Cancer stem cells (CSCs), known also as tumor-initiating cells, are quiescent, pluripotent, self-renewing neoplastic cells that were first identified in hematologic tumors and soon after in solid malignancies. CSCs have attracted remarkable research interest due to their role in tumor resistance to chemotherapy and radiation treatment as well as recurrence. Extensive research has been devoted to the role of CSCs in glioblastoma multiforme (GBM), the most common primary brain tumor in adults, which is characterized by a dismal prognosis because of its aggressive course and poor response to treatment. The aim of the current paper is to provide an overview of current knowledge on the role of cancer stem cells in the pathogenesis and treatment resistance of glioblastoma. The six regulatory mechanisms of glioma stem cells (GSCs)-tumor microenvironment, niche concept, metabolism, immunity, genetics, and epigenetics-are reviewed. The molecular markers used to identify GSCs are described. The role of GSCs in the treatment resistance of glioblastoma is reviewed, along with future treatment options targeting GSCs. Stem cells of glioblastoma thus represent both a driving mechanism of major treatment difficulties and a possible target for more effective future approaches.

Abstract Gliomas are among the most common and aggressive primary brain tumours with dismal prognosis. A lot of research has been directed towards elucidating the molecular basis of these tumours, but few reliable prognostic markers are known. It is necessary to continue to study possible molecular factors that may be involved in development of gliomas or have a prognostic role. CD44 is a marker of neural stem cells and is involved in invasiveness of different tumours. In addition, IDH1 R132H mutant protein is expressed in secondary glioblastomas (GBMs) with much better prognosis. The goal of this study was to evaluate the expression and prognostic role of CD44 and IDH1 R132H in gliomas by immunohistochemistry. In this study, we found that CD44 expression was more prominent in glioblastomas than diffuse astrocytomas and it was not correlated with IDH1 mutational status. CD44 was not found to have a prognostic role in gliomas, in contrast with IDH1 R132H positive status, which was associated with better prognosis. Interestingly, higher CD44 expression values were associated with smaller size of GBMs and female gender indicating that the glioma stem cell population may be altered by gender specific factors and the growth rate of the tumour.

In this study we assessed whether gliomas could be subdivided into different molecular subtypes by immunohistochemistry (IHC) reminiscent of those first described by Verhaak et al. in 2010 (classical, proneural, mesenchymal and neural). We also evaluated the prognostic significance of single molecular factors and searched for significant correlations between markers. In this study, we included 146 patients with glioblastomas (GBMs) and 26 with diffuse astrocytomas (DAs). The glioma samples were tested for PDGFRA, IDH1 R132H, CD44, p53, Ki-67, p21 and p27 expression. We found that gliomas could be subdivided into molecular subtypes by IHC. Fifty per cent of GBMs were of the proneural subtype, 18.5% of mesenchymal subtype and 31.5% were not otherwise classified. However, most of the DAs (92.3%) belonged to the proneural subtype. No prognostic role was found for the molecular subtypes, but predictive roles were noted. Both proneural and mesenchymal molecular subtypes showed a benefit from the addition of chemotherapy and radiotherapy; however, the mesenchymal subtype showed a greater response. Interestingly, the mesenchymal subtype did not receive any benefit from the addition of radiotherapy compared with palliative management and surgery alone. Regarding single molecular markers, only IDH1 R132H was found to have a prognostic role for GBMs. There was a trend towards better survival in tumours with lower PDGFRA expression (p = 0.066). In DAs, PDGFRA and Ki-67 expression had prognostic roles. The following statistically significant correlations were found in GBMs: Ki-67/p53, Ki-67/p27 and p53/PDGFRA; in DAs: p53/PDGFRA, CD44/PDGFRA, and p21/PDGFRA.

