ROMANIAN JOURNAL of MORPHOLOGY and EMBRYOLOGY

Vol. 61 No. 4, October-December 2020

1. Ovarian ectopic pregnancy: the role of complex morphopathological assay. Review and case presentation

Anca-Maria Istrate-Ofiteru, Dan Ruican, Mihaela Niculescu, Rodica Daniela Nagy, Gabriela-Camelia Rosu, Ana-Maria Petrescu, Roxana Cristina Dragusin, Larisa Iovan, George Lucian Zorila, Dominic Gabriel Iliescu

Ovarian ectopic pregnancy (OEP) represents the rarest type of ectopic pregnancy, accounting for 1-3% of this pathology. The diagnosis of this pathology is challenging due to the non-specific clinical aspects and the ultrasound examination hampered by the lack of visible gestational sac in the presence of hematocele and hemoperitoneum. The purpose of the extended histopathological (HP) examination was to identify particular aspects of the OEP trophoblast and to highlight potential local ovarian modifications which can determine pregnancy fixation at this level. The patient presented local favorable conditions for intraovarian nidation, conditions confirmed by the HP classical examination and by the immunohistochemical evaluation. We identified, using classical Hematoxylin-Eosin, Masson s trichrome and Periodic Acid-Schiff (PAS)-Hematoxylin, necrotic hemorrhage, accentuated vascular thrombosis and high density lymphoplasmocytary infiltrate. These modifications increased local adhesivity and cell destruction through hypoperfusion. Anti-cluster of differentiation antibodies (CD34, CD38, tryptase) revealed the low number of intravillous vessels and the high number of macrophages and mastocytes involved in the local inflammatory process heighten. We identified the presence of trophoblast tissue in the ovarian structure using anti-cytokeratin AE1/AE3 (CK AE1/AE3)/anti-cytokeratin 7 (CK7) antibodies. The anti-alpha-smooth muscle actin (alpha-SMA) and anti-vimentin (VIM) antibodies displayed the density of myofibroblasts and intravillous stromal cells and with the aid of anti-progesterone receptor (PR) antibody, we identified the corpus luteum hormonal response in the OEP. The placental villosities present a blocked multiplication process at the anti-apoptotic B-cell lymphoma 2 (BCL2) protein, confirmed by the Ki67 cell proliferation and tumor protein 63 (p63) immunomarkers. Anti-neuron specific enolase (NSE), anti-calretinin and anti-inhibin A antibodies showed the particular aspects of the granulosa and internal theca cells, which may be involved in oocyte release blockage, intraluteal and extraluteal fecundation of the OEP.

Corresponding author: George Lucian Zorila, Teaching Assistant, MD, PhD; e-mail: zorilalucian@gmail.com; Gabriela-Camelia Rosu, Teaching Assistant, MD, PhD; e-mail: nicola_camelia92@yahoo.com

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2. Endocardial fibroelastosis and dilated cardiomyopathy - the past and future of the interface between histology and genetics

Alina Costina Luca, Ludmila Lozneanu, Ingrith Crenguta Miron, Laura Mihaela Trandafir, Elena Cojocaru, Ioana Alexandra Paduret, Doina Mihaila, Maria Magdalena Leon-Constantin, Stefan Chiriac, Alin Constantin Iordache, Elena Tarca

Endocardial fibroelastosis (EFE) signifies the pathological process by which collagen and elastin are focally or diffuse deposited in the endocardium of the left ventricle. The new layer causes left ventricular dysfunction sometimes with fulminant progression to heart failure. EFE is a major component in many congenital heart abnormalities but can also occur in the absence of heart malformations, either as a primary process or in response to cardiac injury. The endothelial-mesenchymal transition (EndMT) abnormalities seem to be main pathogenic factor in fibroelastosis development. The gold standard for diagnosis of primary EFE (pEFE) is the histological examination. Additionally, genetic studies may help to establish the natural course of the disease and to communicate prophylactic measures to family members of the affected child. Moreover, in the newborn, EFE takes the form of dilated cardiomyopathy (DCM) with unfavorable evolution. The proper management should be established considering negative prognostic factors, involving early transplantation, drug therapy and long-term follow-up.

