Role of GATA3 in Early-Stage Urothelial Bladder Carcinoma Local Recurrence.

Background One of the most characteristic features of non-invasive urothelial carcinoma (UC) is its high recurrence rate. Guanine-adenine-thymine-adenine nucleotide sequence-binding protein 3 (GATA3), as a transcription factor, correlates with urothelial differentiation and has been reported with poor prognosis in high-grade UC and recurrence in breast malignancies. As such, we set out to study the specifics of GATA3 in non-invasive UC, emphasizing on prediction for recurrence. Methods The cohort comprised 163 patients, with a follow-up period of five years, including 109 pTa cases and 54 pT1 cases. Immunohistochemical expression of GATA3 was assessed using a histo score (H-score). Kaplan-Meier test was conducted for the time to recurrence, according to the level of expression of GATA3 and the indicators studied. Receiver operating characteristic (ROC) curve analysis was done to determine the role of accuracy and specificity of predictability of the indicators. Results Recurrence within the follow-up period was noted in 41.72% of cases. No recurrence relationship was established for age and gender. GATA3 expression showed a varying H-score. Using ROC curve analysis, a cut-off value of 155 divided UC expression levels into low and high, with a sensitivity of 72.7% and specificity of 78.7% (area under the curve=0.800, 95% confidence interval: 0.696-0.904, p<0.001), further showing an association between high levels of nuclear expression and risk of local recurrence (p<0.0001). Conclusion Herein we have described the sensitivity of high GATA3 expression in non-invasive UC of the urinary bladder and its relation to local recurrence, independent of gender, age, tumor differentiation, and stage.

Intestinal-Type Adenocarcinoma of the Urinary Bladder With Coexisting Cystitis Cystica et Glandularis and Intestinal Metaplasia: A Histopathological Case Report.

Adenocarcinomas of the urinary bladder are exceedingly rare and present in various morphological forms. Virtually all of these are identical to glandular malignant neoplasia native to topographically neighboring organs, where the incidence of adenocarcinoma is also much more common, such as the large intestine. Cases of glandular malignancies of the urinary bladder, therefore, require not only a detailed histopathological evaluation and interpretation but also a detailed clinical and radiological one. These should be performed with the goal of proving the origin of the tumor as one arising from the urinary bladder and not an entry originating from another organ and invading or producing metastasis to it. A controversial etiopathogenic link to urinary bladder adenocarcinoma is that of cystitis cystica et glandularis, which often coexists with the condition. Herein, we present a case report of non-muscle-invasive urinary bladder adenocarcinoma in a previously healthy male patient in his forties with a known history of cystitis cystica et glandularis. The patient presented with gross hematuria, and based on his known urological condition, a cystoscopy with biopsy was performed, showing submucosal proliferation of atypical glands. The detailed clinical and radiological evaluation showed no evidence of malignancy at other sites. As the malignancy was non-muscle-invasive, an intravesical dose of the Bacillus Calmette-Guérin vaccine was administered. The patient was followed up with cystoscopy, and a biopsy showed no evidence of residual malignancy, with cystitis cystica et glandularis persisting. A year following the diagnosis, the patient is still actively monitored, and no recurrence is noted.

Fibroblast Growth Factor-2 and the Invasive Potential in Urothelial Malignancies of the Bladder.

Introduction Urothelial carcinomas represent a distinct group of malignancies with a high recurrence potential. Multiple studies have established a set of interactions between the tumor cells of urothelial neoplasms and the extracellular matrix regarding invasion and tumor progression. In the present study, we evaluated the expression of fibroblast growth factor-2 (FGF2) in early-stage urothelial carcinomas of the urinary bladder (pTa and pT1) regarding the invasive potential of these tumors. Materials and methods A retrospective non-clinical approach was utilized for the study. Tumor tissue sections used for the initial diagnosis were stained by immunohistochemical means with an anti-FGF2 antibody and the expression within the extracellular matrix was evaluated using a histo-score (h-score). Statistical parameters regarding tumor invasion, FGF2 expression pattern and levels, patient demographic characteristics, and disease recurrence were analyzed for significance. Results A total of 163 cases were analyzed, with an h-score of 110 determined as the optimal cut-off value for invasive potential regarding FGF2 expression, with a sensitivity of 75.4% and a specificity of 78.9%. No statistical correlation was established between the demographic profile of the patients and the occurrence of disease recurrence. Conclusion Based on our results, the study of tumor-extracellular matrix interactions in regards to FGF2 expression is a promising field, at least in urothelial malignancies of the urinary bladder, in regards to tumor invasive potential, while it remains unestablished how these interactions affect metastatic potential.