Thyroid nodules are frequent in general population, found in 3.7–7% of people by palpation and 42–67% by ultrasonography (US). The differential diagnosis ranges from papillary (PC), follicular (FC) and medullary (MC) carcinomas to follicular adenoma (FA) and colloid goitre. Cancer risk in thyroid nodules varies: 5% in masses found by palpation, 1.6–15% by US, 3.9–11.3% by computed tomography (CT), 5–6% by magnetic resonance imaging (MRI) and 30–50% by positron emission tomography (PET). The final diagnosis depends on fine needle aspiration (FNA) findings and histopathology. The recent WHO classification (2017) is based on classic morphology, including assessment of invasion and nuclei. New entities are defined to designate tumours with doubtful invasion or controversial nuclear features. By immunohistochemistry, PC expresses HBME-1, TROP2, CITED1 and CK19. Notably, PC can stain for CD20. MC is recognised by neuroendocrine differentiation. To distinguish FA vs. FC, evaluation of HBME-1, p27 and galectin has been suggested. Regarding miRNAs, miR-146b, miR-222, miR-221 and miR-181b are upregulated, while miR-145, miR-451, miR-613 and miR-137 are downregulated in PC. FC features downregulated miR-199a-5p and upregulated miR-197 and miR-346. In MC, miR-21 and miR-129-5p are downregulated. In addition, increased systemic inflammatory reaction can be poor prognostic factor in thyroid cancer. The aim of this chapter is to review classic and innovative histopathology of thyroid nodules for diagnostic pathology practice and research in multidisciplinary thyroid teams.

Gastric cancer induces systemic inflammatory reaction (SIR) manifesting with changes in counts of white blood cell fractions and concentrations of acute phase proteins, clotting factors and albumins.Thus, protein-based scores or blood cell ratios (neutrophil to lymphocyte ratio (NLR); platelet to lymphocyte ratio (PLR)) are used to evaluate SIR.SIR tests are biologically justified by multiple clinically important and fascinating events including bone marrow activation, development of immune-suppressing immature myeloid cells, generation of pre-metastatic niches and neutrophil extracellular trap formation from externalised DNA network in bidirectional association with platelet activation.Despite biological complexity, clinical SIR assessment is widely available, patient-friendly and economically feasible.Here we present concise review on NLR, PLR, Glasgow prognostic score and fibrinogen -parameters that have prognostic role regarding overall, cancer-free and cancer-specific survival in early and advanced cases.Tumour burden can be predicted helping in preoperative detection of serosal or lymph node involvement.Practical consequences abound, including selection of surgical approach in respect to tumour burden, adjustments in treatment intensity by prognosis or evaluation of chemotherapy response.The chapter also scrutinises main controversies including different cut-off levels.Future developments should include elaboration of complex scores as described here.SIR parameters should be wisely incorporated in patients' treatment.

Summary Meningiomas constitute 20-38% of primary intracranial neoplasms. Among these, atypical meningiomas (WHO grade II) comprise 4.7-7.2% of symptomatic cases. The primary goal of surgery is the complete removal of the meningioma, including the attachment to dura mater and bone. Subtotal resection as well as more aggressive histological type and grade are associated with higher recurrence risk. Here we report a 68-year-old male who suffered from multiple (5) meningiomas which necessitated 3 resections within 4 years. The simultaneous occurrence of different tumour grades of malignancy as well as grade progression was evident.

Summary Metastatic tumours in the brain occur more frequently than primary neoplasms. Despite the generally dismal prognosis, neurosurgical resection is indicated in certain patients and can yield prolonged survival. Here we describe an 82-year-old male with a history of neurosurgical resection of a single brain metastasis 6 years ago. Tumour immunophenotype disclosed lung adenocarcinoma with low proliferation fraction. However, the primary tumour remained occult then. At present, 3 new brain metastases were identified by computed tomography. Repeated resection was performed in 2 stages, resulting in removal of 2 metastases. Lung mass was now evident as well. The final diagnosis was lung adenocarcinoma with metachronous brain metastases, stage IV. In conclusion, prolonged survival, in this case 6 years, can be reached even in patients with metastatic cancer by successful selective application of neurosurgical treatment. The biological properties of the tumour including low proliferation also contributed to longer survival and demonstrated surgery as a successful treatment option.

