Critical roles for interleukin 1 and tumor necrosis factor alpha in antibody-induced arthritis.

In spontaneous inflammatory arthritis of K/BxN T cell receptor transgenic mice, the effector phase of the disease is provoked by binding of immunoglobulins (Igs) to joint surfaces. Inflammatory cytokines are known to be involved in human inflammatory arthritis, in particular rheumatoid arthritis, although, overall, the pathogenetic mechanisms of the human affliction remain unclear. To explore the analogy between the K/BxN model and human patients, we assessed the role and relative importance of inflammatory cytokines in K/BxN joint inflammation by transferring arthritogenic serum into a panel of genetically deficient recipients. Interleukin (IL)-1 proved absolutely necessary. Tumor necrosis factor (TNF)-alpha was also required, although seemingly less critically than IL-1, because a proportion of TNF-alpha-deficient mice developed robust disease. There was no evidence for an important role for IL-6. Bone destruction and reconstruction were also examined. We found that all mice with strong inflammation exhibited the bone erosion and reconstruction phenomena typical of K/BxN arthritis, with no evidence of any particular requirement for TNFalpha for bone destruction. The variability in the requirement for TNF-alpha, reminiscent of that observed in treated rheumatoid arthritis patients, did not appear genetically programmed but related instead to subtle environmental changes.

Arthritogenic monoclonal antibodies from K/BxN mice.

Arthritis in the K/BxN mouse model is provoked by pathogenic antibodies (Abs) directed against a ubiquitously expressed protein, glucose-6-phosphate isomerase (GPI). To begin dissecting the repertoire of arthritogenic immunoglobulins (Igs) in the K/BxN model, and to provide a basis for comparison with RA patients we have generated anti-GPI monoclonal Abs (mAbs) from spontaneously activated B cells in the lymphoid organs of arthritic mice. B cell clones with anti-GPI specificities were present at extraordinarily high frequencies in the spleen, and less frequently in other lymphoid organs and in the synovial fluid. None of the anti-GPI mAbs induced arthritis when injected individually into healthy recipients, but most were effective when combined in pairs or larger pools. Arthritogenic combinations depended on mAbs of the IgG1 isotype, which bound to GPI with Kd in the 10(-9) M range, with no indication of cooperative binding between complementing pairs. Pathogenicity was not associated with recognition of a particular epitope, but the ability to form mAb/GPI multimers by simultaneous recognition of different epitopes was clearly required, consistent with the known role of complement and FcRs in this model. Sequence analysis revealed structural similarities amongst the mAbs, indicating that a particular subset of B cells may evade tolerance in K/BxN mice, and that affinity maturation by somatic mutation likely takes place. These results confirm that GPI itself, rather than a cross-reactive molecule, is the target of pathogenic Igs.

Hepatic steatosis in HIV-HCV coinfected patients: analysis of risk factors.

OBJECTIVE: To evaluate the prevalence and severity of steatosis and possible interactions between steatosis, host factors, viral factors, and treatment for HIV infection in HIV-hepatitis C virus (HCV) coinfected patients. METHODS: Steatosis was assessed among 395 HIV-HCV coinfected patients who were enrolled in the ANRS trial HC02 Ribavic and for whom histological data were available. Steatosis was graded as follows: 0 (none); 1 (< 30% hepatocytes containing fat); 2 (30-70%); 3 (> 70%). RESULTS: Steatosis was present in 241 patients (61%), of whom 149 (38%) had grade 1, 64 (16%) grade 2 and 28 (7%) grade 3. In multivariate analysis, the following five independent risk factors were associated with steatosis: HCV genotype 3 [odds ratio (OR), 3.02; 95% confidence interval (CI), 1.91-4.79; P < 0.0001], the mean METAVIR fibrosis score (OR, 1.43; 95% CI, 1.11-1.84; P = 0.0053), the body mass index (BMI; OR, 1.13; 95% CI, 1.05-1.21; P = 0.0013), HCV viral load (OR. 1.65; 95% CI, 1.22-2.23; P = 0.0012) and ferritin (OR, 1.13; 95% CI, 1.06-1.21; P < 0.0003). As HCV genotype 3 was a risk factor for steatosis, further exploratory analyses were stratified according to the HCV genotype (1 and 3). Factors independently associated with steatosis were BMI and HCV viral load in patients with HCV genotype 3 infection and the mean METAVIR fibrosis score, the BMI and ferritin in patients with HCV genotype 1 infection. CONCLUSION: Steatosis is particularly frequent in HIV-HCV coinfected patients, who appear to have the same risk factors for steatosis as HCV monoinfected patients. None of the characteristics of HIV infection, including antiretroviral therapy, was independently associated with steatosis.

