The Rapid Development of Glioblastoma: A Report of Two Cases.

Diffuse astrocytic gliomas and their most common and aggressive representation, glioblastoma (GBM), which as per the 2021 World Health Organization (WHO) guidelines is an isocitrate dehydrogenase (IDH) wildtype without alteration in histone 3 and has glomeruloid vascular proliferation, tumor necrosis, telomerase reverse transcriptase (TERT) promoter mutation, epidermal growth factor receptor (EGFR) gene amplification, or +7/-10 chromosome copy-number changes, are fast-growing tumors with a dismal patient prognosis. Herein, we present cases of a 63-year-old male who, despite no evidence of tumor growth, developed a 6-cm tumor, histologically verified as GBM, WHO CNS grade 4, within eight months, and a 74-year-old female in whom a 1.5-cm tumor grew to 43 mm within 28 days, once again histologically confirmed as GBM, WHO CNS grade 4. Other studies using previous WHO guidelines and including up to 106 cases have shown that these tumors have a daily growth rate of 1.4% and can double their size in a period varying from two weeks to 49.6 days. These growth rates further underline the need for extensive surgical resection as disease progression is rapid, with studies reporting that resection of more than 85% of the tumor volume determined on neuroradiology improves survival compared to biopsy or limited resection and resection of more than 98% of the tumor volume statistically improves patient survival.

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.

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.

Primary abdominal gas gangrene: a report of two autopsy cases.

Primary hepatic gas gangrene is a form of primary abdominal gas gangrene. The condition is caused by Clostridium perfringens, other clostridia, and non-clostridia bacterial species producing gas. Unlike classical gas gangrene or myonecrosis, the disease develops without a wound or a port of entry. Instead, gas-producing bacteria in the gastrointestinal tract colonize an underlying pathological process with foci of necrosis, producing excessive gas and spreading hematogenously to other organs. Herein we present two autopsy cases of primary hepatic gas gangrene diagnosed on autopsy, with the gross and histological changes that can be considered specific for this rare condition. Both patients had severe underlying liver disease-prone for this entity development. The gross changes in the cases are postmortem subcutaneous emphysema, skin bullae with pooled blood, pneumothorax, pneumoabdomen, abundant gas in the circulatory system, porous structure of the internal organs (tissue gas bubbles), and advanced tissue lysis, not corresponding to the post mortem time. Histology showed optically empty areas of varying size in the internal organs, which weave the structure of the organs and rod-shaped bacteria with scarcity or complete absence of inflammatory reaction.

Balkan Endemic Nephropathy: An Autopsy Case Report.

Balkan endemic nephropathy (BEN) is a form of interstitial nephritis seen only in certain geographical areas in the Balkan peninsula. Herein we describe the gross and histological changes in a diseased 42-year-old male Caucasian patient with BEN. All the changes fit the classically described alterations, with copper hue discoloration of the skin of the torso and orange discoloration of the soles and palms. Grossly, the kidneys were atrophic, with the left one weighing 31 grams and the right one 32 grams. Their surface was predominantly smooth with areas of fine granulations and cystic transformations. Histology revealed hyalinization of the glomeruli, predominantly in the external part of the cortex, severe vascular changes, interstitial fibrosis, and scant inflammatory cell infiltrate. The renal pelvis and ureters revealed multiple urothelial papillomas and atypical urothelial hyperplasia. BEN is only one geographical variant of interstitial nephritis caused by exposure to aristolochic acid. Other forms of this condition include Chinese herb nephropathy/aristolochic acid nephropathy, as well as several similar endemic conditions with a yet unestablished link to aristolochic acid.

Temporal Patterns of COVID-19-Associated Pulmonary Pathology: An Autopsy Study.

