Primitive neuroectodermal tumors of the ovary: a multidecade review of the scientific literature.

Primitive neuroectodermal tumor (PNET) is a general term used in scientific literature for a heterogeneous group of small round-cell malignant tumors primarily arising from neural crest cells. These are extremely aggressive neoplasms which usually occur within soft tissue or bone of young adults. Ovarian tumors composed of primitive neuroectodermal elements are extremely rare, with only few case reports in scientific literature. Due to being so exceedingly rare, PNETs are frequently misdiagnosed and there are no standard therapeutic guidelines. Young patients seem to have better prognoses and individualized strategy is recommended. Limited data suggests that various gene deletions as well as amplifications may be crucial factors for tumorigenesis and the aggressive behavior of PNET. In this paper, we performed a brief review of all cases of primary ovarian PNETs published in the scientific literature to date, in regard to their clinical, histopathological, and therapeutic aspects, with the aim to provide a more comprehensive understanding of this exceedingly rare pathology.

A Novel Algorithm for Evaluating Bone Metastatic Potential of Breast Cancer through Morphometry and Computational Mathematics.

Bone metastases represent about 70% of breast cancer metastases and are associated with worse prognosis as the tumor cells acquire more aggressive features. The selection and investigation of patients with a high risk of developing bone metastasis would have a significant impact on patients' management and survival. The patients were selected from the database of Carol Davila Clinical Nephrology Hospital of Bucharest. Their tumor specimens were pathologically processed, and a representative area was selected. This area was scanned using an Olympus VS200 slide scanner and further analyzed using QuPath software v0.4.4. A representative group of approximately 60-100 tumor cells was selected from each section, for which the following parameters were analyzed: nuclear area, nuclear perimeter, long axis and cell surface. Starting from these measurements, the following were calculated: the mean nuclear area and mean nuclear volume, the nucleus to cytoplasm ratio, the length of the two axes, the long axis to short axis ratio, the acyclicity and anellipticity grade and the mean internuclear distance. The tumor cells belonging to patients known to have bone metastasis seemed to have a lower nuclear area (<55 µm2, p = 0.0035), smaller long axis (<9 µm, p = 0.0015), smaller values for the small axis (<7 µm, p = 0.0008), smaller mean nuclear volume (<200 µm3, p = 0.0146) and lower mean internuclear distance (<10.5 µm, p = 0.0007) but a higher nucleus to cytoplasm ratio (>1.1, p = 0.0418), higher axis ratio (>1.2, p = 0.088), higher acyclicity grade (>1.145, p = 0.0857) and higher anellipticity grade (>1.14, p = 0.1362). These parameters can be used for the evaluation of risk category of developing bone metastases. These results can be useful for the evaluation of bone metastatic potential of breast cancer and for the selection of high-risk patients whose molecular profiles would require further investigations and evaluation.

A Systematic Approach of the Intrauterine Morphogenesis of the Human Palpebral Apparatus.

The human eyelid embodies a vast diversity of functions. Acting as a protective shield for the ocular apparatus and as a light regulator in the sight process, eyelids stand a fascinating - yet omitted - role in facial aesthetics, serving as a racial trait by which humankind succeeded to manifest heterogeneity as a species. These assumptions are precisely forecasted right from in-utero life through intricate processes of growth and cell differentiation. In the Department of Anatomy of "Carol Davila" University of Medicine and Pharmacy, we performed morphological assessments on 41 embryos and fetuses with gestational ages ranging from 6 to 29 weeks. This study aims to illustrate the morphogenesis of eyelids in human embryos and fetuses and highlight macroscopic features which could potentially have significant clinical implications in ophthalmic pathology.

Success rate of methotrexate in the conservative treatment of tubal ectopic pregnancies.

