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Considerable changes were introduced into the 5th World Health Organization (WHO) classification of central nervous system (CNS) tumors, published in 2021, including new entities, a clearer classification of previous categories, correlating better with clinical behavior and changes in nomenclature. The number of definitions based on molecular features in addition to histopathology continued to increase. Here, we highlight the basic principles of the 5th CNS WHO classification and discuss glial, glioneuronal, neuronal, choroid plexus, embryonal and pineal tumors, as well as meningiomas in more details. We pay special attention to new entities as well as altered criteria and designations. Our primary goal is to present the "classical" pathological aspects, but the inseparable molecular pathological features are also briefly discussed, to the absolutely necessary extent for comprehension. We aim to provide a guideline to understand the modern classification of CNS tumors for practitioners of neuro-oncology and neuropathology.

Recent advances in molecular diagnostics are transforming the classification of malignant tumours, it has long played a major role in the field of CNS tumours. Examination of 1p/19q codeletion is indispensable in case of diffuse gliomas. Glioblastoma may be diagnosed even in the absence of characteristic morphological features, when EGFR amplification, TERT promoter mutation or +7/-10 copy number abnormalities are present. The number of entities defined by a genetic abnormality is growing. Comprehensive analysis of DNA methylation may be of considerable help in addition to histology and basic molecular studies, especially in case of small samples. Keeping up with the ever-expanding diagnostic repertoire is difficult, however, advantages and disadvantages of these methods and the context in which they may be useful should be understood by those who are involved in the diagnosis of CNS tumours. This summary provides a general overview of the main methods used in molecular diagnostics.

Skin melanoma became one of the most frequent malignancies of the skin mainly due to the increased exposure to environmental UV irradiation. However, this did not lead to the increase of mortality, mainly due to the efficient early diagnostics as well as to the development of new therapies which were based on the identification of the mutation patterns and understanding of the immunobiology. Molecular markers are important to differentiate malignant tumors from precancerous ones but also routinely available to define prognosis. Immunotherapy can be used in any molecular class of melanoma, while target therapy is only available in case of BRAF mutant form. Meanwhile these novel therapies induce new resistance mechanisms based on the development of acquired genetic alterations. Due to these facts the initial molecular profiling of the resected primary tumors must gradually be replaced by continuous monitoring.

Összefoglaló. Bár a SARS-CoV-2-pandémia próbára tette a diagnosztikus kapacitásokat, számos hasznos tapasztalattal is szolgált, melyek alacsonyabb mintaszám mellett nem lettek volna levonhatók. Míg korábban a PCR-vizsgálatok jellemzően diagnosztikus, illetve kvantitatív követési célokat szolgáltak, a járvány során többségbe kerültek a szűrő- és (kezdetben) a felszabadító vizsgálatok. Jól követhető volt, hogy a tesztek piacra juttatásának erőltetett üteme sokszor nem tette lehetővé a teljesen kiforrott koncepciók létrehozását. Tekintettel arra, hogy a molekuláris diagnosztika során nem teljes vírusgenomokat, hanem célszakaszokat mutatunk ki, amelyek aránya a fertőzés egyes szakaszaiban nem feltétlenül állandó, egyre valószínűbb, hogy nem azonos célgének a legmegfelelőbbek diagnosztikus, szűrő- és felszabadító vizsgálatokhoz. A nagy mennyiségű, aspecifikusan végzett vizsgálat még kiváló fajlagosság mellett is a pozitív prediktív érték csökkenéséhez vezethet, amennyiben a fertőzés tényleges prevalenciája a vizsgálati csoportban alacsony. Munkánkban megkíséreljük irodalmi és saját adatok felhasználásával összefoglalni az elmúlt két év fontosabb diagnosztikus tapasztalatait a teljesség igénye nélkül. Orv Hetil. 2021; 162(52): 2071-2078. Summary. Although the SARS-CoV-2 pandemic has been a great challenge for the diagnostic capacities, it also proved to be a unique source of experience. While previously PCR tests had overwhelmingly been used for targeted diagnostic and quantitative follow-up testing, screening and (initially) release tests became far more prevalent during the pandemic. It was well to be seen that the forced pace of bringing tests to market often gave way to not fully mature concepts. The PCR method is based on the detection of sequences, the proportions of which are likely to alter throughout the course of the disease. It is becoming increasingly clear that different target genes might be the best suitable for diagnostic, screening and release testing. Even with specific assays, an unprecedentedly high number of tests might result in the inflation of the positive predictive value, when the true prevalence of the infection remains very low among the tested individuals. Here we try to summarize some of the potentially most relevant diagnostic conclusions of the pandemic so far according to our own data and the literature. Orv Hetil. 2021; 162(52): 2071-2078.