Corresponding author: Elena Cojocaru, Associate Professor, MD, PhD; e-mail: ellacojocaru@yahoo.com; Laura Mihaela Trandafir, Associate Professor, MD, PhD; e-mail: trandafirlaura@yahoo.com

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3. SARS-CoV-2 infection in patients with serious mental illness and possible benefits of prophylaxis with Memantine and Amantadine

Ileana Marinescu, Dragos Marinescu, Laurentiu Mogoanta, Ion Cristian Efrem, Puiu Olivian Stovicek

Patients with serious mental illness are a high-risk category of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients with schizophrenia are not participatory and have increased mortality and morbidity, patients with dementia cannot be cared for while depression, anxiety, bipolar tubing are associated with low immune status. Social stress is amplified by social isolation, amplifying depression and the mechanisms of decreased immunity. Hygiene measures and prophylactic behavior are impossible to put into practice in conditions of chronic mental illness. In coronavirus disease 2019 (COVID-19), the risk for severe development is associated with the presence of comorbidities and immune system deficiency. Prothrombotic status, cytokine storm and alveolar destruction are mechanisms that aggravate the evolution of patients, especially in the context in which they have dysfunction of the autonomic system. The activity of proinflammatory cytokines is accentuated by hyperglutamatergia, which potentiates oxidative stress and triggers the mechanisms of neural apoptosis by stimulating microglial activation. Activation of M1-type microglia has an important role in pathogenesis of major psychiatric disorders, such as major depression, schizophrenia or bipolar disorder, and may associate hippocampal atrophy and disconnection of cognitive structures. Memantine and Amantadine, N-methyl-D-aspartate (NMDA) glutamate receptor inhibitors, have demonstrated, through their pharmacological profile, psychotropic effects but also antiviral properties. In the conditions of the COVID-19 pandemic, based on these arguments, we suggest that they can be associated with the therapy with the basic psychotropics, Memantine or Amantadine, for the control of neuropsychiatric symptoms but also as adjuvants with antiviral action.

Corresponding author: Dragos Marinescu, Professor, MD, PhD; e-mail: marinescu_psy@yahoo.com; Ion Cristian Efrem, Assistant Professor, MD, PhD; e-mail: ic_efrem@yahoo.com

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4. Pediatric nonalcoholic fatty liver disease - a changing diagnostic paradigm

Laura Mihaela Trandafir, Otilia Elena Frasinariu, Maria Magdalena Leon-Constantin, Stefan Chiriac, Mioara Florentina Trandafirescu, Ingrith Crenguta Miron, Alina Costina Luca, Alin Constantin Iordache, Elena Cojocaru

Worldwide, nonalcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease in children and adolescents, but also as a real public health issue. Over the last decades, the increase in the rates of obesity and overweight in children has led to the increase in the worldwide prevalence of pediatric NAFLD. Detection of a hyperechoic appearance of the liver at ultrasounds or elevated levels of transaminases, identified during a routine control in children, suggests NAFLD. The disorder can be diagnosed with either non-invasive strategies or through liver biopsy, which further allows the identification of specific histological aspects, distinct from those found in adults. Since NAFLD is a clinically heterogeneous disease, there is an imperative need to identify noninvasive biomarkers and screening techniques for early diagnosis in children, in order to prevent metabolic and cardiovascular complications later in adulthood. This review emphasizes the main diagnosis tools in pediatric NAFLD, a systemic disorder with multifactorial pathogenesis and varying clinical manifestations.

