ROMANIAN JOURNAL of MORPHOLOGY and EMBRYOLOGY

Vol. 61 No. 1, January-March 2020

1. Rare retroperitoneal conditions that mimic uterine myoma

Razvan Mihai Popovici, Alexandru Carauleanu, Claudia Florida Costea, Irina Daniela Florea, Dragos Viorel Scripcariu, Raluca Anamaria Mogos, Ali Cheaito, Adina Elena Tanase, Raluca Maria Haba, Mihaela Grigore

The most frequent tumoral condition of the uterus is represented by uterine myoma. The diagnosis, in most cases, is established by clinical examination and ultrasound scan. Nevertheless, there are rare cases, in which the surgical findings reveal a retroperitoneal tumor instead of a uterine myoma. These could be represented by schwannomas or Castleman disease. The schwannomas are rarely malignant and arise from the Schwann cells of nerve fibers. These tumors are frequently found at the level of the head, neck and mediastinum and rarely in the pelvis. Generally, schwannomas localized at retroperitoneal level are asymptomatic and with a very slow growth rate. The treatment consists in complete surgical resection. The recurrence rate is low and, generally, the prognosis is good. The Castleman disease is considered a rare entity, but it should be always taken into consideration when it comes to a differential diagnosis in a young patient who presents a retroperitoneal mass at imagery exams. The condition affects the lymphatic system and is characterized by a hyperplasia of the lymph nodes, sometimes associated with herpes virus infection. The clinical picture is often non-specific; the pain may be the only symptom. The imaging methods are not always conclusive for the final positive diagnosis and the histopathological examination is always necessary. Pelvic Castleman disease can be misdiagnosed as myoma or an adnexal tumor. In this article, we review the present knowledge regarding the pathogenesis, pathology and management of these rare retroperitoneal tumors. Both conditions, when located in pelvis must be taken into consideration in the differential diagnosis of uterine myomas, especially in the pedunculated form.

Corresponding author: Claudia Florida Costea, Associate Professor, MD, PhD; e-mail: costea10@yahoo.com; Alexandru Carauleanu, Senior Lecturer, MD, PhD; e-mail: acarauleanu@yahoo.com

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2. Microfluidic endothelium-on-a-chip development, from in vivo to in vitro experimental models

Adriana-Elena Bulboaca, Paul Mihai Boarescu, Carmen Stanca Melincovici, Carmen Mihaela Mihu

In the last years, animal testing in medical research has been a controversial topic because of various reasons, such as ethical considerations and species differences. Therefore, more attention has been given to develop new technologies that can replace animal experiments and create in vitro models. Organ-on-a-chip (OOC) technology is a new and advanced technology based on microfluidic devices that can mimic the structure and function of entire organs and tissues as in vitro models. OOC models are miniature tissues and organs that assign characteristics for three-dimensional (3D) cell culture representation that resemble the original organs, together with their specific microenvironment microfluidic systems and specific biophysical processes, in order to mimic the normal physiological conditions and functionalities of the organs. Existing OOC models, such as liver, pancreas, heart, skin, brain, kidney, vessels, have been developed and designed for a specific function study. This review focuses on the main knowledge concerning OOC research and especially vascular endothelium-on-a-chip (EOC) model, developed in order to offer specific tools for studying vascular functions in physiological and pathological conditions. The field of OOC devices is still at the beginning, but in the future, this technology may have important roles in developing novel therapeutic approaches, offering new therapeutic molecules and providing the first step towards personalized medicine.

Corresponding author: Carmen Stanca Melincovici, Lecturer, MD, PhD; e-mail: cmelincovici@yahoo.com

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3. Genetic aspects in schizophrenia. Receptoral theories. Metabolic theories

Simona Corina Trifu, Anca Vladuti, Antonia Ioana Trifu

Ties between schizophrenia (SCZ) and genetics are undeniably significant issue prone to be discussed in the nowadays psychology. Recent research on this domain focuses more on specific genes and heredity (specifically monozygotic pairs of twins) for diagnosing SCZ, than on environmental influences. SCZ is considered a multifactorial disease, thought to convert from a merger of risk and biological genes and environmental factors that could alter and reshape the trajectory of brain development. On this regard, this review sums up recent and innovative methods of distinguishing schizophrenic features from other mental illnesses in patients, based on chromosomal and genes changes. The term reverse genetics is no longer up to date, being replaced with genome scanning and positional cloning. For many researchers, genome scanning is continuing the reverse of the sensible strategy for detecting various important biological disorders, which may start from the discovery of a protein or any other molecule involved in a biological process, being followed by its gene cloning. Genes being discovered in this manner could become candidate genes for the disease. However, genome scanning occurs through testing each chromosomal segment (or mitochondrial genome) for the counter transmission of the disease.

Corresponding author: Simona Corina Trifu, Lecturer, PhD; e-mail: simonatrifu@yahoo.com

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4. Host immune response in chronic hepatitis C infection: involvement of cytokines and inflammasomes

Mihail Virgil Boldeanu, Isabela Silosi, Andreea Lili Barbulescu, Raluca Elena Sandu, Cristiana Geormaneanu, Vlad Padureanu, Mircea Vasile Popescu-Driga, Ioan Sabin Poenariu, Cristian Adrian Silosi, Anca Marilena Ungureanu, Anda Lorena Dijmarescu, Lidia Boldeanu

Chronic liver disease is a major health issue worldwide and chronic hepatitis C (CHC) is associated with an increased risk of cirrhosis and hepatocellular carcinoma (HCC). There is evidence that the hepatitis C virus (HCV) infection is correlated with immune senescence by way of immune activation and chronic inflammation, which lead to increased metabolic and cardiovascular risk, as well as progressive liver damage. Both the innate and adaptive immunity are firmly tied to the prognosis of an infection with HCV and its response to antiviral therapy. HCV is therefore associated with increased pro-inflammatory status, heightened production of cytokines, prolonged systemic inflammation, as well as increased morbidity and mortality, mainly due to the progression of hepatic fibrosis and HCC, but also secondary to cardiovascular diseases. Viral hepatic pathology is increasingly considered a disease that is no longer merely limited to the liver, but one with multiple metabolic consequences. Numerous in vitro studies, using experimental models of acute or chronic inflammation of the liver, has brought new information on immunopathological mechanisms resulting from viral infections and have highlighted the importance of involving complex structures, inflammasomes complex, in these mechanisms, in addition to the involvement of numerous proinflammatory cytokines. Beyond obtaining a sustained viral response and halting the aforementioned hepatic fibrosis, the current therapeutic treat-to-target strategies are presently focused on immune-mediated and metabolic disorders, to improve the quality of life and long-term prognosis of CHC patients.

