The Role of the NF-kB Pathway in Intracranial Aneurysms.

The pathophysiology of intracranial aneurysms (IA) has been proven to be closely linked to hemodynamic stress and inflammatory pathways, most notably the NF-kB pathway. Therefore, it is a potential target for therapeutic intervention. In the present review, we investigated alterations in the vascular smooth muscle cells (VSMCs), extracellular matrix, and endothelial cells by the mediators implicated in the NF-kB pathway that lead to the formation, growth, and rupture of IAs. We also present an overview of the NF-kB pathway, focusing on stimuli and transcriptional targets specific to IAs, as well as a summary of the current strategies for inhibiting NF-kB activation in IAs. Our report adds to previously reported data and future research directions for treating IAs using compounds that can suppress inflammation in the vascular wall.

Complete oculomotor nerve palsy - first manifestation of gastric adenocarcinoma: clinical experience and literature review.

The diagnosis and management of the alteration of the normal function of the oculomotor nerve (third cranial nerve) varies depending on the characteristics of the paralysis, the age of the patient, and the associated symptoms and signs. Oculomotor nerve palsy may be caused by lesions located anywhere from the oculomotor nucleus to the termination of the third nerve in the extraocular muscles. Although there have been significant advances in neuroimaging to facilitate early diagnosis, the management of a patient presenting with isolated oculomotor palsy is still challenging. This review tackles the case of a 52-year-old patient, with a history of pulmonary tuberculosis (at the age of five), referred to the Department of Ophthalmology, St. Spiridon Emergency Clinical Hospital, Iasi, Romania. The patient had diplopia accompanied by right eyelid ptosis, symptoms that began suddenly 10 days before hospitalization. The clinical examination showed right eye grade II palpebral ptosis, exotropia with limitation of eyeball movements in adduction, supra-∕infraduction. Biomicroscopic examination of the anterior pole revealed the presence of anisocoria and light-near dissociation on the affected side. Numerous investigations were performed to identify the cause, starting with tumoral markers, which were within normal limits. Magnetic resonance angiography (MRA) was performed, and posterior communicating artery aneurysm was ruled out. The endocrinology examination and hormonal laboratory tests were also within normal parameters. Due to suspicions of generalized tuberculosis raised by the infectious disease doctor or presence of secondary lesions, thoraco-abdomino-pelvic computed tomography (CT) scan with contrast agent was done and its findings required gastroenterological exploration. After various explorations, the certainty diagnosis was set by histopathological examination, which revealed gastric adenocarcinoma.

Thymus pathology in myasthenia gravis with anti-acetylcholine receptor antibodies and concomitant Hashimoto's thyroiditis. A four-case series and literature review.

OBJECTIVE: Identifying the morphological features of thymus in patients with myasthenia gravis (MG) with anti-acetylcholine receptor (AChR) antibodies and concomitant Hashimoto's thyroiditis (HT), which were recruited from a single surgical unit of a tertiary referral hospital located in the North-Eastern region of Romania, over a period of 11 years. PATIENTS, MATERIALS AND METHODS: We retrospectively reviewed clinical, imaging, laboratory, thymic pathology, and outcome data that were obtained from medical records of patients with MG and concomitant HT, to whom a thymectomy was performed for a suspected thymic lesion. All the surgical interventions were done in the Third Clinic of Surgery, St. Spiridon Emergency County Hospital, Iasi, Romania, for an 11 years' period, i.e., from January 1, 2000 and December 31, 2010. RESULTS: Four patients (three females and one male) were included. The mean age of the patients at the time of their thymectomy was 40.25 years. Of all patients, 75% had moderate or severe MG, 100% had anti-AChR antibodies, and an electromyographic decrement greater than 25%. All patients have been diagnosed with HT in their past medical history by a full thyroid panel [high thyroid-stimulating hormone (TSH) values, low free thyroxine (fT4) values, and the presence of the anti-thyroid antibodies] and all of them have been treated with Euthyrox. Our four patients expressed different MG subtypes, each of them being associated with different thymus pathology. Thoracic computed tomography (CT) scan revealed heterogeneous mediastinal masses and established the correct diagnosis only in 25% of cases. The pathological exams also revealed a heterogeneous pattern of thymic lesions. In contrast with other studies, our patients with MG with anti-AChR antibodies and concomitant HT presented atrophic thymus more frequently (50%), but with particular morphological changes of Hassall's corpuscles. Also, 25% of cases were diagnosed with thymic lympho-follicular hyperplasia (TLFH) associated with thymic epithelial hyperplasia. In B2 thymoma, neoplastic epithelial cells expressed cytokeratin 19 (CK19) immunoreactivity, high Ki67 labeling index and strong p63 immunopositivity. CONCLUSIONS: In our series, MG and HT occurred simultaneously, or one of them was diagnosed before the other, raising some new questions regarding the immune mechanism of these two autoimmune diseases. Due to the heterogeneous morphological changes of the thymus that we found in this study, we can hypothesize that thymus is involved in the pathogenic mechanism of MG with anti-AChR-antibodies and concomitant HT development.