Role of Cytokeratin 20 as a Predictive and Prognostic Marker in Urothelial Neoplasms.

Introduction Several clinical peculiarities mark urothelial carcinomas and their biological behavior. Key in these are its relatively indolent course before manifestation and its high recurrence rate. So far, no biomarker has been identified as a predictor for these factors. The current study aims to evaluate the role of cytokeratin 20 (CK20) in non-invasive urothelial carcinomas (pTa and pT1) of the urinary bladder and its diagnostic and predictive role in tumor staging and recurrence. Materials and methods The study utilizes a retrospective, non-clinical approach via immunohistochemical marking of the paraffin-embedded tumor tissues for the initial diagnosis. Expression patterns were compared with tumor grade and stage, as well as the incidence of recurrence within a five-year follow-up period. Results A strong statistical correlation was established between expression and tumor grade, with high-grade tumors showing weak to moderate expression of CK20 while low-grade tumors showed an intensive expression pattern. No correlation was noted between the expression pattern, patient age and gender, tumor stage, and the likelihood of local recurrence. Conclusion While CK 20 is a reliable diagnostic marker when used together with other markers, its expression pattern in our study correlated only with bladder urothelial carcinoma grade.

Modified Silver Impregnation Method for Basal Membranes in Renal Biopsies.

Silver impregnation methods are essential in biopsy interpretation in nephropathology with regard to visualizing the basal lamina and its associated changes. The most widely used methods, mainly Jones methenamine impregnation, are time-consuming in their protocols and require multiple microscopy control points. In this report, we propose an alternative, modified method for silver impregnation with methenamine solution with a significantly shorter protocol time and good staining quality, allowing for proper interpretation of basal lamina changes in the glomeruli and blood vessels. Furthermore, unlike some other modified techniques, our proposed protocol does not include microwaving of the solutions but rather a thermostat is used, thereby reducing fire hazards. Implementing the protocol in our everyday practice has reduced sample processing time while not negatively impacting biopsy interpretation.

Light Chain Deposition Disease: A Morphological Case Report.

Light chain deposition disease (LCDD) is a rare condition associated with the overproduction and deposition of monoclonal light chain immunoglobulins. The kidneys are universally affected in LCDD, with the development of renal failure with nephrotic syndrome, microscopic hematuria, and proteinuria. Most cases are associated with a plasma cell neoplasm (multiple myeloma or plasmacytoma) or other lymphoproliferative disorders, with a reasonable number of cases also being idiopathic. Other organs can be affected in rare cases, without producing significant symptoms, predominantly the liver and heart. In this report, we discuss a case of a 72-year-old female presenting with the aforementioned symptoms. Percutaneous ultrasound-guided kidney biopsy revealed nodular sclerosis with periodic acid-Schiff stain (PAS)-positive, Congo red-negative, silver impregnation weakly-positive, and Masson's trichrome-positive (red reaction) deposits with ribbon-like changes together with light chain deposits in the tubular basement membranes. As LCDD was diagnosed, the patient was subjected to further tests, with multiple myeloma of the thoracic vertebrae also being diagnosed. The patient was started on myeloma treatment; however, she subsequently developed a severe lower limb infection that required amputation, after which she developed sepsis and expired.

The Role of Preoperative Neutrophil, Platelet, and Monocyte to Lymphocyte Ratios as Independent Prognostic Factors for Patient Survival in WHO 2021 Glioblastoma: A Single-Center Retrospective Study.