Corresponding author: Andreea Lili Barbulescu, Lecturer, MD, PhD; e-mail: anbarbulescu@gmail.com; Cristian Adrian Silosi, Lecturer, MD, PhD; e-mail: cristian_silosi@yahoo.fr

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5. Abdominal wall endometriosis versus desmoid tumor - a challenging differential diagnosis

Alexandru Carauleanu, Razvan Mihai Popovici, Claudia Florida Costea, Raluca Anamaria Mogos, Dragos Viorel Scripcariu, Irina Daniela Florea, Ali Cheaito, Adina Elena Tanase, Raluca Maria Haba, Mihaela Grigore

Aim: Abdominal wall endometriosis (AWE) in young women, with previous gynecological abdominal surgery, is the first condition considered by many practitioners when a tumor in the region of the scar appears. AWE seems to be caused by an iatrogenic transfer of endometrial cells at the level of the scar. The onset of the disease may be late in many cases. Despite the fact that the disease could be totally asymptomatic, there are certain risk factors that can be identified during the anamnesis, such as: heredity, menarche at the age of >14 years, menstrual cycle <27 days, delayed menopause, excessive alcohol and caffeine consumption. Suggestive signs include cyclic or continuous abdominal pain caused by a palpable abdominal wall mass with a maximum tenderness in the region of the surgical scar. The differential diagnosis is complex and rare entities like desmoid tumors (DTs) must be taken into consideration. Desmoid tumor, or the so-called aggressive fibromatosis (AF), is a rare fibroblastic proliferation. This tumor can develop in any muscular aponeurotic structure of the body and is considered benign but with a high recurrence rate. DTs can cause local infiltration, subsequently producing certain levels of deformity and potential obstruction of vital structures and organs. The differential diagnosis is challenging in this situations, the imagery exams are useful, especially in detecting the precise location of the tumor. The histological examination of the tumor can state the final and precise diagnosis.

Corresponding author: Claudia Florida Costea, Associate Professor, MD, PhD; e-mail: costea10@yahoo.com; Razvan Mihai Popovici, Assistant, MD, PhD; e-mail: razpopovici@yahoo.com

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6. Morphopathological changes in obsessive-compulsive disorder

Ana Miruna Dragoi, Loredana-Georgiana Pecie, Bogdan-Eduard Patrichi, Maria Ladea

The pathophysiology of the obsessive-compulsive disorder (OCD) has been studied for many years using several structural magnetic resonance imaging, discovering that the anomalies of function and structure of the brain are widespread, they involve different areas, structures and circuits with a complex interconnectivity. More than that, these anomalies cover all the life of a patient, from early childhood, due to variations of developmental stages until adult life. The research is highly important also because OCD has a major hereditary factor, with the phenotype variance between 27-47% due to hereditary factors. Under this paper, that follows last 10 years studies in this area, we will find some relevant findings consisting on neuroanatomic changes, the morphology findings of striatum, globus pallidus and thalamus, the blood flow circuit changes in various regions of the brain, brain connectivity and various correlations of them. Not to forget that OCD must be understand as an emotional disorder but in the same time as a cognitive disorder too. This approach highlights the abnormalities that have been found in brain regions involved in the cognitive and emotional behavior, as for example: extended temporal, parietal, and occipital regions, anterior cingulate, frontal gyrus, amygdala.

Corresponding author: Ana Miruna Dragoi; e-mail: anamirunadragoi@gmail.com

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7. Mild TBI in the elderly - risk factor for rapid cognitive impairment in Alzheimer s disease

Puiu Olivian Stovicek, Carol Friedmann, Dragos Marinescu, Ion Alexandru Vaduva, Simona Bondari, Simona Corina Trifu, Ileana Marinescu

In recent decades, traumatic brain injury (TBI) has become one of the most important health problems worldwide and is a major cause of morbidity, mortality and economic losses. Mild traumatic brain injury (mTBI) is less considered, with clinical underestimation leading to an epidemiological underevaluation of its incidence. Many of the signs and symptoms induced by mTBI are difficult to highlight clinically, especially those related to cognitive, behavioral, or emotional impairment. The complexity of the biological mechanisms induced by mTBI in the elderly determines synchronous pathogenic actions in which the vascular, inflammatory and neurodegenerative elements are intertwined. It is difficult to highlight a major pathogenic factor, since they act simultaneously, multimodally, in a real pathogenic cascade. The identification of mTBI and cerebral vascular changes by neuroimaging techniques, transcranial Doppler (TCD) or biological markers, suggests a potential prophylactic intervention by using neuroprotective factors as early as possible. Proper prophylaxis measures with neurotrophic treatment, rebalancing the gamma-aminobutyric acid (GABA)/glutamate balance and combating the chronic inflammatory process, can become important pharmacological therapeutic targets.

Corresponding author: Dragos Marinescu, Professor, MD, PhD; e-mail: marinescu_psy@yahoo.com

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8. MR spectroscopy of the liver - a reliable non-invasive alternative for evaluating non-alcoholic fatty liver disease

Alina Maria Lapadat, Lucian Mihai Florescu, Nicolae Catalin Manea, Dan Ionut Gheonea, Daniel Pirici, Diana Rodica Tudorascu, Razvan Ene, Ioana Andreea Gheonea

Non-alcoholic fatty liver disease (NAFLD) is one of the most common conditions worldwide that targets the liver parenchyma. NAFLD represents an intrahepatic triglyceride accumulation in the absence of excessive alcohol consumption and other diseases that affect the liver parenchyma. The current gold standard for evaluating the amount of intrahepatic fat is represented by liver biopsy, but many patients are reluctant and hardly accept undergoing this procedure due to its invasive nature. The current study addresses this aspect by evaluating the reliability of liver magnetic resonance spectroscopy (MRS) in diagnosing NAFLD, compared to the traditional invasive liver biopsy. The present study included a total of 38 patients based on several well-defined inclusion and exclusion criteria. We used the same NAFLD grading system for both liver MRS and liver biopsy: grade 0: <5% hepatocytes are affected; grade I: 5-33% hepatocytes are affected; grade II: 34-66% hepatocytes are affected; grade III: >66% hepatocytes are affected. Regarding the NAFLD grade, over three-quarters of patients were classified as grade I and grade II, with a strong predilection for men. The current results indicated a significant association between the NAFLD grade indicated by liver MRS and the NAFLD grade indicated by liver biopsy. At the end of our study, we recommend using liver MRS for evaluating and grading NAFLD in association with other parameters like serum triglycerides and body mass index grade as this protocol can enhance early detection and provide an accurate grading that will lead to a proper management of this disease.

Corresponding author: Lucian Mihai Florescu, MD, PhD; e-mail: lucian.florescu@umfcv.ro; Nicolae Catalin Manea, Eng, PhD Student; e-mail: catalin.manea@umfcv.ro

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

Viorel Scripcariu, Delia Gabriela Ciobanu Apostol, Gabriela Florenta Dumitrescu, Mihaela Dana Turliuc, Anca Sava

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.

