Epidemiological and histopathological aspects of ocular melanomas in Northeastern Romania.

Ocular melanoma is a rare but complex disease in current medical practice. Our retrospective study spans over a period of 28 years and analyzed uveal and conjunctival melanomas that were consecutively admitted, diagnosed, and treated in the 2nd Ophthalmology Clinic of Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iasi, Romania. The patients were selected from the records of the Department of Pathology of our Hospital, being diagnosed by standard histopathological techniques. The aim of this study was to summarize the epidemiological and pathological aspects of uveal and conjunctival melanomas in Northeastern region of Romania. In our study, we did not notice a predilection of uveal and conjunctival melanoma to one particular gender. The most common histological subtypes of ocular melanomas were the heavily pigmented spindle cell subtype, followed by the epithelioid subtype. Our patients sought medical help in a timely manner, before the systemic invasion of the disease could develop.

Predictor factors for recurrence in atypical meningiomas.

BACKGROUND AND OBJECTIVES: Atypical meningiomas (AMs), World Health Organization (WHO) grade 2, are a group of tumors with uneven and unpredictable clinical behavior. Our aim was to analyze possible tumor recurrence predictors, and to identify factors that improve progression-free survival (PFS). PATIENTS, MATERIALS AND METHODS: Our retrospective study included 81 patients followed up in the Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iasi, Romania, between 1 January 2010 and 31 December 2020. The histopathological specimens were reviewed according to the WHO 2021 criteria. Analyses included clinical, imaging, pathological and surgical factors. RESULTS: The tumor recurred in 53.1% of the 81 cases within 60 months of surgery. Tumor location (p<0.000), tumor volume (p<0.010), extent of surgical resection (p<0.000) and dural sinus invasion (p<0.001) were predictive factors of recurrence. Gross total resection (Simpson grade I and II) was achieved in 59.2% of patients. Patients with the tumors located in the brain convexity and volume <26.4 cm³ had better survival rates up to recurrence. PFS showed a significant relationship between Simpson grade I-III and biopsy (p<0.000) and was statistically influenced by tumor volume and location, and dural sinus invasion. CONCLUSIONS: AMs are a heterogeneous group of tumors, and we identified posterior fossa location, volume ≥26.4 cm³, Simpson grade III and IV resection and dural sinus invasion as predictive factors for relapse and a shorter PFS. Whereas certain characteristics provide some prognostic value, future molecular characterizations of AMs are necessary, which will support the clinical decision-making process.

Epidemiological and pathological characteristics of spinal metastases from gastrointestinal cancers - a series of 40 cases.

Spinal metastases from gastrointestinal (GI) cancer are rare and as a result there are only case reports or small series in the literature. The aim of our work was to identify the demographic aspects, the location, and the histopathological aspects of spinal metastases from GI cancers diagnosed and treated in a reference Hospital in Romania over a period of nine years, and comparing the data obtained with those from the recent literature. This is a retrospective case series study on spinal metastases from GI cancers, developed in patients older than 18 years that were surgically treated between January 2013 and December 2021 within three Neurosurgery Clinics from Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iasi, Romania, which is a tertiary Hospital in Romania regarding the surgical treatment of spinal metastases. We included in our study the patient's demographic data (age and gender), clinical data (location of spinal metastases), radiological investigations and pathological features of the lesions. Regarding the immunohistochemical stainings, the following antibodies were used: anti-cytokeratin (CK)7, anti-CK20, anti-CK19, anti-caudal-type homeobox 2 (CDX2), anti-human epidermal growth factor receptor 2 (HER2), and anti-Ki67. Our series included 40 adult patients (≥18 years old) with a male:female ratio of 3:1, in favor of male patients. The mean age of all patients was 66.42 years. The primary sites of spinal metastases from GI cancers were from all segments of the GI system: the most frequent, however, was from the colorectal level (40%) and the least from the oral cavity level (2.5%). The most common site of spinal metastases from GI cancer was predominantly lumbar region (47.5%), and the most frequent histological type was adenocarcinoma (57.5%), followed by hepatocellular carcinoma (27.5%), pancreatic ductal carcinoma (5%) and squamous cell carcinoma (2.5%). Our results have important clinical implications because they suggest that there are certain subsets of patients with certain types of GI cancers that cause metastases in certain regions of the spine.

Cervico-Dorsal Intramedullary Spinal Cord Abscess with Aspergillus fumigates following Pulmonary Infection in an Immunocompetent Patient.