Introduction The novel coronavirus variant - severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) and the disease it causes clinically (novel coronavirus disease 2019 or COVID-19) have placed medical science into a frenzy due to the significant morbidity and mortality, as well as the myriad of clinical complications developing as a direct result of infection. The most notable and one of the most severe changes in COVID-19 develops in the lungs. Materials and methods All cases of real-time polymerase chain reaction (rtPCR)-proved COVID-19 subjected to autopsy were withdrawn from the central histopathology archive of a single tertiary medical institution - St. Marina University Hospital - Varna, Varna, Bulgaria. Pulmonary gross and histopathology changes observed on light microscopy with hematoxylin and eosin as well with other histochemical and immunohistochemical stains were compared with the time from patient-reported symptom onset to expiration, to compare the extent and type of changes based on disease duration. Results A total of 27 autopsy cases fit the established criteria. All cases clinically manifested with severe COVID-19. From the selected 27 cases, n=14 were male and n=13 were female. The mean age in the cohort was 67.44 years (range 18-91 years), with the mean age for males being 68.29 (range 38-80 years) and the mean age for females being 66.54 (range 18-91 years). Gross changes in patients who expired in the first 10 days after disease onset showed a significantly increased mean weight - 1050g, compared to a relatively lower weight in patients expiring more than 10 days after symptom onset - 940g. Histopathology changes were identified as intermittent (developing independent from symptom onset and persisting) - diffuse alveolar damage with hyaline membranes - acute respiratory distress syndrome, endothelitis with vascular degeneration and fibrin thrombi; early (developing within the first week, but persisting) - type II pneumocyte hyperplasia, alveolar cell multinucleation and scant interstitial mononuclear inflammation; intermediate (developing within the late first and second weeks) - Clara cell hyperplasia and late (developing after the second week of symptom onset) - respiratory tract and alveolar squamous cell metaplasia and fibrosis. Conclusion COVID-19-associated pulmonary pathology, both gross and histopathology, show a time-related dynamic with persistent early and a myriad of later developing dynamic changes in patients with severe disease. These changes underline both the severity of the condition, as well as the mechanisms and the probability of long-lasting severe complications in patients with post-COVID syndrome.

Primary abdominal gas gangrene: a report of two autopsy cases

Primary hepatic gas gangrene is a form of primary abdominal gas gangrene. The condition is caused by Clostridium perfringens, other clostridia, and non-clostridia bacterial species producing gas. Unlike classical gas gangrene or myonecrosis, the disease develops without a wound or a port of entry. Instead, gas-producing bacteria in the gastrointestinal tract colonize an underlying pathological process with foci of necrosis, producing excessive gas and spreading hematogenously to other organs. Herein we present two autopsy cases of primary hepatic gas gangrene diagnosed on autopsy, with the gross and histological changes that can be considered specific for this rare condition. Both patients had severe underlying liver disease-prone for this entity development. The gross changes in the cases are postmortem subcutaneous emphysema, skin bullae with pooled blood, pneumothorax, pneumoabdomen, abundant gas in the circulatory system, porous structure of the internal organs (tissue gas bubbles), and advanced tissue lysis, not corresponding to the post mortem time. Histology showed optically empty areas of varying size in the internal organs, which weave the structure of the organs and rod-shaped bacteria with scarcity or complete absence of inflammatory reaction.

Protective Effect of Methylxanthine Fractions Isolated from Bancha Tea Leaves against Doxorubicin-Induced Cardio- and Nephrotoxicities in Rats.