An ectopic pregnancy (EP) involves the implantation of the gestational sac outside the uterine cavity. In the event of diagnosing an EP, the current medical approach is to avoid surgery and to preserve fertility whenever possible; therefore, methotrexate (MTX)-based therapy has become prominent in recent years. MTX, a drug usually used to treat severe forms of autoimmune diseases and several types of cancer, has proven its utility in the conservative treatment of EPs. The success rate of MTX correlates with lower values of ß subunit of human chorionic gonadotropin hormone (ß-hCG) serum levels, especially below 2,000 mUI/ml, side effects being insignificant. In the present study, the results obtained concerning the success rate of MTX in the conservative treatment of EPs were obtained at the Department of Obstetrics and Gynecology of the Bucharest University Emergency Hospital from January 2014 to December 2020. The aim of the present study was to highlight the necessity for revising current guidelines for ectopic pregnancy medical treatment in order to manage this pathology optimally and to select carefully the proper treatment, whether medical, surgical or expectant management, so that morbidity is reduced to a minimum.

Polycythemia vera in pregnancy represents a challenge for a multidisciplinary collaboration: A case report and literature review.

Polycythemia vera (PV) is a rare chronic myeloproliferative neoplasm which represents an additional thrombotic factor in pregnancy. PV may be difficult to diagnose, particularly as its incidence is extremely uncommon among young women. The main diagnostic method involves a bone marrow biopsy, and high hemoglobin and platelet counts are usually indicative of the condition, after excluding other more frequent pathologies. PV is associated with a high risk of thrombosis, particularly in pregnancy, and requires anti-platelet treatment. At present, only a limited number of PV cases in pregnancy have been reported in the literature, at least to the best of our knowledge, with the largest case series being a retrospective study that included 25 pregnancies in 15 women. The present study describes the case of a patient diagnosed with JAK2-positive PV and also discusses this rare condition with particular focus on the following: i) The management of PV in pregnancy along with the additional pathologies in this specific case; and ii) the particularities of the pregnancy course. By identifying women suffering from PV superimposed by other possible procoagulant factors and applying the latest standard in healthcare, fetal and maternal prognosis may be significantly improved.

Emerging Therapeutic Concepts and Latest Diagnostic Advancements Regarding Neuroendocrine Tumors of the Gynecologic Tract.

Neuroendocrine neoplasms (NENs) are particularly rare in all sites of the gynecological tract and include a variety of neoplasms with variable prognosis, dependent on histologic subtype and site of origin. Following the expert consensus proposal of the International Agency for Research on Cancer (IARC), the approach in the latest World Health Organization (WHO) Classification System of the Female Genital Tumours is to use the same terminology for NENs at all body sites. The main concept of this novel classification framework is to align it to all other body sites and make a clear distinction between well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). The previous WHO Classification System of the Female Genital Tumours featured more or less the same principle, but used the terms 'low-grade neuroendocrine tumor' and 'high-grade neuroendocrine carcinoma'. Regardless of the terminology used, each of these two main categories include two distinct morphological subtypes: NETs are represented by typical and atypical carcinoid and NEC are represented by small cell neuroendocrine carcinoma (SCNEC) and large cell neuroendocrine carcinoma (LCNEC). High-grade NECs, especially small cell neuroendocrine carcinoma tends to be more frequent in the uterine cervix, followed by the endometrium, while low-grade NETs usually occur in the ovary. NENs of the vulva, vagina and fallopian tube are exceptionally rare, with scattered case reports in the scientific literature.

Ultrasound Pitfalls in a Complex Fetal Cardiac Malformation-Case Report of a New Arteriovenous Central Communication.

Cardiac and cardiovascular malformations are of real interest in terms of definition, epidemiology, and means of early diagnosis by imaging. Although ultrasound examination reaches exceptional performance nowadays, unusual pathologies are still exposed to the risk of either incorrect acquired image or misinterpretation by the specialist in a routine scan. Herein, we present a case of a 20-week-old fetus (from an apparently low-risk pregnancy) with complex cardiac and vascular abnormalities, including an arteriovenous malformation along with ventricular septal defect, ductal coarctation of the aorta, aneurysm of a brachiocephalic vein, and dilation of the entire neck and upper mediastinum venous system, and the limitations that were encountered in the process of diagnosis and management of the case.

A novel histopathological grading system for ganglioglioma.

