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Microsatellite instability (MSI) caused by mismatch repair deficiency (dMMR) is detected in a small proportion of pancreatic ductal adenocarcinomas (PDACs). dMMR and MSI have been associated with responses of metastatic tumors, including PDACs, to immune checkpoint inhibitor therapy. We performed immunohistochemical analyses of a 445 PDAC specimens, collected from consecutive patients at multiple centers, to identify those with dMMR, based on loss of mismatch repair proteins MLH1, MSH2, MSH6, and/or PMS2. We detected dMMR in 1.6% of tumor samples; we found dMMR in a larger proportion of intraductal papillary mucinous neoplasms-related tumors (4/58, 6.9%) than non- intraductal papillary mucinous neoplasms PDAC (5/385, 1.3%) (P = .02). PDACs with dMMR contained potentially immunogenic mutations because of MSI in coding repeat sequences. PDACs with dMMR or MSI had a higher density of CD8+ T cells at the invasive front than PDACs without dMMR or MSI (P = .08; Fisher exact test). A higher proportion of PDACs with dMMR or MSI expressed the CD274 molecule (PD-L1, 8/9) than PDACs without dMMR or MSI (4/10) (P = .05). Times of disease-free survival and overall survival did not differ significantly between patients with PDACs with dMMR or MSI vs without dMMR or MSI. Studies are needed to determine whether these features of PDACs with dMMR or MSI might serve as prognostic factors., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: To describe a large cohort of women with non-puerperal inflammatory breast and to identify characteristics of inflammatory breast cancer., Methods: All patients consulting for inflammatory breast syndrome in the breast unit of our tertiary University hospital between September 2013 and December 2015 were prospectively included. We excluded women who were pregnant or in the postpartum period. Patients underwent systematic clinical examination and imaging (breast ultrasonography and mammography). A biopsy was performed if the clinician suspected a malignant lesion of the breast. Clinicopathologic and radiologic data were registered. Statistics were performed using R (3.0.2 version) software., Results: Among the 76 patients screened and included, 38 (50%) had a malignant lesion at final diagnosis, 21 (27.6%) were diagnosed with infectious disease and 17 (22.4%) with inflammatory disease of the breast. When compared to patients with benign disease, patients with a malignant lesion were significantly older (p = 0.022, CI95% 1.78-14.7), had a significantly bigger palpable mass (p<0.001, CI 95% 22.8-58.9), were more likely to have skin thickening (p = 0.05) and had more suspicious lymph nodes at clinical examination (p<0.001, CI 95% 2.72-65.3). Precise limits on ultrasonography were significantly associated with benign lesions. The presence of a mass (p = 0.04), micro calcifications (p = 0.04) or of focal asymmetry (p<0.001, CI95% 1.3-618) on mammography was significantly associated with malignant disease., Conclusion: Inflammatory breast cancer was common in our cohort of women consulting for inflammatory breast syndrome. Identifying these patients with high-risk malignancy is crucial in the management of an inflammatory breast.

