Alejandra Avagnina

The pan-caspase inhibitor Emricasan (IDN-6556) decreases liver injury and fibrosis in a murine model of non-alcoholic steatohepatitis

Hepatocyte apoptosis, the hallmark of non‐alcoholic steatohepatitis (NASH) contributes to liver injury and fibrosis. Although, both the intrinsic and extrinsic apoptotic pathways are involved in the pathogenesis of NASH, the final common step of apoptosis is executed by a family of cysteine‐proteases termed caspases. Thus, our aim was to ascertain if administration of Emricasan, a pan‐caspase inhibitor, ameliorates liver injury and fibrosis in a murine model of NASH.

Helicobacter pylori associated with glossitis and halitosis.

Background.  Helicobacter pylori is a curved microaerophilic Gram‐negative bacterium considered as a risk factor for gastric cancer. The aim of this study was to find an association between burning sensations, acid taste, halitosis, and lingual hyperplasia with the effect of H. pylori on the mouth.

Primitive Neuroectodermal Tumor of the Lung

Primitive neuroectodermal tumors occur most frequently in bone and soft tissue but have been reported in other locations. Primary lung primitive neuroectodermal tumors without pleural or chest wall involvement are extremely rare. We present a case with immunohistochemical and ultrastructural studies and follow-up of the patient. An 18-year-old man presented with hemoptysis. Chest radiographs revealed a right middle lobe mass, and bronchoscopy showed an endobronchial tumor. The lesion was resected by middle lobectomy. After 2 years, a local recurrence was treated by pneumonectomy. The patient died after surgery. Histologically, the tumor was composed of uniform cells with round nuclei and scanty cytoplasm arranged in cohesive lobules with occasional rosette formation. Immunohistochemically, the tumor was positive for vimentin, CD99, neuron-specific enolase, and neurofilaments. Ultrastructural study revealed neurosecretory granules and cytoplasmic processes. Our case shows the value of immunohistochemistry and electron microscopy in the diagnosis of primitive neuroectodermal tumors in unusual locations.

Helicobacter pylori and oral pathology: Relationship with the gastric infection

Helicobacter pylori (H. pylori) has been found in the oral cavity and stomach, and its infection is one of the most frequent worldwide. We reviewed the literature and conducted a Topic Highlight, which identified studies reporting an association between H. pylori-infection in the oral cavity and H. pylori-positive stomach bacterium. This work was designed to determine whether H. pylori is the etiologic agent in periodontal disease, recurrent aphthous stomatitis (RAS), squamous cell carcinoma, burning and halitosis. Record selection focused on the highest quality studies and meta-analyses. We selected 48 articles reporting on the association between saliva and plaque and H. pylori-infection. In order to assess periodontal disease data, we included 12 clinical trials and 1 meta-analysis. We evaluated 13 published articles that addressed the potential association with RAS, and 6 with squamous cell carcinoma. Fourteen publications focused on our questions on burning and halitosis. There is a close relation between H. pylori infection in the oral cavity and the stomach. The mouth is the first extra-gastric reservoir. Regarding the role of H. pylori in the etiology of squamous cell carcinoma, no evidence is still available.

Severe cholestatic hepatitis as the first symptom of secondary syphilis.

A 57-year-old homosexual patient with controlled hypertension and hyperlipidaemia was referred to us for assessment of a 3-week history of generalized fatigue, anorexia, low-grade fever, and abnormal liver function tests. At physical examination the liver spam was 5 cm at the midclavicular line, he had no skin lesions or peripheral adenopathy. Laboratory evaluation showed the following: alkaline phosphatase (ALP), 1568 IU/L; AST, 139 IU/L; ALT, 315 IU/L; total bilirubin, 0.8 mg/dL; γ -globulins, 2.15 g/L (normal: <1.6 g/L); hematocrit, 35.9% (normal, 45–50%); hemoglobin, 12.4 g/dL (normal, 14–17 g/dL); and sedimentation rate, 93 mm/hr. The patient was on atorvastatin, 40 mg qd; atenolol, 50 mg qd; and aspirin, 325 mg qd. A complete laboratory workup done 2 months before the consultation was normal (Table 1). The patient had no history of recent exposure to hepatitis, drugs, tattoos, body piercing, or transfusions and denied alcohol consumption. Further laboratory tests showed the following: HAV IgG+ IgM−; EBV VCA IgG+ IgM−; CMV IgG+ IgM−; ANA−; ASMA 1/10; AMA 1/50, types 2 and 5; HIV−; anti-HCV; anti-

Pulmonary rhabdomyosarcoma with isolated small bowel metastasis. A report of a case with immunohistochemical and ultrastructural studies.

A unique case of pulmonary rhabdomyosarcoma with an isolated, symptomatic small bowel metastasis is presented. The tumor affected the middle lobe, and was treated with a right pneumonectomy. Eleven months after the operation, an isolated small bowel metastasis, which produced intestinal obstruction, was resected. The patient is currently alive, 11 months after operation. The myogenous nature of the tumor was confirmed by the immunohistochemical demonstration of myoglobin in the pulmonary and enteric lesion by the ultrastructural findings of poorly developed sarcomeres.

Immunohistochemical characterization of neoplastic cells of breast origin.

