Spatial Organization and Correlations of Cell Nuclei in Brain Tumors

Accepting the hypothesis that cancers are self-organizing, opportunistic systems, it is crucial to understand the collective behavior of cancer cells in their tumorous heterogeneous environment. In the present paper, we ask the following basic question: Is this self-organization of tumor evolution reflected in the manner in which malignant cells are spatially distributed in their heterogeneous environment? We employ a variety of nontrivial statistical microstructural descriptors that arise in the theory of heterogeneous media to characterize the spatial distributions of the nuclei of both benign brain white matter cells and brain glioma cells as obtained from histological images. These descriptors, which include the pair correlation function, structure factor and various nearest neighbor functions, quantify how pairs of cell nuclei are correlated in space in various ways. We map the centroids of the cell nuclei into point distributions to show that while commonly used local spatial statistics (e.g., cell areas and number of neighboring cells) cannot clearly distinguish spatial correlations in distributions of normal and abnormal cell nuclei, their salient structural features are captured very well by the aforementioned microstructural descriptors. We show that the tumorous cells pack more densely than normal cells and exhibit stronger effective repulsions between any pair of cells. Moreover, we demonstrate that brain gliomas are organized in a collective way rather than randomly on intermediate and large length scales. The existence of nontrivial spatial correlations between the abnormal cells strongly supports the view that cancer is not an unorganized collection of malignant cells but rather a complex emergent integrated system

Digitization of Pathology Labs: A Review of Lessons Learned

Pathology laboratories are increasingly using digital workflows. This has the potential of increasing lab efficiency, but the digitization process also involves major challenges. Several reports have been published describing the individual experiences of specific laboratories with the digitization process. However, a comprehensive overview of the lessons learned is still lacking. We provide an overview of the lessons learned for different aspects of the digitization process, including digital case management, digital slide reading, and computer-aided slide reading. We also cover metrics used for monitoring performance and pitfalls and corresponding values observed in practice. The overview is intended to help pathologists, IT decision-makers, and administrators to benefit from the experiences of others and to implement the digitization process in an optimal way to make their own laboratory future-proof.Comment: 22 pages, 1 figur

Best Practice Recommendations for the Implementation of a Digital Pathology Workflow in the Anatomic Pathology Laboratory by the European Society of Digital and Integrative Pathology (ESDIP)

The interest in implementing digital pathology (DP) workflows to obtain whole slide image (WSI) files for diagnostic purposes has increased in the last few years. The increasing performance of technical components and the Food and Drug Administration (FDA) approval of systems for primary diagnosis led to increased interest in applying DP workflows. However, despite this revolutionary transition, real world data suggest that a fully digital approach to the histological workflow has been implemented in only a minority of pathology laboratories. The objective of this study is to facilitate the implementation of DP workflows in pathology laboratories, helping those involved in this process of transformation to identify: (a) the scope and the boundaries of the DP transformation; (b) how to introduce automation to reduce errors; (c) how to introduce appropriate quality control to guarantee the safety of the process and (d) the hardware and software needed to implement DP systems inside the pathology laboratory. The European Society of Digital and Integrative Pathology (ESDIP) provided consensus-based recommendations developed through discussion among members of the Scientific Committee. The recommendations are thus based on the expertise of the panel members and on the agreement obtained after virtual meetings. Prior to publication, the recommendations were reviewed by members of the ESDIP Board. The recommendations comprehensively cover every step of the implementation of the digital workflow in the anatomic pathology department, emphasizing the importance of interoperability, automation and tracking of the entire process before the introduction of a scanning facility. Compared to the available national and international guidelines, the present document represents a practical, handy reference for the correct implementation of the digital workflow in Europe.publishedVersio