Background: The purpose of this study was to evaluate the incomplete excision rate of nasal basal cell carcinomas (BCC) resected with different margins to demonstrate that 3-mm surgical margins could be used as safety margins to reduce esthetic consequences with a low risk of incomplete excision., Methods: All patients with BCC of the nose excised from January 1st 2008 to December 31st 2011 were included. Data were analyzed and reviewed retrospectively. Tumors were treated with different surgical margins of excision: 3mm, 4mm, and 5mm. The primary outcome variable was the rate of incomplete excision. Other study variables were the histologic subtype, size, and recurrent lesions., Results: Of the 132 patients, 115 were included corresponding on with 127 BCC. Median age was 75.5 (64-83) and sex ratio M:F=1.05. Of the 127 BCC, 80 were aggressive histologic subtype (63%), and 11 were recurrent (8.7%). The overall rate of incomplete excision was 17.3% (n=22). Of these 22, 17 (77.3%) were of an aggressive subtype. The incomplete excision rates within the groups were 12.5% (n=4), 22.2% (n=10), and 16% (n=8), respectively within the group with 3-, 4- and 5-mm surgical margins. No significant difference was observed between the groups (P=.519). The incomplete excision rate was not independently associated with the surgical margins, histologic subtype and recurrent type (P>.05)., Conclusion: Three-millimeters margins could possibly be used to treat nasal BCC in chosen cases. Regarding the high rate of incomplete excision, reconstruction should be performed after receiving the pathologic report., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Background: Testicular morphology and immunohistochemical studies have never been reported in genetically documented adult patients with 5 alpha-reductase type 2 deficiency (5α-R2 deficiency)., Case Presentation: We describe the testicular histopathology of a 17-year-old XY subject with 5α-R2 deficiency caused by the recurrent homozygous Gly115Asp loss of function mutation of the SRD5A2 gene.We also performed an immunohistochemical analysis in order to further study the relationship between seminiferous tubules structure, Sertoli cell differentiation and androgenic signaling impairment in this case. We thus evaluated the testicular expression of the anti-Müllerian hormone (AMH), androgen receptor (AR) and 3β-hydroxysteroid dehydrogenase (3βHSD). Histological analysis revealed a heterogeneous aspect with a majority (92%) of seminiferous tubules (ST) presenting a mature aspect but containing only Sertoli cells and devoid of germ cells and spermatogenesis. Focal areas of immature ST (8%) were also found. Testicular AR and 3βHSD expression were detected in adult male control, 5α-R2 deficiency and CAIS subjects. However, AMH expression was heterogeneous (detectable only in few AR negative prepubertal ST, but otherwise repressed) in the 5α-R2 deficiency, conversely to normal adult testis in which AMH was uniformly repressed and to an adult CAIS testis in which AMH was uniformly and strongly expressed., Conclusion: Intratesticular testosterone can repress AMH by itself, independently of its metabolism into dihydrotestosterone. We also compare our results to the few post pubertal cases of 5α-R2 deficiency with available histological testicular description, reported in the literature. We will discuss these histological findings, in the more general context of evaluating the fertility potential of these patients if they were raised as males and were azoospermic.

Primary malignant melanoma of sinonasal tract is a rare but severe form of melanoma. We retrospectively analyzed 17 cases and focused on the histologic presentation and the expression of c-Kit, epidermal growth factor receptor (EGFR), cyclin D1/Bcl-1, PS100, and HMB45 and searched for BRAF, NRAS, and KIT mutations that are known to be associated with melanoma subtypes, together with amplifications of KIT, cyclin D1, cyclin-dependent kinase 4, MDM2, and microphthalmia-associated transcription factor using quantitative polymerase chain reaction. In most cases (78%), an in situ component was evidenced. Invasive components were composed of diffuse areas of rhabdoid, epithelioid, or spindle cells and, in most cases, lacked inflammatory reaction, suggesting that an immune escape phenomenon probably develops when the disease progresses. EGFR was rarely and weakly expressed in the in situ component of 2 cases. None of the investigated case showed BRAF V600E, but 1 had a D594G mutation. NRAS mutations in exon 2 (G12D or G12A) were found in 3 cases (18%), and a KIT mutation in exon 11 (L576P), in 1, whereas c-Kit was expressed at the protein level in half of the cases. Amplifications of cyclin D1 were evidenced in 5 cases, confirmed in 3 by fluorescence in situ hybridization, but this was not always correlated with protein expression, found in 8 patients (62.5%), 3 having no significant amplification. In conclusion, primary malignant melanoma of sinonasal tract is not associated with BRAF V600E mutations. Instead, NRAS or KIT mutations and cyclin D1 amplification can be found in a proportion of cases, suggesting that primary malignant melanoma of sinonasal tract is heterogeneous at the molecular level and should not be sensitive to therapeutic approaches aiming at BRAF., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Given the interest in defining biomarkers of asbestos exposure and to provide insights into asbestos-related and cell-specific mechanisms of neoplasia, the identification of gene alterations in asbestos-related cancers can help to a better understanding of exposure risk. To understand the aetiology of asbestos-induced malignancies and to increase our knowledge of mesothelial carcinogenesis, we compared genetic alterations in relevant cancer genes between lung cancer, induced by asbestos and tobacco smoke, and malignant pleural mesothelioma (MPM), a cancer related to asbestos, but not to tobacco smoke. TP53, KRAS, EGFR and NF2 gene alteration analyses were performed in 100 non-small cell lung cancer (NSCLC) patients, 50 asbestos-exposed and 50 unexposed patients, matched for age, gender, histology and smoking habits. Detailed assessment of asbestos exposure was based on both specific questionnaires and asbestos body quantification in lung tissue. Genetic analyses were also performed in 34 MPM patients. TP53, EGFR and KRAS mutations were found in NSCLC with no link with asbestos exposure. NF2 was only altered in MPM. Significant enhancement of TP53 G:C to T:A transversions was found in NSCLC from asbestos-exposed patients when compared with unexposed patients (P = 0.037). Interestingly, TP53 polymorphisms in intron 7 (rs12947788 and rs12951053) were more frequently identified in asbestos-exposed NSCLC (P = 0.046) and MPM patients than in unexposed patients (P < 0.001 and P = 0.012, respectively). These results emphasise distinct genetic alterations between asbestos-related thoracic tumours, but identify common potential susceptibility factors, i.e. single nucleotide polymorphisms in intron 7 of TP53. While genetic changes in NSCLC are dominated by the effects of tobacco smoke, the increase of transversions in TP53 gene is consistent with a synergistic effect of asbestos. These results may help to define cell-dependent mechanisms of action of asbestos and identify susceptibility factors to asbestos.

