Benign TdT-positive cells in pediatric and adult lymph nodes: a potential diagnostic pitfall

Benign TdT-positive cells have been documented in a variety of non-hematopoietic tissues. Scant data are however available on their presence in non-neoplastic lymph nodes. This study is aimed to: (i) characterize the presence/distribution of benign TdT-positive cells in pediatric and adult reactive lymph nodes; (ii) define the phenotype and nature of such elements. This retrospective study considered 141 reactive lymph nodes from pediatric and adult patients without history of neoplastic disease. TdT-positive cells were characterized by immunohistochemical and morphometric analyses and their presence was correlated with the clinical-pathological features. The nature of TdT-positive cells was investigated by: (i) double immunostaining for early lymphoid cell markers; and (ii) assessment of TdT expression in fetal lymph nodes. Sparse TdT-positive cells were documented in all pediatric cases and in most (76%) adult lymph nodes. TdT-positive cell density was higher in children than adults (15.9/mm2 versus 8.6/mm2; P<.05). TdT positivity did not correlate with any clinical and histological parameter and double immunostaining disclosed a phenotype compatible with early lymphoid precursors (positivity for CD34, CD10 and variable expression of CD7). A very high TdT-positive cell density (802.4/mm2) was reported in all fetal lymph nodes. In conclusion, TdT-positive cells are a common finding in pediatric and adult lymph nodes. The interstitial distribution and low number of such cells allows for the differential diagnosis with precursor lymphoid neoplasms. The high density in fetal lymph nodes and the phenotype of such cells suggest their belonging to an immature lymphoid subset gradually decreasing with age

Interacting with a multi AGV system

This paper introduces a novel Human Machine Interface (HMI) that allows users to interact with a fleet of Automated Guided Vehicles (AGVs) used for logistics operations in industrial environments. The interface is developed for providing operators with information regarding the fleet of AGVs, and the status of the industrial environment. Information is provided in an intuitive manner, utilizing a three-dimensional representation of the elements in the environment. The HMI also allows operators to influence the behavior of the fleet of AGVs, manually inserting missions to be accomplished

Spleen histology in children with sickle cell disease and hereditary spherocytosis: Hints on the disease pathophysiology

open2Hereditary spherocytosis (HS) and sickle cell disease (SCD) are associated with splenomegaly and spleen dysfunction in pediatric patients. Scant data exist on possible correlations between spleen morphology and function in HS and SCD. This study aimed to assess the histological and morphometric features of HS and SCD spleens, in order to get possible correlations with disease pathophysiology. In a large series of spleens from SCD, HS and control patients the following parameters were considered: (i) macroscopic features; (ii) lymphoid follicle (LF) density; (iii) presence of peri-follicular marginal zones (MZs); (iv) presence of Gamna-Gandy bodies; (v) density of CD8-positive sinusoids; (vi) density of CD34-positive microvessels; (vii) presence/distribution of fibrosis and SMA-positive myoid cells; (viii) density of CD68-positive macrophages. SCD and HS spleens have similar macroscopic features. SCD spleens had lower LF density and fewer MZs than HS spleens and controls. SCD also showed lower CD8-positive sinusoid density, increased CD34-positive microvessel density and SMA-positive myoid cells, and higher prevalence of fibrosis and Gamna-Gandy bodies. HS had lower LF and CD8-positive sinusoid density than controls. No significant differences were noted in red pulp macrophages. By multivariate analysis, the majority of HS spleens clustered with controls, while SCD grouped separately. A multi-parametric score could predict the degree of spleen changes irrespective of the underlying disease. In conclusion, SCD spleens display greater histologic effacement than HS and SCD-related changes suggest impaired function due to vascular damage. These observations may contribute to guide the clinical management of patients.embargoed_20161128Alaggio, RitaAlaggio, Rita; Gamba, Piergiorgi

Pathobiology of ALK-negative anaplastic large cell lymphoma

The authors revise the concept of ALK-negative anaplastic large cell lymphoma (ALCL) in the light of the recently updated WHO classification of Tumors of Hematopoietic and Lymphoid Tissues both on biological and clinical grounds. The main histological findings are illustrated as well as the phenotypic, molecular and clinical characteristics. Finally, the biological rationale for possible innovative targeted therapies is presented

TOX Expression in Mycosis Fungoides and Sezary Syndrome.

