ABSTRACT: 60th Annual Canadian Association of Neuropathologists Meeting
Abstracts
Canadian Association of Neuropathologists Association canadienne des neuropathologistes
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- Published online by Cambridge University Press:
- 29 July 2021, p. S7
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The Canadian Association of Neuropathologist – Association canadienne des neuropathologistes (CANP-ACNP) held their 60th annual meeting via Zoom from October 15th to 17th, 2020, under the leadership of Dr. Peter Gould, President of the CANP-ACNP, Dr. Peter Schutz, Secretary Treasurer of the CANP-ACNP, and with technical support from CANP administrators Heather Dow and Colleen Fifield.
The academic program comprised 10 scientific abstracts, 10 unknown cases, a symposium on Neuromuscular Pathology, and a Neuropathology Practice lecture by Dr. Emina Torlakovic entitled The Fall and Rise of Immunohistochemistry. The interactive forum on Neuropathology Practice was moderated by Dr. Gould and Dr. Keith and focused on forensic neuropathology in Canada. The Jerzy Olszewski Lecture was delivered by Dr. Alex Rajput and Dr. Ali Rajput on Neuropathology and Saskatchewan Movement Disorders Program. Digital pathology images from the 10 unknown cases are available for viewing online (www.canp.ca) thanks to the CANP webmaster Dr. Andrew Gao.
The Presidential Symposium 2020 on Neuromuscular Pathology featured the David Robertson Lecture given by Dr. Werner Stenzel entitled The Inflammatory Myopathies – Essential Role of Muscle Biopsies for Precise Diagnosis and the Gordon Mathieson Lecture delivered by Dr. Benjamin Ellezam on The Role of Muscle Biopsy in the Molecular Era: Practical Pointers in Diagnostic Pathology of Inherited Myopathies. The program was completed by Dr. Robert Schmidt’s presentation on Perspectives on the Evaluation of Nerve Biopsies, and Dr. Jodi Warman Chardon’s presentation on MRI & Diagnosis of Muscle Disease.
The Mary Tom Award for best clinical science presentation by a trainee went to Dr. Noor Alsafwani (Supervisor Dr. A. Gao), and the Morrison H. Finlayson Award for best basic science presentation by a trainee was won by Dr. Delaney Cosma (Supervisor Dr. R. Hammond).
The following abstracts were presented at the 60th annual meeting of the Canadian Association of Neuropathologists – Association candienne des neuropathologistes (CANP-ACNP) in October 2020.
Congenital CMV Infection Presenting with Massive Intracerebral Hemorrhage
- Barbra deVrijer, Diana Crowley, Delaney Cosma, Giulio Muscedere, Robert Hammond
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- 29 July 2021, p. S8
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Cytomegalovirus (CMV) is among the most common of intrauterine infections against which we have no effective preventative or therapeutic options. The developing nervous system is a frequent target of CMV and while most injuries are subclinical, severe insults leading to microcephaly and migration defects are well known. A 20-week gestational age fetus was found to have several abnormalities on prenatal ultrasound, the most prominent of which was a large echogenic focus in one cerebral hemisphere. Congenital CMV infection was identified by amniocentesis and maternal serology. The pregnancy was ended by early induction of labour for a 368g stillborn infant. Postmortem examination revealed massive intracerebral hemorrhage as the correlate for the sonographic finding. The microscopic examination of the brain was also striking for extensive polymicrogyria, a high burden of CMV and abundant angiocentric CMV pathology. Catastrophic intracerebral hemorrhage has not been previously reported in association with congenital CMV infection. The present case expands the range of potential injuries the developing brain is subject to in the setting of CMV infection and raises the possibility of a direct vascular injury.
