Mitochondrial genome deletion aids in the identification of false- and true-negative prostate needle core biopsy specimens

We report the usefulness of a 3.4-kb mitochondrial genome deletion (3.4 mtdelta) for molecular definition of benign, malignant, and proximal to malignant (PTM) prostate needle biopsy specimens. The 3.4 mtdelta was identified through long-extension polymerase chain reaction (PCR) analysis of frozen prostate cancer samples. A quantitative PCR assay was developed to measure the levels of the 3.4 mtdelta in clinical samples. For normalization, amplifications of a nuclear target and total mitochondrial DNA were included. Cycle threshold data from these targets were used to calculate a score for each biopsy sample. In a pilot study of 38 benign, 29 malignant, and 41 PTM biopsy specimens, the difference between benign and malignant core biopsy specimens was well differentiated (P & .0001), with PTM indistinguishable from malignant samples (P = .833). Results of a larger study were identical. In comparison with histopathologic examination for benign and malignant samples, the sensitivity and specificity were 80% and 71%, respectively, and the area under a receiver operating characteristic (ROC) curve was 0.83 for the deletion. In a blinded external validation study, the sensitivity and specificity were 83% and 79%, and the area under the ROC curve was 0.87. The 3.4 mtdelta may be useful in defining malignant, benign, and PTM prostate tissues.     

Superior semicircular canal dehiscence: oblique reformatted CT images for diagnosis

PURPOSE: To retrospectively determine, by using thin-section multi-detector row computed tomography (CT), whether additional reformations in the planes of Stenver and P?schl change the diagnostic interpretation for superior semicircular canal dehiscence (SSCD) when compared with the diagnostic interpretation of standard coronal reformations for SSCD. MATERIALS AND METHODS: Institutional review board approval was obtained, patient anonymity was maintained, and the study was HIPAA compliant. Twenty-seven patients (17 men, 10 women; average age, 45 years; range, 19-72 years) suspected of having SSCD who underwent temporal bone multi-detector row CT were retrospectively identified from electronic medical records. An additional 27 control subjects (nine men, 18 women; average age, 50 years; range, 18-87 years), who underwent temporal bone multi-detector row CT for other reasons, were retrospectively selected from the same period. Two neuroradiologists with certificates of added qualification, one with 5 years and one with 9 years of experience interpreting temporal bone CT images, independently reviewed the 108 temporal bones twice. One review was restricted to transverse images and coronal reformations. The other review used transverse images, coronal reformations, and oblique reformations in the planes of Stenver and P?schl. The observers were blinded to clinical history, and the two reviews took place 3 months apart to avoid recall bias. The primary outcome measure was the intraobserver discordance rate between the two reviews. kappa Statistics were used to evaluate both intraobserver and interobserver variability. Results: Observer 1 diagnosed SSCD in 25 of 108 (23%) temporal bones and had no discordances between the two reviews. Observer 2 diagnosed SSCD in 21 of 108 (19%) temporal bones and had one intraobserver discordance. After a post hoc consensus review of this one discordance, the radiologic diagnosis remained equivocal. The discordance involved the right temporal bone of a patient suspected of having SSCD in the left temporal bone, so no clinical follow-up was available. CONCLUSION: Coronal reformations from multi-detector row CT of the temporal bone are sufficient for the evaluation of SSCD. Additional reformations in the planes of Stenver and P?schl do not change the radiologic diagnosis and may be reserved for equivocal or confusing cases.     

Proximal nerve root spinal hemangioblastomas: presentation of three cases, MR appearance, and literature review