Background: Pigmented mammary tumours are rare. Herein, we report the third case of primary pigmented breast adenocarcinoma in a male patient with clinical mimicking of nodular melanoma of the nipple., Patients and Methods: A male patient presented with a pigmented nodule of the right nipple. Histological examination of the lesion showed dermal and subcutaneous adenocarcinomatous proliferation. The perilesional stroma contained melanin both inside and outside macrophages, leading us to conclude on primary pigmented breast adenocarcinoma clinically mimicking nodular melanoma of the nipple., Discussion: Local production of melanin by neoplastic cells in the mammary carcinoma was postulated as the cause of hyperpigmentation of the tumour. Other possible causes are transfer of melanin from overlying melanocytes of the pigmented areolar epidermis to the underlying neoplastic cells, or melanin synthesis by intratumoral melanocytes migrating from the epidermis (which strikes us as the most convincing interpretation for the reported case)., Conclusion: Breast adenocarcinoma is a rare tumour in men and may present clinically as a pigmented lesion of the nipple, resulting in the problem of differential diagnosis with primary or metastasised nodular melanoma., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Desmoplastic mesothelioma is unusual variant of malignant mesothelioma. The diagnosis of desmoplastic mesothelioma represents one of the most difficult exercises in pleural pathology (with poor interobservers agreement) because of their abundant collagen with relatively low cellularity. The clinical course is often rapid with visceral metastases. Bony metastases have only rarely been noted. We report our case of desmoplastic mesothelioma with vertebral metastases. Our focus is to distinguish this entity from fibrous pleurisy and localized fibrous tumors, to explain histological and immunohistochemical features with review of the literature., (Copyright © 2011. Published by Elsevier Masson SAS.)

