Ioannis Venizelos

An unusual case of posttransplant peritoneal primary effusion lymphoma with T-cell phenotype in a HIV-negative female, not associated with HHV-8

Primary effusion lymphoma (PEL) is a recently individualized form of non-Hodgkin’s lymphoma (WHO classification) that mainly develops in HIV infected males, more frequently in homosexuals and advanced stages of the disease (total CD4+ lymphocyte count below 100–200/μL). Occasionally, it appears in other immunodepressive states (such as solid organs transplant period) and even, although very rarely, in immunocompetent patients. From a pathogenetic point of view, PEL has been related to Kaposi’s sarcoma associated herpes virus (also named human herpesvirus 8, HHV-8), an etiological factor of Kaposi’s sarcoma. The relative infrequency of this disease, the absence of wide casuistics allowing a better characterization, and its unfavorable outcome support the need of a deeper knowledge. We present here the clinical-biological findings of a patient, HIV -seronegative, who was diagnosed with peritoneal PEL of T-cell origin, and not HHV-8-associated, five years after renal transplantation.

Induction of hepatic haematopoiesis with fibronectin expression by EMT stromal cells during the second trimester of development

In an initial period of vertebrate phylogeny (bone marrow-less vertebrates), lymphohaematopoiesis takes place in numerous organs containing a suitable microenvironment. Among other organs (i.e., gonads, kidney and spleen), the liver is apparently the most appropriate site for homing and differentiation of haematopoietic cell precursors. Interaction between haematopoietic cells and stromal cells is important for regulation of haematopoiesis. Numerous soluble and membrane-bound factors directly regulating haematopoiesis have been documented, but little is known about the effect of the foetal hepatic epithelial-to-mesenchymal transition (EMT) stromal cells’ activity and their product-fibronectin, on foetal hepatic haematopoiesis. The binding of late-stage erythroid cells to FN has been well characterised and is believed to be critical for the terminal stages of erythroid differentiation. The intention of this article is to provide a quantitative overview of FN, produced by hepatic EMT stromal cells, in foetal hepatic haematopoiesis during the first and second trimester of development. Paraffin-embedded specimens from the liver of 30 human embryos in the first and second trimesters of gestation were investigated by conventional histology and immunohistology for the presence of FN and specific haematopoietic cell types. The staining intensity, and localisation of FN and haematopoietic markers in sequential sections were examined. Furthermore, double immunohistochemical staining was performed to assess simultaneous detection of FN and haematopoietic markers. FN was expressed in the EMT stromal cells of the hepatic portal triads more strongly during the second trimester than the first. Furthermore, an intense immunostaining for haematopoietic lineages, and especially for erythropoiesis, was observed in the second trimester compared to the first. The results of the double immunostaining disclosed an intimate co-expression of the FN and CD haematopoietic markers. Foetal hepatic EMT stromal cells provide a unique microenvironment that supports the emergence, expansion and maintenance of human foetal haematopoietic development during the mid-gestational stage. FN produced by the EMT stromal cells follows a time course parallel to that of haematopoiesis. We suggest that in foetal liver, phenotypic modifications of EMT stromal cells expressing FN concerning the cell adhesion capacity of the protein are associated with proliferation and differentiation of specific haematopoietic cell lineages during the second trimester of gestation, probably reflecting the increasing demand of the growing foetus for mature erythroid and myeloid cells.

