Cytomegalovirus load in inflamed intestinal tissue is predictive of resistance to immunosuppressive therapy in ulcerative colitis.

OBJECTIVES: Previous studies have suggested an association between cytomegalovirus (CMV) infection and steroid-refractory inflammatory bowel disease. In this study, the use of CMV DNA load during acute flare-ups of ulcerative colitis (UC) to predict resistance to immunosuppressive therapy was evaluated in intestinal tissue. METHODS: Forty-two consecutive patients (sex ratio M/F: 0.9, mean age: 43.6 years) hospitalized for moderate to severe UC and treated with IV steroids were included prospectively. A colonoscopy was performed for each patient at inclusion; colonic biopsy samples of the pathological tissue, and if possible, of the healthy mucosa, were tested for histological analysis and determination of CMV DNA load by real-time polymerase chain reaction assay. Patients were treated as recommended by the current guidelines. RESULTS: Sixteen patients were found positive for CMV DNA in inflamed intestinal tissue but negative in endoscopically healthy tissue; all of these patients were positive for anti-CMV IgG, three exhibited CMV DNA in blood, and none was positive for intestinal CMV antigen by immunohistochemistry detection. In the 26 remaining patients, no stigmata of recent CMV infection were recorded by any technique. By multivariate analysis, the only factor associated with CMV DNA in inflammatory tissue was the resistance to steroids or to three lines of treatment (risk ratio: 4.7; 95% confidence interval: 1.2-22.5). A CMV DNA load above 250 copies/mg in tissue was predictive of resistance to three successive regimens (likelihood ratio+=4.33; area under the receiver-operating characteristic curve=0.85). Eight UC patients with CMV DNA in inflamed tissue and therapeutic failure received ganciclovir; a clinical remission was observed in seven cases, with a sustained response in five of them. CONCLUSIONS: The CMV DNA load determined in inflamed intestinal tissue predicts resistance to steroid treatment and to three drug regimens in UC. Initiation of an early antiviral treatment in these patients might delay the occurrence of resistance to current treatments.

Primary central nervous system lymphoma: immunohistochemical profile and prognostic significance.

Primary central nervous system lymphoma (PCNSL) is a rare subtype of non-Hodgkin lymphoma (NHL) with extranodal location affecting only the CNS, meninges and eye, without visceral or lymph node involvement. Its incidence has increased sharply over the past three decades, especially in immunocompetent subjects. Most PCNSL cases are diffuse large B-cell lymphomas (DLBCLs). However, it differs from nodal DLBCL in that it has a worse prognosis. DLBCLs are a heterogeneous entity and according to new genomic discoveries, classifications into prognostic subgroups have been embarked upon. Two prognostic algorithms were then prepared using a panel of immunohistochemical markers (CD10, Bcl6, MUM1/IRF-4, and Bcl2), thus categorizing DLBCL into two subgroups, GCB (germinal centre B-cell-like) or non-GCB, and into Group 1 or Group 2. Our goal is to apply both of these two sub-classifications to 39 PCNSLs, in order to assess their usefulness and prognostic relevance. 74.3% of our PCNSLs were of a non-GCB phenotype, corresponding to an activated postgerminal origin. They were evenly distributed across G1 and G2. Two- and 5-year overall survival rates were 34.8% and 19.6%, respectively. Younger age (<65) and a therapeutic combination of chemotherapy and radiotherapy significantly improved our patients' survival rates. The other clinical or biological markers tested had no prognostic impact. The two classifications did not reveal any significant survival difference. The recent discovery of a specific "transcriptional signature" of PCNSL, marking them out of DLBCL could account for the irrelevance of such prognostic classifications to PCNSL.

Accuracy and feasibility of electromagnetic navigated bronchoscopy under nitrous oxide sedation for pulmonary peripheral opacities: an outpatient study.