Analysis of the different histologic lesions observed in transbronchial biopsy for the diagnosis of acute rejection. Clinicopathologic correlations during the first 6 months after lung transplantation.

Acute rejection is an extremely common complication of lung transplantation. (1) To appreciate the interobserver variation in the interpretation of histologic findings and (2) to assess the efficacy of transbronchial biopsy (TBB) for acute rejection diagnosis and associated diseases, particularly infection, we performed a retrospective study including 53 consecutive patients who underwent at least one clinically indicated TBB during the first 6 months after lung transplantation. A total of 94 TBB was obtained. The following histologic features observed in TBB specimens-perivascular mononuclear infiltrates, lymphocytic bronchitis/bronchiolitis, and alveolar lesions, were reliably reproduced by 2 pathologists from the same transplant center, with kappa values ranging from 0.79 to 0.82. For identifying perivascular mononuclear infiltrates, discordance between the 2 observers was significantly associated with moderate/severe alveolar lesions. For the diagnosis of acute rejection, perivascular mononuclear infiltrates had a specificity of 96.5%, a positive predictive value of 97.5%, and a sensitivity of 67.7%, whereas lymphocytic bronchitis/bronchiolitis had a specificity of 56.3% and a sensitivity of 19.4%. Interestingly, there was a positive independent correlation between infection and moderate/severe alveolar histologic lesions ( P < .01). In conclusion, the interobserver agreement between experienced pathologists in TBB interpretation is good. Perivascular mononuclear infiltrates remain the cornerstone for acute rejection diagnosis. The presence of moderate/severe alveolar lesions should prompt to search for infection.

[Osteoclastic giant cell tumour of the pancreas]. / Tumeur à cellules géantes ostéoclastiques du pancréas.

Osteoclast giant cell tumours are bone tumours that occur in adults, and that are considered benign by WHO but locally aggressive. Strictly identical tumours are described in the pancreas, without simultaneous bone localization. We report the case of a 62-year woman with an osteoclast giant cell tumour of the distal pancreas, without any epithelial component, which was diagnosed after pancreatic resection and with no signs of recurrence after a 24-month follow-up. These pancreatic tumours are rare, with a very poor prognosis, an unclear histogenesis; they are often confused with pleomorphic or undifferentiated pancreatic carcinomas including a component of osteoclast giant cell. These osteoclast giant cell tumours of the pancreas usually present as large cystic tumours. In certain cases, complete resection can result in long-term survival.

[Lipomatous meningioma: two case reports]. / Méningiome lipomateux: à propos de deux cas.

Lipomatous meningiomas are rarely encountered and are included in the World Health Organization's (WHO) group of metaplastic meningiomas. We report two cases of these tumors. The presenting symptoms were headaches in one case and seizure in the other. Radiologically, these tumors were extra-axial and unique. One tumor displayed fat accumulation, while the other had the appearance of a conventional meningioma. Microscopically, these tumors corresponded to meningothelial and transitional meningiomas containing a variable proportion of adipose tissue composed of mature adipocytes or lipoblasts. Fat content was high in one case and moderate in the other, thus explaining the radiological findings. Expression of epithelial membrane antigen and progesterone receptors was present in meningothelial, adipocyte-like, and lipoblast-like cells. These immunohistochemical results suggest that lipid accumulation in meningioma should be considered a transformation of meningothelial cells rather than a true metaplasia.