The L-phenylalanine oxidase IL4I1 inhibits T-cell proliferation in vitro through H(2) O(2) production, and is highly expressed in tumor-associated macrophages. IL4I1 is also detected by immunohistochemistry in neoplastic cells from several B-cell lymphomas and some non-lymphoid tumors. To evaluate IL4I1's effect on tumor growth, we developed a mouse melanoma model constitutively coexpressing IL4I1 and the GP33 epitope. After GP33 vaccination, tumors developed more frequently in mice injected with IL4I1-expressing cells in comparison with mice receiving control cells. Tumor escape was preceded by a rapid diminution of IFN-γ-producing cytotoxic antitumor CD8(+) T cells. Moreover, tumor incidence was already increased when only 20% of the injected cells expressed IL4I1. The minimal IL4I1 activities leading to tumor escape were close to those detected in human melanoma and mesothelioma. Thus, we demonstrate the immunosuppressive functions of IL4I1 in vivo and suggest that IL4I1 facilitates human tumor growth by inhibiting the CD8(+) antitumor T-cell response., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Epidemiological studies have shown that asbestos fibers constitute the major occupational risk factor and that asbestos acts synergistically with tobacco smoking to induce lung cancer. Although some somatic gene alterations in lung cancer have been linked to tobacco smoke, few data are available on the role of asbestos fibers. P16/CDKN2A is an important tumor suppressor gene that is frequently altered in lung cancer via promoter 5'-CpG island hypermethylation and homozygous deletion, and rarely via point mutation. Many studies suggest that tobacco smoking produces P16/CDKN2A promoter hypermethylation in lung cancer, but the status of this gene in relation to asbestos exposure has yet to be determined. The purpose of this study was to investigate the mechanism of P16/CDKN2A alterations in lung cancer in asbestos-exposed patients. P16/CDKN2A gene status was studied in 75 human non-small-cell lung cancer (NSCLC) cases with well-defined smoking habits, and detailed assessment of asbestos exposure, based on occupational questionnaire and determination of asbestos bodies in lung tissue. The results of this study confirm published data on the effect of tobacco smoke on P16/CDKN2A gene alterations, characterized by significantly higher P16/CDKN2A promoter hypermethylation in heavy smokers (more than 40 pack-years (P-Y)) than in smokers of less than 40 P-Y. These results also demonstrate a higher incidence of loss of heterozygosity and homozygous deletion in asbestos-exposed cases, after adjustment for age and cumulative tobacco consumption, than in unexposed cases (P=0.0062). This study suggests that P16/CDKN2A gene inactivation in asbestos-exposed NSCLC cases mainly occurs via deletion, a feature also found in malignant mesothelioma, a tumor independent of tobacco smoking but associated with asbestos exposure, suggesting a possible relationship with an effect of asbestos fibers.

Background: Non-organ-specific autoantibodies (NOSAs) are frequently found in the sera of patients with Hepatitis C Virus (HCV) infection. However, no conclusive answers have been produced concerning the clinical relevance of these antibodies., Aim: To determine whether a relationship might exist between the presence of NOSA and the severity of liver disease in chronic hepatitis C., Methods: 186 treatment-naïve chronic hepatitis C patients were studied consecutively for autoantibodies. Liver biopsies were analyzed according to the Metavir score., Results: NOSAs were present in 75 patients (40%). Anti-nuclear antibodies were found in 32% of patients (speckled pattern), anti-smooth muscle in 15% without F-actin specificity, anti-mitochondria in 0.5%, and anti-LKM1 in 0.5%, respectively. No liver-cytosol1 or soluble liver antigen antibodies were detected. There was a highly significant correlation between the positivity of NOSA and the degree of inflammation and hepatocellular injury (p = 0.001) and also with the degree of fibrosis (p < 0.0001). The presence of NOSA was associated with higher aspartate aminotransferase, gamma-glutamyl-transpeptidase, gamma-globulin and immunoglobulin G levels. By contrast, no differences were observed regarding age, gender, route of infection, duration of disease, HCV genotypes or viral load., Conclusion: NOSAs were associated with the most severe forms of chronic HCV infections.

Classic anatomical methods have failed to determine the precise location, origin and nature of nerve fibres in the inferior hypogastric plexus (IHP). The purpose of this study was to identify the location and nature (adrenergic and/or cholinergic) of IHP nerve fibres and to provide a three-dimensional (3D) representation of pelvic nerves and their relationship to other anatomical structures. Serial transverse sections of the pelvic portion of two human male fetuses (16 and 17 weeks' gestation) were studied histologically and immunohistochemically, digitized and reconstructed three-dimensionally. 3D reconstruction allowed a 'computer-assisted dissection', identifying the precise location and distribution of the pelvic nerve elements. Proximal (supra-levator) and distal (infra-levator) communications between the pudendal nerve and IHP were observed. By determining the nature of the nerve fibres using immunostaining, we were able to demonstrate that the hypogastric nerves and pelvic splanchnic nerves, which are classically considered purely sympathetic and parasympathetic, respectively, contain both adrenergic and cholinergic nerve fibres. The pelvic autonomic nervous system is more complex than previously thought, as adrenergic and cholinergic fibres were found to co-exist in both 'sympathetic' and 'parasympathetic' nerves. This study is the first step to a 3D cartography of neurotransmitter distribution which could help in the selection of molecules to be used in the treatment of incontinence, erectile dysfunction and ejaculatory disorders.