BACKGROUND: Recent studies have described the promising method of electromagnetic navigated bronchoscopy (ENB) for diagnosis of peripheral solitary nodules. However, they require general anaesthesia or intravenous sedation. We wanted to know if ENB could be applied more easily in outpatients. OBJECTIVES: We prospectively evaluated the accuracy and the feasibility of ENB under local anaesthesia and nitrous oxide/oxygen inhalation as unique sedation in outpatients. METHODS: After mapping time, the bronchoscopic procedure was carried out under local anaesthesia and nitrous oxide/oxygen inhalation with the unique help of the ENB to confirm the right position of the extended working channel before sampling. The primary end point was the accuracy of ENB and the secondary end point was the feasibility in outpatients. RESULTS: Among 54 screened patients, 53 completed the study protocol. The overall diagnostic success rate to diagnose malignancy was 71.4% in tumours of 28 mm in median size. ENB classified correctly peripheral lesions according to malignity in 41 cases (30 cases of cancer, 11 benign diagnosis) and failed in 12 cases (1 probable lung metastasis, 11 lung cancers). All patients but 1 were dismissed 1 h after the procedure and the tolerance of the procedure was excellent in all cases except 2 (agitation and anxiety). In two cases (4%) a pneumothorax was recorded, 1 requiring drainage with a chest tube during a short hospitalisation. CONCLUSIONS: ENB under nitrous oxide/oxygen sedation seems to be an accurate and safe procedure. In our series, it allowed us to obtain the diagnosis in 71.4% of the tumours, with a good tolerance and an outpatient strategy.

Atypical presentations of solitary fibrous tumors of the central nervous system: an analysis of unusual clinicopathological and outcome patterns in three new cases with a review of the literature.

Central nervous system (CNS) solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms recognized less than a decade ago. Approximately 60 cases of SFT have been reported in the central nervous system. We describe three atypical SFTs of the CNS, two intracranial and one within the spine. One intracranial SFT arose from the sella turcica and expanded into the suprasellar areas. It relapsed twice during the 3 years following partial resection, and the MiB 1 labeling index steadily increased without obvious malignant transformation. The second SFT arose from the confluence of the sinuses, widely invaded the lateral sinus and adjacent bones, had a low MiB 1 index and has not recurred after 5 years. The intraspinal tumor occurred at T5-T7 in a patient with multiple café-au-lait spots, was predominantly myxoid and developed a second similar lesion at S3-S5 14 years later. The MiB 1 index was lower in the second tumor. Immunohistochemistry confirmed that all were SFTs. These atypical presentations gave us an opportunity to provide further information about the natural histological course of CNS SFTs.

Peroxisome proliferator activated receptor gamma immunohistochemical expression in human papillary thyroid carcinoma tissues. Possible relationship to lymph node metastasis.

BACKGROUND: Peroxisome proliferator activated receptor gamma (PPARgamma) involvement in thyroid tumorigenesis has recently been studied, especially in follicular neoplasms. Conflicting results concerning the regulation of this receptor in human papillary carcinoma have been reported. Therefore, we quantitatively assessed PPARgamma immunohistochemical expression in papillary carcinoma in comparison with other types of thyroid tumors and we evaluated its relationship with clinical criteria of aggressiveness. MATERIALS AND METHODS: Immunohistochemistry (IHC) was performed on 56 human thyroid papillary carcinomas (PTC), 9 follicular carcinomas (FTC), 20 follicular adenomas (FA) and 18 Hürthle cells adenomas. PTC were divided into subgroups according to some aggressiveness criteria: tumor size, capsular invasion, lymph node metastasis. Immunostaining was semi-quantitatively analyzed using image analysis software. RESULTS: Strong nuclear PPARgamma expression was detected in a large number of PTC (42%), similar to that found in FTC (44%) or FA (63%). Only Hürthle cell adenoma showed a significantly lower proportion of PPARgamma-positive immunoreactivity (11%, p<0.05). Cases of PTC-associated lymph node metastasis showed a higher percentage of PPARgamma-positivity than other case categories (63% vs. 20%), a result which was also noticed when comparing large PTC with infracentimentric tumors (60% vs. 39%, p<0.05). CONCLUSION: These results, combined with recently published data, suggest that the intense PPARgamma immunostaining revealed in PTC could be related to high wtPPARgamma gene levels. Moreover, they corroborate a strong relationship between PPARgamma expression and tumor progression. PPARgamma IHC evaluation is not a valuable differential diagnostic tool for thyroid tumors but it could be a reliable marker of papillary carcinoma aggressiveness and a potential predictor for an eventual therapy by PPARgamma agonists.

[Intestinal ganglioneuromatosis diagnosed in adult patients]. / La ganglioneuromatose intestinale diagnostiquée chez l'adulte.

