A Free Community Approach to Classifying Disease

Defining and classifying disease is at the heart of medical practice, but the process is slow and laborious. A new "open source" approach could be faster and more democrati

Primary diffuse large B-cell lymphoma of the CNS, with a “Lymphomatosis cerebri” pattern

We describe an unusual case of lymphomatosis cerebri in a middle-aged lady presenting with rapid-onset dementia. The lymphomatous infiltrate, instead of forming mass lesions, percolated throughout the brain parenchyma, which is often missed on a stereotactic biopsy and hence warrants caution and awareness about this entity. The nonspecific symptoms at presentation and a variable picture at imaging make this entity diagnostically challenging

The role of immunohistochemistry in medullomyoblastoma – a case series highlighting divergent differentiation

<p>Abstract</p> <p>Aims</p> <p>To analyse the histo-morphology of cases of medullomyoblastoma and identifying its divergent differentiation.</p> <p>Methods</p> <p>A retrospective review of all cases reported as medulloblastoma between the period of Jan 2000 to Dec 2006 was carried out on Hematoxylin and eosin (H & E) stained slides. The cases were screened on light microscopy for primitive neuroectodermal component of a medulloblastoma accompanied by areas of "myoid" differentiation, identified on the basis of presence of strap cells (indicating a clear skeletal muscle differentiation) and/or large anaplastic cells with vescicular nuclei and moderate to abundant amount of eosinophilic cytoplasm. All these cases were subjected to a panel of immunohistochemical stains, including Desmin, GFAP, NFP, HMB45, SMA, S100, CK and EMA. Ultrastructral analysis was done on tissue obtained from paraffin blocks in 2 cases.</p> <p>Results</p> <p>Male predominance (M:F = 5:1) was noted with an incidence of five percent of all cases of medulloblastoma (6 out of 120 cases) over a period of 6 years. Primitive neuroectodermal areas were accompanied with areas of "myoid" differentiation, 5 cases showing strap cells. Two cases with epithelial and cartilaginous differentiation were seen. Three cases showed focal melanocytic differentiation, identified only on HMB45 immunostaining. Four cases showed glial differentiation. Neuronal differentiation again was very focally seen in two cases, of which one was identified only by NFP immunostain. Seventh case is included in the study, however it is not considered to calculate incidence as it occurred beyond the period of 6 years of records search.</p> <p>Conclusion</p> <p>Medullomyoblastoma is a rare childhood tumor of cerebellum. Majority of cases reveal divergent differentiation, which are identified with the help of panel of immunostains indicating multi-potential nature of primitive neuroectodermal cells.</p

Imatinib Inhibits GH Secretion From Somatotropinomas

Background: Imatinib, a tyrosine kinase inhibitor, causes growth failure in children with chronic myeloid leukemia probably by targeting the growth hormone (GH)/insulin like growth factor-1 (IGF-1) axis. We aim to explore the imatinib targets expression in pituitary adenomas and study the effect of imatinib on GH secretion in somatotropinoma cells and GH3 cell line.Materials and Methods: The expression pattern of imatinib's targets (c-kit, VEGF, and PDGFR-α/β) was studied using immunohistochemistry and immunoblotting 157 giant (≥4 cm) pituitary adenomas (121 non-functioning pituitary adenomas, 32 somatotropinomas, and four prolactinomas) and compared to normal pituitary (n = 4) obtained at autopsy. The effect imatinib on GH secretion, cell viability, immunohistochemistry, electron microscopy, and apoptosis was studied in primary culture of human somatotropinomas (n = 20) and in rat somato-mammotroph GH3 cell-line. A receptor tyrosine kinase array was applied to human samples to identify altered pathways.Results: Somatotropinomas showed significantly higher immunopositivity for c-kit and platelet-derived growth factor receptor-β (PDGFR-β; P &lt; 0.009 and P &lt; 0.001, respectively), while staining for platelet-derived growth factor receptor-α (PDGFR-α) and vascular endothelial growth factor (VEGF) revealed a weaker expression (P &lt; 0.001) compared to normal pituitary. Imatinib inhibited GH secretion from both primary culture (P &lt; 0.01) and GH3 cells (P &lt; 0.001), while it did not affect cell viability and apoptosis. The receptor tyrosine kinase array showed that imatinib inhibits GH signaling via PDGFR-β pathway.Conclusion: Imatinib inhibits GH secretion in somatotropinoma cells without affecting cell viability and may be used as an adjunct therapy for treating GH secreting pituitary adenomas

A study of Smad4, Smad6 and Smad7 in Surgically Resected Samples of Pancreatic Ductal Adenocarcinoma and Their Correlation with Clinicopathological Parameters and Patient Survival