Invasive forms of aspergillosis of the nervous system are relatively rare and are usually diagnosed in immunocompromised patients. We present the case of a young female patient, treated in the last two months with corticosteroids and antifungal drug for pulmonary aspergillosis, who developed progressive paraparesis. An intramedullary abscess at the C7-D1 level was identified and the lesion was treated with a combination of surgery and antifungal therapy. Histopathologic findings of surgical specimens showed myelomalacia with Aspergillus hyphae and a peripheral rim of neutrophils. We consider that the use of multiple drugs and corticosteroids for our patient's initial community pneumonia could be the factor that transformed her into a mildly immunocompromised individual and permitted the Aspergillus spp. to disseminate through the blood and into the spinal cord. Moreover, we highlight the fact that more attention should be paid to living and working conditions of the patients, as a simple colonization of the lung with Aspergillus spp. could develop, in a short time, into an invasive disease with a high risk of mortality.

Clinicopathological characteristics and prognostic factors of atypical meningiomas with bone invasion: a retrospective analysis of nine cases and literature review.

BACKGROUND: Meningiomas are the most common primary neoplasms of the central nervous system in adults, arising from the arachnoid cap cells. Thus, grade 2 meningiomas are situated on the border between benignity and malignancy. Among the many prognostic factors that have been investigated in these tumors, bone invasion is one of them. OBJECTIVE: The aim of our study was to identify whether bone invasion influences tumor recurrence and progression-free survival (PFS) in patients with atypical meningiomas (AMs). PATIENTS, MATERIALS AND METHODS: Out of 81 patients with AMs followed over a period of five years, we identified nine patients with bone invasion. We analyzed their demographic, clinical, imaging, and pathological characteristics, such as age, gender, radiological aspects, morphological features, extent of resection, recurrence rate, and PFS over a follow-up period of 60 months. Bone invasion was determined based on preoperative, surgical, and pathological reports. RESULTS: Out of the nine patients with bone invasion, four had convexity meningiomas, four had parasagittal meningiomas and one had a falcine meningioma. Regarding tumor recurrence∕progression, most patients (n=6) recurred within the first 24 months after surgery. Our study showed that the early recurrence/progression of tumor (at 12 months) correlated with extensive presence of malignancy criteria, especially with the presence of 15-18 mitoses∕10 high-power fields, as well as with large foci of spontaneous necrosis, but also with tumor bone infiltration, extensive bone lamellae destruction, and tumor infiltration of adjacent muscle with its atrophy due to tumor compression. Patients with bone invasion had a PFS of 29.3 months, compared to patients without invasion who had a higher PFS (49.3 months). Significant statistical associations were observed between bone invasion and tumor recurrence (p=0.002) and PFS (p=0.004). CONCLUSIONS: Our study emphasizes the importance of a thorough histopathological examination of the surgical specimen, which can provide significant data for the assessment of the progression of an AM [World Health Organization (WHO) grade 2] with bone invasion. AM infiltration in adjacent bone and muscle increases the rate of tumor recurrence and decreases PFS over a follow-up period of 60 months.

Humps and bumps of head: review of meningiomas of the scalp.

Meningiomas are a type of tumor that arises from meningothelial cells and primarily develops in intracranial space, being some of the most common benign tumors of the central nervous system. However, meningiomas can rarely occur on the scalp and are called primary cutaneous meningiomas. Since the pathogenesis of these lesions is still uncertain, these tumors still pose challenges in terms of histopathological diagnosis. In this review, we will discuss the main cases of scalp meningiomas in the literature, their classification, pathological and immunohistochemical diagnosis, differential diagnosis with other scalp lesions and the most effective treatment. This study highlights the importance of immunohistochemistry in the differential diagnosis of skin lesions located on the scalp.

Anatomical study of circle of Willis on fresh autopsied brains. A study of a Romanian population.

Because the circle of Willis (CoW) supplies blood to the brain in case of occlusion of one of the cerebral arteries, identification of any change in its classical shape could be useful in the assessment of cerebrovascular morbidity. The purpose of our research was to study the anatomical variants of CoW identified on fresh brains obtained at the clinical autopsies of adult deceased patients belonging to a specific population (Northeastern region of Romania), as no data are available for Romania population up to date. The study group included consecutive patients who died in Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iasi, Romania, due to medical causes between January 1, 2014 and June 30, 2016, to whom a clinical autopsy was performed. From a total of 96 circles of Willis, 29.17% presented an atypical morphology. We identified eight types of anatomical variants, which affected simultaneously both the posterior and the anterior parts of CoW in 46.42% of cases. The most frequent anatomical variants were hypoplasia (20.91%), followed by the absence of an artery (3.06%), and partially fetal type artery (2.04%). 67.86% of atypical CoW exhibited more than one anatomical variant of an artery in one circle. We identified nine of the 23 morphological patterns that were published to date, and also nine new types. Our research proved that in the population living in the Northeastern part of Romania the anatomical variations of circles of Willis are very polymorphic, with particular morphological aspects.

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.

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.

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.

Clinical and immunohistopathological study of conjunctival melanocytic lesions in pediatric and adolescent patients. A case series.