Gangliogliomas are central nervous system tumors located in the temporal lobe of young patients, frequently associated with epilepsy. In this paper, we propose a grading system based solely on histopathological criteria. We reevaluated all cases of ganglioglioma, atypical ganglioglioma, and anaplastic ganglioglioma diagnosed between 2011 and 2020 in the Pathology Department of the Emergency Clinical Hospital Bagdasar-Arseni, based on the type of glial mitoses, the number of neuronal and glial mitoses, presence of necrosis, microvascular proliferation, eosinophilic granular bodies, hypercellularity, presence and disposition of inflammatory infiltrate and atypical pleomorphism. Based on the proposed grading system, a score of 0-4 corresponded to a benign ganglioglioma, 5-9 to an atypical ganglioglioma, and 10-18 to an anaplastic ganglioglioma. The survival rates were 90% for benign ganglioglioma, 71.43% for atypical ganglioglioma, and 62.54% for anaplastic ganglioglioma. One case of benign ganglioglioma underwent a malignant transformation into anaplastic ganglioglioma, and recurrences were noticed in 28.57% of atypical ganglioglioma cases and 30.7% of all anaplastic gangliogliomas. The presence of rare glial mitoses and hypercellularity was correlated with mortality in cases of atypical ganglioglioma. We believe this histopathological scoring system could be used as a three-tier system to identify atypical ganglioglioma cases that are bound to have an aggressive course of evolution and require close follow-up. The other option would be to convert it to a two-tier grading system that can separate low-grade gangliogliomas from high-grade ones. The latter category can encompass both atypical and anaplastic ganglioglioma due to the high mortality of both entities.

Glycogen-rich clear cell carcinoma of the breast with solid papillary pattern: Two cases with heterogeneous clinicopathological features.

Invasive breast cancer is a heterogeneous disease, both in its histopathological classification and clinical course. Glycogen-rich clear cell carcinoma of the breast is an extremely rare subtype of invasive breast carcinoma, accounting for up to 3% of all breast carcinomas. The tumor is composed of polygonal cells with abundant clear cytoplasm containing glycogen and has a very controversial prognosis. Solid papillary pattern is an uncommon morphological variant of breast carcinoma which is associated with indolent behavior in the absence of an invasive component. To date, there are only three cases of glycogen-rich clear cell carcinoma with solid papillary pattern reported in the English literature. In this article, we present two cases of glycogen-rich clear cell carcinoma of the breast, encountered in our daily clinical practice over a period of 5 years (2015-2020) and perform a brief review of currently published literature. Unlike most cases of glycogen-rich clear cell carcinoma documented to date, follow-up of our case featuring solid papillary pattern revealed extremely favorable clinical outcome, suggesting a better prognosis for tumors with this morphology.

Breast cancer mortality gaps in Romanian women compared to the EU after 10 years of accession: Is breast cancer screening a priority for action in Romania? (Review of the Statistics).

Breast cancer remains the most common cause of morbidity and mortality by cancer in females worldwide, even though it is largely preventable through population screening. Despite notable progress in the last years in the EU, breast cancer screening programs still maintain wide variations among countries and socio-economic groups. This statistical review aimed to investigate the breast cancer-related health gaps in Romanian women compared to the average EU female population after 10 years of accession (2007-2016). We evaluated breast cancer-related deaths, age-standardized mortality rates and contribution of breast cancer to life expectancy. Trends and percentage changes were compared between Romania and EU-27 for breast cancer, all cancer and all causes of mortality. We found a higher increase of breast cancer deaths in Romania, an increasing trend of mortality (opposite to EU) and a contribution to life expectancy at birth that increased gradually from 0.45 to 0 48 years. All these health gaps compared to EU are aggravated by the fact that no population screening for breast cancer is organized in the country. The opportunities for organizing such a program are consistent, but they should be increased in the future, in order to control the health gap between Romania and EU.

Implications of human T-lymphotropic virus in pregnancy: A case report and a review of the diagnostic criteria and management proposal.