Corresponding author: Delia Gabriela Ciobanu Apostol, Assistant Professor, MD, PhD; e-mail: delia.ciobanu@umfiasi.ro; Dana Mihaela Turliuc, Associate Professor, MD, PhD; e-mail: turliuc_dana@yahoo.com

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10. Severe traumatic brain injury (TBI) - a seven-year comparative study in a Department of Forensic Medicine

Razvan Stefan Tolescu, Marian Valentin Zorila, Mircea-Sebastian Serbanescu, Kamal Constantin Kamal, George Lucian Zorila, Ilie Dumitru, Charoula Florou, Laurentiu Mogoanta, Ion Alexandru Vaduva, Liliana Stanca, Roxana Eugenia Zavoi

Deaths caused by traumatic brain injury (TBI) increase in incidence every year worldwidely, mainly in developing countries. Thus, World Health Organization (WHO) estimates that in 2020, TBI will become the third main cause of death. In our study, we evaluated the deaths caused by TBI recorded within the Institute of Forensic Medicine of Craiova, Romania, between 2011 and 2017. Therefore, according to age, the cases were divided into two groups: people aged 0-18 years old (including 18 years old) and people aged over 18 years old (a total of 1005 cases, of which 971 were adults and 34 included in the age group 0-18 years old). In both groups, most patients were males from the rural area. In adults, falling was the main legal entity of the cases, followed by car accidents (which were the most common in children). In both groups, in car accidents, most of them were pedestrians and car occupants. Various aggressions (human, animal, self-injury) were found in 94 (9.68%) of the adult cases and in four (11.76%) cases of children. Another parameter under study was the blood alcohol concentration, being observed that most of the subjects with positive blood alcohol content died from car accidents. By evaluating the Glasgow Coma Scale (GCS) score as a prognostic factor, most of the subjects presented third and fourth degree coma at admission; still, 5.14% of the adult patients who deceased had GCS score 15 at admission, death occurring probably by developing some intracranial hematomas in time. Regarding the morphology of the lesions, most patients presented various forms of cranial fractures, 185 (19.05%) adults in association with extradural hemorrhages/hematomas, but also there were four cases with extradural hematomas without any cranial fractures. In children, there was highlighted a single case of extradural hemorrhage under the fracture line. Seventy-eight percent of the adults and 44.12% of children presented subdural hematomas associated with other meningo-cerebral lesions. Also, 83.63% of the adults and 97% of children presented brain contusions. In both groups, brain laceration was observed in approximately 50% of the cases.

Corresponding author: Mircea-Sebastian Serbanescu, Lecturer, MD, PhD; e-mail: mircea_serbanescu@yahoo.com; George Lucian Zorila, University Assistant, MD, PhD; e-mail: zorilalucian@gmail.com

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11. Congenital cataract - clinical and morphological aspects

Catalina-Ioana Tataru, Calin-Petru Tataru, Adrian Costache, Ovidiu Boruga, Mihail Zemba, Radu Constantin Ciuluvica, George Sima

Congenital cataract is one of the main causes of blindness in newborns and children. According to the World Health Organization (WHO), there are about 14 million children suffering from congenital cataract. Our study is based on 82 children, males - 46 (56.1%) and females - 36 (43.9%), with congenital cataract operated in the same ophthalmological centre in Bucharest, Romania. Of the 82 patients, 49 (59.76%) had bilateral cataract and 33 (40.24%) unilateral cataract. Clinically, the most frequent was the total cataract, followed by lamellar, nuclear and cerulean. We employed nine surgical approaches in our patients, depending on the type of intraocular lens (IOL). Morphologically, obvious changes were rendered evident at the level of anterior and posterior capsules, as well as subcapsular.

Corresponding author: Mihail Zemba, Lecturer, MD, PhD; e-mail: mhlzmb@yahoo.com; Radu Constantin Ciuluvica, Lecturer, MD, PhD; e-mail: raduciuluvica@yahoo.com

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12. Saccular function evolution related to cochlear implantation in hearing impaired children

Romica Sebastian Cozma, Maria Cristina Hera, Mihail Dan Cobzeanu, Raluca Olariu, Oana Roxana Bitere, Cristian Martu, Lucia Corina Dima-Cozma, Cristina Gena Dascalu, Madalina Gabriela Georgescu, Violeta Necula, Luminita Mihaela Radulescu

Vestibular sensorial input is essential for psychomotor development of the very small children. In consequence, possible vestibular impairment induced by cochlear implantation in deaf children could affect the balance and walking learning process. Some of cochlear implanted children can present congenital vestibular deficit. The anatomical and embryological relation between auditory and vestibular system explains why congenital neurosensorial hearing loss may associate vestibular impairment. The cochlear implant surgery presents a vestibular lesion risk. Bilateral vestibulopathy, as it appears in early childhood, has a poor prognosis for the psychomotor and cognitive development. Even probably rare, bilateral vestibulopathy induced by simultaneous bilateral cochlear implantation can delay the acquisition of motor skills. This pathology can be avoided by an appropriate surgical indication related to the vestibular preoperative status. This study reports the vestibular saccular functional modifications after the cochlear implantation in children. The cervical vestibular evoked myogenic potentials (cVEMPs) were performed in children before and after the cochlear implantation. Since previous studies report different vestibular impairment related to the portelectrode insertion approach, another objective of our study was to assess the saccular postoperative status depending of the insertion by cochleostomy (CO) or through the round window (RW). We performed cVEMPs for 80 patients (135 cochlear implanted ears) before and after cochlear implantation. We have detected preoperative saccular areflexia in 33 (24.4%) ears. In the group of 102 (75.6%) ears with preoperative normal saccular function, 72 (70.6%) ears preserved the cVEMP response after the surgery, while in 30 (29.4%) ears the cVEMP response was lost. Reporting our findings to the portelectrode insertion method, we found normal saccular function in 73.3% of the cochlear implanted ears by RW surgical approach and in 68.42% ears by CO approach. These results suggest that the RW portelectrode insertion is the recommended strategy in order to avoid the saccular vestibular impairment.

Corresponding author: Raluca Olariu, MD, PhD; e-mail: dr.olariu_raluca@yahoo.com; Mihail Dan Cobzeanu, Professor, MD, PhD; e-mail: cobzeanu_dan@yahoo.com

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13. Clinical, histopathological and immunohistochemical behavior of peri-implant soft tissue

Monica Mihaela Iacov-Craitoiu, Mihai Craitoiu

The presence of foreign materials in the tissues, represented in the present study by the insertion of dental implants, creates artificial structures that can sometimes cause adverse consequences, which implies the obligation to perform a complex medical assessment before inserting dental implants. This assessment appreciates the quality of the tissue, depending on which the use of a certain type of biomaterial is indicated and focuses on a certain surgical technique. We assessed the clinical, histopathological (HP) and immunohistochemical (IHC) aspects of peri-implant soft tissue in patients who did not show mobility or imagistic signs of bone resorption, three months after implant insertion, some of them showing no inflammatory clinical signs. Immunohistochemically, on the sections of the peri-implant mucosa, we assessed the presence of mast cells, vascularization and the process of angiogenesis. Mast cells are key cells actively involved in the pathogenesis of peri-implant inflammation, having an immunomodulatory role. Vasodilation and angiogenesis, determined by the release of chemical mediators by degranulation of mast cells under the action of pathogens, induce tissue remodeling, ensuring the healing and formation of a tissue to form a barrier that effectively prevents the development of a bacterial biofilm. Thus, the control of the activity of these cells is important for the management of the local inflammatory process. The correlations between the clinical, HP and IHC behavior of the peri-implant soft tissue bring important information for the clinic, emphasizing the need to identify a therapeutic strategy to modulate mast cell activity, in order to prevent and treat peri-implant disease, to ensure osseointegration and longer survival of the dental implant.