Treatment outcomes in 1p19q co-deleted/partially deleted gliomasa

AbstractBackground:Radiotherapy with procarbazine, lomustine, and vincristine improves overall survival (OS) in patients with 1p19q co-deleted anaplastic oligodendroglioma/anaplastic oligoastrocytoma.Methods:This retrospective analysis investigated outcomes in patients with 1p19q co-deleted/partially deleted oligodendroglioma, oligoastrocytoma, anaplastic oligodendroglioma, or anaplastic oligoastrocytoma. OS and progression-free survival (PFS) were analyzed using the Kaplan-Meier method and prognostic factors using the Cox proportional hazard model.Results:A total of 106 patients (between December 1997 and December 2013) were included. Median age was 40 years (19-66), 58 were male (55%), Eastern Cooperative Oncology Group performance status was 0 in 80 patients (75%). 1p19q status was co-deleted in 66 (62%), incompletely co-deleted in 27 (25%), and 1p or 19q loss alone in four (4%) and nine (8%) patients, respectively. Isocitrate dehydrogenase-1 R132H mutation was found in 67 of 85 patients with sufficient material. Upfront treatment was given in 72 (68%) patients and temozolomide alone in 52 (49%). Median time to radiotherapy in 47 patients (44%) was 34.7 months and 41.2 months in 9 patients with co-deleted/incompletely co-deleted anaplastic oligodendroglioma/anaplastic oligoastrocytoma who received upfront temozolomide alone. Median OS was not reached and 5-year OS was 91% for all groups (median follow-up, 5.1 years). On multivariable analysis for all patients, receipt of therapy upfront versus none (p=0.04), PS 1 versus 0 (p&lt;0.001) and 1p19q co-deletion/incomplete deletion versus 1p or 19q loss alone (p=0.005) were prognostic for PFS. Isocitrate dehydrogenase-1 status was not prognostic for PFS.Conclusions:With similar survival patterns in low-grade/anaplastic gliomas, molecular characteristics may be more important than histological grade. Longer follow-up and results of prospective trials are needed for definitive guidance on treatment of these patients.</jats:p

Periventricular nodular heterotopia and bilateral intraventricular xanthogranulomas in 22q11.2 deletion syndrome

22q11.2 deletion syndrome (22q11DS) is the most common pathogenic copy number variant in humans. Neuropsychiatric phenotypes, including schizophrenia, are prominent. Imaging studies of individuals with this syndrome show a variety of abnormalities that may indicate abnormal neuronal migration. Here we present the neuroimaging and neuropathologic features of a 22q11DS patient with bilateral periventricular nodular heterotopias (PNH) and intraventricular xanthogranulomas that were identified by post-mortem examination. Keywords: 22q11.2 Deletion Syndrome, periventricular nodular heterotopia, neuronal migration, xanthogranulom

Nonstenotic carotid plaque on CT angiography in patients with cryptogenic stroke

Objective: To determine whether large (≥3 mm thick) but nonstenotic (<50%) carotid artery atherosclerotic plaque predominantly occurs ipsilateral rather than contralateral to cryptogenic stroke. Methods: This was a cross-sectional observational study. Using a stroke registry, we identified consecutive patients with anterior circulation embolic stroke of undetermined source (ESUS). Using CT angiography, we measured carotid plaque size (thickness, mm) and carotid artery stenosis (North American Symptomatic Carotid Endarterectomy Trial method) for each patient. We dichotomized plaque size at several predefined thresholds and calculated the frequency of plaque size above each threshold ipsilateral vs contralateral to stroke. Results: We included 85 patients with ESUS. Plaque with thickness ≥5 mm was present ipsilateral to stroke in 11% of patients, and contralateral in 1% (9/85 vs 1/85; p 0.008). Plaque with thickness ≥4 mm was present ipsilateral to stroke in 19% of patients, and contralateral in 5% (16/85 vs 4/85; p 0.002). Plaque with thickness ≥3 mm was present ipsilateral to stroke in 35% of patients, and contralateral in 15% (30/85 vs 13/85; p 0.001). There was no difference in percentage stenosis ipsilateral vs contralateral to stroke (p 0.98), and weak correlation between plaque size and stenosis (R 2 0.26, p < 0.001). Conclusions: Large but nonstenotic carotid artery plaque is considerably more common ipsilateral than contralateral to cryptogenic stroke, suggesting that nonstenotic plaque is an underrecognized cause of stroke. We measured plaque size using CT angiography, a method that could be easily implemented in clinical practice