Primary MALT lymphomas of the stomach: A pathological study of 18 cases

AIM It is doubtful that whoever is suffering from gastric malt lymphoma will escape from the disease, if treated with medication against helicobacter pylori. MATERIAL AND METHODS A cohort of 18 patients was analysed. Ten hosts had primary gastric malt lymphoma and were treated with gastric resection as the initial therapy. Eight hosts received antibiotics against Helicobacter pylori as the initial treatment. In all 18 patients Helicobacter pylori status, endoscopic findings and pathology features were evaluated. Immunohistochemistry was performed to assess the bcl-2 and p53 status. RESULTS Patients with low grade malt lymphoma: a) were Helicobacter pylori positive (5 of 5); b) had a superficial lesion (5 of 5); c) had no lymph node involvement (5 of 5); and d) were downstaged by comparison to patients with high grade tumor. Bcl-2 was positive in 4 of 5 low grade tumors, and p53 was positive in 12 of 13 high grade ones. Investigation of patients with 5-year follow up (n = 18) revealed that all but one low-grade tumors remained superficial with no progression. These tumors were bcl-2+/p53-, and the one with a bcl-2+/p53+ immunophenotype progressed to an ulcerated low-grade tumor after disappearance of Helicobacter pylori. Complete regression was found in 6 of 8 patients from the non surgically treated group (n = 8) after Helicobacter pylori eradication. These tumors were superficial/low grade/node negative/bcl-2+/p53 inconclusive (n = 2), superficial/low grade/node negative/bcl-2+/p53- (n = 2), and ulcerative/high grade/node negative/bcl-2+/p53- (n = 2). The two persistent tumors were ulcerative/high grade/node negative/bcl-2+/p53+. CONCLUSION Gastric malt lymphoma Helicobacter pylori+/superficial/low grade/bcl-2+/p53- will disappear after Helicobacter pylori eradication.

Normal development of fetal hepatic haematopoiesis during the second trimester of gestation is upregulated by fibronectin expression in the stromal cells of the portal triads

OBJECTIVE in midtrimester fetuses the principal site of hematopoiesis is the liver. In hematopoietic organs, stromal cells such as fibroblasts, epithelial cells, and macrophage-like cells develop networks to maintain hematopoiesis, i.e. hematopoietic stem cell self-renewal, proliferation, and growth, by interaction with hematopoietic progenitor cells. ECM glycoproteins produced by the stromal cells are known to play a critical role in the regulation of cell growth and differentiation. Numerous soluble and membrane-bound factors directly regulating haematopoiesis have been documented, but little is known about fetal hepatic stromal cell activity and stromal extracellular matrix protein-fibronectin, on fetal hepatic haematopoiesis. The binding of late stage erythroid cells to fibronectin has been well characterized and is believed to be critical for the terminal stages of erythroid differentiation. The intention of this article is to determine the role of fibronectin in fetal hepatic hematopoietic proliferation and differentiation in different stages of development. MATERIAL AND METHOD we examined and compared the immunohistochemical expression of fibronectin in the hepatic stromal portal fields in the 1st, 2nd, and 3rd trimester of gestation respectively, in relation to the appearance of CD34 progenitor hematopoietic, stromal progenitor and vascular endothelial positive cells. RESULTS our results demonstrated a quantitative difference in the second trimester of gestation concerning the expression of fibronectin in the connective tissue stroma of the hepatic portal fields over the equivalent expression of the protein in the first (p < 0.0001, t-test) and third trimester (p < 0.0001, t-test). Similar changes in the above period were found concerning the expression of CD34 during the second trimester of gestation, over the first (p < 0.0001, t-test) and third trimesters (p < 0.0001, t-test), suggesting a direct involvement of fibronectin in the sustaining of hematopoietic activity. CONCLUSIONS our data provide evidence that an ECM glycoprotein component, fibronectin, plays a relevant role in hematopoiesis through interaction between stromal cells and hematopoietic progenitor cells.

Primary combined carcinoid and adenocarcinoma of the ileum associated with transitional carcinoma of the bladder. Single case report

Composite neoplasms, carcinoid and adenocarcinoma have been reported to occur in several parts of the body, including the stomach, ampulla of Vater, large bowel, lung, and urinary bladder. Here we report a case of a 74-year-old male with a composite carcinoid-adenocarcinoma of the ileum associated with a transitional cell carcinoma of the bladder. The microscopical examination of the composite tumor showed an admixture of typical carcinoid tumor and moderately a differentiated adenocarcinoma. Immunohistochemically, the two components showed clear-cut differentiations. A review of the literature revealed that this is the first reported case of composite carcinoid-adenocarcinoma of the ileum associated with transitional cell carcinoma of the urinary bladder.