Role of copeptin in the diagnosis of traumatic neuroendocrine dysfunction.

Traumatic neuroendocrine dysfunction may present with diabetes insipidus (DI) or with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Both these pathologies involve a disturbance in the antidiuretic hormone (ADH) secretion, causing dysnatremias. Diagnosis of posttraumatic ADH dysfunction is hampered by technical difficulties in ADH assessment, and relies mostly on non-specific serum sodium, serum and urine osmolality and diuresis, often leading to misdiagnosis in the acute care setting. Research now focuses on the diagnostic role of copeptin, a peptide secreted together with ADH in an equimolar fashion, and which can be accurately evaluated. Recent studies identified cut-off values of 2.6 pmol/L for baseline copeptin and of 4.9 and 3.8 pmol/L for hypertonic saline infusion and arginine infusion stimulated copeptin, respectively, for the diagnosis of DI in patients with polyuria-polydipsia syndrome. Although SIADH is more difficult to be explored due to its heterogeneity, a ratio of copeptin to urinary sodium below 30 pmol/mmol identifies euvolemic hyponatremia. Exploring the role of copeptin assessment in patients with traumatic brain injury (TBI) in the acute phase may improve their diagnosis accuracy, management and outcome.

Morphological aspects of the vasculogenesis and angiogenesis during prenatal edification of the circle of Willis: a review.

In the literature, there are many articles reporting anatomical variations of circle of Willis (CoW), defined as those changes that lead to the inability of this anastomotic structure to maintain adequate brain flow. Because there is such a wide variation in the configuration of the CoW, its anatomical variations affect the hemodynamics of blood flow, thus contributing to the development of aneurysms or stroke. As such, we consider that a good knowledge of the embryological development of the constituent arteries of the CoW can shed some light on the causes of the appearance of its anatomical variants. Reviewing literature, we will present the embryological development of the constituting arteries of the CoW and will begin with vasculogenesis and angiogenesis of the vascular system as a whole. Then, we will focus on the embryological development of the internal carotid artery (ICA) and its branches because, starting with the embryological day 24, these arteries are the first vessels that begin to develop to provide the necessary blood for the primitive brain. As the hindbrain increases its volume, a larger amount of nutrients is needed. Because a larger amount of blood is required to be provided by the primitive ICAs, there is a need for arterial capacity development and thus the posterior circulation begin to take shape. At this stage, the posterior circulation consists of a plexiform arterial network that receives blood from the carotid artery through the carotid-vertebrobasilar anastomoses. At the 5-8 mm embryonic stage, these anastomoses begin to regress, and the basilar artery and vertebral arteries become independent of the ICA. We are pointing out on the process of regression of these primitive vessels, emphasizing the fact that their persistence represents the starting point for the appearance of anatomic anomalies of the CoW, which are identified in the adult individuals. In this review, we also present and illustrate some developmental abnormalities of the anterior and posterior parts of the CoW.