AIM: Intestinal ganglioneuromatosis is essentially described in children and rarely in adults. The purpose of this study was to evaluate the clinical pathological patterns of intestinal ganglioneuromatosis diagnosed in adult patients. MATERIALS AND METHODS: Ten patients were included in this study (6 men, 4 woman; mean age=55.4 years). The diagnosis was established from ileocolorectal biopsies (n=5) or from a surgical specimen (n=5). An immunohistochemical study was performed with antibodies directed against S100 protein, synaptophysin, PGP9.5, neurofilament, tau protein, c-Kit and c-Ret. Clinical symptoms, endoscopic data and outcome were retrospectively reviewed. RESULTS: The diagnosis of intestinal ganglioneuromatosis was established solely on the basis of the microscopic examination in all 10 cases. Three patients presented with acute occlusion. The endoscopic examination showed unusual spasticity of the colon or colectasia in 5 cases, raspberry-like polyps in 2 cases and finger-like polyps in 3 cases. Ganglioneuromatosis was characterized by diffuse Schwann cell hyperplasia expressing S100 protein in close contact to nerve fibers expressing neurofilament, tau protein, synaptophysin, PGP9.5 and to ganglion cells expressing c-Ret. There was no hyperplasia of interstitial cells of Cajal. Intestinal ganglioneuromatosis was localized in the mucosa in 9 cases and extended through the entire intestinal wall in 1 case. The finger-like polyps corresponded to ganglioneuromatosis, while the raspberry-like polyps corresponded to adenomas. Two patients had von Recklinghausen's disease, 1 had multiple endocrine neoplasia type 2B and 1 had Cowden's disease. Intestinal ganglioneuromatosis was associated with nonfamilial adenomatous polyposis in 2 patients and colonic adenocarcinoma in 1 patient. The patients with finger-like polyps had no associated disease. CONCLUSION: Intestinal ganglioneuromatosis in adults is distinctive from that in children. In adults, intestinal ganglioneuromatosis is always a microscopic diagnosis although finger-like polyps observed at colonoscopy may be suggestive. Gastroenterologists must be aware of the higher risk of occlusion and intestinal neoplasia.

[Adenocarcinomas of the stomach and distal esophagus. Incidence and phenotypic characteristics of EBV-associated cases in the Lyons area, France]. / Adénocarcinomes de l'estomac et de l'oesophage distal. Incidence et caractéristiques phénotypiques des cas associés au virus Epstein-Barr (EBV) en région lyonnaise.

AIMS: Our study aimed to evaluate the incidence of EBV-associated adenocarcinomas of the stomach and distal esophagus in Lyons area and to assess their phenotypic characteristics. METHODS: 85 cases of gastric adenocarcinomas and 40 cases of esophageal adenocarcinomas were screened for EBV by in situ hybridization (EBER-1 and -2) and immunohistochemistry (LMP1 and EBNA-1); all cases positive for EBER by in situ hybridization were studied by PCR for demonstration of EBV DNA. The clinical, histological and immunophenotypic features of EBV-associated adenocarcinomas were assessed. RESULTS: 5 cases of EBV-associated adenocarcinomas, all gastric, were identified in our series (5.8%); one was diagnosed in a migrant from Algeria, a region of high endemia of EBV infection. 3 cases were located in the proximal stomach, 1 in the distal; 1 was diffuse. 4 cases were of the intestinal histological type. Proliferation index and microvessel density were high in all 5 cases. The expression of tumor markers was markedly heterogeneous from one case to another. CONCLUSIONS: Our study shows that EBV infection is restricted to gastric adenocarcinomas. Its incidence is evaluated to 5.8% in our series: this shows that Lyons area must be considered as a low risk area. In the absence of specific histological or phenotypic features, the screening of EBV+gastric adenocarcinomas is possible only with special techniques.

Monosomy 7 and absence of 12q amplification in two cases of spindle cell liposarcomas.