Learning ObjectivesConsider intracerebral hemorrhage in the range of potential outcomes in congenital CMV infection
Describe how polymicrogyria may result from an insult during proliferation and migration
Discuss possible mechanisms of injury to the developing brain by CMV
Brain Toxoplasmosis Comorbid with Autoimmune Disease: Complicated Immune Response And Case Demonstration
- Alice Graham, Crystal Fong, Asghar Naqvi, Jian-Qiang Lu
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- 29 July 2021, p. S8
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Toxoplasmosis is an opportunistic infection caused by Toxoplasma gondii (TG), commonly involving the brain. Symptomatic clinical disease of TG infection is much more commonly associated with immunodeficiency; clinicopathological manifestations of brain toxoplasmosis are linked to individual immune responses including brain infiltration of T-cells that are thought to fight against toxoplasmosis. In patients with autoimmune diseases, immune status is typically characterized by T-cell infiltration and complicated mainly by immunosuppressant and/or immunomodulatory treatment. In this study, we demonstrate clinical and radiological features correlated with pathological features of brain toxoplasmosis at different disease stages in a patient with coexisting autoimmune diseases, including systemic lupus erythematosus and autoimmune hepatitis. The infiltration of CD8+ T-cells in toxoplasma immunostaining-positive acute lesions was greater than that in toxoplasma immunostaining-negative chronic lesions. We also review previously reported cases of brain toxoplasmosis with comorbid autoimmune diseases. Our present case and literature review suggest that brain toxoplasmosis in patients with autoimmune diseases may be asymptomatic unless disease complications occur; it may present as an incidental finding at postmortem examination of rapidly developed lesions. T-cell infiltration in patients with autoimmune diseases and coexisting toxoplasmosis may be at least partially reduced; ultimately, the roles of T-cell infiltration in brain toxoplasmosis deserve further investigation.
Learning ObjectivesDiscuss complicated immune response to toxoplasmosis in patients with autoimmune diseases.
Describe clinical, radiological, and pathological features of brain toxoplasmosis in patients with autoimmune diseases.
Small Vessel Vasculitis in Biopsies Of Anti-mog Encephalitis
- Bradley M. Chaharyn, Christopher P. Dunham
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- 29 July 2021, pp. S8-S9
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We report the neuropathology of two pediatric brain biopsy cases associated with serum anti-myelin oligodendrocyte glycoprotein (MOG) positivity. Descriptions of anti-MOG associated neuropathology are limited, with initial reports describing various patterns of inflammatory demyelination. Our first patient presented with confusion, speech abnormalities and personality changes following a treated strep throat infection. Our second patient had a past medical history of neurofibromatosis type 1 (NF1) and presented with hypersomnolence and focal neurological deficits. MRI abnormalities included diffuse scattered T2 FLAIR hyperintensities +/- enhancement. CSF was positive for anti-MOG antibodies in both cases, while one case exhibited additional anti-NMDA-R antibodies. Brain biopsies revealed vasocentric mononuclear inflammation featuring a predominance of lymphocytes that included intramural forms, as well as diffuse microglial activation, but no evidence of microglial nodules or microorganisms. One case demonstrated mild perivascular demyelination. The prevailing pattern in both cases was suggestive of “small vessel childhood primary angiitis of the central nervous system” (SVcPACNS). Our results parallel recent reports of anti-MOG neuropathology describing small vessel vasculitis, contrary to initial and subsequent reports that describe “encephalitis”. The foregoing suggests that the neuropathology associated with serum anti-MOG positivity may be broader than first appreciated. Moreover, this pattern of vasculitis might have implications for the natural history of this nascent disorder.
Learning ObjectivesDefine anti-MOG encephalitis.
Recognize the pathologic spectrum of reported cases of anti-MOG encephalitis.
Contrast the pathologic features of pediatric and adult CNS vasculitis.
Describe the histologic overlap of vasculitis and encephalitis.
Spectrum Of White Matter Changes In Ischemic Lesions
- Murad Alturkustani, Lee -Cyn Ang
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- 29 July 2021, p. S9
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Morphological studies on cerebral ischemia concentrate mainly on the grey matter and white matter changes are regarded as secondary or overlapping injuries. Immunohistochemical (IHC) studies to highlight the combination of various cellular changes in ischemic white matter but have not well documented. We selected 11 archival cases of 3 different ischemic processes (i.e. large vessel occlusion, small vessel occlusion, and hypoperfusion) with survival period range 2-35 days from the ischemic event. The white matter was examined using HE-LFB histochemistry, APP, GFAP, and HLA-DR immunostains focusing on myelin, axonal, astrocytic and microglial changes respectively. The various white matter changes are probably reflective of the different mechanism, duration, severity and extent of ischemia. The APP-IHC shows patchy axonal expression, swelling, and finally complete axonal loss. HLADR-IHC highlights early microglial injuries (fragmentation of processes), complete cell loss, and subsequent replacement by cells of macrophage phenotype. Surrounding the ischemic areas are reactive microglia. Astrocytic changes range from fragmentation of processes (clasmatodendrosis) to different stages of cell loss. Astrocytic swelling tends to occur with cerebral edema. Large vessel occlusion results in complete tissue loss while in small vessel disease the damage is more selective. The injury is generally more subtle in hypoperfusion but can be pronounced focally. Our study has documented the spectrum of white matter injury in different scenarios of cerebral ischemia.