Human T-lymphotropic virus (HTLV) is considered to be the most highly oncogenic existing virus, being the cause of several fatal diseases such as adult T cell leukemia-lymphoma (ATL) and HTLV-I-associated myelopathy (HAM). The main transmission methods are unprotected sexual intercourse, vertical transmission and breastfeeding and direct exposure to infected blood or tissue. The identification of infected mothers prior to delivery is a highly important step in preventing mother to child transmission. Universal antenatal screening for HTLV is not recommended in Romania, although there are sufficient data demonstrating the risk of vertical transmission. We present the case of an HTLV-1-infected pregnant woman, with an aim to highlight: i) points of strategy for the management of HTLV during pregnancy; ii) the particularities of the course of pregnancy; and iii) the aspects that show the importance of knowing the status regarding the HTLV infection antepartum. The case was particular due to the ascendant proviral load during the pregnancy period, which led to the initiation of antiretroviral therapy and the particular pregnancy outcome with preterm rupture of membranes and fetal growth restriction. According to current recommendations, pregnant women infected with HTLV-1 should be advised to refrain from donating blood, body organs, or other tissues. There is no evidence of the number of individuals infected with this virus in Romania at present, and the diagnosis can only occur by chance. A specific treatment or immunization for HTLV infection does not currently exist, thus preventive methods are the only tool to reduce the prevalence and mortality of this infection.

Prenatal Ultrasound Diagnosis of Double Aortic Arch versus Right Aortic Arch Variant in Vascular Ring Formation - Case Report and Review of the Literature.

Double aortic arch represents a congenital vascular malformation that is characterized by the development of a complete vascular ring around the esophagus and trachea due to an anomaly in the development of branchial arteries. We present the case of a 31-year-old gravida that was referred for fetal ultrasound anomalies screening at 22 weeks and six days of gestation. Routine ultrasound scanning of the fetus revealed a structural aortic arch anomaly consistent with a double aortic arch, with no other cardiac and diextracardiac congenital structural malformations. Knowledge of embryology and imaging spectrum of aortic arch anomalies that are able to form vascular rings around the trachea and esophagus are essential for an accurate antenatal diagnosis and therefore, for a correct clinical management.

VACTERL association in a fetus with multiple congenital malformations - Case report.

VACTERL represents an acronym for a broad spectrum of congenital anomalies such as vertebral anomalies, anorectal anomalies (anal atresia), cardiac anomalies, tracheoesophageal fistula or atresia, renal anomalies, and limb anomalies. We present the case of a male fetus with multiple anomalies consistent with VACTERL association such as scoliosis, imperforate anus, common truncus arteriosus, tracheoesophageal fistula associated with inferior esophagus atresia, polycystic kidneys, with short right ureter, lower limb hypoplasia micrognathia, hygroma, duodenal atresia, and cloacal malformation, with an aberrant omphalomesenteric duct. The presented case highlights the crucial importance of pathologists specialized in the dissection and confirmation of fetal abnormalities as an essential part of the multidisciplinary team that establishes the management of complicated pregnancies with this type of pathology.

Practical aspects regarding the histopathological grading and anaplastic transformation of gangliogliomas - a literature review.

Ganglioglioma represents a benign central nervous tumor, occurring predominantly in the pediatric population and affecting the temporal lobe. It is also renowned for its epileptogenic potential. However, to date, there are numerous uncertain features about this tumor, especially about its grading system. In the former World Health Organization (WHO) Classification of central nervous tumors system, gangliogliomas could have been attributed one out of three grades: grade I (benign), grade II (atypical), and grade III (anaplastic). The new classification systems have renounced to atypical ganglioglioma nomenclature, due to the lack of histopathological criteria for this entity. Another controversial aspect of grade I ganglioglioma is its potential to transform into a malignant tumor, namely, most frequently an anaplastic ganglioglioma. Based on our knowledge, there are no literature reviews to date focusing on anaplastic transformation potential. The present paper encompasses all anaplastic transformation of gangliogliomas and has analyzed the time frame between the two events, the age of the patients and its relationship to the complete or subtotal resection and administration of radiotherapy. Thirty-three cases of malignant transformation of ganglioglioma have been reported so far in the literature, with 54.54% of them undergoing progression to anaplastic ganglioglioma and 21.21% to anaplastic ganglioglioma. Median age was 26 years, and the cases were evenly distributed between the two genres. Only 27.27% of all evaluated cases had been administrated adjuvant radiotherapy, and only 44% of the latter have had an incomplete tumoral resection.