HIV coinfection does not compromise liver histological response to interferon therapy in patients with chronic hepatitis C.

OBJECTIVE: Although discrepancies between histological and virological responses to anti-hepatitis C virus (HCV) therapy are well-established in HIV-negative patients, the liver histological outcome has never been assessed in HIV-HCV co-infected patients receiving anti-HCV therapy. We compared histological responses to interferon (IFN) alpha therapy between HIV-positive and HIV-negative injecting drug users (IDU) and determined factors associated with histological response. DESIGN: Retrospective cohort study. SETTING: Hepatology unit of a tertiary referral hospital. PATIENTS/INTERVENTIONS: Seventy-nine HCV-infected IDU (32 HIV-positive) receiving a 6-month course of IFN-alpha2b therapy, 3 x 106 U three times a week. PRIMARY OUTCOME MEASURE: Histological response, defined by a > or =2 point decrease in total Knodell score measured on paired liver biopsies over a 2-year follow-up period. RESULTS: The sustained response rate to IFN therapy was lower in HIV-positive patients than in HIV-negative patients (6.2% versus 29.8%;P = 0.012). Conversely, the rates of histological response (40.6% versus 36.2%) were not different between HIV-positive and HIV-negative patients. Independent factors associated with histological response were first total Knodell score (P = 0.0007) and sustained response to IFN therapy (odds ratio, 12.34; P = 0.005). Histological response was observed in 25% of IFN non-responders whatever their HIV status. In HIV-positive patients, the CD4 cell count did not influence the histological response. CONCLUSIONS: in HIV-HCV co-infected patients treated with IFN, liver histological improvement is frequently observed, similarly to that observed in HIV-negative patients. Such beneficial effect of interferon therapy supports early treatment of chronic hepatitis C in HIV-infected patients.

Gene therapy for hepatocellular carcinoma using non-viral vectors composed of bis guanidinium-tren-cholesterol and plasmids encoding the tissue inhibitors of metalloproteinases TIMP-2 and TIMP-3.

Metalloproteinases (MMPs) and their natural inhibitors (TIMPs) contribute to the regulation of tumor microenvironment. Their expressions are deregulated in almost all human cancers. We report a novel approach to gene therapy of hepatocellular carcinoma (HCC), using repeated injections of DNA plasmids encoding the tissue inhibitors of metalloproteinases (TIMPs) TIMP-2 or TIMP-3, and a novel competent formulation of gene transfer based on nontoxic cationic cholesterol derivatives. The new gene delivery system was efficient in demonstrating the antitumor efficiency of TIMP-2 or TIMP-3 in inhibiting tumor growth of human HuH7 HCC cells xenografted into nude mice. We show, for the first time, an in vivo effect of TIMP-3 in delaying HCC tumor growth. No treatment-related toxicity was noted. An inhibition of angiogenesis and tumor necrosis accompanied the inhibitory effects of TIMP-2 or TIMP-3 on tumor expansion and invasion. We also report a bystander effect produced by transfected HuH7 tumor cells mixed with untransfected cells in 1:1 ratio in culture that resulted in killing 98% of cells within 96 h. In addition, the soluble forms of TIMP-2 and TIMP-3 expressed by transfected cells exerted a cytotoxic effect on untransfected HuH7 cell cultures. Taken together, these results demonstrate the potential efficacy of repeated treatment of secreted TIMP-2 and TIMP-3 for the design of nonviral gene therapy for hepatocarcinoma.

Role of replicative senescence in the progression of fibrosis in hepatitis C virus (HCV) recurrence after liver transplantation.