We previously reported a strong IL4I1 gene expression in primary mediastinal B-cell lymphoma (PMBL) and recently identified the protein as a secreted L-phenylalanine oxidase, physiologically expressed by myeloid cells, which inhibits T-cell proliferation in vitro. Here, we analyzed the pattern of IL4I1 protein expression in 315 human lymphoid and non-lymphoid malignancies. Besides PMBL, IL4I1 expression in tumors was very frequent. IL4I1 was detected in tumor-associated macrophages from most of the tumors and in neoplastic cells from follicular lymphoma, classic and nodular lymphocyte predominant Hodgkin lymphomas and small lymphocytic lymphoma, three of which are germinal center derived. IL4I1-positive tumor cells were also detected in rare cases of solid cancers, mainly mesothelioma. The enzymatic activity paralleled protein expression, suggesting that IL4I1 is functional in vivo. Depending on the tumor type, IL4I1 may impact on different infiltrating lymphocyte populations with consequences on tumor evolution. In the particular case of follicular lymphoma cells, which are susceptible to antitumor cytotoxic T cells killing but depend on interactions with local T helper cells for survival, a high level of IL4I1 expression seems associated with the absence of bone marrow involvement and a better outcome. These findings plead for an evaluation of IL4I1 as a prognosis factor.

Objectives: Deletion of short arm of chromosome 4 is difficult to ascertain prenatally, and can be missed., Methods: A prenatal suspicion of 4p- syndrome was thoroughly investigated by using two-dimensional and three-dimensional sonography, with a description of the fetal face dysmorphological pattern. The cytogenetic confirmation, obtained by karyotype and FISH technique, allowed a precise description of the prenatal abnormalities. Post-termination tridimensional helicoidal scanner of the fetal face was performed., Results: The main anomaly discovered using two-dimensional sonography was the presence of a strikingly thick prefrontal edema (8 mm, twice the normal values, at 22 weeks: 3.81 +/- 0.62 mm). Three-dimensional sonography showed the classical postnatal profile, with the phenotypic aspect of a 'Greek warrior helmet'. Nasal bones were normal in size and placement, confirmed by helicoidal scanner., Conclusion: Prenatal diagnosis of 4p deletion syndrome can be difficult, and it is the presence of prefrontal edema, associated with more subtle facial anomalies (short philtrum, microretrognathia) which should trigger cytogenetic investigation for 4p- deletion, even with only borderline growth retardation., (Copyright 2005 John Wiley & Sons, Ltd)

Objectives: The precise location, origin and nature of nerve fibers innervating the male urethral sphincter have not been clearly established. Classical anatomical studies based on cadaver dissections have provided conflicting results concerning the location of somatic and autonomic nerve fibers. This study was designed to identify nerve fibers innervating the male urethral sphincter and to provide a three-dimensional representation of their tissue relations in the human male fetus., Materials and Methods: Histology and immunohistochemistry (Hematein-Eosin-Safran, Luxol Fast Blue, Protein S 100 immunolabeling and smooth fibers actin immunolabeling) were performed in male external urethral sphincter of ten male fetuses (114-342 mm crown-rump length). Three-dimensional reconstruction of the urethral structure and innervation were obtained from serial sections using Surf Driver 3.5.3 software., Results: The three-dimensional reconstruction of the same section levels with different strains allowed to identify the precise structure of the muscular layers and the nature of nervous elements (myelinated and unmyelinated), their distributions and their relations with the urethral wall, the prostate and the seminal vesicles., Conclusion: Histological and immunohistochemical three-dimensional reconstruction of the nervous elements of the urethral sphincter gives a very didactical understanding of the three dimensional arrangement of the urethral nerves and their relationships with the urethral layers. It allows a better understanding of the origin, the course and the nature of the nervous elements participating in the urinary continence.