Peripheral-type primitive neuroectodermal tumor of the ovary with EWSR1-FLI1 fusion transcript: a case report and brief review of literature.

Primitive neuroectodermal tumors (PNETs) of the ovary are extremely rare tumors composed of undifferentiated small cells with round nuclei and scant cytoplasm. They are rare in general and extremely rare in the female gynecological tract, where they most commonly affect the ovary, followed by the uterine corpus. The most common presenting symptoms are abdominal pain, bloating and the presence of a pelvic mass. Diagnosis mainly relies on immunohistochemical and fluorescence in situ hybridization (FISH). Due to the rarity of these tumors, there are no standard therapeutic guidelines and treatment consists of surgery, various chemotherapy regimens and/or radiotherapy. In this article, we report the case of a 30-year-old female with peripheral-type PNET (pPNET) of the ovary featuring Ewing sarcoma breakpoint region 1-Friend leukemia integration 1 (EWSR1-FLI1) fusion transcript, confirmed by next-generation sequencing (NGS).

Ductus venosus reversed flow in omphalocele: Could it be a prognostic factor for long-term neurological impairment?

Omphalocele (exomphalos) represents one of the most frequent congenital abdominal wall defects. It presents as a defect of inconstant size and is located on the midline, at the base of the umbilical cord, the skin, fascia, and abdominal muscles being absent at this level. Omphaloceles are classified as liver-containing or non-liver-containing, the latter containing primarily bowel loops. We present the case of a 37-year-old pregnant woman with an early diagnosis of liver-containing omphalocele associating ductus venosus reversed flow, with the aim to highlight the importance of the first-trimester morphology scan and to develop a pilot study regarding the neurological development of infants after surgical repair of giant omphaloceles. The particularity of this case consists of a fetus with a positive diagnosis of a giant liver-containing omphalocele but with a small abdominal wall defect during the first-trimester morphology scan at 13 weeks and 3 days of gestation which associated ductus venosus reversed flow, presenting a normal karyotype postabortum. With a small defect, we can speculate the risk of strangling besides the mechanical traction exercised on the ductus venosus generating fetal distress, specifically fetal hypoxia at an early gestational age. In conclusion, the main issue, in this case, was if the fetal omphalocele and ductus venosus reversed flow indicated fetal hypoxia, what was the obstruction effect on the oxygenated blood pathway caused by the abdominal defect, and which were the long-term effects on infants with this complex pathology with an unknown outcome.

Novel Perspectives Regarding CD34 Immunoexpression Patterns in Gangliogliomas.

Gangliogliomas are extremely rare central nervous tumors composed of an admixture of glial and neuroepithelial elements. Gangliogliomas mainly affect the temporal lobe and occur in the pediatric population. There are several controversies in the scientific literature regarding these tumors, which debuted with the exclusion of grade II gangliogliomas in the 2006 edition of the current World Health Organization (WHO) classification. The upcoming edition due in the last months of 2021 is not expected to include changes regarding the current classification of glio-neuronal tumors. This vision has led to a number of articles that have pushed for the reintroduction of this category. However, these articles support the reintroduction of this degree in terms of prognosis and evolution, without providing clear criteria for the inclusion of certain gangliogliomas in this category. On the other hand, there are uncertainties about the relationship of gangliogliomas with focal cortical dysplasia. The coexistence of the two entities, as well as their succession are occasionally encountered in practice and have led to numerous studies that have tried to clarify the relationship between them. The most common and most accessible element in routine practice is the immunoreactivity for CD34. Both entities express this marker, and dual lesions express the highest percentage of immunoreactivity for CD34. In this article, we study the expression of CD34 on a series of cases including both grade I gangliogliomas and anaplastic gangliogliomas diagnosed between 2011 and 2020 in a Neuropathology Unit in Bucharest Romania.