Introductions Immuno-oncology is a rapidly developing field wherein tumor-immune system interactions can be harnessed for diagnostics. Herein, we set out to establish the role of the immune system response, as measured by preoperative neutrophil, platelet, and monocyte to lymphocyte ratios (NLR, PLR, and MLR) as prognostic markers for patient survival based on the newly defined criteria for glioblastoma (GBM). Materials and methods The study included patients diagnosed with GBM at a four-year interval. Exclusion criteria were patients subject to reoperation in the time period; tumors in more than one system; a history of hematological and autoimmune diseases; and cases with infectious or other inflammatory conditions. Data regarding patient demographics and preoperative blood counts were pulled from patient records and compared to postoperative survival. Results A total of 22 patients fit the established criteria, with a male to female ratio of 2.14:1, a mean age of 66.23 years, and a mean survival of 255.72 days (8.04 months, range 24-801 days). Eight patients had an elevation of NLR and five of PLR, with no statistical correlation to survival. Six patients had an increase in MLR with a statistically significant (p=0.0044) shorter postoperative survival. Synergic increases in NLR and PLR did not show significance, while synergic increases with MLR showed no added benefit. Conclusion Preoperative MLR, but not NLR or PLR, is a promising independent biomarker for patient survival in GBM. It is suggested that elevations in these ratios directly correlate to tumor biological potential.

Diaph3 underlines tumor cell heterogeneity in glioblastoma with implications for treatment modalities resistance.

INTRODUCTION: Glioblastoma (GBM) is the most aggressive central nervous system (CNS) tumor with astrocytic differentiation. The growth pattern of GBM mimics that of the precursor cell migration during the fetal development of the brain. Diaphanous homolog (Diaph3) has been established to play a role in both CNS maturation and cancer progression as it is required both for cell migration and division. Furthermore, Diaph3 has been shown to play a role in malignant disease progression through hyperactivation of the EGFR/MEK/ERK in loss of expression and its overexpression correlating to hyperactivity of the mTOR pathway, both of which are with a well-established role in GBM. Herein, we aimed at establishing the diagnostic role of Diaph3 immunohistochemistry expression patterns in GBM and their possible implications for molecular response to different therapies. MATERIALS AND METHODS: The study utilized a retrospective nonclinical approach. Results of Diaph3 immunohistochemical expression were compared to healthy controls and reactive gliosis and statistically analyzed for correlation with neuroradiological tumor parameters and patient survival. RESULTS: Healthy controls showed individual weakly positive cells, while reactive gliosis controls showed a strong expression in astrocytic projections. GBM samples showed a heterogeneous positive reaction to Diaph3, mean number of positive cells 62.66%, median 61.5, range 12-96%. Areas of migrating cells showed a strong diffuse cytoplasmic reaction. Cells located in the tumor core and those in areas of submeningeal aggregation had no antibody expression. Statistical analysis revealed no correlation with tumor size or patient survival. CONCLUSION: The different expression pattern of Diaph3 in healthy controls, reactive gliosis and GBM shows promise as a clinical differentiating marker. Despite Diaph3 expression not correlating with survival and tumor size in GBM, there is an accumulating body of evidence that Diaph3 correlates with mTOR activity and can thus be used as a predictor for response to rapamycin and taxanes, clinical studies of which have shown promising, if mixed results in GBM.

Reclassification of Glioblastoma Multiforme According to the 2021 World Health Organization Classification of Central Nervous System Tumors: A Single Institution Report and Practical Significance.