Molecular classification of lung cancer developed in the past decades to the level where even the rare genetic alterations are included. Unfortunately, adenocarcinoma benefited from this development almost exclusively. Furthermore, the tumor-agnostic novel therapy indications influence the molecular diagnostics of lung cancer including microsatellite status, tumor mutation burden or NTRK fusion gene determinations. On the other hand, the still low resection rate of lung cancer and limited availability of tumor tissue for diagnosis opened the way of routine use of liquid biopsy technologies. The routine use of target therapies triggered the development of various genetic resistance mechanisms, the monitoring of which gradually became a standard of monitoring of the disease. Beside the "targeted" diagnostics, multigene panel testing or whole exome sequencing are more frequent, resulting in a more complex genetic picture of lung cancer. This requires the categorization of genetic alterations into predictive levels for standard, investigational or hypothetic target therapies in the molecular pathology reports.

Prostate cancer seems to be two diseases: a localized early cancer and a castration-resistant metastatic cancer. While in the localized form the most prevalent genetic alterations are the translocations of the ETS genes, in the castration-resistant form the most prevalent genetic alteration affects androgen receptor and oncosuppressors TP53 and PTEN. The main drivers of the genetic progression of prostate cancer are defects of the DNA-repair systems which are also responsible for the familiar disease. Several prognostic genomic classifiers have been developed and validated clinically which are able to guide management of the early diseases. Today the most useful predictive genetic testing is that of the androgen receptor but others are becoming equally important which can predict taxane resistance.

Owing to our rapidly expanding knowledge on the genetic background of various oncohematologic diseases and the introduction of novel targeted therapies, molecular genetic techniques have been playing an increasingly important role in the diagnostics and follow-up of hematological malignancies. The various DNA- and RNA-based in situ hybridization, polymerase chain reaction and sequencing technologies are of key significance in diagnostics, classification and prognostic assessment of these diseases, as well as in the monitoring of minimal residual disease and selection of the most appropriate targeted therapy. This review provides an overview on the background and applications of the molecular methods most commonly used in oncohematological diagnostics.

Meningiomas represent nearly one-third of all adult primary brain tumours. According to their clinical and histologic appearance, they can be divided into WHO grades I-III. Almost 90% of meningiomas are benign, showing favourable response to conventional therapies, however, patients diagnosed with grade 2 and 3 tumours may have a poor prognosis. In addition, high frequency of tumour recurrence renders treatments more challenging even in benign meningiomas. Molecular-pathological profiling of meningiomas could lead to development of more effective therapies. Although the cytogenetic background of these tumours are already well-characterised, the majority of related genes and mutations is still unknown. Recently, high-throughput techniques enabled better characterisation of mechanisms involved in meningioma development, progression and recurrence. Furthermore, epigenetic dysregulation could offer new opportunities for both diagnosis and treatment of meningiomas. We provide a comprehensive overview of cytogenetic and molecular genetic defects as well as epigenetic alterations in meningiomas. Many of these may serve as biomarker or therapeutic target in the near future.

The continuously increasing incidence of melanoma and new developments in the therapy of metastatic disease require accurate diagnosis in all stages of melanoma. This study overviews the development of diagnostics tools in recent years/decades that are used in everyday medical practice such as optical diagnostic tools utilized for diagnosing primary tumors, sentinel lymph node biopsy, developments in molecular diagnostics, as well as the role of PET/CT in imaging techniques.

