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Free Neuropathology 5:29 (2024) |
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Meeting Abstracts |
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35th Australian and New Zealand Society for Neuropathology (ANZSNP) |
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Saturday 31 August - Sunday 1 September 2024 |
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Submitted: 24 October 2024 Accepted: 25 October 2024 Published: 18 November 2024 |
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The ANZSNP scientific meeting 2024 was held in the scenic city of Queenstown, New Zealand on 31 August and September 1. Dr Fouzia Ziad, President of the ANZSNP and Dr Laveniya Satgunaseelan, Secretary /Treasurer of the ANZSNP were the convenors of the meeting. The meeting was co-badged with the Australasian Winter Conference on Brain Research (AWCBR) 2024. There were 55 registrants from Australia, New Zealand, USA, Europe and Asia. The academic program covered a wide range of neuropathology topics ranging from neuro-trauma to neuro-oncology. The neuro-oncology sessions featured a series of lectures on updates in the classification and diagnosis of various CNS tumours delivered by keynote speaker Prof Arie Perry, UCSF. Dr Thomas Robertson presented an approach to frozen sections in surgical neuropathology. An interactive session on the RCPA Neuropathology Quality Assurance Program (QAP) was organised with the QAP convenor, Dr Barbara Koszyca. Prof David Capper delivered the plenary lecture on “DNA methylation profiling and its practical implications” during the combined session with AWCBR attendees. Combined sessions also featured presentations on non-neoplastic conditions such as neurotrauma and neurodegeneration, comprising of presentations from invited faculty including Prof Michael Buckland, Dr Helen Murray and Prof Glenda Halliday. Four scientific research papers and 3 interesting cases were selected for oral presentation by the scientific committee. The meeting concluded with a plenary lecture delivered by Prof Arie Perry on “Biomarkers in Neuro-oncology”. Two of the research paper presentations were eligible for the Bill Evans Memorial award for postgraduate students or trainees. The prize was awarded to Dr Monish Maharaj for his presentation “DNA Methylation Profiling to categorise meningioma recurrence risk: optimisation of resource allocation for patient selection”. The feedback from the participants suggested that the meeting was well organized and appreciated for its educational content.
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Keywords: ANZSNP, 35th ANZSNP Scientific Meeting 2024, Australian and New Zealand Society for Neuropathology (ANZSNP), Queenstown, New Zealand |
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Table of contents
Research paper oral presentation abstracts
Abstract 1 Free Neuropathol 4:29:4 Saliva Swabs: A game-changer for concussion diagnosis and management Tandia Gooch1,2, Ewan Kennedy3, Regis Lamberts2, Sarah Appleby1
Introduction: Rugby is a physically demanding sport, as a result the injury of concussion is prevalent among players. Concussions are highly individual injuries and challenging to diagnose, leading to underdiagnosis and inadequate management among community rugby players. The Sport Concussion Assessment Tool (SCAT6) is currently recommended for concussion diagnosis in rugby, alongside clinical evaluation. However, this assessment is not feasible during a typical 15-minute general practitioner appointment. Additionally, SCAT6's reliability varies, with players often showing performance fluctuations even without a concussion. It also depends on players self-reporting symptoms, which often overlap with those experienced in the general population. Therefore, a quick, simple test identifying physiological markers and indicating physiological recovery is needed. Small non-coding RNAs (sncRNAs), which regulate gene expression, have shown promise as biomarkers for concussion. Aims: This study aims to validate the ability of a panel of 14 sncRNAs to diagnose concussions in community and adolescent rugby players. Furthermore, it seeks to determine the right time for a player to return to play post-concussion using the a sncRNA test. Methods: Data is collected at the Otago Concussion Clinic. Medical information and saliva swabs from players are obtained 48 hours and 19 days after injury. SncRNA analysis of the saliva samples will be conducted by Marker Health. Conclusion: This research has the potential to improve diagnosis of concussions in community rugby players using a simple saliva test. Therefore, it might improve outcomes for players affected by concussions and reduce the risk of subsequent concussions, thereby enhancing overall player safety.
