Atypical Glomus Tumor in the Mediastinum: A Case Report with Immunohistochemical and Ultrastructural Studies

A case is reported of atypical glomus tumor occurring in the posterior inferior mediastinum of a 26-year-old woman complaining of severe back pain. The tumor was composed of atypical small, round tumor cells with scattered mitotic figures. In addition to sheet-like, diffuse proliferation of the tumor cells, some areas of the tumor contained small “glo-moid” cells arranged in organoid and hemangiopericytoma-like patterns. Immunohistochemically, many tumor cells were positive for muscle-type actins and a few cells were focally positive for desmin. Ultrastructural studies revealed smooth muscle features of tumor cells, that is, pinocytotic vesicles, external laminas, dense plaques, and occasional thin filaments with dense bodies. The patient remained well for 5 years and 4 months after the operation without additional radiation and chemotherapy. The tumor was diagnosed as an atypical, or low-grade malignant, glomus tumor morphologically. It seems important to recognize the presence of this type of tumor in sites other than extremities and to differentiate it from other malignant small, round cell tumors.     

Rho kinases regulate endothelial invasion and migration during valvuloseptal endocardial cushion tissue formation.

Rho-associated kinase (ROCK) is a downstream effector of small Rho-GTPases, and phosphorylates several substrates to regulate cell functions, including actin cytoskeletal reorganization and cellular motility. Endothelial-mesenchymal transformation (EMT) is a critical event in the formation of valves and septa during cardiogenesis. It has been reported that ROCK plays an important role in the regulation of endocardial cell differentiation and migration during mouse cardiogenesis (Zhao and Rivkees [2004] Dev. Biol. 275:183-191). Immunohistochemistry showed that, during chick cardiogenesis, ROCK1 and -2 were expressed in the transforming and migrating endothelial/mesenchymal cells in the outflow tract (OT) and atrioventricular (AV) canal regions from which valvuloseptal endocardial cushion tissue would later develop. Treatment with Y27632, a specific ROCK inhibitor, of cultured AV explants or AV endothelial monolayers of stage 14-minus heart (preactivated stage for EMT) on three-dimensional collagen gel perturbed the seeding of mesenchymal cells into the gel lattice. In these experiments, Y27632 did not suppress the expression of an early transformation marker, smooth muscle alpha-actin. Moreover, Y27632 inhibited the mesenchymal invasion in stage 14-18 AV explants, in which endothelial cells had committed to undergo EMT. ML-9, a myosin light chain kinase inhibitor, also inhibited the mesenchymal invasion in cultured AV explants. These results suggest that ROCKs have a critical role in the mesenchymal cell invasion/migration that occurs at the late onset of EMT.     

B-cell precursors differentiated from cord blood CD34+ cells are more immature than those derived from granulocyte colony-stimulating factor-mobilized peripheral blood CD34+ cells

Umbilical cord blood (CB) has been widely used instead of bone marrow (BM) and peripheral blood (PB) for stem cell transplantation (SCT). However, problems of sustained immunodeficiency after CB transplantation remain to be resolved. To elucidate the mechanism of immunodeficiency, we compared the characteristics of B cells differentiated in vitro from CD34+ cells of CB with those of PB. Purified CD34+ cells from CB and PB were cultured on murine stroma cell-line MS-5 with stem cell factor and granulocyte colony-stimulating factor for 6 weeks. The B-cell precursors (pre-B cells) that differentiated in this culture system, were analysed as to their immunoglobulin heavy chain (IgH) variable region gene repertoire and the expression of B-cell differentiation-related genes. CD10+ CD19+ pre-B cells were differentiated from both PB and CB. Although the usages of IgH gene segments in pre-B cells differentiated from CB and PB were similar, the N region was significantly shorter in CB-derived than PB-derived cells. Productive rearrangements were significantly fewer in cells of CB than PB in the third week. Among a number of B-cell differentiation-related genes, the terminal deoxynucleotidyl transferase (TdT) gene was not expressed in CB-derived cells during the culture. These results indicated that immature features of pre-B cells from CB, such as lack of TdT expression, and a short N region and few productive rearrangements in the IgH gene, might cause the delay in mature B-cell production.     

