Phenotype, genotype and clonality of Reed-Sternberg cells in nodular sclerosis Hodgkin's disease: results of a single-cell study

The genotype and clonality of Reed-Sternberg (RS) cells in Hodgkin's disease (HD) has remained a controversial issue, largely due to the scarcity of RS cells in tissues and the limitations of the techniques used to resolve this issue. Southern hybridization and polymerase chain reaction (PCR) assays using DNA extracted from tissues can only document clonal gene rearrangements, but do not indicate which cellular population is responsible for such rearrangements. To overcome the limitations of these previous techniques for studying the genotype and clonality of RS cells, we analysed single RS cells with a single-cell PCR assay to detect immunoglobulin heavy chain gene (IgH) rearrangements and X-chromosome inactivation. Six cases of nodular sclerosis (NS) HD were studied. The RS cells displayed a B-cell phenotype in three cases and a null-cell phenotype in the other three cases. IgH rearrangements were detected in the RS cells of the three cases with a B-cell phenotype, but not in the other cases. In these three cases the IgH rearrangements in the RS cells were polyclonal, although a subpopulation of clonal RS cells was documented in one case. The finding that the RS cells with IgH rearrangements were not monoclonal was supported in one case by studying the pattern of X-chromosome inactivation in single RS cells by a single-cell human androgen receptor gene (HUMARA) PCR assay. Our results indicate that NSHD begins as a polyclonal process in which a clonal RS cell population may arise; and that the RS cells in a subset of NSHD show evidence of B-lineage differentiation.     

Dose-response effects of prenatal phenytoin exposure in rats: effects on early locomotion, maze learning, and memory as a function of phenytoin-induced circling behavior

Pregnant Sprague-Dawley CD rats were administered 0, 100, or 200 mg/kg of phenytoin on days E7-18. Litters were reduced to 12, balancing for sex. Mean (+/- S.E.) maternal serum concentrations of total phenytoin 1 hr after dosing on E18 were 15.1 +/- 3.1 and 20.9 +/- 4.3 micrograms/ml in the PHT-100 and PHT-200 groups, respectively. Determinations of unbound concentrations revealed the drug to be 89% serum protein bound in both phenytoin groups. Maternal phenytoin concentrations in rats are, therefore, comparable to those seen therapeutically in humans with epilepsy. The PHT-200 group had elevated early postnatal mortality, while the PHT-100 group did not differ from controls. Phenytoin induced the typical dose-dependent increase in preweaning square-field locomotor activity. When this effect was compared to a new circular open field it was found that this device clearly distinguished phenytoin's effects. Phenytoin offspring also showed the typical dose-dependent abnormal circling behavior. Phenytoin offspring exhibited large dose-dependent increases in errors in a complex water maze, an effect which persisted even when rats exhibiting abnormal circling were excluded from the analyses. Offspring were also assessed for ability to locate a hidden vs. visible platform in an open swimming tank. Controls and PHT-100 offspring showed large improvements in performance when the hidden platform was made visible, but the PHT-200 offspring did not. Finally, offspring were assessed for working memory in an appetitive radial-arm maze. Both phenytoin groups exhibited impaired performance as measured by the number of reinforcements obtained in the first 8 arms visited.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multiple congenital hemangiopericytomas of the head and neck

Hemangiopericytoma is a vascular tumor arising from contractile cells, the pericyte of Zimmermann. The neoplasms most frequently involve deep musculature; however, 16% occur in the head and neck region. The case presented here represents the rare occurrence of multiple congenital hemangiopericytoma of the head and neck. In older patients, these rather poorly differentiated tumors recur locally after excision in 50%–80% of cases depending on the organ site involved. Distant metastasis to lung or bone may follow. Congenital hemangiopericytomas appear to follow a more benign clinical course, possibly due to a more superficial location and a tendency to transform into hemangioendotheliomas. Recommended treatment is wide local excision and long-term follow-up.     

