Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease of controversial origin recently recognized as a neoplasm deriving from plasmacytoid dendritic cells (pDCs). Nevertheless, it ...remains an orphan tumor with obscure biology and dismal prognosis. To better understand the pathobiology of BPDCN and discover new targets for effective therapies, the gene expression profile (GEP) of 25 BPDCN samples was analyzed and compared with that of pDCs, their postulated normal counterpart. Validation was performed by immunohistochemistry (IHC), whereas functional experiments were carried out ex vivo. For the first time at the molecular level, we definitely recognized the cellular derivation of BPDCN that proved to originate from the myeloid lineage and in particular, from resting pDCs. Furthermore, thanks to an integrated bioinformatic approach we discovered aberrant activation of the NF-kB pathway and suggested it as a novel therapeutic target. We tested the efficacy of anti-NF-kB-treatment on the BPDCN cell line CAL-1, and successfully demonstrated by GEP and IHC the molecular shutoff of the NF-kB pathway. In conclusion, we identified a molecular signature representative of the transcriptional abnormalities of BPDCN and developed a cellular model proposing a novel therapeutic approach in the setting of this otherwise incurable disease.
To date, no good marker for screening or disease monitoring of endometrial cancer (EC) is available. The aims of this study were to investigate HE4 gene, protein expression and serum HE4 (sHE4) ...levels in a panel of ECs and normal endometria (NEs) and to correlate sHE4 with patient clinicopathological characteristics and prognosis.
Using quantitative real-time PCR we tested 46 ECs and 20 NEs for HE4 gene expression. Protein expression was analysed by immunohistochemistry on tissue microarrays in 153 ECs and 33 NEs. Pre-operative serum samples from 138 EC and 76 NE patients were analysed with HE4-EIA assay. Association between sHE4 and patient clinicopathological characteristics or outcome was evaluated.
Protein and HE4 gene were significantly upregulated in EC tissues and sera, compared with controls. High sHE4 levels were significantly associated with worse EC clinical characteristics. By univariate survival analysis, high sHE4 levels significantly correlated with decreased overall survival, progression-free survival and disease-free survival, retaining their independent prognostic value on the poorly differentiated EC cohort.
We demonstrate, for the first time, that high sHE4 levels correlates with an aggressive EC phenotype and may constitute an independent prognostic factor for poorly differentiated-ECs. Determination of sHE4 could be clinically useful in identifying high-risk EC patients for a more aggressive adjuvant therapy.
The often touted attractive attributes of printed/organic electronics are its mechanically flexible form-factor, low-cost, green, on-demand printing, scalability, low-power operation, and ...intelligence (signal processing) - ideally, the creation of intelligent lightweight electronics printed by simple ubiquitous printing processes, and integrated into new ways to exploit its mechanically flexible form-factor. Printed/Organic Electronics, now an industry on its own right and recognized as one of the key technological enablers for the Internet of Things, is largely complementary to silicon because the printed transistors are slow and the printed elements are large. The sanguine projected growth of the 29 B market today to 73 B by 2027 assumes that `intelligence' (analog, mixed-signal and digital signal processing) would be realizable. Nevertheless, many of the said attributes of printed/organic electronics remain a challenge. In this paper, we exemplify this with a comprehensive and critical review and tabulation of the state-of-the art printed digital, analog, and mixed-signal circuits. We further review the application space of printed/organic electronics and the supply chain, including their classifications and delineate the associated challenges in each constituent chain. These challenges, largely unresolved, are indeed formidable, and are discussed with a critical circuits and systems perspective. Our review depicts that contemporary design philosophies and methodologies for silicon are largely inadequate for printed/organic electronics. To this end, we discuss esoteric analog and digital design philosophies and methodologies, with emphasis on co-design and co-optimization between the different constituent supply chains that may potentially circumvent the said formidable challenges, and discuss the associated penalties thereto.
Background
Rosettes are a specific form of a white shiny structure seen with polarized dermoscopy. The precise morphological correlate and optical explication are not known.
Objective
To estimate the ...frequency of rosettes in ex vivo dermoscopy and to find explication and morphologic correlate of this dermoscopic feature.
Methods
A series of 6108 consecutive skin biopsies were examined with ex vivo dermoscopy and when rosettes were present serial transverse sections with polarization were examined.
Results
In this series of 6108 consecutive skin biopsies, rosettes were found on ex vivo dermoscopy in 63 cases. When multiple we observed that they are always oriented at the same angle. Transverse sections with polarization of these lesions proved that smaller rosettes are mainly caused by polarizing horny material in adnexal openings, and larger rosettes by concentric perifollicular fibrosis.
Conclusions
Rosettes are an optical effect of crossed polarization by concentric fibrosis or horny material and hence are not lesion‐specific.
An accurate diagnosis of clinically distinct subgroups of aggressive mature B cell lymphomas is crucial for the choice of proper treatment. Presently, precise recognition of these disorders relies on ...the combination of morphological, immunophenotypical, and cytogenetic/molecular features. The diagnostic workup in such situations implies the application of costly and time-consuming analyses, which are not always required, since an intensified treatment option is reasonably reserved to fit patients. The Italian Group of Haematopathology proposes herein a practical algorithm for the diagnosis of aggressive mature B cell lymphomas based on a stepwise approach, aimed to select cases deserving molecular analysis, in order to optimize time and resources still assuring the optimal management for any patient.
Summary
Background
Long‐term oral nucleos(t)ide analogue (NUC) therapy in hepatitis B virus (HBV)‐related compensated cirrhotics prevents clinical decompensation but not hepatocellular carcinoma ...(HCC) development.
Aims
To define the clinical features and outcomes of HCC in long‐term NUC‐treated HBV patients.
Methods
All HCCs developing between 2005 and 2016 in NUC‐treated HBV patients under surveillance were studied, excluding those that occurred within the first 6 months of therapy. Clinical features of HCC, alpha faetoprotein (AFP) patterns and patients' outcome were studied.
Results
Seventy‐six HCC patients were included. Median age was 67 (40‐83) years, 84% males, 96% Caucasian, 95% HBeAg‐negative, 96% with undetectable HBV DNA, 83% with normal ALT levels, and 92% with compensated cirrhosis. Median serum AFP levels were 4 (1‐3615) ng/mL (>7 ng/mL in 36%). HCC was monofocal in 78%, had a median diameter of 20 (6‐57) mm and was in its early stage in 92% which allowed potentially curative treatments in 78% (39% ablation, 28% surgical resection, 11% liver transplantation). Overall, a complete response was obtained in 61 (80%) patients: in 40 after a first‐line treatment, in 3 after the second–line treatment, in 2 after the third‐line treatment, while 16 underwent liver transplantation (8 as second line). During 45 (7‐144) months after HCC diagnosis, 19 patients died, 84% from HCC progression. The median time to recurrence was 20.2 (3‐53) months, and the cumulative 5‐year liver‐related survival was 74%.
Conclusions
HCCs developing in patients under long‐term NUC treatment were single, small tumours, amenable to curative therapies able to confer excellent 5‐year survival rates.
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