease. High TAM count results in an adverse overall outcome in cHL and is significantly correlated to VD. Since VD has no prognostic relevance, the adverse effect of TAMs is presumably unrelated to angiogenesis.