The Myth of Prometheus in metastatic meningioma to the liver: from craniotomy to hepatectomy.

Metastases from intracranial meningiomas are rare, and among them, meningiomas with hepatic dissemination are extremely rare. Therefore, there are currently no guidelines for staging and treatment of metastatic disease in meningioma, a disease that is a challenge for both the clinician and the pathologist. Our literature review revealed 24 cases of liver metastases originating from intracranial meningiomas. We used them to analyze the pathological patterns of dissemination and to assess the different management strategies available, the most efficient and beneficial being surgery and chemotherapy, especially in the case of meningiomas with hepatic and∕or systemic dissemination.

Brain metastases originating in breast cancer: clinical-pathological analysis and immunohistochemical profile.

The incidence of brain metastases (BMs) originating in breast cancer (BC) is increasing due to advances in imaging techniques, which can detect such events early, and due to new therapies that can ensure longer survival. We performed a retrospective study on patients with BMs originating in BC and receiving surgical treatment in Neurosurgery Clinics of Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iasi, Romania, from January 2018 to December 2019. We identified 10 consecutive patients who underwent a craniotomy for a BMs originating in a BC (either for diagnostic purpose or with therapeutic intent). Clinicopathological data were collected from the electronic medical record and included the patient demographics (age at diagnosis of their BM), morphological characteristics of BM [location, cytopathological features, histopathological (HP) subtype, and immunohistochemical features, i.e., cytokeratin 5∕6 (CK5∕6), mammaglobin, estrogen receptor (ER), progesterone receptor (PR), and Ki67 labeling index (LI)], and time from BC diagnosis to BM diagnosis. Ninety percent of patients were in their sixth and seventh decades of life, with a median age of 57.9 years (47-65 years). Median time from BC diagnosis to BM was 34.42 months. Fifty percent of BMs were located in the parietal lobes, and 70% of all cases have multiple (≥2) BMs. All cases (100%) had a cytopathological examination, showing a hypercellular pattern, with poorly cohesive clusters of mild or pleomorphic cells, with nuclei with homogeneously distributed fine granular chromatin membrane, and with small or enlarged and irregular nucleoli. The dominant histopathology was invasive breast carcinoma of no special type (IBC-NST) (70%), but we also identified specific subtypes, i.e., tubular carcinoma (TC) (20%) and invasive micropapillary carcinoma (IMPC) (10%). Correlating location with HP subtypes of BMs from BC, IBC-NST and IMPC were located mostly in parietal lobes, and TC developed only in the occipital lobe. We found three patterns of immunostaining: (i) CK5∕6 +∕-, mammaglobin+, ER+, PR-, which was much more characteristic for IBC-NST; (ii) CK5∕6-, mammaglobin+, ER-, PR-, being identified in tubular breast carcinoma; (iii) CK5∕6 +∕-, mammaglobin-, ER-, PR-, which were revealed by invasive micropapillary breast carcinoma. Our study revealed the fact that BMs originating in BC show heterogeneity of hormone receptor status, although morphologically there is not so much diversity. We also found a very variable Ki67 LI, which correlated especially with the morphological subtype.

Clinical, histopathological and immunohistochemical features of brain metastases originating in colorectal cancer: a series of 27 consecutive cases.

