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The abnormal expression of gastric M1/MUC5AC mucin in precancerous lesions and colon cancer evidenced by immunohistochemistry led us to check for its presence in the mucus obtained directly from patients undergoing surgery for cancerous (adenocarcinoma) or inflammatory (diverticulitis or ulcerative colitis) diseases. In parallel, the authors quantified aberrant crypt foci (ACF) and their immunolabelling by M1/MUC5AC in mucosae of cancer and diverticulitis patients. Immuno-Radio-Metric Assay of M1/MUC5AC mucin developed by the authors was used to detect M1/MUC5AC mucin in the colonic mucus scraped from surgical specimens. M1/MUC5AC mucin was detected in the mucus of 51/69 (74%) patients with colon adenocarcinoma, versus 7/27 (26%) patients with diverticulitis (threshold: 30 units of M1 mucin per mg protein, area under ROC curve: 0.80). M1/MUC5AC was present in significantly (p < 0.001) larger amounts in the mucus of cancer versus diverticulitis patients. All (10/10) patients with ulcerative colitis tested showed levels above the threshold and their mucosae were strongly labelled with the anti-M1/MUC5AC antibody by immunohistochemistry. Patients with cancer exhibited 3 fold more ACF than those with diverticulitis, but no significant difference was observed in the mean size and M1/MUC5AC expression pattern of ACF between these two groups. The expression of M1/MUC5AC was in correlation with their size. In macroscopically normal mucosa, ACF were the most important source of M1/MUC5AC mucin. Testing of M1/MUC5AC can enhance the detection of precancerous lesions and colon cancer.

For making medical decisions, healthcare professionals require that all necessary information is both correct and easily available. We address the issue of integrating anatomical pathology department information into the electronic healthcare enterprise. The pathology workflow from order to report, including specimen processing and image acquisition was modelled. An integration profile - pathology general workflow- was created in the framework of the Integrating the Healthcare Enterprise (IHE). This Integration Profile relies on 8 transactions based on HL7 or DICOM standards. An important issue was to define information entities (order, imaging study and report) and real-world objects (specimen, tissue sample, slide, etc.). Joint efforts between IHE and DICOM WG26 has resulted in a proposed common model for "specimen" usable for both HL7 and DICOM transactions related to anatomic pathology.

Angioimmunoblastic T-cell lymphoma (AITL) represents a distinct entity among peripheral T-cell lymphomas (PTCLs). The cellular origin of AITL remains unknown, although a possible derivation from follicular helper T cells (TFH) has been suggested based on the CD4/Bcl-6 phenotype. It has been recently shown that expression of CXCL13, a chemokine critically involved in B-cell migration into germinal centers, is characteristic of TFH cells, as compared with other T helper subsets. We compared CXCL13 expression in 29 AITLs, 20 PTCLs, unspecified, 10 anaplastic large cell lymphomas (ALCL), and 4 other PTCLs. We showed that CXCL13 is expressed by AITL (29 of 29, 100%) and a subset of PTCL, unspecified (6 of 20, 30%), which all showed borderline features with AITL, but in only 1 of 10 (10%) ALCLs, and 0 of 4 other PTCLs. Two-color immunostainings further showed that CXCL13 was found in the cytoplasm of atypical CD5-positive T cells that expressed CD10. We conclude that CXCL13 expression is a common characteristic of AITL, which can help to delineate the morphologic spectrum of the disease, and further supports its derivation from TFH cells. CXCL13 expression may also provide an additional useful tool for the diagnosis of AITL.