Corresponding author: Maria Magdalena Leon-Constantin, Associate Professor, MD, PhD; e-mail: leon_mariamagdalena@yahoo.com; Stefan Chiriac, Assistant Professor, MD, PhD; e-mail: stefannchiriac@yahoo.com

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5. Immunological and hormonal mechanisms in Alzheimer s disease

Simona Corina Trifu, Andrian Tibirna, Ana Miruna Dragoi, Bogdan Mihai Cristea

Alzheimer s disease (AD) is a disorder which is today treated and approached at the crossroad of two medical specialties - psychiatry and neurology. The insidious onset which can often mimic depressive disorders or other type of psychiatric disorders, the behavioral changes, the paranoid thoughts usually send people to the psychiatrist, while the brain changes observed on magnetic resonance imaging (MRI) scans and other imaging techniques may indicate the need for neurological monitoring also. The complex symptomatology and progression of this dementia requires a multidisciplinary approach and recent studies focused on adding a third perspective: a metabolic one. The common findings regarding type 2 diabetes and AD made some researchers to informally name it the third type diabetes. This mini review aims to highlight the mechanisms through which brain insulin resistance can lead to cognitive impairment and to make a short overview of the current findings which demonstrate why insulin may be a promising adjunctive treatment of Alzheimer s dementia, for certain patients.

Corresponding author: Ana Miruna Dragoi; e-mail: anamirunadragoi@gmail.com; Simona Corina Trifu, Lecturer, PhD; e-mail: simona.trifu@umfcd.ro

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6. Genetics of congenital solid tumors

Maria Claudia Jurca, Marius Evelin Ivascu, Aurora Alexandra Jurca, Kinga Kozma, Ioan Magyar, Mircea Ioan Sandor, Alexandru Daniel Jurca, Dana Carmen Zaha, Cristina-Crenguta Albu, Carmen Pantis, Marius Bembea, Codruta Diana Petchesi

When we discuss the genetics of tumors, we cannot fail to remember that in the second decade of the twentieth century, more precisely in 1914, Theodore Boveri defined for the first time the chromosomal bases of cancer. In the last 30 years, progresses in genetics have only confirmed Boveri s remarkable predictions made more than 80 years ago. Before the cloning of the retinoblastoma 1 (RB1) gene, the existence of a genetic component in most, if not all, solid childhood tumors were well known. The existence of familial tumor aggregations has been found much more frequently than researchers expected to find at random. Sometimes, the demonstration of this family predisposition was very difficult, because the survival of children diagnosed as having a certain tumor, up to an age at which reproduction and procreation is possible, was very rare. In recent years, advances in the diagnosis and treatment of these diseases have made it possible for these children to survive until the age when they were able to start their own families, including the ability to procreate. Four distinct groups of so-called cancer genes have been identified: oncogenes, which promote tumor cell proliferation; tumor suppressor genes, which inhibit this growth/proliferation; anti-mutational genes, with a role in deoxyribonucleic acid (DNA) stability; and micro-ribonucleic acid (miRNA) genes, with a role in the posttranscriptional process.

Corresponding author: Alexandru Daniel Jurca, Assistant Professor, MD, PhD; e-mail: claudiajurca70@yahoo.com; Marius Bembea, Professor, MD, PhD; e-mail: bembea13@yahoo.com

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7. Adipocytes, mast cells and angiogenesis

Domenico Ribatti, Tiziana Annese, Roberto Tamma

Healthy adipose tissue contains a wide variety of innate and adaptive immune cells, including macrophages, dendritic cells, mast cells, eosinophils, neutrophils, and lymphocytes. Numerous signaling molecules in the adipose microenvironment can positively or negatively modulate angiogenic processes, regulate the interaction between the vascular system and adipocytes, and participate in tumor progression. Mast cells are involved in the new formation or metabolism of fat, are present in abundant quantities in fatty tissue, among fat cells, and a number of mediators released from mast cells play a role in adipogenesis. Moreover, mast cells produce several pro-angiogenic factors and are involved in tumor angiogenesis. In this context, the angiogenic effect might be amplified when the adipocytes and mast cells act in concert, and treatment of adipose tissue- and mast cell-associated cancers with anti-angiogenic drugs may represent an alternative or adjuvant strategy for the treatment of these tumors.

