Biosafety in surgical pathology in the era of SARS-Cov2 pandemia. A statement of the Italian Society of Surgical Pathology and Cytology

Surgical pathology units face chemical and biological risks. While chemical risks have been intensely evaluated since the formalin ban, less attention has been drown to biological risks. The actual epidemiologic situation due to the SARS-CoV-2 pandemia has raised a series of questions, which need to be addressed as soon as possible. We have to pursue two lines of action: on one hand we must immediately adopt urgent measures to reduce the risk of SARS-CoV-2 infection of laboratory personnel, and on the other hand, we must address crucial technical and organizational aspects of biological risk reduction, preserving as much as possible the quality of tissue and cell samples. The evaluation of biological risk is an analytical process which involves different steps: a) characterization of the hazard (also known as risk assessment) and b) definition of a risk reduction strategy (also known as risk mitigation) 1. Risk assessment implies a) the identification of the intrinsic biologic characteristics of the infectious agent, and b) the identification of the laboratory procedures related to the agent. The intrinsic biologic characteristics of infectious agents are classified in 4 risk groups (RG) by the laboratory biosafety manual of the WHO 2. The RG range from level 1 (RG1) which includes microorganisms that are unlikely to cause human or animal disease, to level 4 (RG4) which includes pathogens which cause serious diseases, that can be readily transmitted from one individual to another, and for which effective treatment and preventive measures are not usually available. Risk mitigation includes the definition of the appropriate a) level of biosafety of the laboratory, b) type of personal protection equipment (PPE), c) type of infrastructure and equipment, and d) education of involved personnel. Laboratory biosafety is graded in 4 levels (BSL-1 to BSL-4) as exhaustively described in the laboratory biosafety manual of the WHO 2, and these levels are usually also defined by law (in Italy by the D. Lgs. 81/2008). BSL are a series of protections, which include individual safeguards designed to protect laboratory personnel, as well as the surrounding environment and community. The biosafety level required in laboratories derives from the characterization of the risk, and is not automatically derived from the risk group to which the pathogenic agent belongs. It is obvious that the biosafety level for a laboratory which cultivates a RG3 agent, will be higher than the level needed for a laboratory which performs diagnostic tests on inactivated biomaterials on the same agent. Specific checklists, derived from the WHO laboratory biosafety manual, which in Italy are also defined by the National Institute of Labor Safety Insurance (Istituto Nazionale Assicurazione Infortuni sul Lavoro) in its 6th Fascicle published in 2010 3 are necessary to verify the compliance of a given laboratory with the required biosafety level

Management of the corpse with suspect, probable or confirmed COVID-19 respiratory infection \u2013 Italian interim recommendations for personnel potentially exposed to material from corpses, including body fluids, in morgue structures and during autopsy practice.

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BCL3-rearrangements in B-cell lymphoid neoplasms occur in two breakpoint clusters associated with different diseases

The t(14;19)(q32;q13) often juxtaposes BCL3 with IGH resulting in overexpression of the gene. In contrast to other oncogenic translocations, BCL3-rearrangement (BCL3-R) has been associated with a broad spectrum of lymphoid neoplasms. Here we report an integrative whole-genome sequence, transcriptomic, and DNA methylation analysis of 13 lymphoid neoplasms with BCL3-R. The resolution of the breakpoints at single base-pair revealed that they occur in two clusters at 5' (n=9) and 3' (n=4) regions of BCL3 associated with two different biological and clinical entities. Both breakpoints were mediated by aberrant class switch recombination of the IGH locus. However, the 5' breakpoints (upstream) juxtaposed BCL3 next to an IGH enhancer leading to overexpression of the gene whereas the 3' breakpoints (downstream) positioned BCL3 outside the influence of the IGH and were not associated with its expression. Upstream BCL3-R tumors had unmutated IGHV, trisomy 12, and mutated genes frequently seen in CLL but had an atypical CLL morphology, immunophenotype, DNA methylome, and expression profile that differ from conventional CLL. In contrast, downstream BCL3-R neoplasms were atypical splenic or nodal marginal zone lymphomas (MZL) with mutated IGHV, complex karyotypes and mutated genes typical of MZL. Two of the latter 4 tumors transformed to a large B-cell lymphoma. We designed a novel FISH assay that recognizes the two different breakpoints and validated these findings in 17 independent tumors. Overall, upstream or downstream breakpoints of BCL3-R are mainly associated with two subtypes of lymphoid neoplasms with different (epi)genomic, expression, and clinicopathological features resembling atypical CLL and MZL, respectively