Corresponding author: Monica Mihaela Iacov-Craitoiu, Associate Professor, MD, PhD; e-mail: mcraitoiu@yahoo.com

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14. Malignant phyllodes tumors of the breast associating malignancy of both mesenchymal and epithelial components (invasive or in situ ductal carcinoma)

Codrut-Cosmin Nistor-Ciurba, Oana Somcutian, Ioan Cosmin Lisencu, Florin Laurentiu Ignat, Gabriel Lucian Lazar, Dan Tudor Eniu

Phyllodes tumors of the breast are biphasic tumors consisting from an epithelial component and a mesenchymal component. Usually, the mesenchymal component of the tumor is the one who dictates the malignancy of the biphasic proliferation. Presence of the malignancy of the both, epithelial [under the form of invasive carcinoma or ductal carcinoma in situ (DCIS)] and mesenchymal components is very rare. Most of the data available from the literature refers to single case presentations. This paper presents the experience of Prof. Dr. Ion Chiricuta Oncological Institute (IOCN), Cluj-Napoca, Romania, with the malignant phyllodes tumors with both epithelial and mesenchymal components showing malignancy. Over two decades (1999-2018), four cases of malignant phyllodes tumors with concomitant epithelial and mesenchymal malignancy were found and presented as a case series. Two out of four cases were malignant phyllodes tumors harboring invasive breast carcinomas (one case with associated DCIS and one case of pure invasive carcinoma) and two cases were malignant phyllodes tumors with the epithelial component showing DCIS. Average follow-up period was 67 months (from 39 to 132 months) with a disease-free survival of 58 months.

Corresponding author: Ioan Cosmin Lisencu, MD, PhD; e-mail: cosminlisencu@yahoo.com

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15. Cardiac axis evaluation as a screening method for detecting cardiac abnormalities in the first trimester of pregnancy

Florina Nela Osvar, Adrian Claudiu Ratiu, Florica Voita-Mekeres, Gheorghe Florin Voita, Mihaela Gabriela Bontea, Mariana Racovita, Gabriel Mihai Mekeres, Florian Dorel Bodog

Congenital cardiac abnormalities refer to especially anatomic malformations of the heart that normally occur during fetal heart development, before eight weeks after conception. Aim: The aim is to investigate the association between cardiac axis and congenital heart abnormalities for a potential underline clinical application of cardiac axis evaluation during detection by abnormalities at the time of first trimester ultrasound. It is known that aneuploids can be associated in almost half of cases with cardiac abnormalities, so the angle of the cardiac axis could be a potential indirect marker for the detection of aneuploids in the first trimester of pregnancy. Being easy to obtain, from the cross-section at the chest level with the visualization of the four chambers, does not require additional sections to those provided in the current guides, we aim to prove its usefulness in diagnosing aneuploids and congenital cardiac abnormalities along with the translucent nuchal flow, at the level of the venous duct and the presence of tricuspid regurgitation. Conclusions: Cardiac axis has a higher value for the detection of congenital cardiac abnormalities with respect to the nuchal translucency, tricuspid regurgitation and inverted A wave at the level of the venous duct.

Corresponding author: Florica Voita-Mekeres, Lecturer, PhD; e-mail: mekeres_florina@yahoo.com; Gheorghe Florin Voita, PhD Student; e-mail: voita_florin@yahoo.com

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16. The sphenoethmoidal sinus and the modified anatomy of the related structures

Mugurel Constantin Rusu, Sorin Hostiuc, Andrei Gheorghe Marius Motoc, Carmen Aurelia Mogoanta, Julietta Cristina Sava, Mihai Sandulescu

The anterior extent of the sphenoidal sinus in the posterior ethmoid was less investigated. Our purpose was to study whether, or not, the occurrence of a sphenoethmoidal sinus (SES) relates to a sagitally-shortened ethmoid. A retrospective cone-beam computed tomography (CBCT) was performed on 36 patient files. In six patients were found SES extended anteriorly above the posterior third of the middle turbinate (MT). Two of these patients had bilateral SES with ethmoidal chambers included in the lateral and superior nasal walls and draining in the sphenoethmoidal recesses. The correlation between the nasion-to-concha sphenoidalis distance and the presence of SES was statistically significant (less than 40 mm in SES cases and more than 40 mm in non-SES cases). We also found: (i) superior turbinates (STs) with ethmoidal and sphenoidal insertions on one side and ethmoidal and maxillary insertions on the opposite side (the maxillary insertion of ST modifies surgical landmarks and was not previously reported), (ii) MT perforation and (iii) pterygoid recess of the maxillary sinus located beneath the pterygopalatine ganglion fossa. The SES thus shortens sagitally the lateral nasal wall but does not modify its morphology. The MT perforation, ST maxillary insertion and the pterygoid recess are rare anatomic variants not reported previously in our knowledge.

Corresponding author: Mugurel Constantin Rusu, Professor, MD, PhD, Dr. Hab.; e-mail: mugurel.rusu@umfcd.ro

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17. Automated Gleason grading of prostate cancer using transfer learning from general-purpose deep-learning networks

Mircea-Sebastian Serbanescu, Nicolae Catalin Manea, Liliana Streba, Smaranda Belciug, Iancu Emil Plesea, Ionica Pirici, Raluca Maria Bungardean, Razvan Mihail Plesea

Two deep-learning algorithms designed to classify images according to the Gleason grading system that used transfer learning from two well-known general-purpose image classification networks (AlexNet and GoogleNet) were trained on Hematoxylin-Eosin histopathology stained microscopy images with prostate cancer. The dataset consisted of 439 images asymmetrically distributed in four Gleason grading groups. Mean and standard deviation accuracy for AlexNet derivate network was of 61.17+/-7 and for GoogleNet derivate network was of 60.9+/-7.4. The similar results obtained by the two networks with very different architecture, together with the normal distribution of classification error for both algorithms show that we have reached a maximum classification rate on this dataset. Taking into consideration all the constraints, we conclude that the resulted networks could assist pathologists in this field, providing first or second opinions on Gleason grading, thus presenting an objective opinion in a grading system which has showed in time a great deal of interobserver variability.