INTRODUCTION: Brain metastases (BMs) originating in colorectal cancer (CRC) have a significant importance for patients' survival. Because in literature there are only isolated case reports and only few series published on this issue, we aimed to assess the incidence of BMs from CRC, to identify patient's characteristics and BMs clinical, histopathological (HP) and immunohistochemical (IHC) features, and to compare the data we obtained with those from literature. PATIENTS, MATERIALS AND METHODS: We present a retrospective study of 27 histologically confirmed cases of BMs from CRC among all 1040 patients who received metastasectomy in the Department of Neurosurgery, Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iasi, Romania, in an eight-year period (January 2011 to December 2018). Patients' characteristics (gender, age), primary tumor location, time from primary tumor surgery to BMs surgery and BMs features (number, location and HP characteristics) were investigated. Histochemical [Alcian Blue (AB) and Periodic Acid-Schiff (PAS)] staining and IHC stainings for cytokeratin (CK) 7, CK20, caudal-type homeobox 2 (CDX2) and human epidermal growth factor receptor 2 (HER2)∕neu were performed on all available BMs specimens. RESULTS: There were 27 consecutive patients with BMs from CRC, corresponding to 2.59% of all patients with BMs during the eight-year period we have studied, most of them being diagnosed and treated in 2016. Male:female ratio was 1.45. The mean age for all patients at diagnosis of the BMs was 62.25 years (range: 40-79 years). The origin of the primary cancer was mainly the colon (62.96% of all cases). Of all 27 patients, only two (7.4%) presented neurological symptoms without a diagnosis of CRC. BMs were identified in a period ranging from six months to 70 months after the initial diagnosis. The average time between diagnosis of the primary tumor and of the BMs was 25.92 months. At the moment of the diagnosis of BMs, 17 (62.96%) patients also had other systemic metastases. Most of the cases (55.55%) were situated in the supratentorial compartment. IHC stainings were negative for CK7 and positive for CK20 and CDX2 in all BMs from colonic adenocarcinomas (ADCs), a profile consistent with a non-neuronal and gastric origin. AB and PAS stainings revealed pools of extracellular mucin, especially in cases of mucinous ADC. Ki67 labeling index ranged between 90% and 100%. IHC staining with anti-HER2∕neu antibody showed in 25 (96.15%) cases a strong and diffuse aberrant nuclear staining. CONCLUSIONS: BMs originating in CRC represent a rare pathology and have particular clinical and IHC features that could vary from one series to another series. In a few cases, BMs may be diagnosed in the absence of a known CRC diagnosis and in these situations, the correct diagnosis is of interest. However, a panel of antibodies can help in establishing a correct diagnosis. Our study was among the first to analyze the HER2∕neu expression pattern in BMs from CRC and we found a strong aberrant nuclear expression of this molecular marker on IHC investigation. Related to the data published so far in the literature, it is possible that HER2∕neu aberrant expression in the tumor nuclei of the BMs from our series may express the metastatic tumor cell phenotype that was previously subjected to cytostatics and radiation therapies. As such, we suggest that HER2∕neu aberrant expression in BMs originating in CRC could represent a proof for the worst prognosis of these patients.

Protection measures against SARS-CoV-2 infection for cytopathology and histopathology laboratories personnel: practical recommendations.

In the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, healthcare workers are at high risk to be infected with this new coronavirus, particularly when they handle not only patients, but also their body fluids. In Romania, even though the protective measures to be used by medical staff in emergency departments, clinical departments, radiology departments, clinical laboratories and morgues services are well known, there is little information about the protection of medical staff in the laboratories of cytopathology and histopathology. In this article, we will discuss the transmission routes of the new coronavirus, the surfaces it could contaminate in a hospital, as well as the modalities of its inactivation. We will present some guidelines for preparing the pathology departments to face the pandemic situation like the present one. Also, we will point out some possible recommendations/suggestions for protective measures to be taken by laboratory staff during the cytological and histopathological procedures when they manipulate body fluids or surgical samples of patients with suspected or confirmed coronavirus disease 2019 (COVID-19). Laboratory personnel should be aware that any body fluid or surgical specimen that arrives in the laboratory may contain SARS-CoV-2 and, as such, they should act after new working procedures. We recommend restraint from performing extemporaneous examination (smear and frozen section) and cytopathological examination in laboratories that do not have adequate condition for handling and processing Hazard Group 3 (HG3) pathogens, as SARS-CoV-2. Also, laboratory personnel should pay attention to instruments, technical equipment, or environmental surfaces as these also can be contaminated with the new coronavirus.