Mammography using an ultrahigh-strip-density, stationary, focused grid

A 1-mm-thick, stationary, ultrahigh-strip-density, focused grid was evaluated with respect to patient radiation dose and mammographic image quality as it affected the resolution of microcalcifications and masses. Radiographic technique was varied to determine the most useful alteration to improve image quality with the grid. Results from 89 patients demonstrated that no improvement in diagnostic ability was found in women with fatty breasts. As breast density increased, the advantage of the grid technique became more apparent. Grid mammography also often solved the problem of questionable microcalcifications with improved visualization of their number and geometry.     

Mantle-zone lymphoma. An immunohistologic study

Mantle-zone lymphoma (MZL) is a histologically distinctive variant of follicular lymphocytic lymphoma which is characterized by a proliferation of atypical small lymphoid cells as wide mantles around benign-appearing germinal centers. Immunoperoxidase stains were performed on fixed and processed lymph nodes from four patients with MZL. Three cases were of the intermediate lymphocytic type, and one was of the small cleaved lymphocytic type. In all cases, the small lymphoid cells of the mantle zones did not stain. A monoclonal population (IgM, lambda) of plasma cells and large lymphoid cells was demonstrated predominantly in the paracortical areas in one case. In all cases, small numbers of plasma cells and large lymphoid cells in the follicle centers stained in a polyclonal pattern, confirming the benign nature of the centers. These findings suggest that follicular lymphomas of the mantle-zone type are exceptions to the theory that follicular B-cell lymphomas are derived from follicular center cells. Apparently, the lymphoid cells of MZL home to the mantle zones of secondary follicles, where they surround, proliferate, and eventually obliterate residual benign germinal centers.     

Epstein-Barr virus--associated lymphoproliferative lesions

From this review of the natural history of EBV infection in humans, it is clear that the virus has evolved to a symbiotic state with humans. Once individuals are infected, EBV establishes a permanent infection that is maintained at a low level by replication of the virus in the oropharyngeal region with subsequent seeding of circulating B-lymphocytes. Individuals with normal immune systems are able to control the pronounced proliferative potential of EBV-infected cells and thus prevent the emergence of lymphoproliferations. Disease states result when the immune system is altered by other infections, developmental conditions, immunosuppressive agents, or debilitating circumstances such as cancer or starvation. In some cases, localized lymphoproliferations resembling large-cell non-Hodgkin's lymphomas can result that are monoclonal by immunoglobulin gene rearrangement studies. Remarkably, many of the localized masses will regress if the immunosuppressive agents or condition can be ameliorated in these individuals. In patients with hereditary immune deficiencies, these localized masses can progress to a fatal disease without further cytogenetic events. Burkitt's lymphoma, which is associated with EBV infection, appears to result when EBV-driven lymphoproliferations undergo cytogenetic translocations involving predominantly chromosome 8. Most of the conditions that are associated with EBV can be diagnosed by accurate application of EBV-serology, examination of peripheral blood films, a careful history and physical examination, and, in some cases, more sophisticated techniques such as the establishment of lymphoblastoid cell lines, EBNA staining, DNA probes, and pedigree analysis.     

Superparamagnetic iron oxide: enhanced detection of focal splenic tumors with MR imaging

Superparamagnetic iron oxide (AMI-25), a reticuloendothelial cell-specific contrast agent for magnetic resonance (MR) imaging, was evaluated for its ability to permit detection of splenic metastases in 18 patients. Superparamagnetic iron oxide, at a dose of 30 mumol of iron per kilogram, decreased the signal intensity of spleen from 19.5 +/- 4.8 to 3.1 +/- 2.2 (spin-echo sequence, repetition time msec/echo time msec = 1,500/42; P less than .05), without changing the signal intensity of tumor. As a result, the tumor-spleen contrast-to-noise ratio increased from 0.2 (tumor isointense relative to spleen) to 18.0 (tumor hyperintense relative to spleen). As a consequence of increased contrast, splenic tumors were detected in four of 18 patients (45 individual lesions; P less than .05), whereas nonenhanced MR imaging permitted detection of splenic lesions in only two of 18 patients (four individual lesions). Maximum tumor-spleen contrast was achieved within 60 minutes after intravenous administration. These initial clinical results indicate that MR imaging with superparamagnetic iron oxide may offer improved accuracy in the diagnosis of splenic tumors.