BackgroundAfter skin cancer, breast cancer is the most common malignancy in women. Tumors of unknown origin account for 5-15% of malignant neoplasms, with 1.5% being breast cancer. An immunohistochemical panel with conventional and newer markers, such as mammaglobin, was selected for the detection of neoplastic cells of breast origin. The specific objectives are: 1) to determine the sensitivity and specificity of the panel, with a special emphasis on the inclusion of the mammaglobin marker, and 2) to compare immunohistochemistry performed on whole tissue sections and on Tissue Micro-Array.MethodsTwenty-nine metastatic breast tumors were included and assumed as tumors of unknown origin. Other 48 biopsies of diverse tissues were selected and assumed as negative controls. Tissue Micro-Array was performed. Immunohistochemistry for mammaglobin, gross cystic disease fluid protein-15, estrogen receptor, progesterone receptor and cytokeratin 7 was done.ResultsMammaglobin positive staining was observed in 10/29 cases, in 13/29 cases for gross cystic disease fluid protein-15, in 20/29 cases for estrogen receptor, in 9/29 cases for progesterone receptor, and in 25/29 cases for cytokeratin 7. Among the negative controls, mammaglobin was positive in 2/48, and gross cystic disease fluid protein-15 in 4/48.ConclusionsThe inclusion of MAG antibody in the immunohistochemical panel for the detection of tumors of unknown origin contributed to the detection of metastasis of breast cancer. The diagnostic strategy with the highest positive predictive value (88%) included hormone receptors and mammaglobin in serial manner.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1366310812718988

779 PF-03491390 PAN-CASPASE INHIBITOR DECREASES LIVER INJURY AND FIBROSIS IN A MURINE MODEL OF NON-ALCOHOLIC STEATOHEPATITIS (NASH)

with 5% of patients who received the BAP placebo in the SOC arm. Lymphopenia was the most common reason for discontinuation of BAP. There were 2 deaths reported in the study (primary varicella and B-cell lymphoma) and these were considered related to study medication and a potential consequence of the lymphopenia. Conclusions: When combined with the SOC, BAP increased the rate of RVR and cEVR in genotype 1 patients; however, the drug did not confer an SVR advantage due in part to frequent safetyrelated dose reductions and discontinuations for both BAP and SOC. Further development of BAP has been halted because of the unfavourable benefit:risk ratio. Investigations are ongoing to explore the mechanism of BAP-related toxicity.

Sentinel Lymph Nodes Study: How to Do it Right? The Argentinean Experience

To the Editor: We would like to express our opinion about the article by Treseler et al. (1). We congratulate them on the exhaustive review of the most recent and relevant information about sentinel lymph nodes (SLN) evaluation and its clinical implications. In this letter we would like to stress some points regarding molecular studies. Even though most published data have shown a decrease in overall and disease-free survival in patients with micrometastases detected by hematoxylineosin (HE) or immunohistochemistry (IHC), the latter is not routinely recommended for clinical practice in most countries (1). However, retrospective studies of serial sections with HE have revealed metastases in approximately 30% of cases (2). To date, molecular-techniques for detection of specific markers by Retro Transcription-Polymerase Chain Reaction (RT-PCR) are only used for experimental purposes. In the last few years, several molecular markers has been proposed in the literature, such as CEA, PIP, CK19, MUC1, PSE, mammaglobin (MAG) A, and MAG-B (3). Recently, worldwide literature has demonstrated that MAG is the most sensitive and specific (3–6). Over the last 2 years, our research group has pioneered the study of MAG (both isoforms A and B) in Argentine. The purpose of our study was to analyze the presence of messenger RNA of MAG A and B in breast SLN by RT-PCR, and to correlate these findings with routine techniques (HE and IHC). To date, this experimental protocol includes 40 patients, all of them with primary tumor size £3 cm, and no palpable axillary lymphadenopathies. Conventional techniques (HE) showed metastases in 4 ⁄ 40 cases. We found 5 ⁄ 40 cases with IHC (Cytokeratin AE1-AE3), one of them negative with HE. Molecular biology techniques revealed 12 ⁄ 40 positive SLN with MAG A and B by RT-PCR, which comprised the five above-mentioned cases (four cases were positive with MAG-A, three with MAG-B, and five with both). Our study is one of the first designs using an RT-PCR multiplex, which includes both isoforms of MAG (A and B), in an attempt to increase the detection rate. Our results with molecular biology (12 ⁄ 40) are similar to other published data (3,7,8). Multiplex RT-PCR technique for MAG A and B proves to be specific and sensitive. To date, the only patient with HE(+), IHC(+), MGBA(+), and MGB-B(+) had disease relapse at 23 months of follow-up. All the other patients appear to be disease-free. However, we believe that they should be followed up for a longer period of time to determine whether there is a significant impact of RT-PCR positive findings. Our study has shown the Argentinean experience with a known molecular marker but with a novel approach to RT-PCR technique. Finally, we hope to encourage the development of new research protocols that include the use of molecular techniques in SLN evaluation. Based on current knowledge, we think other experimental protocols including more patients and a longer follow-up should be further developed, in order to assess their real prognostic value.

Soft Tissue Metastasis as Initial Manifestation of Pleural Malignant Mesothelioma: A Case Report

Distant metastases of pleural malignant mesothelioma (MM) are infrequent. We report a case of MM that presented as a skeletal muscle metastasis. This type of presentation has not been previously reported. A 38-year-old male complained about a mass in his right forearm. The tumor showed the histologic pattern, immunohistochemical phenotype, and ultrastructural features of an MM. In the clinical work-up, the x-ray film and computed tomography scan demonstrated pleural effusion and diffuse pleural thickening in the right hemithorax. The pleural biopsy showed an epithelial MM. The patient died from local progression of the disease 6 months after the diagnosis. No other distant metastases were clinically evident. Our case shows the importance of including MM in the differential diagnosis of metastatic neoplasms in skeletal muscle and the usefulness of ancillary techniques in the diagnosis of mesothelial neoplasms.