Introduction The 2021 World Health Organization (WHO) classification of tumors of the central nervous system (CNS) has introduced significant changes to tumor taxonomy. One of the most significant changes in the isolation of isocitrate dehydrogenase (IDH) mutant forms of glioblastoma multiforme (GBM) into separate entities, as well as no longer allowing for entries to be classified as not otherwise specified (NOS). As a result, this entity now includes only the most aggressive adult-type tumors. As such, established prognostic factors no longer apply, as they now form the criteria of different disease entries or have been established based on a mixed cohort. Herein, we aimed to reclassify glioblastoma cases diagnosed per the 2016 WHO tumors of the CNS classification into the 2021 WHO tumors of the CNS classification and establish a patient survival pattern based on age, gender, tumor location, and size as well as tumor O-6-methylguanine-DNA methyltransferase (MGMT) mutation. Materials and methods A retrospective, non-clinical approach was utilized. Biopsy specimens of adults diagnosed with GBM, WHO grade 4, NOS in the period February 2018-February 2021 were reevaluated. The data regarding the patient's gender and age were withdrawn from the medical documentation. Immunohistochemistry was performed with mouse monoclonal anti-IDH R132H and rabbit polyclonal anti-MGMT. Radiology data on tumor location and size were pulled from the radiology repository. Data were statistically analyzed for significance, using Kaplan-Meier survival analysis, with a 95% confidence interval and p<0.05 defined as significant. Results A total of 58 cases fit the set criteria, with eight of them (13.7%) harboring an IDH R132H mutation and were hence reclassified as diffuse astrocytoma IDH-mutant, WHO CNS grade 4. The cases that retained their GBM classification included n=28 males and n=22 females, a male to female ratio of 1.27:1, and a mean age of 65.3 years (range 43-86 years). The MGMT mutational status revealed a total of n=17 positive cases (35%), while the remaining cases were negative. No hemispheric predilection could be established. Lobar predilection was as follows: temporal (37.78%), parietal (28.89%), frontal (24.44%), and occipital (8.89%). The mean tumor size measured on neuroradiology across the cohort was 50.51 mm (range 20-76 mm). The median survival across cases was 255.96 days (8.41 months), with a range of 18-1150 days (0.59-37.78 months). No statistical correlation could be established between patient survival and gender, hemispheric location, lobar location, and tumor size. A significant difference in survival was established only when comparing the 41-50 age groups to the 71-80 and 81-90 age groups and MGMT positive versus negative tumors (p=0.0001). Conclusion From a practical standpoint, the changes implemented in the new classification of CNS tumors define GBM as the most aggressive adult type of tumor. Based on their significantly more favorable prognosis, the reclassification of IDH mutant forms of astrocytomas has had little epidemiological impact on this relatively common malignancy but has significantly underlined the dismal prognosis. The changes have also led to MGMT promoter methylation status being the only significant prognostic factor for patient survival in clinical use, based on its prediction for response to temozolomide therapy in this nosological unit clinically presenting when it has already reached immense size.

Frank's sign and paired ear creases of the helix : Current concepts of significance for morbidity.

Frank's sign (FS) was described in 1973 as an auricular marker for cardiovascular disease presenting as a crease of the auricular lobule. Since its first clinical description, there have been multiple studies underlining the role of FS in a myriad of conditions, such as atherosclerosis, hypertension, cerebrovascular disease, peripheral artery disease, metabolic diseases as well as studies looking at physiological differences in the auricular shape that may mimic FS; however, a complex study to comprehensively analyze the clinical, gross, and histological findings of patients with FS has not yet been performed. Most studies focused on a specific system, mechanism of disease entry. This short review tries to summarize the current knowledge of FS in relation to diseases as well as its clinical classification, histology, and association with the recently described paired ear creases of the helix, as an attempt to reveal the dubious role of FS as a possible prognostic and predictive marker.

Myeloproliferative Neoplasm and Myelodysplastic Syndrome-Associated Renal Disease: A Histopathological Report of Two Cases.

Myeloproliferative neoplasms (MPN) are clonal disorders of hematopoietic stem cells with a proliferation of one or more myeloid lineage and mature cell overproduction, while myelodysplastic syndrome (MDS)/MPN simultaneously show aspects of MDS and MPN, leading to partially ineffective hematopoiesis with associated dysplastic changes. This spectrum of disorders includes chronic myeloid leukemia, polycythemia vera, primary myelofibrosis, and essential thrombocythemia. MDS/MPN are classically not associated with renal complications; however, an accumulating body of evidence suggests that multiple growth factors, cytokines, endothelial damage, and an activated complement system in these patients can induce glomerulopathy, as nearly a third of these patients present with advanced renal disease on diagnosis, which is unlikely to be age or hypertension-related. In this report, we present two cases of patients with MPN/MDS, a 45-year-old male with essential thrombocythemia and a 73-year-old male with polycythemia vera, both of whom developed generalized edema and were referred to our institution from their outpatient nephrologists due to accompanying proteinuria. Renal biopsy of the first patient revealed mesangiocapillary and mesangioproliferative MPN-associated glomerulopathy. In contrast, the second patient was diagnosed with MPN/MDS-associated segmental mesangial proliferative glomerulonephritis and renal vasculature drug toxicity. Both patients were started on treatment - corticosteroid as per consensus.

Quantitative Analysis of Tumor-Associated Mast Cells in Recurrent and Non-recurrent Urothelial Bladder Cancer in Stage pTa and pT1.