Background: Glial tumours represent the most frequent type of primary brain cancers. Gliomas are characterized by heterogeneity that makes the diagnosis, histological classification and the choosing of correct therapy more difficult. Despite the advances in developing therapeutic strategies patients with malignant gliomas have a poor prognosis; therefore glial tumours represent one of the most important areas of cancer research. There are no detailed data on the epidemiology of gliomas in Hungary., Methods: In the first section of our publication, we analysed the histological diagnosed cases between 2007 and 2011 at the Institute of Pathology, University of Debrecen Medical and Health Science Centre. We analyzed the incidence of 214 high-grade gliomas by tumor grades, gender, age, and the anatomical localization., Results: The majority of cases were glioblastoma (182 cases), and the remaining 32 cases were anaplastic gliomas. The mean age of patients was 57 years (+/- 16.4), and the male:female ratio was 1.1:1. The most frequent area of tumors was the frontal lobe followed by the temporal, parietal and occipital lobe. We include new findings published recently about glioma pathogenesis, molecular pathways, mutant genes and chromosomal regions. We explain briefly the role of selected important genes in glioma genesis and give an update on knowledge provided by modern molecular methods, which could beneficially influence future therapy and the diagnosis of gliomas.

In recent years, medicine has taken some important first steps toward a major paradigm shift that could result in a landslide for personalized therapies. Indeed, evidence-based medicine seems to yield to personalized medicine in multiple areas, including both the thinking patterns of healthcare workers and everyday medical practice. Nevertheless, although a steadily increasing number of personalized treatment modalities have recently become available for patients, so far, no breakthrough can be seen in the paradigm shift from evidence-based medicine to personalized therapy. We believe that a more efficient identification and utilisation of future and already known biomarkers, respectively, might be the key to speed up this progress. In line with this, biomarkers are becoming increasingly important tools in late stage research, drug development and in clinical practice, as well. Correct classification of biomarkers becomes especially important, as different types of biomarkers provide markedly different information to drug developers and health care professionals.

Hepatocellular carcinoma (HCC) is a tumor with rather bad prognosis. Recent years, however, have seen considerable progress in the diagnostics and treatment of this disease, contributing to better understanding of its molecular pathogenesis. Large regenerative nodules, low and high grade dysplastic nodules are premalignant alterations of HCC developing on the grounds of cirrhosis. Microscopically the WHO distinguishes trabecular, acinar (pseudoglandular), scirrhous and solid forms. Special histological subtypes are the clear cell, fibrolamellar and mixed hepato-cholangiocellular variants. The prognostic significance of these histological types is argued. The fibrolamellar, non-cirrhotic form of HCC occurring in young age is considered to be of better prognosis, but this is probably due to the fact that this type is not accompanied by cirrhosis. Certain tumor markers may help the diagnosis, such as alpha-fetoprotein (AFP), glypican-3, survivin, the recently described agrin and claudins, furthermore, the hepatocyte specific antigen (HSA), which confirms the hepatocytic origin of the tumor. Recently, the diagnostic significance of microRNAs, primarily of the hepatocyte-specific mir122 has also emerged. In addition to the Barcelona Clinic Liver Cancer (BCLC) staging classification which determines the course of therapy, the molecular classification of HCC is based on key molecular alterations, many of which are observable in all HCC cases, whereas some alterations are only detectable in certain tumors.

In the 3rd year of the program 8 new molecular diagnostic services have been introduced to clinic in the management of breast-, lung-, colorectal cancers as well as in GIST and melanoma. Two patents have been filed for innovative modulation of mito/motogenic signaling pathways in cancer cells. In preclinical models of human cancer a functional imaging technique was developed to detect vascular eff ects of erythropoietin. Using a genomic approach, the sequential changes in human melanoma during systemic dissemination were determined revealing several novel potential prognostic factors and some interesting novel targets for therapy.

There is no doubt that molecular targeted therapy has increasing importance in clinical oncology. Markers related to the molecular targets can help in the prediction of the antitumoral effect as well as in the positive or negative selection of patients. Such a marker is KRAS, since its mutation inhibits the effectiveness of anti-EGFR monoclonal antibodies in the treatment of advanced and/or metastatic colorectal cancer. To identify KRAS mutations different methods and techniques are available. A voluntarily performed study served to control the validity of our methods. As a result the 7 partcipating laboratories approached but not fulfilled (except one) the criteria set by EPS. A joint discussion helped to call the attention to some technical and financial problems. The key conditions to recognize mutational status of KRAS or other similar markers are the accredited laboratory for molecular diagnostics and the validated method. The improvement of the quality of such techniques is supported by the fact that more and more drugs can be used only after the obligatory measurement of relevant molecular target(s).