Corresponding author: Domenico Ribatti, Professor, MD, PhD; e-mail: domenico.ribatti@uniba.it

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8. Depression and anxiety in recurrent giant cell tumor of bone

Mara Jidveian Popescu, Mihai Ciprian Stoicea, Ileana Marinescu, Razvan Silviu Cismasiu, Puiu Olivian Stovicek, Catalina Tudose, Adela Magdalena Ciobanu

Giant cell tumor of bone (GCTB) is a benign neoplasia more frequently encountered in young females. The pathogenic and evolutionary dynamics of the disease is strongly influenced by the presence of depression and cellular mechanisms, especially proinflammatory and immune. Although it is not a malignant tumor, it is often recurrent, which determines a high level of depression, anxiety, and fear of the patients. Cytokine mechanisms, especially through increased tumor necrosis factor alpha (TNFalpha) and interleukin-6 (IL-6), as well as the involvement of the receptor activator of nuclear factor-kappa B (RANK)-RANK ligand (RANK-L) system, can be correlated with the risk of malignancy. Unfavorable evolution is associated with persistent pain, difficulties of movement and body dysmorphic symptoms. The diagnosis is based mainly on histopathological (HP) assessment. The patients can be treated with pharmacological agents (Denosumab), surgery with tumor excision, reconstruction or osteosynthesis, and radiotherapy. Patients with GCTB require HP and imaging evaluations, especially of relapses, to detect the risk of metastasis or malignancy, simultaneously with psychological and psychiatric monitoring to detect depression, addictive behaviors, and suicide risk. It is necessary to evaluate in a multidisciplinary team to avoid unfavorable oncological and psychiatric developments. Through its clinical, HP, and therapeutic features, GCTB has multiple connections with the psychological and psychopathological dimension.

Corresponding author: Puiu Olivian Stovicek, Lecturer, MD, PhD; e-mail: puiuolivian@yahoo.com

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

Anca Sava, Claudia Florida Costea, Serban Turliuc, Lucian Eva, Mihaela Dana Turliuc, Gabriela Florenta Dumitrescu, Gabriela Dimitriu, Valeriana Vornicu, Liliana Baltag, Marius Gabriel Dabija

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

Corresponding author: Claudia Florida Costea, Associate Professor, MD, PhD; e-mail: costea10@yahoo.com; Serban Turliuc, Associate Professor, MD, PhD; e-mail: serban_turliuc@yahoo.com

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10. Tissue microarrays - brief history, techniques and clinical future

Alina Elena Stefan, Daniela Gologan, Matthew O. Leavitt, Sorin Musat, Iancu Emil Plesea, Liane Gloria Raluca Stan, Razvan Mihail Plesea, Manuella Militaru

Introduction and Aim: There is a growing need for better, cheaper and faster histopathological diagnostic. The authors reviewed the main steps of the efforts towards the improvement of the pre-analytical phase of tissue processing for histological examination. Results: Since their introduction decades ago tissue microarrays (TMAs) proved their value by increasing efficiency, standardization and accuracy of many histological techniques, such as histochemistry, histoenzymology, immunohistochemistry, in situ hybridization, etc. By allowing the simultaneous analysis and comparison of multiple different tissues on a single histology slide (up to 1000 individual samples), TMAs are also having a significant economic advantage (consumables and labor). From its first description until recent years, the TMA techniques have evolved steadily but slowly despite many attempts to adapt it for clinical diagnostics. In this paper, we are reviewing the main techniques of obtaining TMA blocks from the beginning to the present day, as well as recent developments that are expanding their scope into high accuracy/efficiency clinical diagnostics. Conclusions: Considering recent developments, we believe that the prospect of high-throughput histology might be achievable in the not-so-distant future.

Corresponding author: Sorin Musat, Senior Scientist; e-mail: sorin@lumea.net

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11. Hepatic pathological features in naïve patients with chronic hepatitis C who have developed thyroid disorder

Viorel Biciusca, Mihaela Popescu, Ileana Octavia Petrescu, Ionelia Sorina Stan, Patricia Durand, Mihai Petrescu, Rodica Velea, Diana Maria Trasca, Iulian Alin Silviu Popescu, Ion Udristoiu, Cristina Maria Marginean, Diana Rodica Tudorascu, Florin Petrescu