Virtual endoscopy is a new method for studying the colon; it consists in acquisition of CT and MR images and to elaborate them with a workstation, to create endoluminal vision as like as traditional colonscopy, permitting the complete exploration of colonic lumen, also with stenotic tumors. The analysis of the differences between CT and MR colography shows like these two techniques present both advantages and disadvantages, such as the impossibility to perform MR in patients with pace-maker or in claustrophobic patients and the impossibility to perform CT with iodated agents in patients with renal failure or with a story of adverse reactions. The increased use of these techniques is due to the high sensitivity of last-generation CT and MR machine, to the increased spatial resolution, to specific softwares for digital cleaning of colon, to the introduction of high-end workstations and to the possibility of computed assisted diagnosis (CAD). So, it is desiderable that the increasing spread of multidetector CT devices and the future technical innovations, should have the effect to increase culture and experience in various diagnostic centers about CT-colography, making possible the spreading of virtual endoscopy as a screening tool.

For medical decisions, healthcare professionals need that all required information is both correct and easily available. We address the issue of integrating anatomical pathology department to the healthcare enterprise. The pathology workflow from order to report, including specimen process and image acquisition was modeled. Corresponding integration profiles were addressed by expansion of the IHE (Integrating the Healthcare Enterprise) initiative. Implementation using respectively DICOM Structured Report (SR) and DICOM Slide-Coordinate Microscopy (SM) was tested. The two main integration profiles--pathology general workflow and pathology image workflow--rely on 13 transactions based on HL7 or DICOM standard. We propose a model of the case in anatomical pathology and of other information entities (orders, image folders and reports) and real-world objects (specimen, tissue samples, slides, etc). Cases representation in XML schemas, based on DICOM specification, allows producing DICOM image files and reports to be stored into a PACS (Picture Archiving and Communication System.

CD10 expression is considered as a marker of centrofollicular-derived diffuse large B-cell lymphomas (DLBCL). The aim of our study was to determine retrospectively among 98 patients with DLBCL, enrolled in the LNH93 trial of the Groupe d'Etude des Lymphomes de l'Adulte (GELA) and homogeneously treated with high-dose cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like regimen [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone (ACVBP)], the expression of CD10 using immunohistochemistry and its correlation with morphological features and clinical parameters. Of the 98 patients studied, 33 (34%) expressed CD10. There was no correlation among clinical parameters, International Prognostic Index risk groups and CD10 expression, with the exception of lactic dehydrogenase levels, which were lower in CD10-negative cases (P=0.005). There was no significant correlation between CD10 expression and morphological subtyping of DLBCL. Indeed, centrofollicular-derived DLBCL may present with numerous immunoblasts or as an immunoblastic lymphoma. Overall survival rate and event-free survival were not significantly different according to CD10 expression (P=0.44 and P=0.34 respectively). Therefore, it appears that CD10 expression does not influence survival or event-free survival in DLBCL.

Background: Data are still conflicting on the indication of front-line autologous stem-cell transplantation (ASCT) as consolidation for aggressive lymphoma. To assess the therapeutic effect of ASCT among different aggressive lymphoma subtypes, we conducted a matched-control analysis by pooling the data from two Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials., Patients and Methods: Between October 1987 and September 1998, 330 patients received ASCT after achieving complete remission with the ACBVP induction regimen. The histological slides showed: B aggressive non-Hodgkin's lymphoma (B-NHL) in 249 patients (75%), T-NHL in 52 patients (15%) (including 23 T anaplastic) and non-classified NHL in 29 patients. The age-adjusted International Prognostic Index (aaIPI) was 2 or 3 in 66%. Patients were matched with controls from the same GELA database but treated with chemotherapy only., Results: ASCT did not benefit non-anaplastic T-NHL patients [5-year overall survival (OS) 44% (chemotherapy) versus 49% (ASCT), P=0.87; disease-free survival (DFS) 38% versus 45%, P=0.89] in comparison with B-NHL [5-year OS 77% (chemotherapy) versus 79% (ASCT), P=0.64; DFS 67% versus 72%, P=0.13]. However, for B-NHL patients with aaIPI score 2 or 3, the benefit of ASCT was significant., Conclusions: This cohort study confirms the high efficacy of front-line ASCT in responding aggressive B-NHL patients with adverse prognostic factors.