Background Urothelial carcinoma of the urinary bladder (UCUB) is a common malignancy in both genders with a very high recurrence rate. There has been increasing evidence for a correlation between tumor-associated mast cells (TAMC) and tumor growth and recurrence rates. In the present study, we set out to establish a link between TAMC and the clinical morphological characteristics of UCUB in stages pTa and pT1. Methodology A retrospective non-clinical approach was used, with two groups of patients with UCUB. A total of 163 patients were included, 95 in the non-recurrent group and 68 in the recurrent UCUB group. Estimation of TAMC was performed on histological slides from the initial biopsy material using Giemsa and Toluidine blue staining. The collected data were statistically analyzed using the Kaplan-Meier curve, Mann-Whitney test, receiver operating characteristic curve, and chi-square analysis. Results Statistical analysis revealed that TAMC in the tumor stroma shows a positive correlation with local recurrence, with no statistical significance to the time of recurrence. No correlation showed statistical significance with pT stage, grade, gender, and age. Conclusions The amount of TAMC in UCUB correlates positively with the rate of local recurrence. The depicted correlations are similar to those established in mammary carcinoma, some lymphoproliferative disorders, and pancreatic and prostate malignancies.

Experimental Model of Subclinical Vitamin K Deficiency.

INTRODUCTION: Vitamin K (VK) is a co-factor in the post-translational gamma glutamic carboxylation of Gla-proteins. VK-dependent coagulation factors are carboxylated in the liver by VK1. Osteocalcin and Matrix-Gla protein (MGP) are carboxylated in extrahepatic tissues by VK2. A model of VK deficiency would be suitable for studying extrahepatic Gla-proteins provided that severe bleeding is prevented. AIM: The aim of this work was to adapt an established protocol of vascular calcification by warfarin-induced inactivation of MGP as a calcification inhibitor, in an attempt to create a broader state of subclinical VK deficiency and to verify its safety. MATERIALS AND METHODS: Two consecutive experiments, each lasting 4 weeks, were required to modify the dosing schedule of warfa-rin and VK1 and to adapt it to the Wistar rats used. The original high doses of warfarin used initially had to be halved and the protective dose of VK1 to be doubled, in order to avoid treatment-induced hemorrhagic deaths. The second experiment aimed to confirm the efficacy and safety of the modified doses. To verify the VK deficiency, blood vessels were examined histologically for calcium deposits and serum osteocalcin levels were mea-sured. RESULTS: The original dosing schedule induced VK deficiency, manifested by arterial calcifications and dramatic changes in carboxyl-ated and uncarboxylated osteocalcin. The modified dosing regimen caused similar vascular calcification and no bleeding. CONCLUSION: The modified protocol of carefully balanced warfarin and VK1 doses is an effective and safe way to induce subclinical VK deficiency that can be implemented to investigate VK-dependent proteins like osteocalcin.

Quantitative Analysis of Tumor-associated Tissue Eosinophilia in Recurring Bladder Cancer.

The relatively high incidence of recurrence of bladder cancer is a serious problem in clinical practice. At present, there are no objective microscopic criteria for evaluation of the tendency for local relapse. Besides the phenotypic properties of the tumor parenchymal cells, possible signs in regard to recurrence could also be derived from the peculiarities of the tumor stroma. The stromal reaction, manifested by inflammatory infiltration in the tumor is considered to influence the biological behavior of tumors. Also, a relationship has been reported between the number of eosinophils and the survival of patients. The aim of the present study is to analyze tumor-associated tissue eosinophilia (TATE) and to compare TATE density in the initial foci of age and gender-matched 156 cases of recurrent and non-recurrent bladder cancers; the tumors that have relapsed within six months after removal and contained statistically significant greater numbers of eosinophils in primary cancer sites. These results suggest that TATE may be one of the probable prognostic signs for local relapse of urothelial cancer.

A Comparative Review of Demographics, Incidence, and Epidemiology of Histologically Confirmed Intracranial Tumors in Brazil and Bulgaria.

