Amyloid imaging with 18 F-labeled radiotracers will allow widespread use, facilitating research, diagnosis, and therapeutic development for Alzheimer disease. The purpose of the study program was to compare cortical amyloid deposition using 18 F-florbetaben and PET in controls and subjects with mild cognitive impairment (MCI), frontotemporal lobar degeneration (FTLD), dementia with Lewy bodies (DLB), vascular dementia (VaD), Parkinson disease (PD), and Alzheimer disease (AD). Methods: One hundred nine subjects in 3 clinical studies at Austin Health were reviewed: 32 controls, 20 subjects with MCI, and 30 patients with AD, 11 with FTLD, 7 with DLB, 5 with PD, and 4 with VaD underwent PET after intravenous injection of 300 MBq of 18 F-florbetaben. Standardized uptake value ratios (SUVR) using the cerebellar cortex as a reference region were calculated between 90 and 110 min after injection. Results: When compared with the other groups, AD patients demonstrated significantly higher SUVRs (P , 0.0001) in neocortical areas. Most AD patients (96%) and 60% of MCI subjects showed diffuse cortical 18 F-florbetaben retention. In contrast, only 9% of FTLD, 25% of VaD, 29% of DLB, and no PD patients and 16% of controls showed cortical binding. Although there was a correlation between Mini Mental State Examination and b-amyloid burden in the MCI group, no correlation was observed in controls, FTLD or AD. Conclusion: 18 F-florbetaben had high sensitivity for AD, clearly distinguished patients with FTLD from AD, and provided results comparable to those reported with 11 C-Pittsburgh Compound B in a variety of neurodegenerative diseases.

In past years, association of primary cutaneous B-cell lymphoma (CBCL) with infection by Borrelia burgdorferi has been reported in a few patients. The evidence for a pathogenetic role was based on clinical grounds or raised titre of antibodies in serum. Both methods, however, do not prove the association between the micro-organism and the CBCL, especially in countries where infection by Borrelia burgdorferi is endemic. Moreover, the exact percentage of Borrelia burgdorferi-positive CBCL is not known. We retrieved from our files 50 cases of CBCL to perform PCR analysis of Borrelia burgdorferi DNA on paraffin-embedded tissue sections. Only patients with primary CBCL were selected. In all cases, monoclonality of the infiltrate was confirmed by immunohistological pattern of immunoglobulin light chains or molecular analysis of JH gene rearrangement, or both. Specific DNA sequences of Borrelia burgdorferi were identified in cutaneous lesions from 9 patients (follicle center lymphoma: 3/20; immunocytoma: 3/4; marginal zone B-cell lymphoma: 2/20; diffuse large B-cell lymphoma: 1/6). Specificity was confirmed by Southern blot hybridisation in all positive cases. We could show that Borrelia burgdorferi DNA is present in skin lesions from a small proportion of patients (18%) with various types of CBCL. Our results may have therapeutic implications. In analogy to Helicobacter pylori-associated MALT-lymphomas, which in some cases can be cured by eradication of Helicobacter pylori infection, a proportion of CBCL may be cured with antibiotic therapy against Borrelia burgdorferi. Although yet speculative, adequate antibiotic treatment for patients with primary CBCL should be considered before more aggressive therapeutic options are applied, particularly in countries where infection by Borrelia burgdorferi is endemic. PCR analysis of Borrelia burgdorferi DNA is a fast test that should be performed in all patients with CBCL to identify those who more likely could benefit from an early antibiotic treatment.

Apoptosis is a form of cell death involved in the regulation of cell number in various organs and tumors. Quantitative determination of cell loss through apoptosis in histological sections requires, in addition to counts of apoptotic cells, information on the duration of the histologically visible stages of apoptosis. Here we describe a method to determine the duration of apoptosis in (i) normal and (ii) putative preneoplastic tissue of the liver. (i) Female rats were treated with high doses of the hepatomitogen cyproterone acetate (CPA) to induce liver hyperplasia. After stopping CPA treatment, the hyperplasia partially regressed and excessive hepatocytes were eliminated by apoptosis. CPA was given to block the initiation of apoptosis, and thereafter the time course of elimination of apoptotic cell residues (apoptotic bodies, ABs) from the liver was studied. The mean duration of the histological stages of apoptosis was found to be approximately 3 h. (ii) Phenotypically altered cell foci in rat liver were produced by a single dose of N-nitrosomorpholine and subsequent promotion for 39 weeks with phenobarbital (PB). PB was withdrawn to stop foci growth and to stimulate apoptosis. Then rats were retreated with PB to block initiation of apoptosis in foci. The results indicate that the majority of apoptotic bodies in foci disappeared within 4 h after PB, suggesting that the stages of apoptosis are as short in foci as in normal liver. Finally a simple formula is given to calculate the cell loss rate by apoptosis. The method presented may provide data for quantitative cancer risk assessment from mathematical models of carcinogenesis.