Mycosis fungoides (MF) and Sezary syndrome (SS) are the two most common type of cutaneous T-cell lymphoma (CTCL). Currently, no markers can be clearly related to prognosis or to differential diagnosis between early stages and inflammatory benign diseases (IBD). The thymocyte selection-associated high mobility group box factor (TOX), has been proposed as a possible marker in differential diagnosis between early CTCL stages and IBD. Recently TOX has been related to prognosis. We aimed to investigate whether TOX may be a diagnostic or prognostic marker. MF and SS biopsies between 2010 and 2020 were retrieved. New tissues slides were stained with an anti-TOX antibody, (Clone NAN448B). On each slide, 5 fields were examined at high magnification (400×), to evaluate the percentage of marker-positivity in a quantitative way. Thirty-six patients (12 females and 24 males) and 48 biopsies were collected. Nine patients had multiple biopsies. TOX expression in MF/SS cases showed an increase from early to advanced phases. TOX was not regarded as a prognostic marker due to the absence of significant changes by comparing early MF cases with reactive conditions. TOX statistical significance increased in patients alive with disease and in those dead of disease (p = 0.013 and = 0.0005, respectively) as compared with patients in complete remission. Our results show that TOX should be regarded more as a prognostic than a diagnostic marker.This research received no external fundingS

Pathobiology of Anaplastic Large Cell Lymphoma

The authors revise the concept of anaplastic large cell lymphoma (ALCL) in the light of the recently updated WHO classification of Tumors of Hematopoietic and Lymphoid Tissues both on biological and clinical grounds. The main histological findings are illustrated with special reference to the cytological spectrum that is indeed characteristic of the tumor. The phenotype is reported in detail: the expression of the ALK protein as well as the chromosomal abnormalities is discussed with their potential pathogenetic implications. The clinical features of ALCL are presented by underlining the difference in terms of response to therapy and survival between the ALK-positive and ALK-negative forms. Finally, the biological rationale for potential innovative targeted therapies is presented

The effects of primary care monitoring strategies on COVID-19 related hospitalisation and mortality: a retrospective electronic medical records review in a northern Italian province, the MAGMA study

Background: Most symptomatic SARS-CoV-2 infections produce mild to moderate symptoms. Although most patients are managed in the outpatient setting, little is known about the effect of general practitioners' (GP) management strategies on the outcomes of COVID-19 outpatients in Italy. Objectives: Describe the management of Italian GPs of SARS-CoV-2 infected adult patients and explore whether GP active care and monitoring are associated with reducing hospitalisation and death. Methods: Retrospective observational study of SARS-CoV-2 infected adult outpatients managed by GPs in Modena (Italy) from March 2020 to April 2021. Information on management and monitoring strategies, patients' socio-demographic characteristics, comorbidities, and outcomes (hospitalisation and death due to COVID-19) were retrieved through an electronic medical record review and analysed descriptively and through multiple logistic regression. Results: Out of the 5340 patients from 46 GPs included in the study, 3014 (56%) received remote monitoring, and 840 (16%) had at least one home visit. More than 85% of severe or critical patients were actively monitored (73% daily) and 52% were visited at home. Changes over time in patients' therapeutic management were observed in concordance with the guidelines' release. Active daily remote monitoring and home visits were strongly associated with reduced hospitalisation rate (OR 0.52, 95% CI 0.33-0.80 and OR 0.50, 95% CI 0.33-0.78 respectively). Conclusion: GPs effectively managed an increasing number of outpatients during the first waves of the pandemic. Active monitoring and home visits were associated with reduced hospitalisation in COVID-19 outpatients