Doxorubicin is an anthracycline antibiotic that is used for the treatment of various types of cancer. However, its clinical usage is limited due to its potential life-threatening adverse effects, such as cardio- and nephrotoxicities. Nonetheless, simultaneous administration of doxorubicin and antioxidants, such as those found in green tea leaves, could reduce cardiac and renal tissue damage caused by oxidative stress. The methylxanthine fraction isolated from Bancha tea leaves were tested in vitro for its antioxidant activity and in vivo for its organoprotective properties against doxorubicin-induced cardio- and nephrotoxicities in a rat model. The in vivo study was conducted on male Wistar rats divided into 6 groups. Methylxanthines were administered at high (5 mg/kg body weight) and low (1 mg/kg body weight) doses, while doxorubicin was administered at a cumulative dose of 20 mg/kg body weight. Serum creatinine, uric acid, and urea concentrations, as well as serum enzyme levels (creatinine kinase (CK), creatinine kinase MB fraction (CK-MB), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH)) and electrolytes (Na+, K+, and Cl-), were analysed. In addition, histological analysis was performed to assess cardiac and renal tissue damage. The concomitant administration of Bancha methylxanthines and doxorubicin showed a dose-dependent reduction in the serum biochemical parameters, indicating a decrease in the cardiac and renal tissue damage caused by the antibiotic. Histological analysis showed that pretreatment with methylxanthines at the dose of 5 mg/kg resulted in an almost normal myocardial structure and a significant decrease in the morphological kidney changes caused by doxorubicin exposure compared with the group that received doxorubicin alone. The putative mechanism is most likely related to a reduction in the oxidative stress caused by doxorubicin.

Late Pathomorphological Features of the Endocrine Pancreas in Patients With Type 2 Diabetes Mellitus.

Introduction Islet amyloid polypeptide (IAPP) amyloidosis is a pathologic alteration of the pancreas, represented by abnormal accumulation of amylin in the interstitial tissue. Amylin is a neuroendocrine hormone, co-secreted with insulin by beta cells and participating in downstream regulation of postprandial glycemia. This report aims to examine IAPP amyloidosis as a late consequence of poor control of blood glucose levels in patients with type 2 diabetes mellitus (T2DM) who have been referred for autopsy. Materials and methods A total of 34 consecutive autopsies performed at the St. Marina University Hospital, Varna, Bulgaria, carried out by a single pathologist were included in the study. Samples from the tail of the pancreas were obtained to evaluate the state of the changes and were analyzed together with the specific organ changes associated with T2DM, as well as the medical documentation of the patients. Results Of the 34 autopsies, 10 cases (six females and four males) were included in the study, seven of whom had a medical history of T2D. The average age was 65.7 years (range 50 to 85 years). In all of the cases, morphological features of fibrosis and lipomatosis were present, with one of the patients having signs of pancreatic amyloidosis - Congo red positive deposition of pink, amorphous material in the extracellular matrix. Conclusion The described pathological alterations in all of the cases illustrate the progressing impairment of the structure of the pancreas, especially beta cells dysfunction in late stages of T2D, and highlight IAPP amyloidosis as the cause of irreversible damage of the isles of Langerhans and beta cell death.

Hans Joachim Scherer and His Impact on the Diagnostic, Clinical, and Modern Research Aspects of Glial Tumors.

The historical descriptions of glial tumors are often poorly understood and interpreted. The gross and histological depictions of glial tumors are often credited to Virchow, and while the first true histological description is truly his, gross descriptions can be traced back to the beginning of the 1800s, with their classification and histogenesis attributed to Percival Bailey and Harvey Cushing. Without any question, the most prominent and under-credited researcher in the field of glioma pathobiology was the German neuropathologist Hans Joachim Scherer. Despite the limited armamentarium available to him, his systematic approach led to conclusions, some of which have now been molecularly explained today while some are still being widely researched. Scherer defined pseudopalisadic necrosis as a pathognomonic feature of glioblastoma multiforme (GBM), as well as secondary features due to tumor growth, known collectively as secondary Scherer figures, for example, neuronal and vascular satellitosis, tract and subpial aggregation. All these features are key points in the modern histological diagnosis of glial tumors. Other contributions by Scherer include the definition of glomeruloid vascular proliferation and his conclusion that they are caused by vascular factors released by the tumor, decades before vascular endothelial growth factor and its receptors were discovered and their role in glioma evolution was established. Furthermore, he concluded that GBMs can arise de novo (primary) or from a preceding lower-grade glioma (secondary). All his contributions find their place in all modern aspects of glioma research, with some giving a simple explanation of the phenomena observed in glial tumors.