Purpose: Improved survival has been observed in aggressive non-Hodgkin's lymphoma (NHL) patients with adverse prognostic factors when autotransplantation (ASCT) was performed after complete remission. However, there is no agreement on the prognostic factors for patients treated with ASCT. We aimed to estimate the prognostic effect of clinical and biologic variables on relapse and survival rates by pooling the data from two trials., Patients and Methods: Of the patients treated in the LNH87 and LNH93 trials, 330 under age 60 years achieved complete remission after high-dose cyclophosphamide, doxorubicin, vincristine, and prednisone, and received consolidative ASCT; 16% of patients had T-cell NHL. The International Prognostic Index (IPI) score was 0 for 11%, 1 for 23%, 2 for 51%, and 3 for 15%. Univariate and Cox multivariate survival analyses were retrospectively performed on this population., Results: Overall survival was 75 +/- 5% at 5 years and disease-free survival (DFS) 67 +/- 5%. For T-cell NHL, these scores were 54% and 44%, respectively. The IPI score had no prognostic value and only the following parameters adversely affected overall survival and DFS (P <.05): marrow involvement; more than one extranodal site; histology (nonanaplastic T-cell v others); and type of anthracycline (mitoxantrone v doxorubicin, for DFS only)., Conclusion: These results suggest that ASCT can prevent relapse in patients with adverse IPI factors. However, patients presenting with a nonanaplastic T-cell phenotype, more than one extranodal site, or marrow involvement still have a higher risk of relapse. These factors should be taken into account when designing post-ASCT maintenance studies.

We describe the case of a 51-yr-old man with systemic sarcoidosis, complicated by the occurrence of a lymphoproliferative disease following a 36-month (duration) immunosuppressive treatment with methotrexate (MTX) and methylprednisolone. Four years after the onset of sarcoidosis, the patient presented a large necrotizing anal fistula. Pathological examination of this lesion showed a diffuse polymorphic infiltrate containing large Epstein-Barr virus (EBV)-positive lymphoid cells associated with areas of necrosis, all features similar to classical B-cell lymphoproliferative disorders occurring in immunosuppressed solid-organ recipients. MTX has been recently implicated in the development of lymphoproliferative disease in connective tissue diseases. This case supports the hypothesis that immunosuppression therapy may contribute to an increased risk for the development of EBV-associated lymphoproliferative disorders in patients suffering from sarcoidosis.

We report a case of a 42-yr-old woman with Langerhans cell histiocytosis (LCH) confined to the thyroid and associated with lymphocytic thyroiditis and a papillary microcarcinoma. This patient remains free of symptoms 14 mo after surgery. Thyroid LCH is rare. In children, it usually occurs as part of a multisystemic disease, whereas it is usually exclusive in adults. Isolated thyroid LCH is frequently associated with another thyroid disease, especially lymphocytic thyroiditis, suggesting that it is a reactive process rather than a neoplastic proliferation. The prognosis of isolated thyroid LCH is good. However, because it can rarely precede or reveal a multisystemic disease, additional investigations as well as a prolonged follow-up are justified.

Collagenous gastritis is an exceptional entity with eight cases documented to date characterized by the presence of a thick subepithelial collagen band associated with an inflammatory infiltrate of the gastric mucosa. The aim of our study was to describe the clinical and histologic characteristics of six new cases of collagenous gastritis. All cases showed a subepithelial collagen band that averaged 30 microm but often measured up to 120 microm. This finding was almost always accompanied by mixed chronic inflammation in the lamina propria and by surface epithelial damage of varying severity. Our study seems to delineate two subsets in patients with collagenous gastritis: 1) collagenous gastritis occurring in children and young adults presenting with severe anemia, a nodular pattern on endoscopy, and a disease limited to the gastric mucosa without evidence of colonic involvement, and 2) collagenous gastritis associated with collagenous colitis occurring in adult patients presenting with chronic watery diarrhea. These findings highlight the fact that subepithelial collagen deposition may be a generalized disease affecting the entire gastrointestinal tract.