Pathobiology of Hodgkin Lymphoma

Despite its well-known histological and clinical features, Hodgkin's lymphoma (HL) has recently been the object of intense research activity, leading to a better understanding of its phenotype, molecular characteristics, histogenesis, and possible mechanisms of lymphomagenesis. There is complete consensus on the B-cell derivation of the tumor in most cases, and on the relevance of Epstein-Barr virus infection and defective cytokinesis in at least a proportion of patients. The REAL/WHO classification recognizes a basic distinction between lymphocyte predominance HL (LP-HL) and classic HL (cHL), reflecting the differences in clinical presentation and behavior, morphology, phenotype, and molecular features. cHL has been classified into four subtypes: lymphocyte rich, nodular sclerosing, with mixed cellularity, and lymphocyte depleted. The borders between cHL and anaplastic large-cell lymphoma have become sharper, whereas those between LP-HL and T-cell-rich B-cell lymphoma remain ill defined. Treatments adjusted to the pathobiological characteristics of the tumor in at-risk patients have been proposed and are on the way to being applied

T-Cell Lymphoblastic Lymphoma Arising in the Setting of Myeloid/Lymphoid Neoplasms with Eosinophilia: LMO2 Immunohistochemistry as a Potentially Useful Diagnostic Marker

Simple Summary Rarely, T-lymphoblastic lymphoma (T-LBL) may develop in the setting of myeloid/lymphoid neoplasms with eosinophilia. Given important therapeutic implications, it is crucial to identify T-LBL arising in this particular context. LIM domain only 2 (LMO2) is known to be overexpressed in almost all sporadic T-LBL and not in immature TdT-positive T-cells in the thymus and in indolent T-lymphoblastic proliferations. We retrospectively evaluated the clinical, morphological, immunohistochemical and molecular features of 11 cases of T-LBL occurring in the setting of myeloid/lymphoid neoplasms with eosinophilia and investigated the immunohistochemical expression of LMO2 in this setting of T-LBL. Interestingly, 9/11 cases were LMO2 negative, with only 2 cases showing partial expression. In our study, we would suggest that LMO2 immunostaining, as part of the diagnostic panel for T-LBL, may represent a useful marker to identify T-LBL developing in the context of myeloid/lymphoid neoplasms with eosinophilia. Background: Rarely, T-lymphoblastic lymphoma (T-LBL) may develop in the setting of myeloid/lymphoid neoplasms with eosinophilia (M/LNs-Eo), a group of diseases with gene fusion resulting in overexpression of an aberrant tyrosine kinase or cytokine receptor. The correct identification of this category has relevant therapeutic implications. LIM domain only 2 (LMO2) is overexpressed in most T-LBL, but not in immature TdT-positive T-cells in the thymus and in indolent T-lymphoblastic proliferations (iT-LBP). Methods and Results: We retrospectively evaluated 11 cases of T-LBL occurring in the context of M/LNs-Eo. Clinical, histological, immunohistochemical and molecular features were collected and LMO2 immunohistochemical staining was performed. The critical re-evaluation of these cases confirmed the diagnosis of T-LBL with morphological, immunohistochemical and molecular features consistent with T-LBL occurring in M/LNs-Eo. Interestingly, LMO2 immunohistochemical analysis was negative in 9/11 cases, whereas only 2 cases revealed a partial LMO2 expression with a moderate and low degree of intensity, respectively. Conclusions: LMO2 may represent a potentially useful marker to identify T-LBL developing in the context of M/LNs-Eo. In this setting, T-LBL shows LMO2 immunohistochemical profile overlapping with cortical thymocytes and iT-LBP, possibly reflecting different molecular patterns involved in the pathogenesis of T-LBL arising in the setting of M/LNs-Eo