Knowing the hepatic pathological features encountered in patients with chronic hepatitis C (CHC) and the fact that extrahepatic manifestations occur only in people with certain characteristics of the immune system, we tried to evaluate, qualitatively and semi-quantitatively, the liver pathological aspects encountered in 96 patients with CHC, previously untreated with Interferon (naïve), who showed or did not show signs of thyroid disorder (TD), hospitalized in the 2nd Medical Clinic of the Emergency County Hospital, Craiova, Romania, within a period of five years (2007-2012). Following hormonal, immunological, and thyroid ultrasound investigations, 14 (14.58%) of the 96 patients showed signs of TD. The main clinical forms of TD in the studied patients with CHC were autoimmune thyroiditis and subclinical hypothyroidism. In the patients with CHC with TD, we found mild chronic hepatitis in 14.28% of cases, the appearance of moderate chronic hepatitis was found in 71.42% patients, and the appearance of severe chronic hepatitis was found in 14.28% patients, while in the patients with CHC without TD we found chronic mild hepatitis in 62.19% of cases, the appearance of moderate chronic hepatitis was met in 32.92% patients, and the appearance of severe chronic hepatitis was found in 4.87% of patients. Mild and moderate fibrosis were found only in CHC patients without TD in a percentage of 25.6% and 65.85%, respectively, while severe fibrosis was found at 12.19% among CHC patients without TD and 92.85% among CHC patients with TD. The pathological aspect of liver cirrhosis was found only in those with TD (7.14%). In conclusion, the pathological features which define the liver necroinflammatory process, as encountered at the pathological examination in CHC patients with TD are the same as in any active chronic hepatitis, the differences being represented by the higher percentage of the periportal and the preseptal necrosis (piecemeal necrosis), as well as by the higher score of portal inflammation. In addition, the severe hepatic fibrosis and the histopathological appearance of the liver cirrhosis have only defined the cases of CHC with TD.

Corresponding author: Iulian Alin Silviu Popescu, Lecturer, MD, PhD; e-mail: alin_psi@yahoo.com; Diana Maria Trasca, Lecturer, MD, PhD; e-mail: dianamaria2103@gmail.com

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12. Biodistribution of essential oil-conjugated silver nanoparticles

Oana Gherasim, Alexandru Mihai Grumezescu, George Dan Mogosanu, Bogdan Stefan Vasile, Cornelia Bejenaru, Ludovic Everard Bejenaru, Ecaterina Andronescu, Laurentiu Mogoanta

The beneficial synergy between antimicrobial silver nanoparticles (AgNPs) and essential oils (EOs), with therapeutic effects that have been acknowledged and explored for a long time, opens the way towards developing new and promising alternatives for anti-infective therapies. With the aim to improve the cytocompatibility and stability of AgNPs and to overcome the volatilization of EOs, AgNPs conjugated with sage (Salvia officinalis) and cinnamon (Cinnamomum aromaticum) EOs were obtained in our study. The synthesis process was realized either by classical or ultrasound-assisted chemical reduction. Compositional and microstructural characterization of the as-obtained Ag@EO NPs was performed by X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The biodistribution of Ag@EO NPs was evaluated on a mouse animal model.

Corresponding author: Alexandru Mihai Grumezescu, Associate Professor, Eng, PhD; e-mail: grumezescu@yahoo.com

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13. Perineal eventration after abdominoperineal resection for rectal cancer: anatomical, surgical and clinico-pathological landmarks

Dan Cristian Moraru, Dragos Viorel Scripcariu, Dan Ferariu, Viorel Scripcariu, Bogdan Filip