Aims: The presence of Epstein-Barr virus (EBV) was studied in 56 gastric carcinomas from Western patients by in-situ hybridization for EBV-encoded RNAs (EBER). EBV-positive and negative carcinomas were compared for various pathological parameters including p53 overexpression., Methods and Results: EBERs transcripts were detected in seven cases overall: four cases of 52 conventional carcinomas (7. 7%) and three cases of four gastric carcinomas with lymphoid stroma (75%). EBER positivity was diffuse in five cases and restricted to a localized area of the tumour in two cases of conventional carcinoma. A monoclonal EBV genomic pattern was demonstrated in the case tested by Southern blot analysis. By immunohistochemical analysis, neither EBV latent or lytic cycle proteins nor C3d/EBV receptor were expressed by neoplastic cells. EBER positivity was significantly correlated with prominent lymphoid reaction (P = 0.0002) which was associated with numerous PS100-positive dendritic cells and with HLA-DR expression by tumour cells (P = 0.03). p53 immunoreactivity in more than 30% of tumour cells was detected in 25 out 49 EBV-negative cases and was absent in EBV-positive cases except in one case with focal EBER-positivity., Conclusions: Focal staining for EBER is an unusual finding in the setting of gastric carcinoma and these results suggest that there might be two types of EBV-associated gastric carcinoma in which the viral infection will play a different role. The presence of a stromal lymphoid reaction which is strongly correlated with EBV positivity, is associated with antigen-presenting ability by HLA-DR-positive tumour cells or abundant dendritic cells. The function of p53 appears preserved in all EBV-associated carcinomas except in one case with focal EBER expression whereas the immunohistochemical pattern of p53 is suggestive of a mutational phenomenon in 51% of EBV-negative cases.

We describe an original distinct type of ovarian small cell carcinoma: large cell variant. The distinctive histologic features of tumor cells were the presence of large nuclei with prominent nucleoli and abundant eosinophilic cytoplasm. Immunohistochemistry revealed strong diffuse vimentin, smooth muscle actin positivity and slight reactivity with epithelial markers. Electron microscopy showed aggregates of intermediate filaments, intercellular attachments and no dense core granules. This tumor is associated with paraendocrine hypercalcemia in two thirds of cases. Parathyroid hormone-related protein was focally positive. This tumor is characterized as a very lethal neoplasm, occurring primarily in young women.

Background: The aim of this study was to prospectively compare the diagnostic accuracy of videoendoscopy, with and without Lugol staining, for the detection of esophageal cancer in alcoholic or smoking patients older than 40 years., Methods: Daily alcohol and tobacco consumption and overt and latent symptoms were noted. The 158 patients included were examined by videoendoscopy and with Lugol dye., Results: The mean consumption of alcohol and tobacco was 86 +/- 49 gm/day for 26 +/- 11 years, and 30 +/- 18 pack-years, respectively. Twenty-five patients had no symptoms. Before Lugol staining, 12 patients had endoscopically identified cancerous lesions. After Lugol staining, 13 patients had 17 esophageal cancers, 3 of which were high-grade dysplasia. The prevalence of esophageal cancer was 8.2%: 95% CI [4,14]. Dye-free surfaces were significantly larger than the endoscopic patterns observed before Lugol staining (11.6 +/- 9.2 cm2 vs 1.4 +/- 1.7 cm2; p < 0.02)., Conclusions: In an alcoholic smoking population, the prevalence of esophageal cancer detected by endoscopy is high and not related to symptoms described by patients. Lugol staining only moderately improves the diagnostic accuracy of videoendoscopy; its main advantage is the assessment of the mucosal extension of esophageal cancer.