Learning ObjectiveDescribe the cellular and immunohistochemical changes in the ischemic white matter
Relevance of tissue eosinophilia in subdural hematomata
- Benjamin Davidson, Michael Cusimano, David G. Munoz
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- 29 July 2021, p. S9
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Chronic subdural hematomata (CSDH) are treated by evacuation. Recurrence occurs in 3-20% of cases, but the factors determining its occurrence have not been determined. Having observed that eosinophil cell infiltrates are often present in the outer membrane of CSDH, our aim was to determine whether such infiltrates are associated with risk of recurrence. Histological sections of the resections from 72 patients with primary CSDH (Mean age 73.4) and 16 with recurrent CSDH (Mean age 72.1) stained with H&E were graded by blinded observers for eosinophilic cell infiltrates using a semiquantitative 0 to 3 scale. The risk of recurrence requiring reoperation (RrR) in primary CSDH was 11.1%, and 12.5% in recurrent CSDH (meaning third surgery was required). A dense (grades 2 or 3) eosinophilic infiltrate was present in 22.2% of primary CSDH; the RrR was 0% in these cases, as compared with 14.8% in cases with sparse (grades 0-1) eosinophilic infiltrate. Among recurrent CSDH cases, 12.5% (2/15) showed a dense eosinophilic infiltrate; the RrR was also 0%, contrasting with 14.3% in those with sparse eosinophilic infiltrate. We conclude that eosinophils either play a role or are a marker of a process leading to stabilizing CSDH, making them less prone to rebleeding. Abstract not previously published
Learning ObjectivesDescribe the risk of recurrence following surgical evacuation of chronic subdural hematomata
Recognize the variable presence of eosinophils in chronic subdural hematomata
Cite the presence of eosinophils is predictive of absence of recurrence
Subpial Thorn-shaped Astrocytes Are Prevalent In Guam ALS/PDC
- G.G. Kovacs, J.L. Robinson, D.P. Perl, V.M.Y. Lee, J.Q. Trojanowski
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- 29 July 2021, pp. S9-S10
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Guam amyotrophic lateral sclerosis/parkinsonism-dementia complex is a progressive neurodegenerative disorder characterized by neuronal and glial tau pathologies. With the aim to evaluate aging-related tau astrogliopathy (ARTAG) we examined the collection at the University of Pennsylvania, consisting of blocks of the frontal parietal, temporal, and occipital cortices. Formalin fixed, paraffin-embedded tissue blocks were evaluated using anti-tau antibodies PHF-1 and AT8. In addition to neuronal and oligodendroglial tau pathology, granular/fuzzy astrocytes in the gray matter and thorn-shaped astrocytes (TSAs) in subpial location were also observed. Twenty-one out of 33 cases (63%) showed subpial TSAs diffusely along the cortical surface in one or more cortical regions. Accumulation of TSAs in the depth of the sulci were seen in 41% in the temporal, 7% in the frontal and 14% in parietal cortex. This was not associated with perivascular neuronal tau pathology in the depth of the sulci. Accumulation of TSAs in the depth of cortical sulci in this cohort is approximately 20 times more frequent than reported in a European aging cohort. The presence of subpial TSAs in the depth of cortical sulci in CTE and Guam PDC, and less frequently in aging brains, might suggest common mechanisms.
Learning ObjectivesDescribe the spectrum of neuropathology in Guam ALS/PDC
Describe the frequency of tau positive cortical subpial thorn-shaped astrocytes
Complex Protein Astrogliopathy in an Octogenarian
- G.G. Kovacs, S. Klotz, P. Fischer, M. Hinterberger, G. Ricken, S. Hönigschnabl, E. Gelpi
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- 29 July 2021, p. S10
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Combination of multiple neurodegenerative proteinopathies is frequent in the elderly. We report the case of an octogenarian who attempted suicide and deceased after hospital admission. Anatomical mapping was performed in several cortical and subcortical brain regions using antibodies against phospho-tau, 4R tau, 3R tau, phospho-TDP-43, ubiquitin, α-synuclein, Aβ and p62. Unexpectedly, histopathologic examination showed prominent subpial, subependymal, grey and white matter, and perivascular aging-related tau astrogliopathy (ARTAG) affecting cortical and subcortical brain regions. This pathology was associated with intermediate Alzheimer’s disease neuropathologic change, cerebral amyloid angiopathy, Lewy-body-type and astroglial synuclein proteinopathy and a multiple system TDP-43 proteinopathy involving also the astroglia. This unusual case of extensive and widespread ARTAG with a complex multiproteinopathy may represent an independent disease entity in the elderly with tau astrogliopathy as the leading force.