BACKGROUND: Conjunctival pigmented neoplasia can be benign, premalignant or malignant tumors. Our study aims to establish the epidemiological, gross morphological and immunohistopathological features of the conjunctival pigmented lesions in pediatric and adolescent patients (<18 years), to establish an accurate diagnosis. PATIENTS, MATERIAL AND METHODS: This is a retrospective case series study conducted within two Ophthalmology Clinics from Iasi, Romania, on seven pediatric and adolescent patients. Using the Clinical Observation Chart and the Pathology Registers over a six-years period (January 2015-December 2021), we noted the patients' demographic data, clinical data, and ophthalmological investigations of the lesion, as well as the type of their treatment. All histological sections stained with Hematoxylin-Eosin (HE) and with five antibodies [pan-cytokeratin (pan-CK) AE1∕AE3, S100 protein, Melan A, human melanoma black 45 (HMB45), and Ki67] were re-examined by four pathologists for each case, to identify the type of the conjunctival lesion and its histological and immunohistochemical features. RESULTS: The mean age of all patients was 10.28 years, and the female∕male ratio was 1.3. Right eye was more often affected (71.42%). 71.42% of cases presented an elevated lesion, 57.14% of cases showed a lightly pigmented lesion, but 14.28% of cases exhibited a pink lesion and this feature described the inflamed juvenile conjunctival nevus. In all cases (100%) the conjunctival pigmented tumor was removed with safety margins. The microscopic examination revealed a compound melanocytic nevus in 57.14% cases, a junctional conjunctival nevus in 14.28% cases, an inflamed juvenile nevus in 14.28% cases, and a conjunctival melanoma arising from a pre-existing nevus in 14.28% cases. In all cases of nevi, the nevoid melanocytes showed strong immunopositivity for Melan A and S100 protein, variable and weak immunopositivity for HMB45, and a mean Ki67 labeling index of 1.71%. Conjunctival melanoma revealed strong immunopositivity of tumor cells for HMB45, Melan A and S100 protein, and a Ki67 labeling index of 20%. In all cases, the conjunctival epithelium showed strong immunopositivity for pan-CK AE1∕AE3. All our cases (100%) had a favorable outcome after the surgical removal of the tumor. CONCLUSIONS: Any excision of a conjunctival pigmented lesion must be subject to a systematic immunohistopathological examination, and there is a set of antibodies (anti-HMB45 and anti-Ki67) that are useful for differential diagnosis between a conjunctival nevus and a conjunctival melanoma.

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 significance of erythropoietin and insulin administration on survival of fat tissue after autologous fat transplantation in Wistar rats. An experimental study.

Autologous fat transfer is widely used by plastic surgeons for aesthetic and reconstructive purpose, but it has a great disadvantage because of its high variability rate of resorption. Numerous studies have examined the use of different agents to increase the viability of fat grafts. The results were discouraging because the use of a single angiogenic factor to stimulate fat graft angiogenesis may be inappropriate. We proposed to use two pharmacological factors, erythropoietin (EPO) and insulin (INS), in order to decrease the resorption rate, to improve graft vascularization, and to reduce the number of complications. Twenty-four Wistar male rats were randomly divided in four groups (I-IV) of six animals each. The rats belonging to control group were given autologous transfer of simple fat. In group II, the graft was improved with EPO, in group III with INS, and in group IV both pharmacological agents were administered. Histological evaluation of the grafts at two months after injection demonstrated adipocyte survival in all four groups. The volume of the graft has progressively decreased in all groups and the difference in graft volume at one and two months after transplantation was not significant. The highest maintenance of fat graft volume (95%) at two months was observed in group IV, followed by group II and group III. Necrotic cystic changes and increased fibrosis were most extensive in the control group. The combination of INS with EPO may have a synergistic and additive effect. Efficient administration and dose optimization of these growth factors are important things to consider in the future.

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.

Clinical-pathological correlations in Warthin tumors of parotid gland: a series of 10 cases.

Warthin tumor is described using various terms, such as papillary cystadenoma lymphomatosum, adenolymphoma or monomorphic adenoma. It is a medical condition related to the salivary glands, namely a benign cystic tumor which contains an epithelial component and an abundant lymphoid stroma. It is also named Warthin tumor after Aldred Scott Warthin, the pathologist who described this entity in 1929 by observing it in two patients. Warthin tumor is a benign one and ranks secondly in terms of the most common not malignant salivary gland tumor located in the parotid gland. Because of its cystic nature, from the clinical point of view, it appears to be a slow-growing tumor often fluctuant on palpation. In terms of the treatment of choice, complete excision with wide tumor-free margins is preferred. The aim of the present article is to evaluate possible correlations between clinical-pathological features and postoperative complications in a target group made up of 10 patients diagnosed with Warthin tumor of the parotid gland admitted for surgery in a period of 21 years and to compare the results with literature.

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.