BACKGROUND: Although hepatitis C virus (HCV) recurrence is almost universal after orthotopic liver transplantation (OLT), the impact of viral infection on liver graft is highly variable and difficult to predict. Because of the possible relationship between replicative senescence (RS) and the accelerated development of liver fibrosis, we aimed to assess the potential role of RS in the severity of HCV-related chronic hepatitis recurrence after OLT. METHODS: One hundred three liver biopsies from 56 patients receiving transplants for HCV-related cirrhosis were studied, including 30 revascularization biopsies and 52 and 21 biopsies performed during and beyond the first year of OLT, respectively. The presence of senescent cells in liver grafts was assessed by the senescence-associated beta-galactosidase (SA-beta-Gal) staining method. Chronic hepatitis was defined by fibrosis stage and necrotico-inflammatory activity grade using the METAVIR score. RESULTS: A total of 34 of the 103 (33%) frozen liver biopsies displayed SA-beta-Gal-positive cells, including 6 (20%) of the revascularization biopsies, 14 (34%) of the biopsies performed within the first year, and 10 (46%) of the biopsies performed beyond 1 year of follow-up. The presence of senescent cells in revascularization biopsies was significantly associated with the degree of ischemic necrosis at time of OLT (P = 0.01) and hepatitis C recurrence in the first year after OLT (P = 0.05). Furthermore, the presence of RS in the biopsy performed within the first year was associated with further development of fibrosis (P = 0.05). CONCLUSIONS: These data show that RS has a significant impact upon the course of liver transplantation, especially in the long-term progression of fibrosis observed in HCV-infected patients.

Differential expression of perforin and granzyme B in the liver of patients with chronic hepatitis C.

T lymphocytes have been reported to be the predominant inflammatory cells in the liver of patients with chronic hepatitis C. On activation, CD8+ T lymphocytes can exert their cytolytic activity by releasing their granule components, notably perforin and granzyme B. The aim of the present study was to assess whether the granule cytolytic pathway was used by liver-infiltrating CD8+ T lymphocytes. Immunostaining for perforin and granzyme B was performed in 25 patients with chronic hepatitis C, according to the disease activity and their virologic status. Cells stained for perforin and for granzyme B represented 0.15% and 0.10% of the total liver-infiltrating CD8+ T lymphocytes, respectively. Perforin was expressed mainly by activated CD8+ T lymphocytes located in liver lobules. In contrast, granzyme B was expressed mainly by activated CD8+ T lymphocytes located in interface hepatitis and portal tracts. The results were similar in the different groups of patients, whatever the disease activity. In conclusion, this is the first study showing a differential expression of granule components of CD8+ T lymphocytes in the same tissue in vivo. Perforin and granzyme B may be differently expressed by liver-infiltrating CD8+ T lymphocytes, according to their localization in the different specific compartments of the liver, in patients with chronic hepatitis C.

Early expression of adhesion molecules after lung transplantation: evidence for a role of aggregated P-selectin-positive platelets in human primary graft failure.

BACKGROUND: Primary graft failure (PGF) secondary to ischemia-reperfusion injury is the main cause of death in the first month after lung transplantation. The aim of this study was to identify early cellular and immunologic events associated with PGF in human lung transplants. METHODS: Induction of P-selectin, E-selectin and intercellular adhesion molecule-1 (ICAM-1) and evaluation of leukocytes and platelets accumulation were investigated in 18 post-reperfusion surgical specimens of lung allografts by an immunohistochemical technique. RESULTS: Selectins were restricted to the venular plexus after reperfusion as in the normal lung, whereas ICAM-1 was induced in all cases on alveolar capillaries. Numerous polymorphonuclear cells (18 of 18 cases) and aggregated platelets (7 of 18 cases) were identified along the venular plexus after reperfusion. Compared with the other patients, those with aggregated P-selectin-positive platelets were characterized by a longer duration of mechanical ventilation (p < 0.01), a lower PaO2/FiO2 ratio (p < 0.01) and the presence of radiologic edema (p < 0.05) within the first 3 post-operative days. CONCLUSIONS: We showed in the reperfused lung a distinct expression of adhesion molecules on venous and capillary pulmonary endothelia that may influence the role of leukocytes and platelets during the early course of transplantation. Furthermore, the knowledge of an association between the presence of P-selectin-positive platelet aggregates and PGF criteria might have implications for graft management and therapeutic strategies.