Corresponding author: Liliana Streba, Teaching Assistant, MD, PhD; e-mail: liliana.streba@umfcv.ro

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18. Is there a relationship in-between ovarian endometriosis and ovarian cancer? Immunohistochemical profile of four cases with coexisting ovarian endometriosis and cancer

Roxana-Cleopatra Penciu, Iulia Postolache, Liliana Steriu, Silvia Izvoranu, Andrei-Adrian Tica, Iulia-Diana Mocanu, Vasile Sarbu, Mariana Deacu, Irina Tica, Gabriela-Izabela Baltatescu, Oana-Sorina Tica, Vlad-Iustin Tica

Endometriosis (EMs) is a benign disease characterized by the presence of endometrial tissue outside the uterine cavity. EMs associated with ovarian cancer (OC) has a relative low incidence (5% to 10%), sometimes with evidence of a transition stage through atypical EMs (1.6% cases). We have assessed 135 consecutive patients with either EMs or OC and, out of them, our study reports on four cases of ovarian EMs and OC: two cases with endometrioid OC and two cases with high-grade serous OC (HGSOC). Cases with EMs and HGSOC are extremely rarely reported in the literature - we could find not more than 30 cases. The main objective of our research was to observe the possible similarities between EMs and OC. Secondly, we analyzed the differences between EMs associated with endometrioid OC and EMs associated with HGSOC. We evaluated them in terms of clinical status (age, stages of EMs and OC) and immunohistochemical (IHC) expression of estrogen receptor (ER), progesterone receptor (PR), Ki67, p53, p16, Wilms tumor 1 (WT1), cluster of differentiation (CD) 34 and CD10 immunomarkers - we could not find in the literature all these markers assessed, in the same time, to such samples. Our results indicated that there are no similarities between EMs and OC and no atypical EMs was identified in our cases. We recorded higher values of ER expression in EMs associated with HGSOC than in EMs associated with endometrioid OC. Higher values of ER expression were also recorded in OC than in endometriotic foci. There were no differences in proliferative rate of endometriotic foci associated with endometrioid OC, compared to EMs associated with HGSOC. An aberrant IHC expression for p53 protein and p16 protein was noted only in HGSOC. Also, a positive immunostaining for Wilms tumor 1 (WT1) was identified only in HGSOC. Higher values of microvessel density were recorded in OC but not in endometriotic foci. We concluded that there were no similarities between EMs and OC for the cases included in our study, but we noticed differences in terms of Ki67 index and also between hormonal receptors expression in EMs associated with HGSOC, comparing with EMs associated with endometrioid OCs. These results may represent a brick for future researches on the less understood EMs associated with type II of OCs, especially with HGSOC. Identifying the best marker, which can predict the risk of developing OC for the patients with EMs, may lead to discover new specific therapeutic agents and, therefore, a better, tailored, therapy.

Corresponding author: Irina Tica, Associate Professor, MD, PhD; e-mail: irinatica@gmail.com

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19. Pointing on the early stages of maxillary bone and tooth development - histological findings

Radu Braescu, Sergiu Daniel Savinescu, Monica Silvia Tatarciuc, Irina Nicoleta Zetu, Simona Eliza Giusca, Irina-Draga Caruntu

Although the morphological stages of tooth development, in parallel with maxillary bone construction, are known for decades, the intimate mechanisms of early development of the oral cavity structures and tooth s proper and associated tissues are still incompletely elucidated. Nowadays, the research in embryology was shifted from the morphological to the molecular and genetic approach. This new approach is accomplished by using in vivo and in vitro experimental studies performed on animal models and cell lines. The interest in the knowledge of these events at gene and molecular level is still current, aiming to sustain the progress in the endorsement of novel regenerative and restorative therapies. However, the morphological standpoint maintains its interest, because the extrapolation of the results of experimental studies in humans requires a strong confirmation. Within this context, our work aims to analyze the histological characteristics of the maxillary bone and integrated tooth germs during the early stages of embryonic development. The study group consisted in mandible fragments obtained by dissection of the cephalic extremities collected from fetuses aged from 10 to 24 weeks, after medical or spontaneous abortions. The tissue specimens were processed for the histological exam. The histoarchitectonic traits of the initial stages of mandibular bone tissue and tooth development were assessed. The results revealed the dynamics of the ossification stages, from stages of early-dispersed intramembranous ossification to the organization of the dental alveoli, incorporated step-by-step in the maxillary body, and the simultaneous presence of tooth germs with different sizes and shapes, in accordance with the development stage. Our study complements the existing data regarding the embryonic period, bringing an important contribution for the enlargement of existing morphological, visual information for maxillary bone and tooth development.

Corresponding author: Simona Eliza Giusca, Lecturer, MD, PhD; e-mails: simonaelizagiusca@gmail.com, simona-eliza.giusca@umfiasi.ro

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20. Immunophenotypical alterations with impact on the epithelial-mesenchymal transition (EMT) process in salivary gland adenoid cystic carcinomas

Iulia Cristiana Belulescu, Claudiu Margaritescu, Cristiana Iulia Dumitrescu, Maria Cristina Munteanu, Otilia Clara Margaritescu

Adenoid cystic carcinoma (ACC) is one of the most common malignant salivary glands neoplasms with an indolent clinical course, slow-growing but locally aggressive and quite often with delayed recurrence and distant metastasis. In order to elucidate this tumoral behavior, we conducted an immunohistochemical study investigating the alterations of epithelial phenotype with anti-cytokeratin (CK) AE1/AE3 and anti-E-cadherin antibodies, and the acquisition of mesenchymal phenotype with vimentin, fibronectin, N-cadherin and P-cadherin in salivary ACCs. Thus, we recorded a reduction of CK AE1/AE3, E-cadherin, P-cadherin and fibronectin reactivity in the solid variant and especially in the cells from the periphery of invasive neoplastic proliferations, regardless histological type. These phenotypical alterations suggest the involvement of the epithelial-mesenchymal transition (EMT) process in the progression of salivary ACCs.

Corresponding author: Claudiu Margaritescu, Professor, MD, PhD; e-mail: c_margaritescu2000@yahoo.com; Maria Cristina Munteanu, Lecturer, MD, PhD; e-mail: cristina_omf@yahoo.com

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21. Injectable platelet-rich fibrin influences the behavior of gingival mesenchymal stem cells

Sofia Iozon, Gabriela Valentina Caracostea, Emoke Pall, Olga Soritau, Ionut Daniel Manaloiu, Adriana-Elena Bulboaca, Mihaela Lupse, Carmen Mihaela Mihu, Alexandra Livia Roman