Intracranial tumors (ICTs) attract numerous scientific teams and tremendous financial resources worldwide. These lesions of the central nervous system (CNS) can be both benign and malignant in biological behavior as well as local or metastatic in origin. We compared data from two studies on primary and metastatic ICTs from Brazil and Bulgaria, based on histopathologically confirmed ICTs from tertiary health centers. Primary ICTs significantly outweigh the frequency of metastatic ICTs. Primary ICTs represent 86.45% in Brazil and 69.17% in Bulgaria, with around 60% of their totals being malignant. There is a statistical dominance of tumors from the neuroepithelial origin, with the most common entry being glioblastoma multiforme. The second-most common primary ICT group comprises tumors of meningeal origin. Metastatic ICTs show great variance; 13.55% in Brazil and 31.38% in Bulgaria of all ICT cases being attributed to them. However, metastatic ICTs are even a more diverse group than neuroepithelial tumors, with the majority of this group comprising metastatic colorectal adenocarcinoma (almost exclusively in males), metastatic breast adenocarcinoma in females, metastatic pulmonary carcinomas (primarily from the non-small cell group with a male predominance), and metastatic melanoma with an even gender ratio.

Cell biology of glioblastoma multiforme: from basic science to diagnosis and treatment.

First described in the 1800s, glioblastoma multiforme (GBM), a class IV neoplasm with astrocytic differentiation, as per the revised 2016 World Health Organization classification of tumors of the central nervous system (CNS) is the most common malignant tumor of the CNS. GBM has an extremely wide set of alterations, both genetic and epigenetic, which yield a great number of mutation subgroups, some of which have an established role in independent patient survival and treatment response. All of those components not only represent a closed cycle but are also relevant to the tumor biological behavior and resistance to treatment as they form the pathobiological behavior and clinical course. The presence of different triggering mutations on the background of the presence of key mutations in the GBM stem cells (GBMsc) further separates GBM as primary arising de novo from neural stem cell precursors developing into GBMsc and secondary, by means of aggregated mutations. Some of the change in cellular biology in GBM can be observed via light microscope as they form the cellular and tissue hallmarks of the condition. Changes in genetic information, resulting in alteration, suppression and expression of genes compared to their physiological levels in healthy astrocytes lead to not only cellular, but also extracellular matrix reorganization. These changes result in a multiform number of micromorphological and purely immunological/biochemical forms. Therefore, in the twenty-first century the term multiforme, previously outcast from nomenclatures, has gained new popularity on the background of genotypic diversity in this neoplastic entry.

Demographics of Head and Neck Cancer Patients: A Single Institution Experience.

Introduction Head and neck cancer (HNC) comprises a diverse group of oncological entities, originating from various tissue types and organ localizations, situated in the topographical regions of the head and neck (H&N). This single institution retrospective study was aimed at establishing the HNC patient demographics and categorizing the individual incidence of H&N malignancies, regarding their organ of origin and main histopathological type. Materials and methods All histologically verified cases of HNC from a single tertiary referral center were reviewed in a descriptive retrospective manner. Data sampling period was 47 months. Results Male to female ratio of the registered HNC cases was 3.24:1. The mean age of diagnosis was 63.84 ± 12.65 years, median 65 years. The most common HNC locations include the larynx 30.37% (n = 188), lips and oral cavity 29.08% (n = 180), pharynx 20.03% (n = 124) and salivary glands 10.94% (n = 68), with other locations such as the external nose, nasal cavity and sinuses and auricle and external ear canal harboring a minority of the cases. The main histopathological groups include squamous cell carcinoma 76.74% (n = 475) and adenocarcinoma 6.14% (n = 38), with other malignant entries such as other epithelial malignancies, primary tonsillar, mucosa-associated lymphoid tissue or parenchymal lymphomas, connective tissue neoplasias, neuroendocrine and vascular malignancies diagnosed in a minority of cases. Conclusion Considered to be relatively rare, HNC represents a diverse group of oncological entities with individual and specific demographic characteristics. The reported single institution results appear representative of the national incidence and characteristics of HNC.

Demographics and Incidence of Histologically Confirmed Intracranial Tumors: A Five-year, Two-center Prospective Study.