Objectives: The precise location, origin and nature of nerve fibers innervating the urethral sphincter have not been clearly established. Classical anatomical studies based on cadaver dissections have provided conflicting results concerning the location of pudendal and autonomic nerve fibers. This study was designed to identify nerve fibers innervating the urethral sphincter and to provide a three-dimensional representation of their tissue relations in the female human fetus., Materials and Methods: Histology and immunohistochemistry (Masson's Trichromic, Luxol Fast Blue, Protein S 100 immunostaining and smooth fiber actin immunostaining) were performed on the external urethral sphincter of ten female fetuses with a crown-rump length of 112 to 340mm. Three-dimensional reconstructions of the urethral structure and innervation were obtained from serial sections using Surf Driver 3.5.3 software (David Moody and Scott Lozanoff)., Results: Three-dimensional reconstructions of the same sections with different stains demonstrated the precise structure of the muscle layers (smooth and striated muscle fibers) and nerve fibers (myelinated and unmyelinated) and their relations with the urethra and vaginal wall. The proximal third consisted of a circular smooth muscle sphincter, the middle third consisted of two circular layers of smooth and striated muscle fibers and the distal third consisted of a circular layer of smooth muscle fibers surrounded by an omega-shaped layer of striated muscle fibers. In the proximal third of the urethral sphincter, myelinated fibers were identified running with unmyelinated fibers from the pelvic plexus. These fibers were closely related to the lateral and anterior aspects of the vagina. Unmyelinated fibers entered the smooth muscle part of the sphincter at 4 o'clock and at 8 o'clock. Most myelinated fibers entered the sphincter at 3 o'clock and at 9 o'clock., Conclusion: Histological and immunohistochemical three-dimensional reconstruction of the anatomical structures of the urethral sphincter provides a better understanding of the origin and nature of the Innervation participating in urinary continence. It provides a very informative view of the three-dimensional arrangement of sphincter muscle layers.

The structure of the striated urethral sphincter, the so-called rhabdosphincter, remains the subject of controversy. There are two main concepts regarding its structure: either it is a part of the urogenital diaphragm, or it extends from the base of the bladder up to the urogenital diaphragm and is an integral part of the urethra. It is also uncertain whether it possesses a somatic innervation or a mixed innervation (i.e. autonomic and somatic). The purpose of this study was to show the precise location of the nerves running to the urethra, and to try to determine their exact nature. Histology and immunohistochemistry were performed in the external urethral sphincter of ten male fetuses (114-342 mm crown-rump length, or between 14 and 40 weeks of gestation). A three-dimensional (3D) reconstruction of the urethral structure and its innervation was made from serial sections. The 3D reconstruction of the same section levels with different strains allowed us to identify the precise structure of the muscle layers (smooth and striated muscle fibres) and the nature of the nerve elements (myelinated and unmyelinated), their distributions and their relationship to the urethral wall, the prostate and the seminal vesicles. Histological and immunohistochemical 3D reconstruction of the anatomical elements of the urethral sphincter helps us to understand the 3D arrangement of the sphincter muscle layers. It also provides a better understanding of the origin and nature of the nerve elements that play a role in urinary continence.

The aim of this study was to assess the prevalence and prognostic value of major alterations of portal flow in patients with steroid-treated alcoholic hepatitis. Fifty patients with severe, histologically proven alcoholic hepatitis were enrolled. Clinical data, liver test results, and hepatic Doppler ultrasound findings were collected at inclusion and at month 2. Patients were followed for 1 year or until death. Major changes in portal flow were defined as reversed or alternating flow in the portal trunk and/or in intrahepatic portal branches. Changes in portal flow were observed in 24 (48.0%) of 50 and 17 (39.5%) of 43 patients at inclusion and month 2, respectively. Univariate analysis showed that age older than 50 years, steatosis less than 20% on initial liver biopsy, presence of major changes in portal flow, Child-Turcotte-Pugh score higher than 12, factor V level higher than 45%, and hepatofugal splenic blood flow were associated with a lower 1-year survival. Cox regression analysis showed that steatosis < 20% (relative hazard [RH] = 9.3, P = .0009) and major changes in portal flow (RH = 3.1, P = .04), were independently associated with poor survival. In conclusion, major changes in portal flow are frequent in patients with severe alcoholic hepatitis. Altered portal flow and steatosis < 20% are new prognostic factors in steroid-treated alcoholic hepatitis and must be taken into account in patient management.

