Splenic littoral cell hemangioendothelioma in a patient with crohn's disease previously treated with immunomodulators and anti-TNF agents: A rare tumor linked to deep immunosuppression

Th e risk of malignancy in Crohn ’ s disease (CD) has been well described. Moreover, immunomodulators, uch as azathioprine (AZA) and 6-mercaptopurine (6-MP), and biological agents, such as infl iximab and adalimumab, may promote carcinogenesis ( 1 – 3 ). Splenic littoral cell tumors are recently described tumors of vascular origin composed of endothelial cells, with typical microscopic and immunohistochemical features of splenic sinus lining cells ( 4 ). Clinical findings are not specific, and outcome is unpredictable but usually benign, although a few cases with a malignant behavior have been reported ( 5,6 ). We report a 58-year-old Caucasian man with a long history of ileocolonic CD

Keratin 7 expression as an early marker of reflux-related columnar mucosa without intestinal metaplasia in the esophagus

BACKGROUND: The role of Barrett esophagus in carcinogenesis is widely accepted, but the significance of esophageal columnar mucosa without histological intestinal metaplasia, known as columnar-lined esophagus, is debated. MATERIAL/METHODS: We studied 128 patients free of Helicobacter pylori with reflux-related symptoms and columnar mucosa in the esophagus at endoscopy, 106 patients with Barrett esophagus (referred to as the Barrett group) and 22 patients without intestinal metaplasia (columnar group). Samples from 20 subjects free of H. pylori were used as controls. Immunostaining for keratin 7 (KRT7), keratin 20 (KRT20), caudal type homeobox 2 (CDX2), mucin 2, oligomeric mucus/gel-forming (MUC2), and tumor protein p53 (TP53) was assessed. RESULTS: Samples taken 1 cm above the gastroesophageal junction showed KRT7 staining in all cases in the Barrett and columnar groups and none in the control group. Immunostaining for TP53 was absent in the control group, and more frequent in the columnar group (7, 31.8%) compared with the Barrett group (14, 13.2%, P=0.033). In the columnar group, low grade dysplasia and TP53 expression was seen in 7 of 22 biopsy specimens (31.8%) at baseline and in 4 additional specimens after 2 years, for a total of 11 specimens (50.0%). CONCLUSIONS: The expression of KRT7 might help to explain the pathological, reflux-related nature of columnar-lined esophagus, as aberrant expression in a very early stage of the multistep Barrett esophagus progression. Expression of KRT7 may occur in basal glandular cells as a result of their multipotentiality and susceptibility to immunophenotype changes induced by reflux

Stromal SPARC contributes to the detrimental fibrotic changes associated with myeloproliferation whereas its deficiency favors myeloid cell expansion.

In myeloid malignancies, the neoplastic clone outgrows normal hematopoietic cells toward BM failure. This event is also sustained by detrimental stromal changes, such as BM fibrosis and osteosclerosis, whose occurrence is harbinger of a dismal prognosis. We show that the matricellular protein SPARC contributes to the BM stromal response to myeloproliferation. The degree of SPARC expression in BM stromal elements, including CD146(+) mesenchymal stromal cells, correlates with the degree of stromal changes, and the severity of BM failure characterizing the prototypical myeloproliferative neoplasm primary myelofibrosis. Using Sparc(-/-) mice and BM chimeras, we demonstrate that SPARC contributes to the development of significant stromal fibrosis in a model of thrombopoietin-induced myelofibrosis. We found that SPARC deficiency in the radioresistant BM stroma compartment impairs myelofibrosis but, at the same time, associates with an enhanced reactive myeloproliferative response to thrombopoietin. The link betwen SPARC stromal deficiency and enhanced myeloid cell expansion under a myeloproliferative spur is also supported by the myeloproliferative phenotype resulting from the transplantation of defective Apc(min) mutant hematopoietic cells into Sparc(-/-) but not WT recipient BM stroma. Our results highlight a complex influence of SPARC over the stromal and hematopoietic BM response in myeloproliferative conditions

A parafoveal retinal cones analysis using adaptive-optics retinal camera in patients with primary open angle glaucoma

Objectives: To study the density, spacing, and regularity of retinal cone photoreceptors using an Adaptive Optics (AO) retinal camera (Rtx1TM, Imagine Eyes, Orsay, France) in patients with Primary Open Angle Glaucoma (POAG) and to compare the outcomes with those of healthy age-matched control subjects. Methods: The study included 43 eyes with POAG and 31 eyes of normal subjects. POAG patients were divided into three groups according to the severity of the visual field defect. The AO Rtx1TM was used to obtain images of the parafoveal cone mosaic to calculate cone values. Analysis was performed at two and four degrees of eccentricity from the fovea along the four meridians (nasal, temporal, superior, inferior). Results: In POAG eyes, the mean ± standard deviation (SD) cone density at 2° considering all meridians was significantly lower than in normal controls (23,058.6 ± 3532.0 cones/mm2, and 25,511.7 ± 3157.5 cones/mm2, respectively; p = 0.003). Cone spacing was 7.3 ± 0.5 μm in POAG and 7.0 ± 0.4 μm in normal controls (p = 0.005), and cone regularity was 90.5 ± 4.9% and 93.5 ± 1.9% in POAG and normal controls, respectively (p < 0.001). At 4° similar trends were observed. However, no significant differences were found among patients with different severity of POAG (p > 0.05). Conclusions: Using AO Rtx1TM, significant differences in retinal photoreceptors mosaic pattern were found between POAG eyes and age-matched controls, indicating a reduction in photoreceptors in POAG. No significant differences in retinal photoreceptor values were found among the three POAG groups