Perineal eventration (PE) is a rare complication after the lower rectal cancer resection surgery, affecting the quality of life of the patient. In 5.5 years of evolution, out of 620 patients with rectal cancer treated by curative surgery, 176 patients with lower ampullary rectal cancer treated by abdominoperineal resection (APR) with the closure of the defect by direct suture of the perineal floor were selected. Ten (5.6%) of them were diagnosed with PE. This paper shows the results of a retrospective study, which compares the clinico-pathological and therapeutic aspects of a subgroup of 166 patients (subgroup I) with APR without PE and a subgroup of 10 patients (subgroup II) with PE. Starting from the question of whether aspects can influence the evolution of PE, we aimed to investigate the similarities and differences between these two groups, from the histological, clinical and therapeutic points of view. Regarding the tumor, node, metastasis (TNM) staging, we encountered the following aspects: for the subgroup II with PE, pT3 predominated, stages N0 and N1 were equal (50%) and the absence of metastases (M0) was found in all cases; in subgroup I, pT3 and N0 also predominated, followed by N1 and N2, and for stage M, M0 is predominant, followed by M1. For the clinical profile of the PE group, the symptoms were characteristic, with the presence of the usual triggering factors [hysterectomy, radiochemotherapy and wide resection surgery - extralevatorial APR]. The therapeutic approach revealed various aspects, including plastic surgery procedures (direct closure, meshes, flaps) used in pelvic reconstruction. The accurate surgical technique applied in order to achieve oncological safety allowed for a longer survival, which favored the appearance of PE in addition to the other favoring factors. Our results underlined the clinico-pathological profile of the two subgroups, without being able to establish a correlation with the appearance and evolution of PE. However, the clinico-pathological risk factors for this condition are not yet fully defined. Therefore, reports based on the experience in the diagnosis and treatment of PE should bring valuable data, aiming to create the knowledge framework for prevention.

Corresponding author: Dragos Viorel Scripcariu, Assistant Professor, MD, PhD; e-mail: dragos-viorel.scripcariu@umfiasi.ro

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14. The morphological changes of the colonic goblet cells and mucin profile in oncohematological patients under Epirubicin-based chemotherapy

Coralia Adina Cotoraci, Alciona Sasu, Alexandru Fica Mircea Onel, Dana Iovanescu, Eftimie Miutescu, Sami Gharbia, Alina Liliana Ciceu, Hildegard Herman, Anca Oana Hermenean

Changes in the lining of the small intestine following chemotherapy have been extensively studied, although also occurs in the large intestine. The aim of this study was to assess the consequences of Epirubicin-based therapy on goblet cells (GCs) and mucus production on colonic mucosa, immediately and after short-time of chemotherapy administration to oncohematological patients, by clinical and histopathological analysis. We assessed the mucus production, composition, and distribution by Alcian Blue (pH 2.5)-Periodic Acid-Schiff (PAS) staining, alongside with the immunoexpression of mucin (MUC)2, MUC4 and inflammatory markers in a series of oncohematological patients, immediately and after short-time of Epirubicin-based chemotherapy cumulative therapy cessation. We showed that GCs number decrease slightly at 48 hours, while mucous secretion became mixed (with a few neutral) after three weeks. Overall, the secretion was increased immediately after the Epirubicin administration, due to the activation of inflammatory pathways, assessed by increased immunostaining of tumor necrosis factor-alpha (TNF-alpha) at 48 hours. The MUC2 and MUC4 showed a decreased immunoexpression at 48 hours after the Epirubicin administration compared to controls and partially restored three weeks after the cessation. Overall, it is highly plausible that all these key players revolve around the chemotherapy-induced mucositis in oncohematological patients and highlights the morphofunctional particularities of the GCs, which further modulates the clinical outcome of the patient.

Corresponding author: Coralia Adina Cotoraci, Professor, MD, PhD; e-mail: ccotoraci@yahoo.com

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15. Gastric cancer - histopathological correlations between tumor and non-tumor gastric mucosa changes

Ion Paun, Andrei Ionut Costin, Vlad Denis Constantin, Ion Lomaca, Nicolae Gabriel Ianosi, Bogdan Socea, Cristina Violeta Tutunaru, Ovidiu Mircea Zlatian, Simona Laura Ianosi, Carmen Daniela Neagoe, Antoanela Valentina Crafciuc, Marius Ionut Stancu

