First reported case of Ehrlichia ewingii involving human bone marrow.

A 65-year-old female with a history of multiple tick bites presented with fever and pancytopenia. Intracytoplasmic rickettsial morulae were detected on peripheral smear and bone marrow biopsy specimens, and PCR amplified Ehrlichia ewingii DNA from both specimens. To our knowledge, this is the first report of E. ewingii infection of human bone marrow.

Pan myeloid antigen-negative pediatric acute megakaryoblastic leukemia.

Acute megakaryoblastic leukemia (AMKL) is a relatively common type of acute myeloid leukemia in children. We describe two unusual cases of AMKL that by flow cytometry (FC) lacked expression of any commonly evaluated myeloid antigens. One case presented as a periorbital myeloid sarcoma and clinically was thought to be a solid tumor. In both cases, the leukemic blasts were variably positive for the megakaryocytic marker CD61. Cytogenetics confirmed the presence of the t(1;22) in one case. Cytogenetics and inclusion of megakaryocytic markers in FC panels when evaluating pediatric specimens is critical for appropriate diagnosis for myeloid antigen negative AMKL.

Clinical Utility of CT-based Attenuation-correction in Myocardial Perfusion SPECT Imaging.

Objectives: We aimed to investigate and compare the role of computed tomography (CT)-based attenuation-corrected images (AC) with non-attenuation-corrected images (NAC) obtained by single-photon emission computed tomography/computed tomography (SPECT/CT) myocardial perfusion imaging (MPI). Methods: The data of 124 patients who were applied one-day stress-rest Tc-99m sestamibi SPECT/CT MPI and who had coronary angiography (CAG) results within ±3 months were retrospectively reviewed. AC and NAC images were visually evaluated by two nuclear medicine specialists in a consensus. CAG results were used as the reference standard. Results: Specificity, sensitivity, and accuracy were calculated as 66%, 61%, 71%, 79% and 69%, 70% for AC and NAC imaging in the whole group, respectively. There was no statistically significant difference between AC and NAC images for specificity, sensitivity, and accuracy in the male and female subgroups. In the diagnosis of right coronary artery (RCA) disease, CT AC significantly increased the specificity from 87% to 96%. However, in the left anterior descending artery (LAD) region, the specificity was significantly reduced from 95% to 77%. Conclusion: CT-based AC did not significantly contribute to diagnostic performance for increased specificity for the RCA and reduced specificity in the LAD region. Therefore, AC images should always be evaluated side by side with NAC images to benefit from the different advantages of both techniques.

The expression of vascular endothelial growth factor and its receptors in port-wine stains.

OBJECTIVE: To investigate the expression of vascular endothelial growth factor (VEGF) and its receptor (VEGF-R2) in port-wine stains (PWSs). DESIGN: An immunohistochemistry (IHC) study on formalin-fixed, paraffin-embedded specimens. METHODS: Representative sections from surgical resection specimens of 12 PWS patients and 12 control specimens stained with routine IHC by using polyclonal anti-VEGF and anti-VEGF-R2 antibodies. Slides were evaluated semiquantitatively for the intensity of staining for VEGF and VEGF-R2 by using a scoring system varying from 0 to 3+. RESULTS: PWS specimens showed statistically significant overexpression of both VEGF and VEGF-R2 molecules when compared with control specimens (P < 0.005). CONCLUSIONS: VEGF and its receptor may play an important role in the pathogenesis of PWS. It is possible that PWS may progress by hyperplasia in addition to hypertrophy. VEGF-R blockade may have a potential role as a targeted approach in the treatment of this disfiguring condition in the future.

Morphologic manifestations of combined light-chain deposition disease and light-chain cast nephropathy.

There are few data on morphology of light-chain deposition disease (LCDD) of kidney with coexistent light-chain cast nephropathy (LCCN). Here, the authors report the morphology in 23 cases of LCDD and LCCN. They retrospectively evaluated 23 renal biopsies with light (LM), immunofluorescence (IF), and electron microscopy (EM). Twenty-one patients had myeloma, 1 had a monoclonal gammopathy, and in 1 no illness was found. Nodular glomerulosclerosis, the LM lesion suggestive of LCDD, was noted in only 3 of 23 cases. Glomeruli were unremarkable in 16 (69%) cases. The diagnostic casts of LCCN were seen in all biopsies. Linear light chain (LC) immunoreactivity was observed in 23 (100%) cases (18 kappa, 5 lambda); GBM + TBM in 13, TBM only in 7, GBM only in 1, TBM and interstitium in 1, GBM, TBM and mesangium in 1. Casts were positive with same LC in all cases (100%). Fifteen cases (65%) showed granular electron-dense deposits; GBM only in 5, TBM only in 5, GBM and TBM in 4, mesangium in 1. In 8 patients without EM deposits, the diagnosis of LCDD was rendered by IF. Fifteen (65%) had deposits detectable by IF and EM, 8 (37%) had deposits with IF only. LCCN dominated the LM findings in all patients. There were minimal or no glomerular changes by LM. This study shows the lack of characteristic LM findings of LCDD in combined cases of LCDD and LCCN and emphasizes the difficulty for-definitive diagnosis-without IF and EM.

Elevated Expression of Matrix Metalloproteinase-9 not Matrix Metalloproteinase-2 Contributes to Progression of Extracranial Arteriovenous Malformation.