Abstract 2 Free Neuropathol 4:29:5 Identification of recurrent genetic alterations in epigenetic pineoblastoma subtypes by high-resolution whole genome cytogenetics and DNA panel sequencing Torsten Pietsch1, Evelyn Dörner1, Tobias Goschzik1
Genome-wide methylation analyses recently revealed distinct epigenetic pineoblastoma (PBL) subtypes. The aim of the study was to characterize genetic alterations underlying the pathogenesis of pineoblastoma subtypes. Cytogenetic alterations of 83 FFPE materials from patients with PBL confirmed by central reference neuropathology and methylation-based subtyping were analyzed by high-resolution genome-wide molecular inversion probe (MIP) analysis. Mutational status was assessed by next-generation DNA panel sequencing. Clinical follow-up information of 54 patients was available. According to epigenetic consensus PBL subtypes (Liu et al., 2021), our cohort consisted of 48 PBL-miRNA1 (1A, 40; 1B, 8), 19 PBL-miRNA2, 8 PBL-MYC/FOXR2, and 8 PBL-RB1 samples. PBL-miRNA subtype tumors had characteristic, mutually exclusive alterations in microRNA-processing genes; DICER1 mutations (n = 19) and homozygous deletions of the DROSHA locus (n = 17) were most abundant, followed by DROSHA (n = 12) and DGCR8 (n = 2) mutations. The most frequent cytogenetic aberrations in PBL-miRNA were whole chromosome 7 gain (n = 31). PBL-miRNA2 subtype was significantly associated with chromosome 14 loss and DICER1 mutation. In contrast, PBL-miRNA1A/B showed frequent gains of chromosome 14 (n = 21) and also focal gains of the OTX2 oncogene on chromosome 14q (n = 8). In the miRNA subtypes 1A/B, 16 cases cases had polyploid cytogenetics. Survival analysis did not show differences in the PBL-miRNA subtypes 1A, 1B and 2. The epigenetically defined PBL-miRNA subtypes are characterized by distinct cytogenetic alterations and mutational events. Frequent gain of OTX2 may indicate a role of this oncogene in the pathogenesis of PBL. A possible prognostic role of genetic alterations requires investigation in prospective clinical trials.
Abstract 3 Free Neuropathol 4:29:6 DNA-Methylation Profiling to categorise meningioma recurrence risk: optimisation of resource allocation for patient selection Maharaj MM1, Ziad F2, Slatter T3, Jones G4, Saraiva A3, Thotathil Z5, Bhat B3, Gan P1, Hung N3, Jameson M6
Background: The emergence of an integrated classification including morphology, DNA-methylation profiling and copy number changes is leading towards significant changes in meningioma patient management. Global accessibility to methylation profiling remains costly and limited to the research setting in many countries. This requires the development of a strategy to optimise clinical utility.
Aims: Methods: DNA extracted from FFPE samples of 71 patients with resected WHO CNS Grade 2 meningioma using the Infinium HD FFPE Restore Protocol and methylation profiling with the Illumina EPIC (850k) Human Bead Chip (Illumina, San Diego, USA) was conducted. Meningiomas were sub-classified using the integrated system published by Mass SLN et al (2021). Factors including histopathological features, gross total resection, adjuvant therapy, mitotic activity and ethnicity were examined using standardised statistical methods. Results: >50 % of the WHO CNS 2 cohort (n = 71) was classified into the integrated low risk group. Classification demonstrated good correlation with recurrence (p = 0.004). Those without a gross total resection were more likely to recur (55 % vs 26 %). Chordoid subtype was common in Maori population but segregated across all risk groups. Interestingly brain invasion correlated with a more benign methylation class (p = 0.05). Conclusion: The implementation of integrated methylation testing carries significant implications on patient treatment and health economics. Potential WHO CNS 2 subgroups that may merit profiling include those with brain invasion, subtotal resection and certain histopathological subtypes.
Abstract 4 Free Neuropathol 4:29:7 Cell-free DNA in adult diffuse glioma – clinical utility and IDH mutation analysis Nuzhat Husain1, Adil Husain1,2, Sridhar Mishra1
Background: Cell-free DNA (cfDNA) has found utility in diagnosis and management of malignancies with scant literature in Adult Diffuse Gliomas (ADG). Aims: This study aimed to quantify baseline values and serial cfDNA levels in the sera of patients with ADG undergoing radiation therapy comparing responders vs non responders and further to detect IDH1 mutation in cfDNA. Materials and Methods: The study group comprised of histologically confirmed ADG (n = 50), -grade 2 (n = 15), 3 (n = 08), 4 (n = 27) and controls (n = 15). CfDNA was extracted using a ChargeSwitch gDNA 1 ml Serum Kit (Invitrogen) and quantified using SYBR-based qPCR. IDH1 mutation was detected using a castPCR assay, Sanger’s sequencing and Next Generation Sequencing. Results: Serum cfDNA levels were considerably higher in patients with ADG (Median: 113.50 ng/mL; IQR: 44.66–243.20) than in healthy controls (Median: 53.33 ng/mL; IQR: 40.67–73.87) (p = 0.02). cfDNA values were highest in grade 4 (353.53 ± 601.22 ng/mL) followed by grade 2 (201.93 ± 245.35 ng/mL) and 3 (153.67 ± 162.83 ng/mL). The cfDNA level was significantly higher in IDH1WT cases (157.83 ng/mL; IQR: 92.55–667.65) than in IDH1MT cases (69.55 ng/mL; IQR: 49.08–188.35) (p = 0.04). In non-responders, the cfDNA level (Median: 255.6 ng/mL) was significantly higher than that in responders (Median: 66.70 ng/mL) (p = 0.005). In cfDNA of IDHMT ADG, castPCR assay detected the IDH1R132H mutation in 3/26, Sanger’s sequencing failed to detect (0/20) while NGS was positive in 4/7 cases. Conclusion: cfDNA quantity in ADG increases in proportion to the grade of the tumor, responders show higher levels, but the trend is inconsistent across cases. NGS is most sensitive for IDH mutation detection in cfDNA.