In this study, we examined the effects of injectable platelet-rich fibrin (iPRF) on proliferation and osteodifferentiation in mesenchymal stem cells (MSCs) isolated from human gingiva. Gingival MSCs (gMSCs) were grown in experimental culture media with different concentrations of iPRF [5%, 10%, and replacement of fetal calf serum (FCS) in the standard media with 10% iPRF-10% iPRF-FCS]. Immunophenotyping of gMSCs was performed after seven days by flow cytometry, and their proliferation was examined after three and seven days using the Cell Counting Kit-8 method. After 14 days in culture, spontaneous osteogenic differentiation of gMSCs was evaluated via real-time polymerase chain reaction. All gMSCs were positive for cluster of differentiation (CD) 105, CD73, CD90, and CD44, and negative for CD34/45, CD14, CD79a, and human leukocyte antigen, DR isotype (HLA-DR). Reduced expression of some surface antigens was observed in the gMSCs grown in 10% iPRF-FCS medium compared to the other groups. After three days, gMSCs grown in 10% iPRF had proliferated significantly less than the other groups. After seven days, proliferation was significantly higher in the 5% iPRF cells compared to the control, while proliferation in the 10% iPRF and 10% iPRF-FCS groups was significantly lower. No spontaneous osteogenic differentiation was observed in the presence of iPRF, as observed by low runt-related transcription factor 2 (RUNX2) expression. Some expression of secreted protein acidic and cysteine rich (SPARC) and collagen 1 alpha (COL1A) was observed for all the gMSCs regardless of the culture medium composition. gMSCs grown in 10% iPRF had significantly lower SPARC expression. In conclusion, 5% iPRF stimulated gMSC proliferation, and an excessively high concentration of iPRF can impair osteogenic induction.

Corresponding author: Carmen Mihaela Mihu, Professor, MD, PhD; e-mail: carmenmihu2004@yahoo.com

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22. Influences of treadmill speed and incline angle on the kinematics of the normal, osteoarthritic and prosthetic human knee

Daniela Tarnita, Alin Ionel Petcu, Nicolae Dumitru

The objective of this paper is to measure and to study the influence of the treadmill speed and incline angle on the kinematics of flexion-extension angles of the human knee joints during 23 tests of walking overground and on plane and inclined treadmill performed by a sample of 14 healthy subjects and during of seven tests performed by a sample of five patients suffering of knee osteoarthritis (KOA), before and three months after the total knee replacement (TKR) surgery. The medium cycles computed and plotted for all experimental tests performed by the healthy subjects sample and for the osteoarthritic (OA) patients sample before and after TKR surgery are compared and conclusions are formulated.

Corresponding author: Daniela Tarnita, Professor, PhD; e-mail: tarnita.daniela@gmail.com

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23. Histopathological findings in the advanced natural evolution of the SARS-CoV-2 infection

Andreea-Elena Cirstea, Radu Lucian Buzulica, Daniel Pirici, Mihail Constantin Ceausu, Radu Vasile Iman, Ovidiu-Mircea Gheorghe, Simona Daniela Neamtu, Liliana Stanca, Razvan Ene, Samir Kumar-Singh, Laurentiu Mogoanta

We are reporting a case of natural evolution and pathological data from a young person that was diagnosed with coronavirus disease 2019 (COVID-19). All data has been collected from the autopsy of a 30-year-old female, which was performed by the Department of Forensic Medicine from Emergency County Hospital, Drobeta Turnu Severin, Mehedinti County, Romania. The infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed by reverse transcription polymerase chain reaction (RT-PCR) on the lung tissue which was obtained during autopsy. This case provides the opportunity to study the natural evolution of COVID-19 pneumonia in a young person with clinical signs of pneumonia but without associated comorbidities. The patient had not received any treatment. The histopathological examination of the lung revealed a process of productive proliferation, proteinaceous and fibrin-macrophagic interalveolar spaces exudate, and lesions consistent with vasculitis. In the heart, we identified a cardiac thrombus. These changes are likely to suggest an advanced natural evolution of SARS-CoV-2 virus infection.

Corresponding author: Radu Lucian Buzulica, MD, PhD; e-mail: lucianbuzulica@yahoo.com; Laurentiu Mogoanta, Professor, MD, PhD; e-mail: laurentiu_mogoanta@yahoo.com

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24. Clear cell change in follicular adenoma of the thyroid. A diagnostic challenge

Jose-Fernando Val-Bernal, Maria Martino

Clear cells in thyroid neoplasms can take two main forms: balloon-shaped and signet-ring cells. Balloon-shaped cell change in follicular adenoma is rare. A review of the literature has revealed only 20 previously published cases. We report herein a new case in the right thyroid lobe of a 45-year-old man. The clinicopathological data of the 21 cases including our paper have revealed that the ages of the patients ranged from 22-70 years, with a mean of 41.6 years. There was a clear predominance in women (M:F, 1:6). The most frequent location was in either of both lobes (81.8%), rarely affecting the isthmus. One case was observed in an ectopic thyroid in the submandibular region. The size ranged from 0.7-5.5 cm (mean 2.9 cm). The type of surgical intervention where this data was reported it was lobectomy for 10 (55.5%) cases, thyroidectomy for six (33.3%) cases, and simple excision for two (11.1%) cases. In one patient, the lobectomy was accompanied by cervical lymph node dissection. No cases recurred or extended outside the thyroid. The main differential diagnoses include intrathyroidal clear cell tumor of parathyroid origin, clear cell carcinoma of follicular, oncocytic, papillary, medullary or undifferentiated (anaplastic) origin, paraganglioma, metastatic clear cell carcinoma, especially of renal origin, metastatic balloon cell melanoma, and clear large-cell lymphoma. A thyroid lesion showing clear cell change constitutes a diagnostic challenge in cytological and biopsy diagnosis. Careful observation of the routine techniques along with the aid of an adequate immunohistochemical panel is essential to reach a correct biopsy diagnosis.

Corresponding author: Jose-Fernando Val-Bernal, Professor, MD, PhD; e-mail: fernando.val@unican.es

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25. Leiomyosarcoma of the inferior vena cava. Our experience and a review of the literature

Cristian Bogdan Rusu, Lilian Gorbatai, Ludovic Szatmari, Rumelia Koren, Catalina Ileana Bungardean, Bogdan Ovidiu Feciche, Calin Bumbulut, Iulia Madalina Andras, Razvan Rahota, Teodora Telecan, Ioan Coman, Lea Rath-Wolfson, Nicolae Crisan

Leiomyosarcoma (LMS) of the inferior vena cava (IVC) is a rare malignant tumor, accounting for 2% of all LMSs. Less than 400 cases have been reported in literature. Computed tomography (CT) is the most accurate imaging method in assessing the location of the tumor within the IVC and magnetic resonance imaging (MRI) accurately identifies its extent and the potential for surgical resection. We present the case of a patient with inferior vena cava leiomyosarcoma (IVCL), for whom the pathological diagnosis was different from the initially expected one, the tumor appearance on pre-operative imaging mimicking renal cell carcinoma. The intraoperative difficulty of approaching renal hilum and IVC was a factor suggesting the vascular origin of the tumor, which was confirmed at pathological analysis. The extensive defect in the IVC after tumor excision led to the decision of complete transverse suturing of IVC, as significant collateral venous circulation was already present. Because IVCL is a rare disease, there is scarce data regarding the prognosis and treatment options. Long-term survival depends on the extent of the surgery. The need of vascular reconstruction is not always mandatory. Despite high recurrence rates, no consensus regarding adjuvant treatment exists yet. A multidisciplinary approach including surgical oncologists and vascular surgeons is mandatory to achieve the best patient outcomes. Perioperative planning, coordination and adherence to oncological techniques are critical.