Leiden Factor V mutation, associated with resistance to activated protein C, is a prothrombotic state found in 20% of the patients with a first episode of deep-vein thrombosis. We report the case of a 30-Year-old woman with a history of intermittent abdominal pain who developed small bowel infarction requiring extensive small bowel resection. Biological search for prothrombotic disorder showed resistance to activated protein C due to homozygosity for the factor V Leiden mutation. Long-term anticoagulant therapy was initiated. Unexplained abdominal pain may be due to venous mesenteric ischemia, which can be associated with factor V Leiden mutation.

We report a case of nasal NK/T lymphoma occurring in a 42 year old man, after a 2 year history of nasal obstruction initially related to chronic sinusitis. A first superficial biopsy was not contributive. Twenty months later, a second nasal biopsy led to the diagnosis of nasal NK/T cell lymphoma in view of the presence of a pleomorphic lymphoid infiltrate associated with necrosis and angiocentric features. Extensive immunohistochemical studies performed on paraffin and frozen sections together with genotypic analysis supported the NK cell origin of the neoplastic cells. In addition, EBV infection was established by in situ hybridization which showed EBERs transcripts in the nuclei of virtually all neoplastic cells. The tumour rapidly progressed and the patient died six months after diagnosis.

Matrix-degrading metalloproteinases may play a role in the pathophysiology of bronchopulmonary dysplasia (BDP). We, therefore, evaluated correlations between gelatinase activities [metalloproteinase (MMP)-2 and MMP-9] or tissue inhibitor of metalloproteinase (TIMP)-1 levels present in the airways during the initial phase of hyaline membrane disease and the onset of BPD. Tracheal aspirates were obtained within 6 h of birth (day 0) from 64 intubated neonates with a gestational age < or =30 wk. Forty-five neonates were resampled on day 3 or 5. Total MMP-2 level measured by zymography fell with time, whereas total MMP-9 level and TIMP-1 levels, assayed by ELISA, increased; the MMP-9 increase correlated with the increase in airway inflammatory cell numbers. Among the parameters measured on day 0, 3, or 5, lower total MMP-2 level, lower birth weight, and higher fraction of inspired oxygen on day 0 were significantly and independently associated with the development of BPD. In conclusion, MMP-9 level and TIMP-1 levels increased after birth but are not linked to BPD outcome. In contrast, low MMP-2 level at birth is strongly associated with the development of BPD.

We report two cases of malignant lymphoma of B phenotype occurring after therapeutic pneumothorax for tuberculosis. In both cases, outcome was fatal without time for specific treatment. Mainly reported in Japan, this pathology seems to be less frequent in western countries. As for B phenotype lymphoma associated with immunodeficiency, association with Epstein Barr virus is reported. Definite diagnosis is difficult and requires surgical biopsy. Prognosis remains poor with a survival ranging from 3 to 6 month.

We report a case of an adenomatoid tumor of particular location within the pleura, incidentally discovered on a pulmonary lobectomy specimen after surgical resection of a pulmonary squamous cell carcinoma. This adenomatoid tumor appeared as a unique pleural mass located away from the primary carcinoma and consisted of a cellular proliferation organised in tubes and sheets. Adenomatoid tumors are considered as benign tumors of mesothelial nature. Their morphological and immunohistochemical features in association with their location to the pleura, warrant a precise analysis to eliminate malignant tumours such as malignant mesothelioma or metastatic adenocarcinoma.

Study Objective: The aim of the study was to assess diagnosis value of tumor markers for differential diagnosis between mesothelioma and other pleural tumors., Design and Methods: Prospective study of 85 patients attending our hospital with malignant pleural effusion. The diagnostic approach involved routine pleurocentesis followed by pleural needle. When precise diagnosis was not achieved, thoracoscopy with pleural biopsies was performed. Carcinoembryonic antigen (CEA), hyaluronic acid, tissue polypeptide antigen and cyfra 21 to 1 were measured in serum and pleural fluid., Results: By using receiver operating characteristics curves and area under curves, the best diagnostic characteristics were obtained with pleural and serum CEA concentrations. The area under the curve was larger for pleural ACE than for serum ACE. The sensitivity and specificity of a pleural CEA level exceeding 3 ng/mL for ruling out the diagnosis of mesothelioma were 100% and 77%, respectively., Conclusion: A CEA level above 3 ng/mL in pleural fluid eliminated the diagnosis of mesothelioma, whereas the other markers were not sufficiently discriminant. However, despite a negative predictive value of 100% at a cutoff of 3 ng/mL, CEA assay in pleural fluid only avoids a small number of diagnostic thoracoscopies.