<p>Abstract</p> <p>Background</p> <p>Smad4 is the common mediator of the tumor suppressive functions of TGF-beta. Smad6 and Smad7 are the antagonists of the TGF-beta pathway. This study investigates the differential protein expressions of Smad4, Smad6 and Smad7 in tumor as compared to normal tissue of pancreatic ductal adenocarcinoma (PDAC) and compares them with clinicopathological parameters and patient survival.</p> <p>Results</p> <p>There was a significant difference in protein expressions of Smad4 (p = 0.0001), Smad6 (p = 0.0015) and Smad7 (p = 0.0005) protein in tumor as compared to paired normal samples. Loss of Smad7 expression correlated significantly with tumor size (r = 0.421, p < 0.036) and margin status (r = 0.431; p < .032). Patients with moderate to high Smad4 protein expression had a better survival (median survival = 14.600 ± 2.112 months) than patients with absent or weak Smad4 protein expression (median survival = 7.150 ± 0.662). In addition, advanced disease stage correlated significantly with poor prognosis.</p> <p>Conclusion</p> <p>Loss of Smad4 significantly correlated with poor survival of PDAC patients. In the cases where Smad4 is expressed, Smad6 inhibition is possibly a novel mechanism for Smad4 inactivation. Smad7 has a role in pathobiology of PDAC. Further investigation in the roles of Smad6 and Smad7 would help in the identification of novel therapeutic targets for PDAC.</p

Alterations of tumor suppressor gene p16(INK4a )in pancreatic ductal carcinoma

BACKGROUND: Cell cycle inhibitor and tumor suppressor gene p16 / MTS-1 has been reported to be altered in a variety of human tumors. The purpose of the study was to evaluate primary pancreatic ductal adenocarcinomas for potentially inactivating p16 alterations. METHODS: We investigated the status of p16 gene by polymerase chain reaction (PCR), nonradioisotopic single strand conformation polymorphism (SSCP), DNA sequencing and hypermethylation analysis in 25 primary resected ductal adenocarcinomas. In addition, we investigated p16 protein expression in these cases by immunohistochemistry (IHC) using a monoclonal antibody clone (MS-887-PO). RESULTS: Out of the 25 samples analyzed and compared to normal pancreatic control tissues, the overall frequency of p16 alterations was 80% (20/25). Aberrant promoter methylation was the most common mechanism of gene inactivation present in 52% (13/25) cases, followed by coding sequence mutations in 16% (4/25) cases and presumably homozygous deletion in 12% (3/25) cases. These genetic alterations correlated well with p16 protein expression as complete loss of p16 protein was found in 18 of 25 tumors (72%). CONCLUSION: These findings confirm that loss of p16 function could be involved in pancreatic cancer and may explain at least in part the aggressive behaviour of this tumor type

Surgery, Octreotide, Temozolomide, Bevacizumab, Radiotherapy, and Pegvisomant Treatment of an AIP Mutation-Positive Child

UK India Education Research Initiative and the British Council (75-2014; to P.D.)Council of Scientific and Industrial Research, University Grants Commission, for financial support (2061330632; to A.R.).Medical Research Council (MR/M018539/1; to M.K

Invasive micropapillary carcinoma of urinary bladder: A clinicopathological study

Context: Micropapillary variant of urothelial carcinoma (MPUC) is a rare but well-recognized tumor of the urinary bladder. Tumors with micropapillary areas accompanying conventional urothelial carcinoma are more aggressive compared to conventional urothelial carcinoma and show variable keratin 7, keratin 20 and human epidermal growth factor receptor 2 (Her 2)neu expression. Aim: The aim of the study was to analyze the clinical, morphological and immunohistochemical profile of MPUC. Materials and Methods: Transurethral resection of bladder tumor (TURBT) chips of seven cases of invasive MPUC with subsequent cystoprostatectomy specimens of five patients was reviewed. Epithelial membrane antigen (EMA), Keratin 7, Keratin 20, and Her 2 immunohistochemistry were performed in all cases. Follow-up information was available for all patients (2-36 months). Results: All seven patients were male, and their ages ranged from 50 to 62 years. All cases presented with hematuria. The micropapillary pattern was seen in 20-95% of the tumor. All cases showed extensive lymphatic emboli with detrusor muscle invasion. Lymph node metastasis was present in all cases undergoing cystoprostatectomy except one. Keratin 7 and abluminal pattern of EMA positivity were seen in all cases. Keratin 20 was positive in five cases (71%), and Her 2neu positivity was seen in four cases. Three patients died 2, 3, and 6 months after initial diagnosis, among which two were Her 2 positive and one was Her 2 negative. There was no clear prognostic significance of Her 2 positivity. Conclusion: (1) MPUC is a rare but highly aggressive tumor. (2) Micropapillary is usually the predominant pattern. (3) Keratin 7 is expressed universally, whereas Keratin 20 expression is variable. (4) Her 2 expression has no clear influence on the survival