Pathology最新文献

The role of muscle biopsy in the investigation of neuromuscular disease remains firmly established but has evolved. Expertise in diagnostic myopathology remains relevant and supports clinical practice. Neuromuscular disease is rare; thus clinicopathological correlation, or better, collaboration is important. The process starts in the clinic with the identification of patients for whom muscle biopsy will be beneficial for diagnosis and management in a multidisciplinary neuromuscular care setting. In this review article, we describe the current use of muscle biopsy in our adult practice and discuss several carefully selected real cases [e.g., asymmetric hand weakness, dysphagia and proximal weakness, subacute weakness with raised creatine kinase (CK), non-specific presentation], where biopsy and collaboration have been instrumental in achieving the correct diagnosis for the patient. We discuss areas of diagnostic difficulty, such as fairly common starting scenarios leading to unusual entities, atypical presentations of common diseases and novel pathological findings. We will focus on the idiopathic inflammatory myopathies (IIMs), the most common indication for adult muscle biopsies in many diagnostic settings, whereby the use of an integrated clinical-serological-pathological classification is now firmly established. We will also explore the evolving role for and continuing need of muscle biopsy in the genomic era, particularly with assessing the potential pathogenicity of reported genetic variants of uncertain significance (VUS). We describe a pragmatic approach to detecting the more common disorders, which also enables us to distinguish 'the horses from the zebras' and manage diagnostic uncertainty.

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.

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.

Acral melanoma (AM) is the most common subtype of melanoma in the Asian population. Abnormalities in the p16-cyclin D1-CDK4 signalling pathway play a crucial role in the development and progression of AM. However, the CDK4 copy number variations (CNVs) in AM are under-reported. In this study, we investigated CDK4 gene copy number and concurrent molecular changes in a Chinese cohort with AM, to explore CDK4 CNVs and their significance in AM. We examined CDK4 CNVs with fluorescence in situ hybridisation (FISH) in 31 patients with AM. Six patients with CDK4 high-level copy number increase were examined by next-generation sequencing to detect concurrent molecular changes. Using FISH, 12 (12/31, 38.7%) cases showed CDK4 copy number increase, with six (6/31, 19.4%) low-level copy number increase and six (6/31, 19.4%) high-level copy number increase. Five of six CDK4 low-level copy number increase cases were accompanied by polysomy of chromosome 12, while one case was not. Two of six CDK4 high-level copy number increase cases were accompanied by polysomy of chromosome 12, while four cases were not. CDK4 copy number increase was significantly correlated with younger patient age. In six CDK4 high-level copy number increase cases, one case was found to be accompanied by NRAS mutation, one case was accompanied by HER2 mutation, one case was accompanied by BCL2L11 mutation ​and one case was accompanied by BRAF, HER2 and BCL2L11 mutations. Our study confirmed the presence of CDK4 copy number increase in AM cases. Detecting CDK4 copy number increase by FISH can be reliable in the diagnosis of AM. Some CDK4 copy number increases are the results of polysomy of chromosome 12. CDK4 high-level copy number increase coexists with other pathogenic mutations in AM. CDK4 appears to be a promising target for AM treatment and is expected to be combined with other targeted therapies.