Correlation between patterns of DNA mismatch repair hmlh1 and hmsh2 protein expression and progression of dysplasia in intraductal papillary mucinous neoplasms of the pancreas.

Defective DNA mismatch repair results from genetic or epigenetic alterations that most frequently inactivate the genes hMLH1 and hMSH2. This is thought to promote tumourigenesis by accumulation of mutations in oncogenes and tumour suppressor genes. This pathway, first reported in colon cancer, has been recently demonstrated in a subgroup of sporadic pancreatic adenocarcinomas. Intraductal papillary-mucinous neoplasms of the pancreas are a special type of pancreatic tumours, characterised by a spectrum of morphological changes from mild to moderate and to non-invasive, and they may associate with adenocarcinoma. An immunohistochemical study of hmlh1 and hmsh2 protein expression was performed on 26 intraductal papillary-mucinous neoplasms. All tumours showed nuclear expression of hmlh1 and hmsh2 proteins. There were two distinctive patterns of protein expression on the basis of the location of cells expressing these markers: the "normal" pattern, observed mainly in adenoma and rarely in intraductal papillary-mucinous neoplasms with moderate dysplasia and the "dysplastic" pattern, frequently encountered in moderate dysplasia neoplasms, non-invasive and invasive carcinomas. These findings suggest that defective DNA mismatch repair, due to inactivation of hMLH1 and hMSH2, does not play a significant role in the pathogenesis of intraductal papillary-mucinous neoplasms of the pancreas. Two patterns of protein expression were observed and were correlated with the progression of dysplasia in intraductal papillary mucinous neoplasms.

Human chorionic gonadotrophin beta expression in malignant Barrett's oesophagus.

BACKGROUND: Human chorionic gonadotrophin beta (hCGbeta) is expressed in several non-trophoblastic tumours, and this is usually associated with aggressive behaviour. Little is known about hCGbeta expression in Barrett's adenocarcinoma. MATERIALS AND METHODS: We determined the hCGbeta profile in a large series of surgically resected Barrett's adenocarcinoma (a) at mRNA level using real-time quantitative reverse-transcription polymerase chain reaction analysis and (b) at protein level using immunohistochemistry with a polyclonal antibody and with a monoclonal antibody specific for free hCGbeta. We then sought links between the hCGbeta protein expression pattern and clinical and pathological parameters, including patient outcome as well as vascular endothelial growth factor (VEGF) expression. RESULTS: hCGbeta protein expression was observed in 43 of 76 (57%) Barrett's adenocarcinomas. We showed a strong correlation between hCGbeta protein abundance and CGB mRNA level. We observed a statistical link between hCGbeta protein expression and infiltrative tumour type ( P=0.023), perineural neoplastic invasion ( P=0.007) and VEGF protein expression ( P=0.016). hCGbeta expression tended to be associated with a poor outcome (16% versus 36% survival 8 years after resection). CONCLUSION: Expression of hCGbeta correlates with specific infiltrative characteristics and is associated with higher VEGF expression. Both molecules may play a co-ordinated role in the development of Barrett's adenocarcinomas.

Mucinous cystadenoma with mesenchymal over-growth: a new variant among pancreatic mucinous cystadenomas?

We report an unusual type of mucinous cystadenoma of the pancreas, characterised by a predominantly solid gross appearance due to the presence of an abundant ovarian-type stroma. The tumour, located in the body of the pancreas, was discovered after episodes of acute pancreatitis. It was composed of several mucus-secreting benign cysts placed within a highly cellular ovarian-type stroma, composed of undifferentiated spindle cells with mild atypia but without any increase of mitotic activity and with a low proliferative index. These cells expressed oestrogen and progesterone receptors, but they did not express CD34, CD117, p53 protein or bcl-2. Recognition of this peculiar mainly solid mucinous cystadenoma containing an abundant ovarian-type stroma is difficult. It is conceivable that the mesenchymal component described in our case could represent an early stage in the development of sarcoma in mucinous cystadenoma of the pancreas.

Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial.

CONTEXT: Treatment of chronic hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients is a growing concern. Most data on the virologic efficacy and safety of the combination of peginterferon alfa-2b and ribavirin in coinfected patients come from uncontrolled studies. OBJECTIVE: To study the safety and efficacy of peginterferon alfa-2b plus ribavirin vs standard interferon alfa-2b plus ribavirin in HIV-HCV coinfected patients. DESIGN AND SETTINGS: A multicenter, randomized, parallel-group, open-label trial. Patients were enrolled from February 2000 to February 2002 and followed up for 72 weeks. PATIENTS: Four hundred twelve HIV-HCV coinfected patients with detectable serum HCV-RNA, abnormal liver histology, a CD4 cell count of at least 200 x 10(6)/L, and stable plasma HIV-RNA. INTERVENTION: Treatment with ribavirin 400 mg twice a day, orally, plus either peginterferon alfa-2b (1.5 microg/kg subcutaneous injection once a week) or standard interferon alfa-2b (3 million units of subcutaneous injection 3 times a week) for 48 weeks. MAIN OUTCOME MEASURES: Sustained virologic response, defined by undetectable serum HCV-RNA at week 72. RESULTS: More patients had sustained virologic responses in the peginterferon group than in the standard interferon group (27% vs 20%, P = .047). This difference between the treatments was found in patients with HCV genotype 1 or 4 infection (17% for peginterferon vs 6% for standard interferon, P = .006) but was not found in patients with HCV genotype 2, 3, or 5 (44% for peginterferon vs 43% for standard interferon, P = .88). Together, a decline in HCV-RNA of less than 2 log10 from baseline and detectable serum HCV-RNA at week 12 predicted 99% of treatment failures. Histologic activity diminished and fibrosis stabilized in virologic responders. The 2 regimens showed similar tolerability although dose modifications for clinical and biological events were more frequent with peginterferon. Eleven cases of pancreatitis or symptomatic hyperlactatemia were observed, all in patients receiving didanosine-containing antiretroviral regimens. CONCLUSION: In combination with ribavirin, treatment with peginterferon alfa-2b is more effective than standard interferon alfa-2b for HCV infection in HIV-infected patients.

[Inflammatory pseudo-tumor of the liver: is pre-operative diagnosis possible?]. / Pseudo-tumeur inflammatoire du foie: le diagnostic pré-opératoire est-il possible?

UNLABELLED: Inflammatory pseudo-tumors of the liver are rare and difficult to diagnose, mimicking malignant tumors. OBJECTIVES: To specify the circumstances of detection and the clinical, biological, radiological and pathological features of inflammatory pseudo-tumors, in order to improve preoperative diagnosis. METHODS: Diagnosis of inflammatory pseudo-tumors of the liver was performed on surgical specimens in 8 patients from January 1987 to January 2001. We retrospectively analyzed the clinical, biological, radiological and pathological features of these 8 inflammatory pseudo-tumors. RESULTS: All the patients (5 females and 3 males) presented a chronic infectious syndrome and/or previous history of chronic inflammatory disease. The correlation between biological, radiological and pathological aspects showed two distinctive types of inflammatory pseudo-tumors: a type revealed by a biological inflammatory syndrome, with a non encapsulated, heterogeneous and hypervascular lesion at imaging, and a dense fibroblastic inflammatory pseudo-tumor with portal endophlebitis on histology (n=5), and a type without inflammatory syndrome, with an encapsulated, homogeneous, hypovascular lesion at imaging and abundant necrosis on histology (n=3). CONCLUSION: The analysis of previous history, of clinical, biological and radiological presentations, specially MRI, could predict the diagnosis of inflammatory lesion which must be confirmed by trans-parietal biopsy to avoid inappropriate radical hepatectomy.

[An unusual cause of multiple hepatic cysts]. / Kystes multiples du foie: une étiologie inhabituelle.

