Atypical MYC rearrangement pattern of 3? deletion and 5? amplification along with independent IGH rearrangement: A case study

A spectrum of Cellular homolog of the v-myc oncogene (cMYC) alterations such as translocation, overexpression, mutation, and amplification plays an important role in lymphomagenesis, particularly in high-grade lymphomas, and are associated with prognostic significance. Accurate identification of cMYC gene alteration is important for diagnostic, prognostic, and therapeutic implications. With the application of different FISH (fluorescence in situ hybridization) probes that helped overcome the analytical diagnostic challenges as a result of variant patterns, we report rare, concomitant, and independent gene alterations in cMYC and Immunoglobulin heavy-chain gene (IGH) with detailed characterization of its variant rearrangement. Short-term follow-up post R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy seemed to be favorable. Accumulation of many more literature studies on such cases with their therapeutic implications would lead to the categorization of these cases as a separate subclass in large B-cell lymphomas followed by molecular targeted therapy.

Cerebral blastomycosis: a case report.

Blastomycosis is a chronic systemic fungal infection characteristically affecting the skin and lungs. Involvement of the central nervous system (CNS) is unusual, with cases generally presenting with meningitis, and rarely as intracranial mass lesion and solitary or multiple abscesses. Only two cases of intracranial extra-axial blastomycosis have been reported from India, and we report the third case, which presented as meningioma in a 23-year old female.

Neuropathological spectrum of lesions associated with intractable epilepsies: a 10-year experience with a series of 153 resections.

BACKGROUND: Surgical management of intractable epilepsies is currently an established mode of therapy in various clinical settings. AIMS: To retrospectively evaluate the neuropathological findings in both temporal and extratemporal lobe resections in such patients. MATERIALS AND METHODS: The study included resected specimens from patients with intractable epilepsy managed at a tertiary care hospital of India, during a 10-year period (1995-2004). RESULTS: A total of 153 patients, with mean age of 19.4 years and male predominance (73.2%) were included in the study. Overall, there was a predilection for the temporal lobe (73.2%), while 41cases were extratemporal in location. On histopathology, mesial temporal sclerosis (MTS) (24.8%) was the commonest lesion, followed by tumors (19.6%) and isolated focal cortical dysplasia (FCD - 15.11%). Other less common findings included Rasmussen encephalitis, non-specific gliosis and vascular malformations. In addition, 20.9% (32 cases) had dual lesions, majority of which included FCD with ganglioglioma (15 cases) or with dysembryoplastic neuroepithelial tumor (12 cases). In the temporal lobe, neoplasms and dual lesions formed the majority (apart from MTS), unlike dual lesions followed by neoplasms and FCD, in the extratemporal location. CONCLUSION: This series demonstrates that most patients with chronic intractable epilepsy have significant histopathological findings and highlights the neuropathological spectrum of such lesions, in the Indian context. This was similar to that reported from the West, but different from the single Indian series available in the literature. Further, the overall profile of temporal lobe lesions was not different from the extratemporal ones.

Medulloblastomas: new directions in risk stratification.

Medulloblastomas (MBs) are the most common malignant brain tumors in children. Current therapeutic approaches combine surgery, radiotherapy, and chemotherapy. Although, there has been significant improvement in long-term survival rates, the tumor remains incurable in about a third of patients while cognitive deficits and other sequelae of therapy are common among long-term survivors. Hence a major challenge remains to differentiate high-from low-risk patients and to tailor therapy based on the degree of biological aggressiveness. A clinical risk-stratification system has been widely used in MBs based on age, extent of resection and the Chang staging system. However, recent reports indicate that these clinical variables are inadequate methods of defining disease risk. This has prompted search for new markers for MB stratification. Recent studies indicate that the classification of MBs according to profiles of histopathology and molecular abnormalities possibly help better risk-stratification of patients, thereby rationalizing approaches to therapy, increasing cure rate, reducing long-term side effects and developing novel therapeutic strategies. The most accurate outcome prediction till date has been obtained through microarray gene expression profiling. In this article, the current histopathological classification and the recent advances in molecular genetics of MBs are reviewed. Global efforts to translate this knowledge of disease biology into clinical practice especially as outcome predictors are highlighted.

Glioblastoma multiforme with long term survival.

Glioblastoma multiforme (GBM) Patients generally have a dismal prognosis, with median survival of 10-12 months. GBM with long-term survival (LTS) of (3) > or = 5 years is rare, and no definite markers indicating better prognosis have been identified till date. The present study was undertaken to evaluate GBMs with LTS in order to identify additional correlates associated with favourable outcome. The cases were evaluated for relevant clinicopathological data, proliferation index and expression of tumortumour suppressor gene (p53 ), cyclin-dependant kinase-inhibitors (p27 and p16 ) and epidermal growth factor receptor (EGFR) proteins. Six cases of GBM with LTS with an average survival of 9 years (range 5-15 years) were identified. All were young patients with mean age of 27 years (range 8-45 years). Histology of three cases was consistent with conventional GBM, while two showed prominent oligodendroglial component admixed with GBM areas. One was a giant cell GBM, which progressed to gliosarcoma on recurrence. The mean MIB-1LI was 12% (range 6-20%). p53 was immunopositive in 4 out of 5 cases. EGFR and p27 were immunonegative in all, whereas p16 was immunonegative in 3 out of 5 cases. Currently, in the absence of specific molecular and genetic markers, GBM in young patients should be meticulously evaluated for foci of oligodendroglial component and/or giant cell elements, in addition to proliferative index and p53 expression, since these probably have prognostic connotations, as evident in this study. The role of p16 and p27 however needs better definition with study of more number of cases.

Neuropathological spectrum of Rasmussen encephalitis.

BACKGROUND: Rasmussen encephalitis (RE) is a chronic epileptic disorder of unknown etiology, and is clinically characterized by progressive neurological deterioration, focal seizures often progressing to intractable epilepsy, cognitive decline and hemispheric atrophy. AIMS: We report the spectrum of neuropathological changes seen in RE, and discuss the evolutionary mechanisms of this disease. MATERIALS AND METHODS: Surgically obtained specimens from RE patients diagnosed during 2002-2004 at this institute were evaluated for the presence and extent of different histopathological features of RE. The H&E and immunohistochemistry stained slides were also evaluated for the type and distribution pattern of inflammatory infiltrates, along with a semiquantitative evaluation for the severity of inflammation. RESULTS: Four cases of RE were admitted during the study period, all of which presented with partial seizures with successive deterioration to intractable epilepsy. The age at onset varied between 5 and 10 years (mean 7.8 years), with three male and one female patients. Subsequently, all four patients underwent hemispherotomy. Histopathological features of perivascular lymphocytic infiltrate, neuronal loss, microglial nodules, and reactive astrocytosis, with or without evidence of neuronophagia confirmed a diagnosis of RE. These cases also had varying degrees of T-cell-rich (CD3-positive) inflammatory infiltrates and CD68-immunopositive microglial proliferation. It was observed that the severity of inflammation had a trend to inversely correlate with the duration of symptoms. CONCLUSION: It is proposed that an accurate evaluation and histopathological grading of these lesions may possibly have a role in patient prognostication.