The discovery of the circle of Willis as a result of using the scientific method in anatomical dissection.

There are numerous articles on the discovery of this arterial polygon, its history being quite long, beginning with the Antiquity and up to the Modern Era. Making an analysis of the primary and secondary sources on this topic, the purpose of this article is to identify the significant moments of the discovery of this arterial polygon, which is an anatomical structure with great importance for neurologists and neurosurgeons. We will present the contributions to this topic from Renaissance and early Modern Era anatomists, such as Andreas Vesalius, Jean Fernel, Gabriel Fallopius, Giulio Cesare Casseri, Adriaan van den Spiegel, Johann Vesling, and Johann Jakob Wepfer von Schaffhausen. We also pointed out that the contribution of the famous British anatomist Sir Thomas Willis (1621-1675) was the most important one. He published De Cerebri Anatome, in 1664, in which he described the vascular arrangement laying at the base of the brain, accompanying it by the exquisite drawings of Christopher Wren. Thus, he demonstrated to the medical world that he had reached the greatest understanding of the structure and function of the circular arterial anastomosis. For this excellent discovery, his followers honored him by giving his name to this arterial circle.

Tumor recurrence in parasagittal and falcine atypical meningiomas invading the superior sagittal sinus.

OBJECTIVE: Parasagittal and falcine meningiomas are still a challenge in terms of surgical resection. Although maximal safe resection is the main therapeutic approach, numerous postoperative complications can still occur depending on the locations of these tumors. Moreover, previous studies have reported that parasagittal meningiomas have a higher recurrence rate than meningiomas with other locations. PATIENTS, MATERIALS AND METHODS: We retrospectively reviewed 21 patients with parasagittal and falcine atypical meningiomas [World Health Organization (WHO) grade II], nine of whom had their superior sagittal sinus (SSS) invaded by the tumor. We reviewed the demographic information, operative notes, pathological reports, and clinical and imagistic follow-up reports of each patient over a 5-year time span. RESULTS: All the patients were surgically treated, and the tumor removal was grade II according to Simpson's grading system in 47.6% and grade III in 19% of the cases. The SSS was invaded in 42.9% of the patients. No immediate mortality or morbidity was revealed by our study. Tumor recurrence/progression documented on postoperative imaging amounted to 14.3% and 19%, 12 and 24 months after surgery, respectively. Furthermore, 36, 48 and 60 months after the surgery, the recurrence rate remained the same, namely in 9.5% of the cases. The recurrence was higher in patients with SSS invasion than in patients with no SSS invasion. The tumor recurrence was slightly more predominant in women, i.e., 6% higher than in the male group. CONCLUSIONS: In our group of patients with parasagittal and falcine meningiomas, we report a 47.6% Simpson II resection rate and 19% Simpson III resection rate associated with a very low complication rate and no immediately postoperative morbidity and mortality, compared to more aggressive techniques. The recurrence of parasagittal meningiomas predominated after grade III and IV Simpson resection and dural sinus invasion was a negative predictive factor for recurrence. Therefore, the surgery of parasagittal and falcine meningiomas is beneficial, both for tumor control, but also for improving neurological outcome. Aggressive meningioma resection should be balanced with the increased neurosurgical risk.

Morphological and histopathological changes in placentas of pregnancies with intrauterine growth restriction.

