Pathology最新文献

Focal lesions of the human neocortex often cause drug-resistant epilepsy, yet ​surgical resection of the epileptogenic region has been proven as a successful strategy to control seizures in a carefully selected patient cohort. Continuous efforts to study neurosurgically resected brain samples at the microscopic level, i.e., Neuropathology 1.0, unravelled a comprehensive description of the spectrum of underlying aetiologies, e.g., hippocampal sclerosis, congenital brain tumours or cortical malformations as the three most common aetiologies representing almost 80% of the entire lesional landscape. Human brain tissue was also instrumental to discover underlying molecular pathways and common somatic variants, e.g., MTOR, DEPDC5, SLC35A2, BRAF or PTPN11, that helped us to define specific phenotype-genotype associations, thereby promoting novel targets for medical treatment, i.e., Neuropathology 2.0. The increasing gap in accessing necessary resources to perform such studies around the world could be bridged, however, when introducing artificial intelligence (AI)-based algorithms to classify epileptogenic brain lesions on digital slide scans obtained from routine haematoxylin and eosin-stained, formalin-fixed paraffin-embedded tissue sections. This may also provide an advanced prediction of the lesion's phenotype-genotype association in the near future. Thus, digital Neuropathology 3.0 may be the promising next level of laboratory advancement in the realm of neuropathology in focal epilepsy.

Viral infections of the central nervous system (CNS) have been emerging and re-emerging worldwide, and the Australasia region has not been spared. Enterovirus A71 and enterovirus D68, both human enteroviruses, are likely to replace the soon-to-be eradicated poliovirus to cause global outbreaks associated with neurological disease. Although prevalent elsewhere, the newly emergent orthoflavivirus, Japanese encephalitis virus (genotype IV), caused human infections in Australia in 2021, and almost certainly will continue to do so because of spillovers from the natural animal host-vector life cycle endemic in the country. Another orthoflavivirus, Murray Valley encephalitis virus, has re-emerged in Australia. The Hendra henipavirus together with Nipah henipavirus ​are listed as high-risk pathogens by the World Health Organization because both can cause lethal encephalitis. The former remains a health threat in Australasia because bats may still be able to spread the infection to unvaccinated Australian horses and other animals acting as intermediate hosts, and thence to humans. The global COVID-19 pandemic, caused by the emerging severe acute respiratory syndrome coronavirus-2, a virus transmitted from animals to humans that was first described and first arose in China, is associated with acute and long-lasting CNS pathology. Fortunately, the pathology and pathogenesis of these important neurotropic viruses are now better understood, leading to better management protocols and prevention strategies. Pathologists are in a unique position to contribute to the diagnosis and advancement in our knowledge of infectious diseases. This review summarises some of the current knowledge about a few important emerging and re-emerging CNS infections in Australasia and beyond.

In the course of the last decade, the pathological diagnosis of many tumours of the central nervous system (CNS) has transitioned from a purely histological to a combined histological and molecular approach, resulting in a more precise 'histomolecular diagnosis'. Unfortunately, translation of this refinement in CNS tumour diagnostics into more effective treatment strategies is lagging behind. There is hope though that incorporating the assessment of predictive markers in the pathological evaluation of CNS tumours will help to improve this situation. The present review discusses some novel aspects with regard to the pathological diagnosis of the most common CNS tumours in adults. After a brief update on recognition of clinically meaningful subgroups in adult-type diffuse gliomas and the value of assessing predictive markers in these tumours, more detailed information is provided on predictive markers of (potential) relevance for immunotherapy especially for glioblastomas, IDH-wildtype. Furthermore, recommendations for improved grading of meningiomas by using molecular markers are briefly summarised, and an overview is given on (predictive) markers of interest in metastatic CNS tumours. In the last part of this review, some 'emerging new CNS tumour types' that may occur especially in adults are presented in a table. Hopefully, this review provides useful information on 'what's new' for practising pathologists diagnosing CNS tumours in adults.

Intraepidermal squamous neoplasia is a precursor to invasive cutaneous squamous cell carcinoma. The most common type of intraepidermal squamous neoplasia is actinic keratosis (AK), although there is compelling clinicopathological evidence of a second distinct pattern of squamous dysplasia termed Bowen disease (BD). The distinction between these pathways of dysplasia has been inconsistently delineated in the literature. To further investigate the biological differences between AK and BD, a cohort of cases of intraepidermal squamous dysplasia including AK with mild/moderate dysplasia (n=26), AK with severe dysplasia (n=21) and BD (n=47) was prospectively collected. Immunohistochemistry was utilised to assess the protein expression of major tumour suppressor genes including p16, RB-1 and p53. Most cases of BD showed complete loss of RB-1 (∼80%), strong and diffuse positive staining for p16 (∼80%) ​and mutant pattern (diffusely positive or completely negative) of p53 (∼79%). However, lesions of AK showed loss of RB-1 in only 6%, strong and diffuse positive staining for p16 in 4% and mutant pattern of p53 in 85% of case (p<0.001). The statistically significant difference in RB-1 and p16 expressions between AK and BD confirms that the two morphologically distinct types of intraepidermal squamous neoplasia differ in protein expression of major tumour suppressor genes and provide evidence that they represent two distinct genomic pathways of squamous neoplasia. Recognition of clinical and genomic differences between different pathways of squamous neoplasia could potentially have an important role in predicting the biological behaviour and treatment of advanced tumours arising from these precursor lesions.

Medical science has made revolutionary discoveries around the nosology and aetiology of the neurodegenerative diseases. Dementia is the second leading cause of death in Australia. My colleagues and I are now looking at therapeutics which potentially can delay or prevent the onset of Alzheimer's disease (AD). Advances in diagnosis allow detection of preclinical AD. Neuropathologists working closely with chemical and genetic pathologists have a major role to play in pushing diagnostics and therapeutics to the forefront of clinical management of these diseases.