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

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

Predictors of Posterior Cruciate Ligament Degeneration in Osteoarthritic Knees

Purpose.To evaluate the tibial articular cartilage and histology of the posterior cruciate ligament (PCL) in osteoarthritic knees so as to determine predictors of PCL degeneration.Methods.23 advanced osteoarthritic knees (mean patient age, 61 years) treated with total knee arthroplasty (TKA) were prospectively studied. The Knee Society Score was assessed. Osteoarthritic changes on radiographs were graded as mild, moderate, or severe. Tibial articular cartilage erosion was assessed. The appearance of both cruciate ligaments was classified as normal, abnormal (thinner and sclerotic), or ruptured. Both ligaments were examined histologically for degenerative changes. Each degenerative change of the PCL was graded by 2 histopathologists twice separately. Higher scores indicated more severe degeneration.Results.Of the 23 knees, the gross appearance of the anterior cruciate ligaments (ACLs) was normal in 6, abnormal in 11, and ruptured in 6. Histologically, the PCLs were normal in 4, minimally degenerated in 2, mildly in 8, moderately in 5, and severely in 4. The predominant degenerative change was the presence of loose fibrous tissue. ACL appearance correlated positively with PCL degeneration ( r=0.883, p=0.001). The mean Knee Society Score was 24 (range, 0–43), and the mean function score was 30 (range, 5–55). PCL degeneration correlated positively with the Knee Society Score ( r=0.565, p=0.02) but not with the function score ( r=0.061, p=0.447). Anteroposterior instability correlated positively with PCL degeneration ( r=0.691, p=0.01). Erosion in the lateral tibiofemoral compartment and ACL insufficiency were indicators of PCL degeneration (despite a normal appearance). Inter-observer reliability and intra-observer reproducibility were 0.82 and 0.87, respectively.Conclusion.The Knee Society Score, anteroposterior instability, ACL appearance, and erosion in the lateral tibiofemoral compartment are predictors of PCL degeneration and can help decide on the optimal type of TKA implant (PCL-retaining vs. PCL-sacrificing design).</jats:sec