AIM: The definition of fetal growth restriction (FGR) refers to the incapability of a fetus to achieve the appropriate estimated growth, with expected fetal weight below the 10th percentile calculated for its gestational age. Placental factors and hypoxemia are considered to be essential elements with influence on intrauterine growth restriction (IUGR) and fetal death. The purpose of the present study was to investigate the macroscopic and microscopic pathological findings regarding the placentas in pregnancies complicated by influence on IUGR. PATIENTS, MATERIALS AND METHODS: Our study included 42 third-trimester pregnant patients admitted to the Cuza Voda Hospital of Obstetrics and Gynecology, Iasi, Romania, in the last three years. Soon after delivery, the 42 placentas were collected and analyzed; 32 placentas came from cases previously diagnosed with influence on IUGR and were included in our study group. Ten other placentas included in the control group were selected from uncomplicated pregnancies. Standard Hematoxylin-Eosin (HE) staining method, as well as Periodic Acid-Schiff (PAS) staining, and immunohistochemical techniques for cluster of differentiation 31 (CD31) and collagen IV were used in order to highlight the morphological features of the studied placentas. RESULTS: Our study revealed that reduced placental dimensions and eccentric umbilical cord insertion are correlated with the birthweight of the fetuses with IUGR (p<0.05). The most common histological finding in our study group was placental infarction later correlated with IUGR, but a certain causality could not be demonstrated, as this finding was also present in normal pregnancies. Other histopathological findings were also present in the influence on IUGR group, such as fibrin deposits, diffuse calcification, chronic villitis, avascular chronical villi, with no significant statistical correlations. CD31 was strongly immunoexpressed in the villous endothelial cells. Collagen IV presented a strong immunoreaction in the basement membrane and mesenchyme of the placental villi. CONCLUSIONS: Our study revealed a correlation between the dimensions of the diameters and volume of the maternal placenta and the presence of influence on IUGR. Moreover, it confirms the available data suggesting that the place of insertion of the umbilical cord is correlated with the weight of the fetus. Further studies with extended panel antibodies are needed in order to determine and complete the role of these morphological changes in the development of influence on IUGR.

Morpho-functional and radiological approach of poststroke seizures.

Epilepsy is characterized by recurrent seizures that cannot be associated with other specific causes. The presence of a single convulsive or tonic seizure after a stroke does not necessarily mean that a person develops a form of epilepsy unless the convulsions become chronic and recurrent poststroke epilepsy. The purpose of our study is to highlight the existence of a connection between the type and the topography of a vascular stroke on the one hand, and on the other hand, the type of seizures that have occurred and how long they have occurred after the stroke. The study was conducted in a total of 165 patients at the Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iasi, Romania, diagnosed with stroke and spastic seizures after stroke and who survived for at least one year. In this study, the ideal patient should be the patient diagnosed for the first time with temporal lobe epilepsy, followed longitudinally by high-resolution imaging techniques. Studying topography and morphopathology of poststroke sequelae can lead to an increase in accuracy prediction of epilepsy after it.

Protean cytological, histological and immunohistochemical appearances of medullary thyroid carcinoma: current updates.

Medullary thyroid carcinoma (MTC) accounts for only 0.5-3% of all malignant diseases, but is responsible for more deaths every year than all the other endocrine malignancies taken together. Approximately 75-80% of MTCs occur sporadically, while the inherited forms of MTC are responsible for the rest of the cases. The heritable MTC results from a germline mutation in the rearranged during transfection (RET) proto-oncogene and is included into the multiple endocrine neoplasia 2 (MEN2), being associated with other endocrine abnormalities and clinical features. MTC is a neuroendocrine tumor that releases a wide range of secretory products that are responsible for a variety of symptoms, making it difficult to be diagnosed. For this reason, the pathological analysis is of vital importance to ensure that the correct diagnosis is made. This review presents the main data from the contemporary literature related to the pathological diagnosis of a patient with MTC and highlights the wide range of tumor cytological features, the many histological variants, as well as the particular tumor immunophenotype. It also reveals the new approach to this type of cancer in the new World Health Organization (WHO) Classification of Thyroid Tumors (2017) and the reassessment of MTC tumor category in the new American Joint Committee on Cancer∕Tumor, Node, Metastasis (AJCC∕TNM) Staging (2017).

Are there any correlations between demographic characteristics, tumor location, and Ki-67 labeling index in intracranial atypical meningiomas (WHO grade II)?