Thrombophlebitis Migrans (Trousseau Syndrome) in Pancreatic Adenocarcinoma: An Autopsy Report.

First described by a French physician Armand Trousseau, the Trousseau sign of malignancy is a classic example of paraneoplastic syndrome, caused by adenocarcinomas predominantly of the stomach, pancreas, and lung. The condition presents as recurring and migrating episodes of thrombophlebitis that can involve the upper and lower limbs, thoracic and abdominal wall, and the major blood vessels of the abdomen. These recurring episodes may lead to a detachment of a thrombus and the formation of pulmonary thromboembolism (PTE), often proving fatal for the patient. Herein we present a case of a 60-year-old male patient referred for autopsy. The patient was admitted with acute onset of gastrointestinal tract symptoms and after admission, his condition deteriorated rapidly, with new-onset neurological symptoms and an acute massive fatal episode of PTE. Previous medical history was uneventful, apart from several episodes of recurring lower limb thrombophlebitis for the past six months, resulting in two prior episodes of PTE. The autopsy revealed a massive PTE, with multiple thrombi in the venous vessels, including the two common iliac veins and the inferior vena cava. Histological evaluation revealed pancreatic adenocarcinoma with distant metastasis to a number of organs and abdominal thrombophlebitis with embolization of the pulmonary arteries.

The Sixty-five Roses of Cystic Fibrosis: A Report of Two Autopsy Cases with Kidney Involvement.

Cystic fibrosis (CF), also commonly referred to as mucoviscidosis, is a multigene related disorder, involving a defect in the CF transmembrane conductance regulator protein, with over 1,500 genes, being identified with the condition. The most commonly affected organs, often described in the literature, are the lungs, pancreas, intestines, and skin, which is one of the sites for early diagnostic testing. Herein we report two autopsy cases of CF, with multiorgan involvement and some rarely observed and reported changes. Two pediatric cases of clinically confirmed CF were referred for autopsy at the Department of General and Clinical Pathology, St. Marina University Hospital, Varna, Bulgaria. The first case was of a one-year-old female and the second of a six-month-old female. Both cases had classical CF-associated changes in the lungs, liver, pancreas, and small intestine. The kidneys although normal on gross inspection also had severe changes on histology with a compacted matter in the lumen of the distal tubules, some of which had undergone calcification. These histological renal changes are under-reported in literature, thus unlike the classical reported cystic changes we highlight lumen compaction and calcification as the primary histological hallmark in kidneys of patients with CF.

A Practical Approach to the Differential Diagnosis of Intracranial Tumors: Gross, Histology, and Immunoprofile-based Algorithm.

Intracranial tumors are a diverse group of conditions, both benign and malignant, primary and metastatic and always require detailed medical information, radiological reports and deep knowledge of the histological hallmarks and immunohistochemical profile of different types of tumors and tumor-like processes. Despite it clinically often being possible to differentiate between primary and metastatic tumors, based on the tumor location and age of the patient, histological variants and rare tumor entries should always be considered in the histological differential diagnosis. A thorough diagnostic algorithm based on the location of the tumor and its histological features, together with some common pitfalls in immunohistochemical profiling, based on the 2016 revised World Health Organization (WHO) classification of tumors of the central nervous system should be implemented in all cases. Such an algorithm is especially valuable in cases where only small tumor fragments are sent for morphological evaluation, such as in deep parenchyma tumors. In these instances where only small fragments of the tumor are present for histology, some key features, corresponding to the WHO grade, may easily be missed or underreported. Furthermore, the histological verification of the tumor entry is the first, often overlooked, step in defining the presence or absence of WHO grade-specific mutations.

The Final Diagnosis: Colorectal Carcinoma, In the Context of Attenuated Familial Adenomatous Polyposis, Mimicking Pulmonary Carcinoma.