Gastric cancer is a widely geographically distributed malignancy with high prevalence, therefore being a serious health problem that needs standardized methods for early diagnosis and treatment. The aim of the study was to evaluate the correlation of some epidemiological and clinical data with the histological features. The study group was made up of 66 patients that underwent surgical removal of the gastric neoplasm, and the pathological exam showed the morphological features of the tumor, as well as the ones of the unaffected mucosal tissue. Topographically, the highest incidence of the tumor was registered in the gastric antrum, but in recent years, an increased incidence of the superior gastric pole localization was recorded. The macroscopic aspects reveal that the ulcerated type 2 Borrmann is the most frequent, and alongside type 3 Borrmann, the ulcer-infiltrative type represents most of the gastric antrum cancers. The analysis of the tumor invasion showed that most carcinomas underwent surgery when the tumor invaded the serosa (pT3) or even the perigastric tissues (pT4). In our research, we chose Goseki s microscopic classification because of its best coverage of the histological heterogeneity of the gastric carcinomas, providing information about the percentage of the cellular and secretory differentiation with direct impact on the invasion of the tumor. In more than 70% of the cases, the patients showed lesions of severe chronic atrophic gastritis of the non-tumor mucosa. Lately, the incidence of Helicobacter pylori has been 5.5%, lower than indicated by mainstream literature. We observed that the incidence of type 3 incomplete intestinal metaplasia, as the most commonly involved factor in the etiopathogenesis of gastric neoplasms, was encountered in 36.3% of the cases, this percentage rising proportionally with age and being frequently associated with antrum tumors. In conclusion, the permanent analysis of the relation between epidemiological data and some histological features might be relevant for the characterization of the tumoral process or the non-tumor gastric mucosa, leading to an evaluation of the prognosis.

Corresponding author: Simona Laura Ianosi, Professor, MD, PhD; e-mail: simonaianosi@hotmail.com; Antoanela Valentina Crafciuc, MD, PhD Student; e-mail: antoanelacrafciuc@gmail.com

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

Iulia Olaru, Anca Sava, Camelia Tamas, Claudia Florida Costea, Gabriela Florenta Dumitrescu, Aurelian Sorin Pasca, Florin Stefan Olaru, Teodor Stamate

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

Corresponding author: Anca Sava, Professor, MD, PhD; e-mail: dr.anca.sava.68@gmail.com; Camelia Tamas, Lecturer, MD, PhD; e-mail: camelia6ta@yahoo.com

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17. Risk stratification of papillary thyroid microcarcinomas via an easy-to-use system based on tumor size and location: clinical and pathological correlations

Emoke-Andrea Szasz, Adela Corina Nechifor-Boila, Ancuta Elena Zahan, Toader Septimiu Voidazan, Angela Borda

Introduction: We aimed to determine whether two clinically accessible parameters, tumor size and location within the thyroid, correlate with clinicopathological features that are predictors of high risk in papillary thyroid microcarcinomas (PTMCs). Materials and Methods: PTMC cases were obtained from the database of the Department of Pathology, Emergency County Hospital, Targu Mures, Romania. Four tumor groups were created based on tumor size and location: Group I (>=5 mm, subcapsular), Group II (>=5 mm, nonsubcapsular), Group III (<5 mm, subcapsular), and Group IV (<5 mm, nonsubcapsular) PTMCs. Clinicopathological features and follow-up data were compared by univariate and multivariate analysis. Results: Our study included 164 PTMCs (n=70/20/19/55 in Groups I/II/III/IV, respectively). High-grade morphological features, such as plump pink cells (p=0.010), tumor desmoplasia (p=0.022) and sclerosis (p=0.001), infiltrative tumor borders (p=0.005), positive resection margins (p=0.005), invasion into the perithyroid adipose tissue (p=0.001), irregular nuclear membranes (p=0.004), and pseudoinclusions (p=0.001) were significantly more prevalent among Group I PTMCs. Group IV PTMCs were characterized by a paucity of the above-mentioned morphological features, while Group II and III PTMCs displayed intermediate morphological profiles. Conclusions: Group I PTMCs proved to be associated with more aggressive morphological features and might need a more careful clinical approach.