BCL3-rearrangements in B-cell lymphoid neoplasms occur in two breakpoint clusters associated with different diseases

The t(14;19)(q32;q13) often juxtaposes BCL3 with immunoglobulin heavy chain (IGH) resulting in overexpression of the gene. In contrast to other oncogenic translocations, BCL3 rearrangement (BCL3-R) has been associated with a broad spectrum of lymphoid neoplasms. Here we report an integrative whole-genome sequence, transcriptomic, and DNA methylation analysis of 13 lymphoid neoplasms with BCL3-R. The resolution of the breakpoints at single base-pair revealed that they occur in two clusters at 5' (n=9) and 3' (n=4) regions of BCL3 associated with two different biological and clinical entities. Both breakpoints were mediated by aberrant class switch recombination of the IGH locus. However, the 5' breakpoints (upstream) juxtaposed BCL3 next to an IGH enhancer leading to overexpression of the gene whereas the 3' breakpoints (downstream) positioned BCL3 outside the influence of the IGH and were not associated with its expression. Upstream BCL3-R tumors had unmutated IGHV, trisomy 12, and mutated genes frequently seen in chronic lymphocytic leukemia (CLL) but had an atypical CLL morphology, immunophenotype, DNA methylome, and expression profile that differ from conventional CLL. In contrast, downstream BCL3-R neoplasms were atypical splenic or nodal marginal zone lymphomas (MZL) with mutated IGHV, complex karyotypes and mutated genes typical of MZL. Two of the latter four tumors transformed to a large B-cell lymphoma. We designed a novel fluorescence in situ hybridization assay that recognizes the two different breakpoints and validated these findings in 17 independent tumors. Overall, upstream or downstream breakpoints of BCL3-R are mainly associated with two subtypes of lymphoid neoplasms with different (epi)genomic, expression, and clinicopathological features resembling atypical CLL and MZL, respectively

Peri and intraneural mucinosis in painful, interstitial granuloma annulare of the digit

Granuloma annulare (GA) presenting as a painful lesion with acral distribution has been previously described

Sudden Infant Death With Area Postrema Lesion Likely Due to Wrong Use of Insecticide

We report a noteworthy case of a 7-month-old infant who suddenly and abstract unexpectedly died during her sleep. After a complete postmortem examination, review of the clinical history, and detailed death scene investigation, the death remained unexplained, leading to a diagnosis of sudden infant death syndrome. However, an extensive review of the brainstem neuropathology revealed a severe alteration in the area postrema (a highly vascular structure lying at the base of the fourth ventricle outside of the blood-brain barrier). The alteration was likely due to massive and repeated to a common household insecticide in the last few weeks of life. These results provide an explanation for this sudden infant death, allowing a differential diagnosis from sudden infant death syndrome

Applicazioni della PCR e PCR in situ nella diagnosi di infezioni batteriche e virali da biopsie fissate in formalina e incluse in paraffina

In situ PCR, amplification of target DNA sequences in fixed cells, is a very useful molecular biology tecnique with potential to combine the high sensitivity of tube PCR with the precise anatomical localization of the targeted bsequences. It allows the study of low copy viral or bacterial DNA. In this study we document the utility of directin situ PCR with single primer pair by applying it to 3 infectious agents in different model systems: Borrelia burgdorferi in 5 Eritema migrans lesions and 55 primitive cutaneous B cell lymphomas, Chlamydia pneumoniae in 200 autoptic atheromasic lesions, and Papilloma virus in 20 CIN 1 (mild cervical dysplasia). In situ PCR seems to be a very promising tecnique; however, the prerequisite for the success of in situ PCR is conditioned by optimal standardization of the key variables which, on the other hand, are influenced by tissue composition

Localizzazione e valutazione dell’espressione di Chlamydophila pneumoniae mediante RT-PCR in situ

Chlamydophila pneumoniae, an obligate intracellular gram negative bacterium, is involved in a wide spectrum of symptomatic respiratory tract diseases. However more recently it has been reported to be a pathogenic agent in the mechanism leading to atherosclerosis. In the present study the presence of Chlamydophila pneumoniae was assessed, using nested PCR and in situ PCR, while the viability of the microorganism was investigated using RT in situ PCR.The results obtained demonstrated that Chlamydophila pneumoniae was present and alive in the tissues examined.The global concordance of results in the three techniques used was 100%. RT in situ PCR can be considered a precious tool to detect bacterial mRNA in formalin fixed paraffin embedded samples provided an optimal standardization of the key variables is achieved