Recently a new classification of primary cutaneous B-cell lymphomas (PCBCLs) has been proposed by the European Organization for Research and Treatment of Cancer (EORTC)--Cutaneous Lymphoma Project Group. The marginal zone B-cell lymphomas (MZLs) were not included as a distinct entity because of insufficient experience and controversial opinions. We have studied 32 patients (M:F ratio 1.5:1; age range 25-93 years; mean age 49.6 years; median age 50 years) to determine the diagnostic criteria of primary cutaneous MZL and the relationship with other low-grade malignant PCBCLs. For comparison, three patients with immunocytoma were included in the study. Clinically, patients presented with solitary or clustered reddish or red-brown papules, nodules, and plaques, sometimes surrounded by an erythematous halo. Histopathologic sections showed nodular or diffuse infiltrates involving the dermis and subcutaneous fat. Cytomorphologically small to medium-sized cells with indented nuclei and abundant pale cytoplasm (marginal zone cells, centrocyte-like cells) predominated. In addition, scattered blasts, lymphoplasmacytoid cells, and plasma cells were observed below the epidermis and at the periphery of the infiltrates. Reactive germinal centers were present in 75% of the cases. The three cases of immunocytoma showed a more monomorphous pattern with predominance of lymphoplasmacytoid cells. The marginal zone cells showed a CD20+, CD79a+, CD5- and Bcl-2+ immunophenotype. They expressed immunoglobulin G in the majority of the cases. Staining with the monocytoid B cell-related antibody KiM1p gave positive results in all specimens with a typical intracytoplasmic granular pattern. A monoclonal distribution of immunoglobulin light chains was observed in marginal zone cells in 75% of the cases. Germinal centers, when present, were either polyclonal or negative for both kappa and lambda light chains. Monoclonal rearrangement of the JH gene was detected via polymerase chain reaction (PCR) in 18 of 26 investigated specimens. Analysis in 12 patients of the bcl-2/immunoglobulin heavy chain gene rearrangement using PCR yielded negative results. Lesions were treated by surgical excision followed in some patients by local radiotherapy. Systemic antibiotic therapy was administered to three patients, with good response in two. The prognosis is excellent. After a mean follow-up of 47.9 months (range 6-252; median 24) all patients are alive without signs of systemic lymphoma. Primary cutaneous MZL represents a distinct clinicopathologic subtype of low-grade malignant PCBCL.

Cutaneous B-cell infiltrates showing a prominent follicular growth pattern with germinal centers are thought by some authors to represent either marginal zone lymphomas with reactive germinal centers or pseudolymphomas. To establish whether a true primary cutaneous follicular lymphoma exists, we studied biopsies from 15 patients with skin lesions characterized histopathologically by the presence of B-cell infiltrates with follicular pattern. Staging investigations, including bone marrow biopsy, were negative in all patients. All were negative for bcl-2 protein expression and did not present the t(14;18). In all biopsy specimens neoplastic follicles showed 1 or more morphologic or immunophenotypic criteria of malignancy (presence of a reduced mantle zone, absence of tingible body macrophages, reduced proliferation rate). In 9 specimens a monoclonal rearrangement of JH genes could be detected by polymerase chain reaction analysis. After laser beam microdissection, a band of the same length could be observed in 6 probes from different follicles from the same specimen, indicating the presence of the same monoclonal population of follicle center cells. Follow-up examinations in all patients revealed no evidence of extracutaneous spread (mean follow-up, 48.7 months). Our study demonstrates that primary cutaneous follicular lymphoma represents a distinct entity of the cutaneous B-cell lymphomas.

NCT01138111.

No abstract

Brain β-amyloid binding, as measured by [(18)F]florbetaben, increases with age in DS. Subjects with DS who have no evidence of dementia demonstrate brain β-amyloid binding in vivo, suggesting that [(18)F]florbetaben PET imaging may detect β-amyloid in this at-risk population.