Spindle cell liposarcoma (SCL) is a rare malignant adipose tissue tumor presently regarded as a variant of well-differentiated liposarcoma (WDLPS). While WDLPS is cytogenetically characterized by the presence of supernumerary ring or giant chromosomes containing MDM2 amplification, data concerning the genomic alterations of SCL are scarce. Here, we describe the molecular cytogenetic characterization of two SCL cases. In these two cases, we did not identify supernumerary ring or giant chromosomes containing 12q amplification or any other chromosome 12 rearrangement. Instead, we observed a partial or complete monosomy 7 as the sole anomaly or among a few additional simple numeric and structural abnormalities. Monosomy 7 is not usual in adipose tissue tumors. It has been described in myelodysplastic syndromes and acute myeloid or lymphoblastic leukemias, as well as in several benign or malignant solid tumors. Our data suggest that the loss of material from chromosome 7 might play a crucial role in the pathogenesis of some SCL probably through the inactivation of tumor suppressor genes located on chromosome 7. On the basis of cytogenetic and molecular findings, some SCL may constitute an independent entity rather than being regarded as variants of WDLPS.

Combining radioisotopic and blue-dye technique does not improve the false-negative rate in sentinel lymph node mapping for colorectal cancer.

PURPOSE: This study was designed to assess the feasibility of a combined colorimetric and radioisotopic technique in the detection of the sentinel lymph node in colorectal cancer. METHODS: This prospective dual-center study included 64 patients. Using endoscopy on D0, a radiolabeled colloid was injected into the peritumoral submucosa, followed by a lymphoscintigraphy. Intraoperatively, on D1, lymphatic mapping was performed by using a visual method and radioguided detection after subserosal peritumoral injection of patent blue. Twenty-nine patients were injected only with the patent blue, 18 patients only with the radioactive tracer, and the other 17 patients benefited from both techniques. RESULTS: The detection rate was 92 percent. The average number of sentinel nodes harvested was 2.8. Twenty-four of 59 patients were pN+ (40 percent) and in 12 cases the sentinel lymph node was histologically negative, although there was a positive nonsentinel node (false-negative rate, 50 percent). The false-negative rate for the combined, radioisotopic, and colorimetric techniques were 63, 60, and 36 percent, respectively. In four patients, the sentinel node was the only metastatic site (4/24, 17 percent), and in two of these four patients, the sentinel lymph node presented with micrometastases (<2 mm). The radioisotopic technique allowed us to highlight a lateral drainage of two rectal cancers (2/13, 15 percent). The concordance between the blue and radioactive sentinel nodes was 43 percent. CONCLUSIONS: The addition of a radioisotopic method using submucosal injection does not improve the false-negative rate. The sentinel lymph node technique in colorectal cancer is feasible, although the false-negative rate is such that the technique should still be considered as experimental.

Mixed neuronal-glial tumor of the digestive tract: distinctive entity from gastrointestinal stromal tumor?

A 53-year-old-woman presenting with pelvic discomfort was found to have a 9.5 cm tumor located in the wall of the ileon. Light microscopy showed that the tumor was made of fascicles of plump spindle cells and bizarre epithelioid cells. A cuff of lymphoid cells was also present at the tumor margin. The tumor cells strongly expressed tau protein, neuron-specific enolase, protein green product 9.5 and glial fibrillary acid protein (GFAP), but did not show positive immunostaining for S-100 protein, CD34 or CD117. The tumor showed unequivocal ultrastructural evidence of neural differentiation. Skeinoid fibers were scattered throughout the tumor. This is the first mixed neuronal-glial tumor of the digestive tract to be described in the literature. Such histological and immunohistochemical features could be misinterpreted as features of digestive schwannoma. We suggest that this tumor is distinct from gastrointestinal stromal tumors in lacking CD34 and CD117 expression.

Desmoplastic infantile ganglioglioma: a rare tumor with an unusual presentation.

Desmoplastic infantile ganglioglioma (World Health Organization grade I) is a rare neoplasm. Despite their common large size and spectacular radiologic and histologic features, the prognosis after surgical resection is good. We present a new case of this tumor in a 14-month-old boy with a recent history of intracranial hypertension. Magnetic resonance imaging revealed a large tumor involving the left collateral trigone with dilatation of the lateral ventricles. Surgery revealed two separate solid tumors: one in the left falco-tentorial region and the other in the left rolandic area. Microscopic examination showed a proliferation of neoplastic astrocytes in reticulin-rich desmoplastic stroma associated with scattered ganglion cells. One year after surgery follow-up magnetic resonance imaging did not show tumor progression.