Claudin‐7 Expressed on Lateral Membrane of Rat Epididymal Epithelium does not Form Aberrant Tight Junction Strands

Claudins are integral membrane proteins at tight junctions (TJs) and form TJ strands. In the present study, we found that claudin‐7 was localized along the entire lateral membranes of epididymal epithelium, including the apical junctional region throughout the epididymis, but claudin‐8 was restricted to the apical junctional region. This finding raises the possibility that aberrant TJ strands may be formed on lateral membranes. Thus, we focused on examining whether TJ strands exist on lateral membranes of epididymal epithelium. Freeze‐fracture electron microscopy showed that aberrant TJ strands were observed in only a few principal cells in all segments of the epididymis except for the initial segment, indicating that the occurrence of aberrant strands is very rare. Aberrant TJ strands were smooth and not subdivided into individual particles in the protoplasmic face, and complementary grooves in the extracellular face were almost free of particles. Aberrant TJ strands in the distal caput and corpus epididymis were accompanied by many vesicle‐like structures but those in the proximal caput and cauda epididymis were not. These results suggest that most of claudin‐7 in lateral membranes may exist in a nonpolymerized form and may play some different roles other than the formation of TJ strands, for example, in the formation of a pool of claudin proteins or in the reinforcement of cell adhesion. Anat Rec, 1431‐1438, 2007. © 2007 Wiley‐Liss, Inc.     

Malignant peripheral nerve sheath tumor of small round cell type with pleomorphic spindle cell sarcomatous areas

An unusual case of malignant peripheral nerve sheath tumor (MPNST) arising in the posterior mediastinum of a 59-year-old man is reported. Histopathologically, the tumor showed an admixture of a dense proliferation of small round cells resembling a primitive neuroectodermal tumor (PNET) and a pleomorphic spindle cell sarcomatous area. Abortive rosettes, primitive neural tube-like structures, and a few glandular structures were found in the small round cell area. Small round cells were immunoreactive for neural cell adhesion molecule and synaptophysin, but were not immunoreactive for MIC2 and neuron-specific enolase. Pleomorphic spindle cells were occasionally arranged in a storiform pattern and were diffusely immunoreactive for S-100 protein. The MPNST of small round cell type is distinguishable from PNET by its negative immunoreactivity for MIC2, and the present tumor is assumed to be derived from primitive neuroectodermal cells in the peripheral nerve capable of bidirectional (neuron and Schwann cell) differentiation.     

Development of nested PCR based on the ViaB sequence to detect Salmonella typhi.

For a rapid diagnosis of typhoid fever, we developed a nested PCR based on the nucleotide sequence encoding the Vi antigen. All Salmonella typhi strains along with a Salmonella paratyphi C strain were PCR positive. This assay was able to detect S. typhi at the single-cell level.     

Unique properties of fetal lymphoid progenitors identified according to RAG1 gene expression

RAG1/GFP knockin mice were exploited to isolate and characterize fetal lymphoid progenitors. CD11b and IL-7Ralpha are expressed in a developmental stage-dependent fashion, revealing how substantial numbers of early lymphoid progenitors were discarded or neglected in previous studies. The myeloerythroid potential of fetal progenitors in clonal assays declined in synchrony with activation of the RAG1 locus but was not completely extinguished. Lymphoid differentiation corresponded to patterns of gene expression previously found for adult marrow, but no fraction of fetal liver was enriched with respect to B + T progenitors. Also, unlike adults, fetal lymphoid progenitors transiently expressed endothelial cell markers. These findings help to reconcile discrepancies in previous reports and suggest that the fetal immune system arises via unique mechanisms.     

Epitopic heterogeneity of the CD36 antigen expressed by normal and neoplastic endothelial cells. An immunohistochemical study with a novel monoclonal antibody 8C9.

Phenotypic and functional heterogeneity of endothelial cells (ECs) is being recognized with increasing frequency. Here we report a novel murine monoclonal antibody (MoAb), named 8C9, that detects a unique epitope on the leukocyte differentiation antigen CD36 (platelet glycoprotein IV or IIIb) expressed by both normal and neoplastic ECs. In immunohistochemical and flow-cytometric studies, 8C9-immunoreactivity was detected on capillary ECs, adipocytes, monocytes, platelets and a human monocytoid cell line U-937, which are known to express the CD36 antigen. Blocking experiments using U-937 cells and studies on cryostat sections revealed that a murine MoAb OKM5, which detects the CD36 antigen, blocked the binding of 8C9 to its antigen. Immunoblot analysis showed that 8C9 bound to a 97-kDa membrane protein expressed by U-937 cells treated with phorbol ester. These results indicate that 8C9 detects the CD36 antigen. However, the findings that some OKM5-positive normal ECs in the liver, spleen and lymph nodes as well as neoplastic ECs in a cutaneous angiosarcoma did not react with 8C9, together with the fact that the CD36 antigen does not form a complex or associate with other proteins, suggest epitopic heterogeneity of the CD36 antigen expressed by these tissues.