Learning ObjectiveRecognize astroglial protein deposits in neurodegeneration
Somatotroph Adenoma with Dual Transcription Factor Expression
- Shervin Pejhan, Stan VanUum, Neil Duggal, Brian Rotenberg, Michael Mayich, Robert Hammond, Qi Zhang
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- 29 July 2021, p. S10
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A 20-year-old male presented with evidence of gigantism/acromegaly. Endocrinological investigations identified elevated growth hormone levels and a failed glucose tolerance test. Imaging revealed a macroadenoma expanding the sella with encroachment on the optic chiasm and cavernous sinuses. Trans-sphenoidal resection was undertaken and a gross total removal was achieved. Histopathological features were typical of a densely granulated somatotroph adenoma with abundant growth hormone expression, scattered prolactin expression and sparse examples of fibrous bodies. Unexpectedly, the adenoma not only expressed PIT-1 but also SF-1 transcription factors. This finding suggests that the adenoma may have been pluripotent. The prognostic significance of this finding is uncertain although the patient is stable from an endocrinological and imaging perspective approximately one-year post-op. A pituitary adenoma of this nature has not been previously reported. The recent literature on atypical transcription factor expression patterns and revisions to the classification of pituitary adenomas will be reviewed.
Learning ObjectivesAppreciate the rarity of dual transcription factor expression in pituitary adenomas
Rationalize the use of transcription factor characterization in the revised WHO classification of pituitary adenomas
Recipient of the 2020 Morris Finlayson Award (Ms. Delaney Cosma)
Abstracts
Cortical Dysplasia Teaching Pathology to a Machine
- Delaney Cosma, Ali Khan, Robert Hammond
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- 29 July 2021, p. S11
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Many patients with epilepsy do not achieve adequate pharmacologic control of their seizures and must consider surgical options. Many such patients undergo temporal lobectomy and experience a marked reduction in the frequency and severity of their seizures. However, many are less fortunate. One suspected factor for the latter group is the limited ability of clinical imaging to delineate subtle epileptogenic abnormalities, leading to subtotal resection of lesional tissue. A long range goal in this field is to increase the sensitivity and specificity of detecting such abnormalities by “training” MRI with pathology, feature analysis and machine learning. A key component of this is the ability to segment histopathology to facilitate its mapping to co-registered MRI. A foundational step in this process is to determine whether or not algorithms are capable of detecting the architectural abnormalities in cortical dysplasia on the basis of these segmentations. In brief, reliable semi-automated segmentations were developed to extract a number of features including neuron size, clustering, eccentricity, field-fraction and polarity. Feature analyses using t-Distributed Stochastic Neighbor Embedding (t-SNE) plots demonstrate a non-random association between selected features and diagnostic categories. These results indicate that automated algorithms are capable of distinguishing dysplastic from normal cortex on the basis of semi-automated segmentations.
Learning ObjectivesDescribe the value of segmentation in image analysis
Define the role of feature analysis such as t-SNE in high dimensionality histopathology data
Abstracts
Presenter: Werner Paulus, University Hospital Muenster, Muenster. Publishing A High-quality, Non-commercial Neuropathology Journal Without a Publisher: The First Nine Months
- Marta Margeta, Peter Gould, Lili-Naz Hazrati, Veronica Hirsch-Reinshagen, Werner Paulus
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- 29 July 2021, p. S11
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Scholarly communication faces increasing economical and ethical challenges, including pricing policies and overbearing behavior of commercial publishing houses. Based on the hypothesis that a diamond open access neuropathology journal of a high scientific and technical quality can be run entirely by neuropathologists, we launched Free Neuropathology (FNP; freeneuropathology.org) in January 2020. Classical publisher activities, such as copyediting, layout, website maintenance, and journal promotion, are undertaken by neuropathologists and neuroscientists using free open access software. The journal is free for both readers and authors, and papers are published under a Creative Commons BY SA licence, where copyright remains with the authors. Based on 26 articles published by August 2020, it takes FNP 11.1 days from submission to first, and 19.9 days to final, decision. High-quality copyediting, layout, and online publishing in the final format is accomplished in only 8 days. Absence of a commercial publisher enables prioritization of democratic and scientifically-driven decisions on editorial structure, website design, journal promotion, paper formatting, special article series, and number of accepted papers. This new model of journal publishing, which returns the control of scholarly communication to scientists, will be of interest to neuropathologists and wider scientific community alike.
Learning ObjectivesSummarize the current state and driving forces behind commercial and non-commercial scientific publishing in neuropathology.
Describe the advantages and challenges of a non-commercial publishing platform for neuropathology.