A metastatic hepatic process, generally arising from a primary tumor of the gastrointestinal tract, is a common cause of multinodular and/or multicystic liver. If the primary tumor remains unknown in spite of complete and exhaustive explorations, it might be useful to re-evaluate the benign nature of previously resected tumors. We report the case of a 37 year-old woman who presented a multicystic metastatic liver related to a nasal cylindrical cell carcinoma resected 4 years earlier and diagnosed initially "inverted papilloma". Cylindrical cell carcinoma also called "transitional carcinoma" or "schneiderian carcinoma" is rare with only a few cases reported in the literature. Metastases occur generally in the lungs and no previous reported cases mention secondary hepatic location.

[Malignant biliary papillomatosis: analysis of p53 expression]. / Papillomatose maligne des voies biliaires et expression de la protéine p53.

Biliary papillomatosis is a papillary adenomatosis of the biliary mucosa of the extra- and the intrahepatic biliary tree. It is a rare neoplasm difficult to manage, characterized by extensive lesions and a great potential for malignant transformation. We report a case of a 75 year-old man, who presented with malignant papillomatosis of the common bile duct without involvement of the intrahepatic biliary ducts. Duodenopancreatectomy enabled the diagnosis of papillomatosis lined 5.5 cm of the common bile duct which displayed an invasive 1.5 cm papillary carcinoma located in the distal portion of the choledocus. Immunohistochemistry showed strong expression of p53 in the distally located invasive carcinoma and in distant dysplastic lesions. MUC5AC was exclusively detected in both malignant and dysplastic lesions without detection of MUC1 or MUC2. Detection of p53 expression on biliary brush samples could be interesting for the follow-up and the prediction of malignant progression in multifocal biliary papillomatosis.

[Undifferentiated embryonal sarcoma of the liver in an adult: a case report]. / Sarcome indifférencié (embryonnaire) hépatique développé chez un adulte: à propos d'un cas.

Undifferentiated embryonal sarcoma of the liver is rare. It is usually observed in children and adolescents. We report one case of embryonal sarcoma of the liver arising in patient without any antecedent. The only symptom was right scapular pain. The liver scan showed a multicystic lesion suspicious for infectious origin or a tumor. Serologies for ecchinococcus, schistosomiasis and brucellosis were negative. The treatment was a right hepatectomy. On gross examination, the tumor was unencapsulated, multicystic and contained large areas of necrosis admixed with gelatinous areas. Microscopically, there were epithelioid and spindle tumor cells in a myxoïd stroma. Lipoblastic-like or rhabdomyoblastic-like, giant cells and PAS positive hyaline globules in the cell cytoplasm were present. The tumor cells expressed vimentin, cytokeratin (KL1), alpha-1-antitrypsin and smooth muscle actin. This observation shows that embryonal sarcoma of the liver may develop in adult patients and should be taken into consideration in any differential diagnosis of cystic hepatic tumor.

[Acinar cystic transformation of the pancreas (or acinar cell cystadenoma), a rare and recently described entity]. / Un cas d'une lésion rare et récemment décrite: la transformation kystique des acini pancréatiques (ou cystadénome à cellules acineuses).

We report a case of cystic acinar transformation (also known as acinar cell cystadenoma) of the pancreas. A 40-year old woman presented 3 episodes of acute pancreatitis that revealed a multicystic lesion of the ventral part of the head of the pancreas. A Whipple resection was performed. Gross examination of the specimen revealed a well-demarcated multiloculated cyst measuring 4 x 2 cm without communication with the excretory ducts. The cystic spaces contained a non-mucinous fluid. Histological analysis showed numerous various sized cysts that seemed to develop from microcystic structures in the surrounding acinar tissue. The cysts were lined by normal appearing acinar cells, with no atypia, sometimes flattened. Acinar cystic transformation is a rare lesion of the pancreas whose histogenesis is unknown. It should be distinguished from other lesions such as IPMT in order to discuss a surveillance strategy instead of surgical procedure.