Extracranial arteriovenous malformations (AVMs) are rare but dangerous congenital lesions arising from direct arterial-venous shunts without intervening capillaries. Progressive infiltration, expansion, and soft tissue destruction lead to bleeding, pain, debilitation and disfigurement. The pathophysiology of AVMs is not well understood. Matrix Metalloproteinases (MMPs) are thought to play an important role in pathologic processes underlying many diseases. This study investigates the expression of MMP-9 and MMP-2 in aggressive extracranial AVMs. The differential expression of MMP-9 and its regulatory factors is also examined. Herein we demonstrate that mRNA and protein expressions of MMP-9, but not MMP-2, are significantly higher in AVM tissues compared to normal tissues. The serum level of MMP-9, but not MMP-2, is also elevated in AVM patients compared to healthy controls. MMP-9/neutrophil gelatinase-associated lipocalin (NGAL) complex is also significantly increased in AVM tissues. The MMP-9/ tissue inhibitor of metalloproteases-1 (TIMP-1) complex presents as a major form detected in normal tissues. The increased and aberrant expression of MMP-9 and specific MMP-9 forms may help explain the constitutive vascular remodeling and infiltrative nature of these lesions. Specific MMP-9 inhibitors would be a promising treatment for AVMs.

Immature lymphoid cells are a consistent feature of chylothorax in neonates and infants: cytologic features and flow cytometry aid in its distinction from lymphoblastic leukemia/lymphoma.

Chylothorax is rare in young children and occurs secondary to an array of etiologies. In this report, we describe the cytologic and immunophenotypic features of chylothorax in three neonates and infants. In each case, lymphocytes were the predominant cell type and had atypical cytologic features that closely resembled those of malignant lymphoblasts, including larger size, irregular nuclear contours, immature chromatin, presence of nucleoli, and high nuclear-to-cytoplasmic ratios. Flow cytometry (FC) was performed in two cases and revealed a predominant T-cell population with normal expression of T-lineage antigens and no expression of CD34, CD10, or CD1a or coexpression of CD4 and CD8. In summary, chylothorax in neonates and infants are comprised of cytologically immature lymphoid cells. In such cases, FC is useful for distinction between chylothorax and a lymphoblastic malignancy.

Effect of reactive cell density on net [2-14C]acetate uptake into rat brain: labeling of clusters containing GFAP+- and lectin+-immunoreactive cells.

Astrocytic proliferation is a hallmark of brain injury, but the biological functions and metabolic activities of reactive astrocytes in vivo are poorly understood. [2-14C]Acetate, which is preferentially transported into and, therefore, metabolized by astrocytes, was used to assess injury- and trophic factor-induced changes in astrocyte metabolic activity. Local rates of net [2-14C]acetate uptake and glucose utilization (CMR(glc)), determined with [14C]deoxyglucose to assay overall metabolic activity of all brain cells, were assayed 7 days after a cannula placement; adjacent brain sections were immunostained to identify glial fibrillary acidic protein-positive (GFAP(+)) astrocytes and microglia plus macrophages (lectin-positive cells). GFAP(+) cells were abundant in tissue surrounding the cannula compared to the contralateral hemisphere, whereas lectin(+) cells were restricted to the wound boundary. CMR(glc) fell 25% in regions enriched in reactive astrocytes compared to the homologous contralateral hemisphere, whereas [14C]acetate uptake increased slightly (6%) but statistically significantly; metabolism of both tracers in 13 other brain structures was unchanged. Injection of basic fibroblast growth factor (b-FGF) into cerebral cortex or superior colliculus produced fiber-rich cell clusters containing both GFAP(+) and lectin(+) cells that had a 37% increase in [14C]acetate uptake; GFAP(+)-cell density rose in the nearby neuropil but the corresponding change in [14C]acetate uptake was small (6-8%). Sensory stimulation did not alter [14C]acetate uptake into the clusters. Thus, [14C]acetate uptake was relatively stable with respect to changes in the density of reactive astrocytes that are dispersed throughout the neuropil and to changes in cellular activity arising from sensory stimulation. In contrast, b-FGF-induced cell clusters that contain mixed cell types and numerous fibers accumulated higher levels of [14C]acetate, raising the possibility that increased uptake might be due to high numbers of activated astrocytes and, perhaps, acetate metabolism by other cell types.

CD117 expression in glial tumors.

C-kit is a proto-oncogene involved in normal growth and development and neoplastic processes, and its product, CD117, is a highly specific immunohistochemical diagnostic marker for gastrointestinal stromal tumors (GISTs). Because GISTs that express immunohistochemically-detectable CD117 respond dramatically to treatment with tyrosine kinase inhibitors, identification of central nervous system tumors that express CD117 might open new therapeutic approaches for treatment of brain tumors. Specimens from 52 glial tumors of various histologic types and grades were assayed for CD117 immunoreactivity, and about 75% of the tumors were positive for CD117 expression; all except a few exhibited strong cytoplasmic and membranous staining. The proportion of high grade tumors of all tumor types with detectable CD117 immunoreactivity was statistically significantly greater than low grade tumors, and glioblastoma and anaplastic oligodendroglioma showed the highest staining grade. These findings support further investigation into the possibility that CD117 has an important role in growth of glial tumors and that patients with brain tumors expressing CD117 might benefit from treatment with receptor tyrosine kinase inhibitors.