Background∕Aim: Atypical meningiomas (AMs) account for about 30% of all meningiomas and it is difficult to predict their behavior. Nevertheless, the identification of protein markers responsible for the regulation of cell proliferation can be helpful. The purpose of this study is to find possible correlations between demographical characteristics of patients with AMs, tumor anatomic location, and intratumoral immunohistochemical (IHC) expression of Ki-67 labeling index (LI). PATIENTS, MATERIALS AND METHODS: We carried out a retrospective review of 29 patients with intracranial AMs [World Health Organization (WHO) grade II] who underwent resection of AMs at "Professor Dr. Nicolae Oblu" Emergency Clinical Hospital, Iasi, Romania, between January 1, 2014 and December 31, 2016. We searched for their demographic characteristics (age and gender) and tumor location from patients' medical files. The histological slides were reviewed in order to assess the Ki-67 LI. RESULTS: Out of the 29 patients analyzed, 51.72% were females having AMs, with a mean Ki-67 LI of 8.6%, and 48.27% were males with AMs, revealing a mean Ki-67 LI of 8.5%. Considering tumor anatomic location, 82.75% were non-skull base AMs (presenting a mean Ki-67 LI of 8.9%) and 17.24% were skull base AMs (showing a mean Ki-67 LI of 8.2%). Although we did not find any statistically significant correlation between gender, age, tumor anatomic localization, and Ki-67 expression, our study revealed that the mean Ki-67 LI for AMs was 8.7% (ranging from 6% to 15%) and was close to values obtained by other authors. In terms of gender distribution, we have noticed that AMs diagnosed in male patients had a mean Ki-67 LI almost equal to that in female patients even though some studies found Ki-67∕MIB-1 LIs significantly higher in male patients than in female patients. Also, we did not find any significant correlation between Ki-67 LI and tumor anatomic location as reported by other studies. CONCLUSIONS: Despite the fact that statistically we could not find any significant correlation regarding patients' gender and age, tumor anatomic location, and Ki-67 LI expressed by AMs, IHC detection of Ki-67 antigen remains an important tool in addition to routine histological evaluation, which can be used to predict tumor behavior of meningiomas.

Periocular basal cell carcinoma: demographic, clinical, histological and immunohistochemical evaluation of a series of 39 cases.

BACKGROUND: Basal cell carcinoma (BCC) is the most frequent malignant epithelial tumor of the periocular area. The clinical and histological classification of periocular basal cell carcinoma (pBCC) is essential in order to establish the risk of recurrence and to compare the results of the treatment. Until now, there is no unitary histological classification of pBCC. AIM: The aim of this study is to identify the demographic, clinical and histopathological characteristics of adult patients with pBCC, in order to obtain useful data for comparison in other investigations and to identify the histological origin of this eyelid tumor, as there are only hypothesis on this issue. MATERIALS AND METHODS: A descriptive retrospective study was conducted on a series of 39 consecutive patients over the age of 20, who were surgically treated for pBCC in the 2nd Ophthalmology Clinic of the "Prof. Dr. Nicolae Oblu" Emergency Clinical Hospital from Iasi, Romania, over an 11-year period (July 2007-February 2018). The analyzed data were the following: date of resection, patient age at resection, gender, tumor location, histological subtype, and immunohistochemical (IHC) expression patterns of anti-cytokeratin (CK) antibodies (anti-CK AE1∕AE3, anti-CK5∕6, anti-CK7, anti-CK17, anti-CK19, anti-CK20) and anti-epithelial membrane antigen (EMA) antibody. RESULTS: A total of 39 histopathologically diagnosed cases of pBCC were evaluated. The mean age at resection was of 66 years (range: 26-87 years). As for gender, 17 (43.6%) were male patients, with a mean age of 64.84 years (range: 26-78 years) and 22 (56.4%) were female patients, with a mean age of 66.68 years (range: 46-87 years). The pBCC occurred on the right side in 18 (46.2%) cases and on the left in 21 (53.8%) cases. Of all removed specimens, 24 (61.53%) involved the lower eyelid, seven (17.94%) the medial canthus, five (12.82%) the upper eyelid, and three (7.62%) lacked the specification of the site. The most common histological subtype was nodular, accounting for 26 (66.7%) cases. Adenoid BCC was identified in four (10.3%) cases, and morpheaform in one (2.6%) case. Squamous differentiation (basosquamous subtype) was identified in eight (20.5%) cases. The IHC profile of pBCC included: strong immunopositivity for CK AE1∕AE3, and CK17 all histological subtypes, and CK5∕6 positivity only in squamous differentiation areas. No immunopositivity was identified for CK19, CK20, and EMA IHC staining. CONCLUSIONS: Our retrospective study indicates that most of pBCCs developed particularly in elderly female patients and tumors were located in the lower eyelid with a left side and lower eyelid preferences. Most of our pBCC cases were histologically classified as nodular subtype, and morpheaform and basosquamous form affected mostly the lower eyelid. pBCC IHC profile showed a strong immunopositivity for CK17, thus suggesting that the origin of this cancer is in the follicular germinative cells. We can conclude that our results showed a demographic, clinical, histological, and IHC profile which seems to be representative for Central and Eastern European countries, maybe due to the same genetic predisposition and environmental factors.