Summary According to the Centre for Disease Prevention and Control of Latvia data, in 2014 16076 latvians died from cardiovascular diseases and it is 57,03% of all deaths. Changes in myocardium of the diseased hearts are complex and pathogenesis is still not fully clear. Morphopathogenesis of cardiovascular diseases are complex molecular cell changes which include apoptosis, homeostasis regulating factors, and innervation and ischemia markers. In this article we wanted to provide an overview about apoptosis, atrial natriuretic peptide, chromogranin A, neuropeptide-containing innervation, endothelins and vascular endothelial growth factor in pathomorphology of acquired heart diseases and their clinical implications.

Abstract Glioblastoma (GBM) has very poor prognosis despite aggressive therapy including surgical treatment. At present, few molecular markers could clarify GBM prognosis in greater detail. However, better understanding of the molecular pathogenesis would be the mainstay of improved, more personalized treatment modalities. Recent large-scale molecular studies brought new data that altered previous concepts about GBM; even molecular subtypes of GBM have been discovered. We discuss here the classic pathology of GBM along with molecular markers and subtypes of GBM as well as routine applications of these advances.

Abstract Rhabdoid meningioma (RM) is a rare type of meningioma. It is classified as a grade III tumour (anaplastic meningioma) in the recent World Health Organization (WHO) classification of the tumours of the central nervous system (CNS). Here we describe a unique case of RM lacking any features of malignancy. Few cases of low-grade RMs are described in the literature in contrast with the grading of this entity in WHO classification.

Glioblastoma (GBM) is one of the most common and aggressive tumours of the central nervous system (CNS) and represents the highest grade (grade IV) of glioma. Despite the standard therapy with maximal possible resection, followed by radiotherapy and chemotherapy with temozolomide, the prognosis for GBM patients remains dismal. Identification and research of potential molecular and immunohistochemical markers will help to increase our awareness of critical molecular changes in tumorigenesis and increase the possibility of effective molecularly targeted therapy in future. New molecular and immunohistochemical prognostic markers can improve the treatment and even allow patients to be stratified into different prognostic groups, which will make the therapy more personalized. The aim of this research was to evaluate the morphological and immunohistochemical profile of gliomas ‒ glioblastoma (GBM) and diffuse astrocytoma (DA) ‒ as well as to evaluate the prognostic role of single immunohistochemical markers and the possibility of glioma subtyping by immunohistochemistry (IHC). This work was performed as a retrospective study that is based on the analysis of formalin-fixed, paraffin-embedded, surgically treated human glioma tissues. In the study, a comprehensive morphological and immunohistochemical evaluation was performed including analysis of eight immunohistochemical parameters and survival analysis by applying a wide range of descriptive and analytic statistic methods. A total of 172 patients with gliomas were enrolled in the research work, including 146 GBMs and 26 DAs. It was found that GBM patients were characterized by poor prognosis with a median survival time of 7.9 months, which is slightly below the survival rates reported in other countries. From the selected markers, the presence of isocitrate dehydrogenase 1 (IDH1) R132H mutation was the most significant prognostic factor of better survival in gliomas. However, in patients with DAs, high platelet-derived growth factor receptor alpha (PDGFRA) expression was also associated with significantly better survival. Some immunohistochemical markers, such as CD44, p21, p27, PDGFRA and Ki-67 proliferation, are grade-specific parameters in gliomas, thus CD44, Ki-67 and p21 are significantly upregulated; however, p27 and PDGFRA are downregulated in high-grade gliomas such as GBM. Surprisingly, gender-related differences were found in the expression of some immunohistochemical markers, such as p27, CD44 and Ki-67, in gliomas. In GBMs, cell cycle proteins, such as p53, p21 and p27, are involved in a variety of mechanisms that regulate proliferation and angiogenesis. A strong relationship was also found between the expression of PDGFRA and p53 in gliomas. In DAs, PDGFRA correlated inversely with CD44, p21 and microvascular density (MVD). Finally, it was found that subtyping of gliomas is possible by IHC using a limited number of markers – PDGFRA, p53, IDH1, R132H and CD44. In addition, the expression of CD44 was shown to be a reliable indicator of mesenchymal subtype in GBM, which has a worse response to radiotherapy.