BACKGROUND: Hemangioblastomas (HBLs) are relatively uncommon tumors of uncertain histogenesis usually located in the cerebellum or spinal cord. Much less frequently they are identified in extramedullary locations including the filum terminale, proximal nerve roots, or even distal nerves of the peripheral nervous system (PNS). PNS cases not only present diagnostic challenges but also raise interesting questions regarding the common cell of origin for these CNS and PNS neoplasms. Few studies have detailed the neuroimaging characteristics of the rare extramedullary variants. METHODS: Neuroimaging and intraoperative findings of three recent cases of proximal nerve root HBLs are described. The English language literature on extramedullary HBLs is reviewed and discussed, particularly in regards to magnetic resonance (MR) findings and association with von Hippel-Lindau Syndrome (VHL). RESULTS: All 3 of our cases had prominent vessels present within the subarachnoid space on MR scans and all lesions enhanced. All were of intermediate or mildly decreased signal intensity on the T1-weighted images before contrast and were either iso- or hyperintense to spinal cord on the T2-weighted images. Two had probable cystic areas on MR, and all had cystic areas on histologic evaluation. CONCLUSION: These neuroimaging characteristics can serve to distinguish HBLs from the more common benign nerve sheath tumors with which they are most frequently confused. Less than half of all extramedullary HBLs are diagnosed in patients with known VHL. It is important to consider HBLs in the differential diagnosis, as they are vascular and have the propensity for causing significant blood loss at surgery.     

Suprasellar cavernous malformation presenting with extensive subarachnoid hemorrhage

Cavernous malformations are usually intraparenchymal, extra-axial lesions being uncommon. They have very rarely been reported as the cause of subarachnoid hemorrhage. We present a case of hemorrhage related to a cavernous malformation, unusual in two ways. First, it is rare for an intracranial cavernous malformation to present with massive subarachnoid hemorrhage. Secondly, this cavernous malformation lay in the chiasmatic cistern. Received: 21 March 2000 Accepted: 3 October 2000     

Chitinase activity in human serum and leukocytes.

Using colloidal [3H] chitin as a substrate, we provide the first demonstration of a chitinase in human leukocytes; chitinolytic activity in whole and disrupted leukocyte preparations (approximately 0.6 and 5.5 nmol of N-acetylglucosamine [GlcNAc] released min-1 mg of protein-1, respectively) was partially inhibited by the specific chitinase inhibitor allosamidin (9 microM). Following fractionation of the leukocytes, much higher levels of chitinase activity were detected in granulocyte-rich homogenates (approximately 7.2 nmol of GlcNAc released min-1 mg of protein-1) than in lymphocyte- and monocyte-rich homogenates (approximately 0.22 and 0.26 nmol of GlcNAc released min-1 mg of protein-1, respectively). Low levels of chitinase activity were detected in human serum (approximately 4 pmol of GlcNAc released min-1 mg of protein-1). Chitinolytic activity in granulocyte-rich homogenates and serum was partially inhibited by allosamidin (9 microM). Proteins with chitinolytic activities (approximate molecular masses, 48 and 56 kDa) distinct from lysozyme (14.3 kDa) were detected on polyacrylamide gels following the electrophoresis of human granulocyte-rich preparations. Chitinase activity, detected consistently in serum and leukocytes from all human volunteers investigated, may contribute to the protection of the host by cleaving chitin in the cell walls of fungal pathogens.     

Presence and enzymatic activity of prostate-specific antigen in archival prostate cancer samples

Patients with advanced prostate cancer frequently have a poor prognosis as a result of metastasis. The serum prostate-specific antigen (PSA) test is widely used for the diagnosis of prostate cancer. The enzymatic activity of PSA may be involved in the invasion of prostate cancer. We set out to determine the prevalent form of PSA in human prostate adenocarcinoma samples by ELISA and Western blot analysis and its enzymatic activity using a synthetic substrate S-2586 and fibronectin. Our results show that in serum from prostate cancer patients and in tumour homogenates, the prevalent form was PSA bound to alpha1-antichymotrypsin. All homogenates showed enzymatic activity towards a synthetic PSA substrate, whereas only five samples showed activity at 28 kDa towards fibronectin as determined by enzymography, which is most likely due to active PSA. Human prostate cancer LNCaP cells produced largely inactive PSA. In comparison, 22Rv1 cells produced 29-fold less PSA, but with high specific activity. Similarly, our results from the human prostate cancer tissue samples also show that free PSA appears to exist in diverse forms of very different specific activity. Since PSA, as a serine protease, may be involved in the invasion of prostate cancer, our results suggest that prostate cancers have potentially diverse invasive capacity due to differences in specific enzymatic activity of PSA.