Introduction Intracranial tumors (ICTs) are a diverse group of malignancies that pose an immediate threat to patients' lives, no matter their local or metastatic origin, benign or malignant nature. These lesions have severe clinical courses and need to be diagnosed and treated as soon as possible, with pathological verification being the pivotal moment in the process of determining curative modalities. Aim The aim of this study was to compare the incidence of histologically confirmed ICTs in Eastern Bulgaria, based on their type (primary, metastatic, and non-volume occupying lesions (NVOL)), their respective subtypes, and incidence in a descriptive manner. Materials and Methods For a period of five full calendar years (January 1st, 2012 - December 31st, 2016), all histologically confirmed cases of intracranial tumors were prospectively collected from two individual tertiary healthcare institutions. The cases were then statistically analyzed in a descriptive manner, and incidences of primary, metastatic, and NVOL were compared with regards to their specific origins, types, and subtypes. Metastatic tumors were further segregated relative to their intracranial metastatic location. Results The total number of individual ICTs registered in the set timeframe was 822. Primary ICTs represented a total of 66.12% of the histologically confirmed cases, with the most common entries being tumors from a glial and meningeal origin, 30.90% were histologically confirmed as metastatic ICTs, from which the most common entries were of pulmonary origin, and the other 2.94% were NVOL. On behalf of their intracranial metastatic location, metastatic tumors were located predominantly in the supratentorial region, represented as a total of 87.80%, while the other 12.20% were located in the subtentorial region. Based on the descriptive analysis, the annual incidence per 100,000 capita of all ICTs is 9.12, comprised of 6.03 per 100,000 for primary ICTs, 2.82 per 100,000 for metastatic ICTs, and 0.27 per 100,000 for NVOL. The annual incidence of the most commonly diagnosed primary ICTs per 100,000 is 2.36 for meningioma, 2.03 for glioblastoma, and 0.48 for pituitary adenoma. The annual incidence of the most commonly diagnosed metastatic ICTs per 100,000 is 1.32 for lung cancer metastases, 0.28 for gastrointestinal tract (GIT) metastases, 0.22 for melanoma, and 0.17 for breast cancer metastases. Conclusion Based on our results, primary ICTs are operated and biopsied more than two times as much as metastatic ICTs and only a small fraction of neurosurgical interventions are undertaken due to NVOL. Metastatic ICTs are predominantly supratentorial with no evidence of a tumor predominantly metastasizing in the subtentorial region. The demographics reported in the study establish some aspects of age and gender preferences, as well as the annual incidence per 100,000 for the most commonly diagnosed types of ICTs in our population.

Correlation Between Ki-67 Index, World Health Organization Grade and Patient Survival in Glial Tumors With Astrocytic Differentiation.

Background Glioblastoma multiforme (GBM) is a class IV astrocytic tumor, the most malignant of the four groups of World Health Organization (WHO) tumors with astrocytic differentiation. Aim The aim of this study was to estab-lish whether a correlation exists between the Ki-67 index of tumors with astrocytic differentiation, WHO grade, and patient survival. Materials and methods A retrospective non-clinical approach to patient selection was chosen for the aim of the study. A total of 47 patients diagnosed and treated for CNS tumors with astrocytic differentiation in the St. Marina University Hospital, Varna, Bulgaria, from September 2012 to July 2016 were retrospectively included into the study cohort. The cases were tested for their immunohistochemistry (IHC) reaction with Ki-67 after their original Hematoxylin and Eosin and IHC slides were reviewed by a single author and blind coded. The Ki-67 positivity index of the nuclei was estimated after digitalization of the slides and calculated by the ImmunoRatio automated count-ing tool. The individual Ki-67 index and patient survival of each case were statistically compared. Results The histopathological groups, after the blind Ki-67 index automated calculation was carried out, revealed no WHO grade I, two WHO grade II samples, four WHO grade III samples and 41 WHO grade IV cases, and these were included in the analysis. The two samples of WHO grade II astrocytic tumors had a mean Ki-67 index of 25%; however, they comprised tumors with an individual index of 43% and 7%, both individual values with a highly unlikely index for this group. The four samples of WHO grade III had a mean Ki-67 index of 4%, standard deviation ±2.16 (p>0.05), with the lowest index being 1% and the highest one being 6%. Both WHO grade II and III did not include enough samples to allow for a proper statistical analysis of patient survival. The 41 GBM cases had a mean Ki-67 index of 17.34%, standard deviation ±10.79 (p>0.05). Statistical analysis of the Ki-67 index divid-ed dichotomously into two groups and patient survival revealed that cases with a high Ki-67 index had no significant difference in survival when compared to those with low expression. Conclusions Based on the reported results, the mean Ki-67 percentage of positive nuclei in GBM tumor sam-ples cannot be used to estimate the survival of patients. However, Ki-67 remains a valuable IHC pathological tool.