Morphopathological particularities of cerebrovascular diseases for patients in the northeastern area of Romania.

Cerebrovascular diseases (CVD) are pathologies caused by the primary or secondary damage of one or more arteries supplying the brain. Our study aims to create a link between the modifiable risk factors, the affected vascular territory and the clinical manifestation of CVD in patients from our geographical area. Our study proposes the retrospective analysis of a group of 70 patients diagnosed with ischemic stroke with spontaneous hemorrhagic transformation over a period of five years, between April 1, 2015 and April 1, 2018, admitted in the 1st Neurology Clinic, "Prof. Dr. Nicolae Oblu" Clinical Emergency Hospital, Iasi, Romania. The pathology of strokes is determined by risk factors and comorbidities, which have a clear demographic pattern. The existence of a correlation between demographic risk factors of CVD and the clinical manifestation allows for the individualization of a clinical examination protocol leading to a rapid diagnosis.

The History of Arachne Through Historic Descriptions of Meningiomas with Hyperostosis: From Prehistory to the Present.

BACKGROUND: Intracranial meningiomas are brain tumors that have probably been known the longest, largely because of the occasional production of grotesque cranial deformities that have attracted the attention and interest of humankind. Because of the tendency of some intracranial meningiomas to cause skull deformation and thickening, these tumors have given rise to various speculations and theories related to their origin, starting in prehistoric times up to the present. METHODS: From the Steinheim skull and "pharaonic meningiomas" to the first meningioma monograph and the first explanations of Harvey Cushing regarding the mechanism of hyperostosis, this review aims to weave again the story of Arachne. We identify the main contributors who have tried to understand and explain the tendency of some of these tumors to cause hyperostosis or other skull bone involvements. CONCLUSIONS: The contribution of neurosurgeons or pathologists over the centuries is of undeniable importance and is the basis for understanding future molecular mechanisms.

Hydrocephalus of King Charles II of Spain, the Bewitched King.

King of the Spanish Habsburg dynasty and sovereign of the overseas Spanish Empire, Charles II of Spain, was physically disabled, disfigured, mentally retarded, and he proved impotent. He is known in history as El Hechizado (the Bewitched) because both him and the people believed that his mental and physical incapacity were due to a "witchcraft act." Although several authors speculated about different diseases, most of them genetic such as pituitary hormone deficiency, distal renal tubular acidosis, Klinefelter syndrome, fragile X syndrome, or male XX hermaphroditism, the hypothesis of hydrocephalus was not taken into account. We don't have clear elements to hypothesize a certain etiology of Charles II' hydrocephalus; however, we think the herpetic infection he suffered of after his birth should not be ignored.