Sarcoidosis is a multisystem granulomatous disease mostly involving the chest. Sarcoid optic neuropathy is an uncommon but serious manifestation that requires long-term corticosteroid treatment. We report here the case of a 50-year-old black patient complaining of a recent blurred vision on his left eye. The ophthalmologic examination was normal. Goldmann visual field and visual evoked potentials confirmed the diagnosis of retrobulbar optic neuropathy. Sarcoidosis was presumed on a chest radiography and computed tomography and confirmed with a transbronchial biopsy. Symptoms disappeared with intravenous bolus of corticosteroids. Three months later, without treatment, a right inferior eyelid tumor was observed. Magnetic resonance imaging (RMI) showed two orbital masses and multiple meningeal lesions enhancing with contrast suggesting neurosarcoidosis which decreased with a long-term high-dose corticosteroid therapy (1 mg/kg/d). Optic neuropathy is a rare manifestation of neurosarcoidosis, mostly accompanied by optic-disc involvement with papillary lesions. Chest roentgenogram and computed tomography give a presumption of sarcoidosis. But biopsy is mandatory to confirm the diagnosis demonstrating the histologic lesion of a non caseating granulomatous. Corticosteroid therapy is dramatically efficient but sometimes several months treatment is required.

New strategies for cancer therapy must be developed, especially in severe neoplasms such as malignant pleural mesothelioma. Animal models of cancer, as close as possible to the human situation, are needed to investigate novel therapeutical approaches. Orthotopic transplantation of cancer cells is then relevant and efforts should be made to follow up tumour evolution in animals. In the present study, we developed a method for the orthotopic growth of mesothelioma cells in the pleural cavity of Fischer 344 and nude rats, along with a procedure for clinical survey. Two mesothelioma cell lines, of rat and human origin, were inoculated by transthoracic puncture. Body weight determination and chest X-ray analyses permitted the follow-up of tumour evolution by identifying different stages. Autopsies showed that tumours localized on the whole pleural cavity (diaphragm, parietal pleura), mediastinum and pericardium. Tumour morphology and antigenic characteristics were consistent with those of the inoculated cells and were similar in both types of rats inoculated with the same cell type. These results demonstrate that mesothelioma formation in rats can be followed up by clinical and radiographic survey after gentle intrathoracic inoculation of mesothelioma cells, thus allowing the definition of stages of interest for further experimental trials.

We report five cases of herpetic esophagitis in human immunodeficiency virus non-infected patients. Herpetic esophagitis is a frequent infection in immunocompromised patients. However, sixty four cases of herpetic esophagitis have been reported in immunocompetent patients. The infection presents non-specific esophageal symptoms. Diagnosis relies on esophageal histology and viral cultures. Treatment by acyclovir is recommended to prevent severe complications. This infection is probably underestimated in immunocompetent hosts but seems to be more frequent in patients with severe illness that can be responsible for transitory immunodeficiency. Biopsies of esophageal lesions should be systematically performed in these patients.

The purpose of the present study is to report four cases of sinonasal hemangiopericytoma (HP) diagnosed and treated in our department between 1987 and 1998. The pretreatment findings and the treatment are described and discussed in the light of the literature. HP are unusual vascular tumors, featuring pericytes distributed around normal vascular channels. Two of these four cases were located in the nasal cavity and the other two were located in the maxillary sinus. Inside the nasal cavity, HP presented as a protruding reddish-gray mass with marked bleeding on contact. Electron microscopy and immunohistochemical techniques are essential for diagnosis and to distinguish HP from other sarcomatous tumors. Preoperative assessment included routine CT, MRI, arteriography and selective embolization. These tumors must be treated surgically with complete excision. An endonasal approach was performed in two cases of intranasal HP, while a combined external-endonasal approach was required for the other two cases of HP.