Corresponding author: Iulia Madalina Andras, Assistant Professor, MD, PhD; e-mail: dr.iuliaandras@gmail.com

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26. Squamous metaplasia within a sigmoid adenoma. A rare feature

Simona-Andreea Tircol, Andreea Ghidersa, Lucian Negreanu, Maria Sajin, Adrian Vasile Dumitru

Squamous metaplasia occurring within a colorectal polyp is a rare finding, having a reported incidence of approximately 0.44%. The origin of the squamous cells in this type of setting is uncertain (mechanical irritation and chronic inflammation are potential predisposing factors). It has been implied that the significance of squamous metaplasia in colorectal adenomas is that of a preneoplastic lesion for squamous cell and adenosquamous carcinoma, however the evidence to support this statement is scarce. We present a case of a large tubulovillous adenoma located in the sigmoid, with low-grade dysplasia and multiple foci of p16-positive immunoexpression squamous metaplasia in a 54-year-old Caucasian male, presenting with rectal bleeding.

Corresponding author: Lucian Negreanu, MD, PhD; e-mail: lucian.negreanu@umfcd.ro

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27. Male breast involvement in chronic lymphocytic leukemia. A case report and review of the literature

Vasiliki Anagnostopoulou, Niki Mantha, Konstantinos Sapalidis, Eirini Tolparidou, Elisavet Georgiou, Triantafyllia Koletsa

Male breast lymphoma is a rare extranodal lymphoma occupying the mammary gland, and it could be either primary or secondary. A 78-year-old man presented an enlargement of the right breast. He had no medical history of interest. On physical examination, a unilateral, painless breast lump was found, with no skin changes or nipple discharge. There was no palpable lymphadenopathy. Routine laboratory tests revealed leukocytosis and lymphocytosis. Excisional biopsy of the breast lesion revealed mammary tissue infiltration by chronic lymphocytic leukemia (CLL) with plasmacytoid features and immunoglobulin G/kappa monotypic expression. To our knowledge, this is the first report of male breast involvement by CLL. Considering important the collection of clinicopathological data of all reported male breast lymphoma cases, a literature review is presented.

Corresponding author: Triantafyllia Koletsa, Assistant Professor, MD, PhD; e-mail: tkoletsa@auth.gr

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28. Large giant cell tumor of the posterior iliac bone - an atypical location. A case report and literature review

Cosmin Ioan Faur, Daniel Laurentiu Pop, Andrei Gheorghe Marius Motoc, Roxana Folescu, Mirela Loredana Grigoras, Daniela Gurgus, Carmen Lacramioara Zamfir, Mihaela Iacob, Dinu Vermesan, Bogdan Nicolae Deleanu, Horia George Haragus, Daniel Claudiu Malita, Ahmed Abu-Awwad, Ion Lucian Ghiga, Mariana Tudoran

Giant cell tumor (GCT) is a locally aggressive tumor but with benignity features, representing approximately 18% of non-malignant bone tumors in European countries, with slight female predominance. Malignancy in GCT is rare, about <2% of cases and is more common at older ages. Is known that usually occurs at the epiphyses of long bones, but extremely rare may have another location, such as the pelvic bone. An atypical location - the posterior iliac bone, found at a 34-year-old male -, is the case report we studied and described. Starting from the patient s complains, like a mass in the left buttock region described as recently appeared, firm, not-mobile, with no distinctive borders and no tenderness at palpation, and a recent history trauma, multiple investigations have been performed, which have highlighted an osteolytic lesion, close to the sacroiliac joint, only with infiltration of the gluteal, iliac and paravertebral muscles. The treatment of choice was hemipelvectomy, with wide tumoral resection, and selective embolization of the nutrient vessels 24 hours prior to the surgical procedure. At two years postoperative, we found a good functional result and the computed tomography (CT) scan revealed no signs of recurrence.

Corresponding author: Roxana Folescu, Senior Lecturer, MD, PhD; e-mail: roxanafolescu08@gmail.com; Daniel Laurentiu Pop, MD, PhD; e-mail: daniellaurentiupop@yahoo.com

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29. Spontaneous rupture of immature gastric teratoma with hemoperitoneum in a newborn with 3-year follow-up

Chul Kyu Roh, Min Jung Jung, Jiyoon Kim, Susie Chin, Ahrim Moon

Among the subtypes of germ cell tumors, teratomas are the most frequent in the pediatric population and commonly occur in the sacrococcygeal region and the gonads. Less than 1% of all teratoma are found in abdominal organs including the stomach, liver, and kidney. Gastric teratomas are very rare tumors predominantly found in infants. Moreover, an immature gastric teratoma is exceptionally rare. Here, we present a case of immature gastric teratoma with spontaneous rupture in a newborn who was preoperatively diagnosed with neuroblastoma. On the first day after birth, the neonate presented with progressive abdominal distension accompanying respiratory distress. A firm mass was detected during a physical examination of the abdomen. An emergency exploratory laparotomy revealed hemoperitoneum resulting from a rupture of the tumor located in the posterior wall of the gastric antrum. Complete resection of the tumor and gastroduodenostomy were performed. The pathology evaluation revealed a grade 3 immature gastric teratoma with no malignant components. The patient was treated with adjuvant chemotherapy to prevent recurrence, since the tumor was ruptured in the abdominal cavity and the level of alpha-fetoprotein was decreased but still remained high above the normal range after surgery. In conclusion, physicians should be aware of the existence of gastric teratoma as the differential diagnosis of a huge abdominal mass in infants, especially neonates. Complete surgical removal of the tumor and long-term follow-up has been adopted as the standard management for immature gastric teratoma, although there has been controversy with adjuvant chemotherapy.

Corresponding author: Min Jung Jung, MD; e-mail: mj@schmc.ac.k

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30. Fenestration of the cervical internal carotid artery misdiagnosed as dissection

Lucian Marginean, Rares Cristian Filep, Cristian Constantin, Adrian Florian Balasa, Gheorghe Muhlfay

Internal carotid artery (ICA) anatomical variations are relatively rare occurrences during diagnostic imaging procedures. Their presence can have important prognostic consequences in the evaluation of vascular neurological diseases. It is therefore important to have a good knowledge about these variations, in order to avoid unwarranted medical interventions. We present the case of a patient harboring a right ICA fenestration in the cervical segment, misdiagnosed as a dissection on computed tomography angiography, admitted in the Department of Neurology and treated accordingly. The possible pathological and embryological origins of arterial fenestrations are discussed, and a brief review of the literature related to ICA fenestrations is presented.