Congenital systemic candidiasis: a comprehensive literature review and meta-analysis of 44 cases.

Systemic candidiasis is a frequent complication in neonatal units, but congenital systemic candidiasis is an unusual diagnosis, observed in both full-term and preterm infants, with less than 50 cases reported to date. Congenital candidiasis presents with a wide spectrum of symptoms, ranging from diffuse skin eruptions to severe systemic disease, resulting in fetal demise or early neonatal death. Although management guidelines have been published almost two decades ago, due to the rarity of this type of infection, conclusive recommendations are difficult to establish, since they are based on anecdotal experience. In this paper, we present a comprehensive meta-analysis of the current scientific knowledge regarding congenital candidiasis, which spans 54 years and includes a total of 44 cases.

Case report of a novel phenotype in 18q deletion syndrome.

The latest decades are characterized by an enormous progression in the field of human genetics. In consequences, for various phenotypic manifestations, genetic testing could identify a specific underlying cause. An estimated incidence for all types of 18q deletions is one in 55 000 births predominant on females. About 94% of cases with 18q deletion syndrome appearance are de novo, and the remaining 6% are the inherited from a parent carrying a balanced chromosomal translocation. We present the case of a 35-year-old female who was admitted in our Unit for a second ultrasound opinion after being diagnosed at the second trimester scan at gestational age of 21 weeks of pregnancy with multiple brain and heart malformations, having the recommendation for fetal magnetic resonance imaging (MRI). Further investigations included genetic analysis and pathological examination. Major malformations diagnosed and confirmed were agenesis of the corpus callosum, ventriculomegaly with dilated fourth ventricle, partial agenesis of vermis, bilateral anophthalmia with wide nasal base and left cleft lip. Additional, cardiac malformation, with an important ventricular septal defect and overriding aorta were noted. The results of the microarray analysis showed an abnormal fetal karyotype with a loss of 30.5 basis identified in the long arm of chromosome 18. Although most of the cases of 18q deletion are sporadically or de novo, could be cases where the possible existing syndromes can be inherited from a healthy or mild affected parent. Therefore, in order to establish the recurrence risk, parental karyotypes are recommended.

The etiopathogenic and morphological spectrum of anencephaly: a comprehensive review of literature.

Anencephaly is a severe malformation of the central nervous system (CNS), being one of the most common types of neural tube defects. It is defined as total or partial absence of the calvarium, with absence of the brain. Anencephaly has an incidence of 1 to 5 in every 1000 births, and the mortality rate is 100% during intrauterine life or within hours or days after birth. The etiology of anencephaly remains unclear, but various maternal-related environmental and genetic risk factors have been reported, which include diabetes, obesity, exposure to different drugs or toxins, genetic polymorphisms and mutations, as well as positive family history for neural tube defects. One of the most important nutritional factors in the development of anencephaly is folate deficiency. Methylenetetrahydrofolate reductase (MTHFR) gene codes the enzyme involved in the intracellular metabolism of folic acid; the 677C-T polymorphism of this gene causes the thermolability of the enzyme and decreased enzymatic activity, which is also dependent of folate plasmatic level. Etiopathogenesis of anencephaly includes several mutations in various other genes, such as: platelet-derived growth factor receptor alpha (PDGFRA), cadherin epidermal growth factor (EGF) laminin G (LAG) seven-pass G-type receptor 1 (CELSR1), Vang-like 1 (VANGL1) and Vang-like 2 (VANGL2), the last two being involved in the process of neurulation. Screening tests include maternal serum alpha-fetoprotein level and ultrasound (US) examination. During the first trimester US screening, anencephaly is now detected in all cases, but in order to decrease the complication rate of pregnancy termination, the diagnosis should be established as soon as possible, during the pregnancy confirmation US. We conclude that given that anencephaly is a severe malformation of the CNS, morphological characterization could improve the screening by US that is mandatory in the first trimester in order to plan the best, safe and early management.