Phenotypic Cytoskeletal Heterogeneity in Melanoma, a Challenge to the Surgical Pathologist Evaluating a Poorly Differentiated Neoplasm: An Illustrative Case

Characterization of poorly differentiated neoplasms can be a challenging task for the surgical pathologist. It is essential that the entire spectrum of immunomorphologic findings of various tumors be recognized to avoid improper characterization of a given neoplasm, which may in turn adversely affect patient management. Tumor characterization is complicated by the immunomorphologic transformations that malignant cells may undergo by virtue of which they may depart from expression of expected features and acquire new, unexpected characteristics. Traditionally, amelanotic melanomas have been difficult to characterize because of the diversity of their light microscopic morphology (epithelioid, spindle, and combined varieties). As a result, several other neoplasms are usually considered in the differential diagnosis. This report describes a primarily spindle-cell amelanotic melanoma that created a diagnostic dilemma, which could only be resolved by combining the information obtained from extensive evaluation by means of several diagnostic techniques. This case also stresses the phenotypic heterogeneity of the cytoskeleton of malignant melanomas and therefore their varied immunomorphologic characteristics.     

Epithelial cell proliferation in the rat urinary system induced by parenteral injection of lead salts.

In Wistar rats a single intravascular injection of lead nitrate causes substantial cellular proliferation in the proximal tubules of the kidneys and in the epithelium of the renal pelvis, ureters and urinary bladder. The tritiated thymidine labelling index (LI) reaches a peak 18 to 24 h after injection and the mitotic index (MI) increases to a comparable extent 6 to 10 h later. The proliferation is most prominent in the bladder and proximal tubules and is virtually complete at 48 h. After a single intraperitoneal injection the proliferative changes are confined to the ureteric and bladder epithelium. In all affected tissues the proliferation develops without preceding necrosis and appears to be a hyperplastic phenomenon. After intravascular administration the volume of urine and its total protein content are significantly increased and certain proteins were detected which were not present in the urine of saline controls.     

Seizure Disorders: The Changes With Age

Summary: Age has a profound influence on our approach to the convulsive disorders. Age is a variable which is an important determinant for risk factors for epilepsy. Age, as a surrogate of brain maturation, is a determinant of the specific characteristics of the seizure disorder in those with epilepsy, and age-related changes in these manifestations can be identified. Age is a determinant for the occurrence of acute symptomatic seizures in several types of metabolic or central nervous system insults. Age is a determinant for prognosis, whether one considers remission, medication withdrawal in those entering remission, relapse following prolonged remission, or mortality. Last, age per se seems to be a risk factor for epilepsy independent of other factors. This seems particularly true for partial seizures.     

Effects of the 5-HT1A partial agonists gepirone,ipsapirone and buspirone on local cerebral glucose utilization in the conscious rat

The azospirones gepirone (10 mg/kg), ipsapirone (10 mg/kg) and buspirone (10 mg/kg) were examined for their effect on regional cerebral glucose utilization in conscious rats using quantitative 2-deoxyglucose autoradiography. All three 5-HT_1A partial agonists reduced glucose utilization in the hippocampus and dentate gyrus by 20–25% and increased glucose utilization by 38–65% in the lateral habenular nucleus; an important relay between striatal/limbic areas and the mid-brain raphe nuclei. The findings emphasize the potential importance of the hippocampus as a site of action for 5-HT_1A receptor active drugs in vivo and also suggest that functional activity in the striatal/limbichabenular-raphe pathway may be influenced by gepirone, ipsapirone and buspirone.     

Translational crossroads for biomarkers.

A group of investigators met at a Specialized Programs of Research Excellence Workshop to discuss key issues in the translation of biomarker discovery to the development of useful laboratory tests for cancer care. Development and approval of several new markers and technologies have provided informative examples that include more specific markers for prostate cancer, more sensitive tests for ovarian cancer, more objective analysis of tissue architecture and an earlier indication of response to treatment in breast cancer. Although there is no clear paradigm for biomarker development, several principles are clear. Marker development should be driven by clinical needs, including early cancer detection, accurate pretreatment staging, and prediction of response to treatment, as well as monitoring disease progression and response to therapy. Development of a national repository that uses carefully preserved, well-annotated tissue specimens will facilitate new marker development. Reference standards will be an essential component of this process. Both hospital-based and commercial laboratories can play a role in developing biomarkers from discovery to test validation. Partnering of academe and industry should occur throughout the process of biomarker development. The National Cancer Institute is in a unique position to bring together academe, industry, and the Food and Drug Administration to (a) define clinical needs for biomarkers by tumor type, (b) establish analytic and clinical paradigms for biomarker development, (c) discuss ways in which markers from different companies might be evaluated in combination, (d) establish computational methods to combine data from multiple biomarkers, (e) share information regarding promising markers developed in National Cancer Institute-supported programs, and (f) exchange data regarding new platforms and techniques that can accelerate marker development.