Corresponding author: Rares Cristian Filep, MD, PhD Student; e-mail: raresfilep@gmail.com; Cristian Constantin, Associate Professor, MD, PhD; e-mail: cristian.constantin2364@gmail.com

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31. The morphological characteristics of the physically abused child. Report of a case and literature review

Monica Adriana Motorca, Camelia Liana Buhas, Simona Gabriela Bungau, Claudia Teodora Judea-Pusta, Cristina Ariadna Nicula, Marius Rus, Ana Maria Alexandra Stanescu, Alina Cristiana Venter, Camelia Cristina Diaconu, Paula Marian

Child abuse remains a current problem, despite progress in the field of prevention and social assistance. The injuries produced by physical abuse have to be evaluated using scientific methods, in order to be considered as evidences later in Court, but also to ensure the physical and social security of the child. Among the morphological characteristics of the child (on which depends how the lesions are formed, differently in children from adults), there is the strong adherence of the dura mater to the skull bones, this fact preventing the formation of extradural hematomas. Another special aspect is the poor development of skeletal muscle before puberty, which confers poor protection of the internal organs against the traumatic physical agents. This paper presents the particular morphological and histological aspects that can be evidenced by forensic autopsy in children. The study was conducted on a female child, physically assaulted, arrived in the emergency department of the hospital. The death occurred shortly after hospitalization. The investigations revealed multiple external (on the whole body) and internal injuries. According to the statements of those who called the ambulance, the injuries occurred because of falling on the stairs and were considered by the family as being superficial, without requiring medical care. The forensic autopsy, through the external, internal and histopathological examination, highlighted the specific injuries that led to the death, thereby contributing to the elucidation of the tanatogenerative mechanism, of the way the lesions were produced and to the applying the law.

Corresponding author: Camelia Liana Buhas, Associate Professor, MD, PhD, Dr. Hab.; e-mail: cameliabuhas@yahoo.com; Simona Gabriela Bungau, Professor, PhD, Dr. Hab.; e-mail: simonabungau@gmail.com

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32. Primary thyroid angiosarcoma in a non-endemic region - a rare case

Adrian Daniel Tulin, Adelaida Avino, Laura Raducu, Florentina Raluca Tulin, Ovidiu Stiru, Andra-Elena Balcangiu-Stroescu, Delia Timofte, Maria Daniela Tanasescu, Daniela-Gabriela Balan, Cristian-Radu Jecan, Dorin Ionescu

Thyroid angiosarcoma (AS) is a specific type of vascular tumor that arises from the endothelial cells, being highly aggressive, with increased recurrence rates and metastasis. It is characterized by positive endothelial markers and co-positive markers for cytokeratins and epithelial membrane antigen. We are describing the case of a 76-year-old patient who presented to the hospital for dyspnea and asthenia. The clinical and paraclinical investigations confirmed the presence of a right large thyroid nodule, which turned out positive at immunostaining for AS. Even if thyroid AS is a rare type of tumor, mainly described in the Alps, one has to take into account that it can evolve in any other regions and should be considered as a differential diagnosis.

Corresponding author: Laura Raducu, Lecturer, MD, PhD; e-mail: raducu.laura@yahoo.com; Maria Daniela Tanasescu, Assistant Professor, MD, PhD; e-mail: tanasescu2007@yahoo.com

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33. Ectopic lamellar Pacinian corpuscle within the thymus. Atypical or abnormal location?

Ivan Varga, Matej Nosal, Pavel Babal

Lamellar (Pacinian) corpuscle is a cutaneous encapsulated sensory corpuscle, mainly functioning as a rapidly adapting low-threshold mechanoreceptor with characteristic onion skin-like appearance. Even though the Pacinian corpuscle is typically located in the skin, histomorphologically and confirmed by using immunohistochemical methods, we have identified it within the interstitium of the thymus of a newborn with congenital heart defect. To the best of our knowledge, this is the first such account ever to be published. The structure of the thymic Pacinian corpuscle was the same as the Pacinian corpuscle in the skin. The ectopic thymic Pacinian corpuscle can be hypothetically explained as the consequence of impaired migration of neural crest cells, since neural crest-derived cells play an important role in the development of the Pacinian corpuscle, as well as the thymus and heart. In general, the occurrence of ectopic Pacinian corpuscle in different organs is rare. In the scientific literature, there are reports of its sporadic presence in the pancreas, in the lymph nodes, inside the prostate and the urinary bladder wall. Our report presents the first described case of the Pacinian corpuscle in a heterotopic location in the thymus. Similar to other incidental findings of this anatomic structure, explanation of its ectopic development, as well as its local function remains only speculative.

Corresponding author: Ivan Varga, Professor, PhD; e-mail: ivan.varga@fmed.uniba.sk

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34. Ethical review of patient safety and public health in EU clinical trials legislation: impact of COVID-19 pandemic

Anca Parmena Olimid, Daniel-Alin Olimid

Purpose: The study considers the ethical review of the European Union (EU) clinical trials (CTs) legislation, namely the Clinical Trials Regulation (CTR) (EU) 2014/536, the Directive 2001/20/EC and the Guidance on the management of clinical trials during the COVID-19 (coronavirus) pandemic (GMCT) (version 3) issued on 28 April 2020 by the European authorities in the field. Background: The Directive 2001/20/EC focuses the legal provisions for the conduct of CTs by acknowledging the screening role of the Ethics Committees (ECs) and of the national competent authorities (NCA) in the Member States (MS) to protect the CT subject and the personal data. Content: The present article displays the ethical requirements for conducting, monitoring and reporting of the CTs by raising awareness on the: (i) new conceptual framework of the clinical trial, low-intervention clinical trial, non-interventional study and ethics committee; (ii) ethical considerations addressed in Part I and Part II of the assessment report; (iii) evaluation of the coronavirus disease 2019 (COVID-19) pandemic on the current regulatory framework. Conclusions: The CTR stimulates the EU clinical research and enables an independent control with regard to the respect of the interests of the CT subject.

Corresponding author: Anca Parmena Olimid, Associate Professor, PhD; e-mail: parmena2002@yahoo.com

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35. A research on abortion: ethics, legislation and socio-medical outcomes. Case study: Romania

Andreea Mihaela Nita, Cristina Ilie Goga

This article presents a research study on abortion from a theoretical and empirical point of view. The theoretical part is based on the method of social documents analysis, and presents a complex perspective on abortion, highlighting items of medical, ethical, moral, religious, social, economic and legal elements. The empirical part presents the results of a sociological survey, based on the opinion survey method through the application of the enquiry technique, conducted in Romania, on a sample of 1260 women. The purpose of the survey is to identify Romanians perception on the decision to voluntary interrupt pregnancy, and to determine the core reasons in carrying out an abortion.

Corresponding author: Andreea Mihaela Nita, Senior Lecturer, PhD; e-mail: andreea_nita2005@yahoo.com; Cristina Ilie Goga, Assistant Professor, PhD; e-mails: cristin_il@yahoo.com, cristina_ilie.goga@ucv.ro

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