Interesting case presentation abstracts
Case presentation 1 Free Neuropathol 4:29:8 CNS Neuroepithelial tumours with PATZ1 fusion Mike Watson1
CNS neuroepithelial tumours with PATZ1 fusions comprise a heterogenous group. We present two of these tumours, illustrating the diverse clinical presentation and morphology of these lesions. The first occurred in the cervical cord of an 8‑year-old and was thought initially to be an ependymoma. The second case was a left frontal tumour in a 54‑year-old, and the initial impression was of a high-grade glioma, possibly a gliosarcoma. The histology and genetics of this entity are discussed.
Case presentation 2 Free Neuropathol 4:29:9 Two interesting, rare cases of Erdheim Chester disease (ECD) Mehar C Sharma1, Vaishali Suri1, Ajay Garg2, Ashish Suri3
Case 1: This 51‑year-old lady presented with diabetes insipidus in 2001(at the age of 28 years) and diagnosed as case of empty sella syndrome. In 2008 developed pericardial effusion which was tapped thrice and was given a course of ATT without any improvement. In 2013 developed signs and symptoms of raised intracranial pressure and MRI of brain revealed a SOL in pineal region. Subtotal excision of the lesion was done. In 2020 this mass increased in size and subtotal excision of lesion was done. This mass again increased in size and radiotherapy was given. Currently patient is bed ridden and mass has grown into left lateral ventricle. Case 2: A 38‑year-old man presented with signs and symptoms of raised intracranial pressure. MRI brain showed multiple extra axial meningeal bases lesions and was suspected to be a case of NF2 with multiple meningiomas. One of the suprasellar lesion was excised and subjected for histopathological examination. Pathological examination revealed similar features in both cases. Microscopic examination revealed sheets of foamy cells admixed with lymphocytes, plasma cells and fibroblasts. Emperipolesis of lymphoid cells was absent. An occasional tuoton giant cell was noted in second case. Foamy cells were immunopositive for CD163 and CD68 but negative for CD1a, Langerin & S100. Ratio of IGG4 to IGG immunopositive cells was normal. Foamy cells were immunopositive for BRAFv600. BRAF mutation was confirmed by Sanger-sequencing. Conclusion: ECD is a rare histiocytic disorder characterised by admixture of foamy histiocytes and inflammatory cells. Involvement of central nervous system is extremely uncommon and poses a diagnostic dilemma. High index of suspicion is required for its diagnosis and differentiation from other close mimics.
Case presentation 3 Free Neuropathol 4:29:10 Unusual cerebellar vermian lesions – a short case series Nandeesh BN1, Vani Santosh1, Subhas Konar2, Netravathi M3, Yasha TC1
Introduction: The central nervous system is known for its anatomical uniqueness and immune privileges. Despite this, this organ becomes a host for many neoplastic and non–non-neoplastic lesions. Some non-neoplastic lesions occur in such brain regions and present with clinicopathological features that mimic neoplastic conditions. The present study describes a short series (3 unique cases) of rare lesions involving the cerebellum and masquerading other lesions, including a neoplasm. Clinical details: Three cases aged 11, 50, and 67 years presented with headache, vomiting, and cerebellar signs of 2, 8, and one‑week duration. The 2nd case was a known case of seronegative myelopathy on oral steroids and mycophenolate; the 3rd case was a known case of B – CLL (diagnosed two years back) and post-chemotherapy. The first case was negative for any investigated risk factors. The clinical/radiological diagnoses in all three cases included a tumor (medulloblastoma in the first case) and inflammatory/ infective/ deposits. The histology of the lesions revealed irregular confluent necrosis, including the blood vessels and mixed inflammatory cell infiltrate, along with histiocytic aggregates (ill-formed granulomas) and giant cells. All three cases showed typical amoebic trophocytes and cyst forms, indicating a diagnosis of granulomatous amoebic encephalitis (GAE). Discussion: GAE, a rare protozoal infection of high mortality, is caused by Acanthamoeba spp. and Balamuthia mandrillaris. Hence, it is essential to understand the clinicopathological characteristics of this rare infection and offer a timely and accurate diagnosis. Thus, it becomes necessary to consider GAE in the differential diagnoses of an atypical necrotic lesion and (even in an immunocompetent patient) search for the pathogen.
Copyright: © 2024 The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited, a link to the Creative Commons license is provided, and any changes are indicated. The Creative Commons Public Domain Dedication waiver (https://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