The hepatic expression of major histocompatibility complex (MHC) antigens is normally limited. However aberrant expression may occur in cholestatic diseases or following liver transplantation. The aim of this work was to investigate the effect of normothermic ischemia on hepatocellular MHC expression. Temporary (90-min) normothermic ischemia of the liver was induced in inbred rats. There was a significant elevation of aspartate aminotransferase and alanine aminotransferase levels after ischemia, rising to their maximum by 6 h. Histologic findings showed large, confluent areas of necrosis, and preserved areas were seen with centrolobular congestion and macrovacuolar steatosis. Expression of MHC class I and II antigens was detected using the immunoperoxidase technique, 1 h, 12 h, 3 days, 7 days and 1 month after the end of intervention. A marked induction of the expression of class I, but not of class II, MHC antigens was observed on the hepatocyte membranes after ischemia. We suggest that normothermic ischemia can occur postoperatively in human liver transplantation and may cause increased expression of class I MHC antigens on hepatocytes, leading to increased sensitivity of liver allografts to rejection by cytotoxic T cells.

A first case is reported from France of a subcutaneous and muscular tissues invasion by proliferative larval forms of Taenia crassiceps in an AIDS-patient with severe immunodeficiency. These larvae usually develop in rodents whereas the adult form of the cestode is commonly found in foxes. Authors emphasize the differential diagnosis from other human subcutaneous metacestodoses such as T. solium cysticercosis, cenurosis and hydatidosis. The proliferative aspect of the larvae, the recurrence of lesions after surgical removal and the possible invasion of other tissues are elements of a poor prognosis.

Interferons (IFNs) are important cytokines which exhibit antiviral, antitumor, anticellular, as well as immunoregulatory activities. Among these multiple activities, IFNs are potent inducers of MHC antigen expression of a great variety of cells, helper and maturation factors in B-cell antibody production, and macrophage function. IFNs may therefore play a critical role in triggering antigen recognition and allograft rejection. Cyclosporin A (CyA) is a potent immunosuppressor which selectively inhibits helper T-lymphocyte proliferation in response to alloantigen presentation. CyA has been reported to inhibit interleukin 2 and IFNgamma production by helper T lymphocytes. In addition, CyA may induce monocyte production of prostaglandin E2, which then reduces MHC class II expression on endothelial cells, monocytes, and macrophages. However, the clinical use of CyA is plagued by its toxic (in particular nephrotoxic) side-effects. These toxic effects are clearly dose-related. It may be very important to develop new products which can act synergistically with CyA to inhibit lymphokine production. The aim of this study was to investigate the effects of combined IFN-specific antibodies and low dose CyA on cardiac allografts in inbred strains of rats.

Nephrogenic nephroma was individualized by A. Pagès in 1980 as a rare renal neoplasia that mainly occurs in adolescents and adults and presents a benign outcome. The tumor is composed of very small tubular, papillary, and glomeruloid structures. Immunohistochemistry and electron microscopy show that the tumor is a proliferation of primitive epithelial cells that mimic the embryonal nephron. This neoplastic entity has often been confused with a nephroblastoma, although it is a benign tumor that is cured by simple resection. Further studies are needed to define its exact incidence and its histogenesis.

Major histocompatibility complex (MHC) antigens play a major role in the rejection reaction and their increased expression may increase the host response to the foreign graft. Several clinical and experimental studies have demonstrated increased expression of MHC antigens on the different cell components of liver allografts during rejection. However modified expression of MHC antigens may also occur in certain liver diseases, after cholestasis or on a regenerating liver. In this experimental study in inbred rats, we compared the expression of MHC antigens on liver cells during rejection and non-immunological situations (cholestasis, cytolysis, regeneration).

It has been suggested that liver allografts are less sensitive to lymphocytotoxic antibodies than other organ allografts. In this experimental study in sensitized inbred rat recipients, we have used extracorporeal liver hemoperfusion to study interactions between the liver and lymphocytotoxic antibodies. Donor-specific liver hemoperfusion can delay hyperacute rejection of heart allografts and reduce the level of lymphocytotoxic antibodies. Immunofluorescence examination of the hemoperfused liver revealed deposits of C3 on Kupffer cells and of IgG on sinusoidal cells. In control rats in which a third-party liver, a donor-specific splenic or renal hemoperfusion was performed, heart allograft survival was less prolonged. The decrease in antibody levels was not significant and the deposit of C3 and IgG was much less evident. Similarly, previous blockade of the Kupffer cells of the donor-specific hemoperfused liver by dextran sulfate suppressed the effect of liver hemoperfusion. These results support the hypothesis that resistance of the liver to hyperacute rejection might be due to a massive and nontoxic absorption of lymphocytotoxic antibodies onto nonparenchymal liver cells.

