Prospective neuraxis MRI surveillance reveals a high risk of leptomeningeal dissemination in diffuse intrinsic pontine glioma.

Prognosis of diffuse intrinsic pontine gliomas (DIPGs) remains poor. Failure has been predominantly local, with leptomeningeal dissemination (LD) occurring in 4-33% of patients in pre-MRI era series. Routine craniospinal imaging after initial treatment may reveal other relapse patterns relapse. Sixteen consecutive pediatric patients with DIPG treated between 2006 and 2009 were retrospectively reviewed. Treatment regimens, recurrence patterns, survival, and pathologic diagnosis were recorded. Fourteen patients received involved-field radiotherapy to 54 Gy, and two patients received craniospinal irradiation for LD at presentation. Neuraxis MRI was performed at diagnosis and at 4 month intervals following radiotherapy. Fifteen patients have had progression of disease (median progression-free survival 5.0 ± 1.2 months), and 13 patients have died (median survival 9.0 ± 1.4 months). Local failure occurred in 12 patients (75%). LD occurred in nine patients (56%). LD was present at diagnosis in three patients, after initial staging and treatment in six patients, and during autopsy in two patients. Median overall survival was 12.0 ± 3.3 months without LD and 8.0 ± 2.1 months with LD (P = 0.059, log rank test). Median progression-free survival was 9.5 ± 3.9 months without LD and 3.0 ± 2.1 months with LD (P = 0.012, log rank test). The high incidence of LD probably reflects liberal use of spine MRI surveillance. All patients should undergo routine craniospinal imaging at diagnosis and follow-up. Central nervous system prophylaxis should be considered in future clinical trials.

Case Report of a Migrating Bullet: An Unusual Cause of Postmortem Confusion.

Migrating bullets are rare sequelae of penetrating gunshot wounds. Such cases have been described in the neurosurgical literature because they can produce complications in the management of patients such as decline in neurologic status, delays in rehabilitation, and difficulties in bullet removal. In contrast, few postmortem reports have described this phenomenon. We report a case of a gunshot wound in which the projectile entered the left side of the head and traversed to the right frontal area as documented by CT scan on hospital admission. At autopsy, the bullet was noted to have migrated back to the left side of the head from where it was recovered. Medical examiners need to be aware of this unusual phenomenon of retained intracranial projectiles.

Alzheimer's disease: brain desmosterol levels.

Desmosterol is a C27 sterol intermediate in cholesterol synthesis generated during the metabolic pathway that transforms lanosterol into cholesterol. It has become of particular interest in the pathogenesis of Alzheimer's disease (AD) because of the report that the activity of the gene coding for the enzyme DHCR24, which metabolizes desmosterol to cholesterol, is selectively reduced in the affected areas of the brain. Any change in the pattern of C27 sterol intermediates in cholesterol synthesis merits investigation with respect to the pathogenesis of AD, since neurosteroids such as progesterone can modulate the tissue levels. We therefore analyzed the C27 sterol composition using a metabolomics approach that preserves the proportion of the different sterol intermediates. In AD, the proportion of desmosterol was found to be less than that of age-matched controls. The findings do not directly support the focus on Seladin-1, although they could reflect different stages of a slowly progressive disease.

Pancreatic carcinoma with multilineage (acinar, neuroendocrine, and ductal) differentiation.

The preponderance of pancreatic tumors is adenocarcinoma of the ductal type; carcinomas with multiple lineage differentiation are extremely rare. We report an unusual case of pancreatic carcinoma with combined acinar and neuroendocrine differentiation and minor ductal component with concurrent acinar-ductal metaplasia (ADM), an early lesion implicated in ductal carcinogenesis. The patient is a 56-year-old man with vague complaints of dull left upper quadrant pain with radiation across the mid-portion of his abdomen. A computer tomography scan revealed an irregular enlargement of the distal 3.2 cm of the pancreatic body. A distal pancreatectomy was then performed. Histologic examination revealed a pancreatic carcinoma with cellular features of eosinophilic granular cytoplasm and salt-pepper nuclei. The acinar differentiation of the carcinoma was confirmed by positivity on periodic acid-Schiff stain resistant to diastase digestion (dPAS), positivity for antitrypsin on immunohistochemistry (IHC), and presence of zymogen granules on electron microscopy (EM). The neuroendocrine differentiation was evident by positive synaptophysin and chromogranin stain on IHC and neuroendocrine granules on EM. The ductal component was only visible by PAS stain and immunostains for CEA and CK19A and accompanied by a number of the acinar-ductal metaplasia lesions adjacent to the main tumor. Thus, the histological, histochemical, immunohistochemical and electron-microscopic evidence all suggested that the pancreatic carcinoma underwent trilineage differentiation.