Pulmonary carcinoma is one of the most common malignant conditions worldwide. The current case presents a patient with lung lesions clinically and radiologically diagnosed as lung cancer, which was not biopsied due to patient's refusal. The patient was a heavy smoker and prior to the lung lesions, he was diagnosed with chronic obstructive pulmonary disease. Following recurrent hospitalizations, the patient died and he was referred for an autopsy. The autopsy established six lesions in the lung, one in the liver, one in the cerebrum and multiple polyps of the colon, two of which were with a visible invasive growth. The histological sections revealed that the lung, liver, and cerebral lesions were composed of the atypical gland with excessive mucus production. The colorectal specimens revealed benign polyps and colorectal adenocarcinoma. The diagnosis of advanced colorectal adenocarcinoma with multiple metastases in the context of attenuated familial adenomatous polyposis (AFAP) was established due to the combined histological findings, the age of the patient, and the number of benign polyps in the colon.

Histopathological Findings in an Unclassifiable Case of Empty Nose Syndrome with Long-term Follow-up.

One of the major components of the functional process in the nasal cavity is taken up by the respiratory epithelium covering the posterior two-thirds of the nasal cavity. Disruption in the cytoarchitectonics and subcellular changes in this epithelium results in a number of functional changes in the nasal cavity. One of the rare and usually iatrogenic disturbances of this type is described in 1996, although noticed and discussed significantly earlier, by Kern and Stenkvist empty nose syndrome (ENS) or secondary atrophic rhinitis. The clinical hallmarks of ENS are described as paradoxical feeling for nasal obstruction in the presence of actually widened nasal airways. This phenomenon is attributed to the efferent neuronal signal dissociation accompanying the changes in the nasal mucosa. Herein we report the findings in a 50-year-old male. The patient presented with chronic right-sided headache, foul discharge and complaints of a stuffed nose in 2011. Endoscopy and computed tomography (CT) showed complete destruction of the hard plane, nasal septum, and right maxillary septum, leading to a formation of a huge neocavity. Due to the past medical history and the severity of the case biopsy specimens were obtained under general anesthesia. The sections showed severe but unspecific changes of the nasal epithelium with areas of minimal remaining preserved respiratory epithelium. Based on the clinical data and endoscopic, CT and histomorphologic data, despite the case is not applicable to the current classification of ENS, the diagnosis of ENS was accepted based on the combined extensive but unspecific findings. A seven-year follow-up period included multiple hospital admissions for monitoring of the condition and extensive sinus lavage. No advancement was noticed.

On the Concepts and History of Glioblastoma Multiforme - Morphology, Genetics and Epigenetics.

Glioblastoma multiforme (GBM) is a grade IV WHO malignant tumor with astrocytic differentiation. As one of the most common clinically diagnosed central nervous system (CNS) oncological entries, there have been a wide variety of historical reports of the description and evolution of ideas regarding these tumors. The first recorded reports of gliomas were given in British scientific reports, by Berns in 1800 and in 1804 by Abernety, with the first comprehensive histomorphological description being given in 1865 by Rudolf Virchow. In 1926 Percival Bailey and Harvey Cushing gave the base for the modern classification of gliomas. Between 1934 and 1941 the most prolific researcher in glioma research was Hans-Joachim Scherer, who postulated some of the clinico-morphological aspects of GBM. With the introduction of molecular and genetic tests the true multifomity of GBM has been established, with different genotypes bearing the same histomorphological and IHC picture, as well as some of the aspects of gliomagenesis. For a GBM to develop, a specific trigger mutation needs to occur in a GBM stem cell - primary GBM, or a slow aggregation of individual mutations, without a distinct trigger mutation - secondary GBM. Knowledge of GBM has been closely related to general medical knowledge of the CNS since these malignancies were first described more than 200 years ago. Several great leaps have been made in that time, in the footsteps of both CNS and advancements in general medical knowledge.

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.

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.