Hemorrhage has never been described as a complication of gastric heterotopia of the gallbladder. A case of a heterotopic stomach perforated into the Calot's area and causing hematobilia by arteriobiliary fistula in a young man is described. The clinical presentation, radiologic features, operative and histologic findings are presented, as well as the mechanism of hematobilia and the probable embryologic cause. Extensive review of the literature indicates that this case is unique both in its presentation of hematobilia and by the pathologic configuration of the heterotopic gastric tissue.

We describe two patients with alcoholic cirrhosis in whom staphylococcal right-sided endocarditis developed after insertion of a peritoneovenous shunt (PVS). Massive pulmonary embolism caused early death in one patient. In the other patient, staphylococcal septicemia was cured after shunt removal and antibiotic treatment; recurrent endocarditis due to Corynebacterium xerosis ultimately caused the patient's death. No clinical manifestation of tricuspid valve dysfunction was noted in either patient, and right-sided endocarditis was recognized only at autopsy. The protracted contact of the tip of the venous line of PVS with the atrial wall is likely to be a major factor in the development of right-sided endocarditis in these patients.

The authors report the results of postmortem histopathological studies in 12 patients who had been treated by endoscopic obliteration of esophagogastric varices with Bucrylate (isobutyl-2-cyanoacrylate). All patients had cirrhosis; 11 patients were Pugh classe C. Eleven patients had esophageal injections. Acute esophageal lesions were characterized by ulcerations in obliterated varices and diffusion of Bucrylate into the esophageal wall. Chronic lesions were characterized by disappearance of varices and Bucrylate, extending fibrosis of the esophageal wall and re-epithelialization of the mucosa. In one patient who had received gastric injections only, non ulcerated Bucrylate filled gastric varices were seen. Bucrylate seems to have a dual action on esophageal varices: immediate obliteration and acute necrosis of the vascular endothelium. Necrosis causes diffusion of Bucrylate through the esophageal wall, and later, secondary fibrosis whereas the product is progressively eliminated into the esophageal lumen.

A joint prospective long term study of gastric biopsies has been undertaken to survey intestinal metaplasia Types I, II, and III in terms of their incidence, distribution and value in the selection of high risk cancer patients. This study is based on protocols agreed between three centres for endoscopy, histological interpretation, and mucin histochemistry. The results on the first 1350 gastric biopsies examined during 1981-1982 are presented. Intestinal metaplasia was found in 267 biopsies (20%), being common in association with carcinoma (71%), less so in benign conditions such as gastric ulcer (39%), and chronic gastritis (24%), but rare in 'normal' (3%). Type I intestinal metaplasia was predominant (73%) in all the biopsies with intestinal metaplasia and was most common in benign conditions, 70% in gastric ulcer and 76% in chronic gastritis. Type III intestinal metaplasia (incomplete sulphomucin-secreting intestinal metaplasia) was recorded in only 9.8% of all the biopsies with intestinal metaplasia and had a higher incidence in carcinoma (35%), than in benign conditions (7%) (p less than 0.0001). These results suggest that intestinal metaplasia types may have different malignant potential and their identification may be useful in screening patients for early detection of cancer.

Patients presenting genital intraepithelial neoplasia and/or flat condyloma were treated with DTrp6-LH-RH (triptorelin) to induce a transitory suppression of estrogens. This treatment led in some cases to a complete clinical and histological regression accompanied by a disappearance of human papillomavirus sequences as detected by molecular hybridization.