Microenvironment-Centred Dynamics in Aggressive B-Cell Lymphomas

Aggressive B-cell lymphomas share high proliferative and invasive attitudes and dismal prognosis despite heterogeneous biological features. In the interchained sequence of events leading to cancer progression, neoplastic clone-intrinsic molecular events play a major role. Nevertheless, microenvironment-related cues have progressively come into focus as true determinants for this process. The cancer-associated microenvironment is a complex network of nonneoplastic immune and stromal cells embedded in extracellular components, giving rise to a multifarious crosstalk with neoplastic cells towards the induction of a supportive milieu. The immunological and stromal microenvironments have been classically regarded as essential partners of indolent lymphomas, while considered mainly negligible in the setting of aggressive B-cell lymphomas that, by their nature, are less reliant on external stimuli. By this paper we try to delineate the cardinal microenvironment-centred dynamics exerting an influence over lymphoid clone progression in aggressive B-cell lymphomas

Non-Functional Jaw Muscular Activity in Patients with Disorders of Consciousness Revealed by A Long-Lasting Polygraphy

The presence of involuntary, non-functional jaw muscle activity (NFJMA) has not yet been assessed in patients with disorders of consciousness (DOC), although the presence of bruxism and other forms of movement disorders involving facial muscles is probably more frequent than believed. In this work, we evaluated twenty-two prolonged or chronic DOC patients with a long-lasting polygraphic recording to verify NFJMA occurrence and assess its neurophysiological patterns in this group of patients. A total of 5 out of 22 patients showed the presence of significant NFJMA with electromyographic patterns similar to what can be observed in non-DOC patients with bruxism, thus suggesting a disinhibition of masticatory motor nuclei from the cortical control. On the other hand, in two DOC patients, electromyographic patterns advised for the presence of myorhythmia, thus suggesting a brainstem/diencephalic involvement. Functional, non-invasive tools such as long-lasting polygraphic recordings should be extended to a larger sample of patients, since they are increasingly important in revealing disorders potentially severe and impacting the quality of life of DOC patients

Towards a New Assessment Tool for Caregivers of Patients with Disorders of Consciousness: The Social and Family Evaluation Scale (SAFE)

Monitoring the level of responsiveness of patients with Disorders of Consciousness (DoCs) represents an issue in all the settings where there is not the daily presence of clinicians, such as long-term and domestic settings. The involvement of patients’ informal caregivers (i.e., patients’ family) in such a monitoring process is thus fundamental. However, to date, no standardized tailored-made instruments exist that informal caregivers can use without the presence of clinicians, despite evidence illustrating the good accuracy of caregivers when expressing their opinions about the level of responsiveness of DoC patients. The present work aims to set the foundational knowledge, to create a standardized instrument that is able to assess the level of responsiveness of patients with DoCs by their informal caregivers. After selecting and modifying the items to be included in the new scale from the gold standard to diagnose DoCs (i.e., the Coma Recovery Scale-revised), and following a consensus process, we created the Social and Family Evaluation (SAFE) scale for caregivers of patients with DoCs. Although the SAFE needs a validation process, with the present work we provided its preliminary description along with insights into its clinical utility

Towards a New Assessment Tool for Caregivers of Patients with Disorders of Consciousness: The Social and Family Evaluation Scale (SAFE)

Monitoring the level of responsiveness of patients with Disorders of Consciousness (DoCs) represents an issue in all the settings where there is not the daily presence of clinicians, such as long-term and domestic settings. The involvement of patients’ informal caregivers (i.e., patients’ family) in such a monitoring process is thus fundamental. However, to date, no standardized tailored-made instruments exist that informal caregivers can use without the presence of clinicians, despite evidence illustrating the good accuracy of caregivers when expressing their opinions about the level of responsiveness of DoC patients. The present work aims to set the foundational knowledge, to create a standardized instrument that is able to assess the level of responsiveness of patients with DoCs by their informal caregivers. After selecting and modifying the items to be included in the new scale from the gold standard to diagnose DoCs (i.e., the Coma Recovery Scale-revised), and following a consensus process, we created the Social and Family Evaluation (SAFE) scale for caregivers of patients with DoCs. Although the SAFE needs a validation process, with the present work we provided its preliminary description along with insights into its clinical utility.</jats:p

Pathology of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of different conditions which are characterized by hepatic steatosis in the absence of secondary causes. It is currently the most common chronic liver disease worldwide, and its estimated prevalence is about 1.5-6.5%. The only histological finding of steatosis ("simple" steatosis) represents the uncomplicated form of NAFLD, while non-alcoholic steatohepatitis (NASH) is its inflammatory subtype associated with disease progression to cirrhosis and hepatocellular carcinoma (HCC), and represents the major indication for liver transplantation. NASH is still a diagnostic and therapeutic challenge for clinicians and liver biopsy is currently the only accepted method to reliably distinguish NASH from "simple" steatosis. From the histological perspectives, NAFLD and NASH continue to be an area of active interest for pathologists, with a specific focus on better methods of evaluation, morphologic clues to pathogenesis, and predictors of fibrosis progression. This review focuses on histopathology of NAFLD in adults, with the aim to provide a practical diagnostic approach useful in the clinical routine