Corresponding author: Adela Corina Nechifor-Boila, MD, PhD; e-mail: adela.nechifor-boila@umfst.ro

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18. Fortuitous discovery of melanomas in the ENT Department - a histopathological and immunohistochemical study

Cornelia Marina Trandafir, Alina Andreea Tischer, Ioana Delia Horhat, Nicolae Constantin Balica, Adrian Mihail Sitaru, Kristine Guran, Raluca Morar, Flavia Baderca, Emilia Manuela Jifcu, Ion Cristian Mot, Ovidiu Nicolae Burlacu, Marioara Poenaru, Cristian Andrei Sarau

The melanoma, having its origin in the melanocyte cells, is one of the most aggressive forms of skin cancer in the world with one of the highest rates of brain metastasis. The incidence of cutaneous melanoma in the Mediterranean countries varies from three to five cases/100 000 people/year. Its prognosis is based on an early diagnosis. Sinonasal mucosal melanoma (SNMM) is an extremely rare tumor, accounting for 0.3-2% of all melanomas. The non-specific symptomatology is often delaying the presentation of the patient at the hospital and therefore the diagnosis. The SNMM is a highly aggressive tumor, and the presence of metastasis at the diagnosis usually implies a poor prognosis. The management of the melanomas requires a precise pre-therapeutic assessment and a multidisciplinary approach for the diagnosis, with surgical treatment or radiotherapy required in order to ensure a better a quality of life. In this paper, we retrospectively analyzed two cases of mucosal melanoma and one case of cutaneous melanoma of the nose.

Corresponding author: Ovidiu Nicolae Burlacu, MD; e-mail: burlacuovidiu@gmail.com; Ion Cristian Mot, MD; e-mail: cristianmotz@yahoo.com

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19. Prenatal findings and pregnancy outcome in fetuses with right and double aortic arch. A 10-year experience at a tertiary center

Ana-Maria Petrescu, Dan Ruican, Ciprian Laurentiu Patru, George Lucian Zorila, Stefania Tudorache, Alexandru Cristian Comanescu, Anca-Maria Istrate-Ofiteru, Anne Marie Badiu, Mihai Ioana, George Alin Stoica, Dominic Gabriel Iliescu

Objective: Our objective was to evaluate the accuracy of the prenatal diagnosis and the relation between the type of right aortic arch (RAA) with other intra- or extracardiac (EC) and chromosomal anomalies. Methods: A retrospective, observational study was conducted between 2011-2020 in a Romanian tertiary center. All RAA cases, including double aortic arch (DAA), were extracted from the databases and studied thoroughly. Results: We detected 18 RAA cases: five (27.78%) type I (mirror image, V type), 11 (61.12%) type II (U type), and two (11.10%) DAA cases. Heart anomalies were associated in 38.89% (overall), 60% (type I), 36.37% (type II), and 0% (DAA) cases. Tetralogy of Fallot represented the most prevalent cardiac malformation (in 22.23% of cases). EC anomalies were present in 44.44% of fetuses (20% of type I, 54.55% of type II, and 50% of DAA cases). Genetic abnormalities were found in 41.17% of pregnancies, with 22q11.2 deletion in 23.53%. 55.55% of the cases had a good neonatal evolution and 44.45% of the pregnancies were terminated. An overall good outcome of pregnancy was noted in 40% of type I RAA, 63.64% of type II RAA, and 50% of DAA cases. All RAA cases examined in the first trimester were correctly diagnosed. Conclusions: RAA can be accurately diagnosed and classified by means of prenatal ultrasound since early pregnancy. A detailed anatomy scan and genetic testing, including 22q11 deletion, should be offered to all pregnancies when RAA is discovered. When isolated, RAA associates a good outcome, indifferently the anatomical type.

Corresponding author: Ciprian Laurentiu Patru, MD, PhD; e-mail: patru_ciprian@yahoo.com; Anca-Maria Istrate-Ofiteru, MD, PhD; e-mail: ancaofiteru92@yahoo.com

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20. Predictors of early and sustained virological response of viral hepatitis C

Alice Elena Ghenea, Anca Marilena Ungureanu, Adriana Turculeanu, Mihaela Popescu, Mara Carsote, Maria Loredana Tieranu, Eugen Nicolae Tieranu, Corina Maria Vasile, Ramona Cioboata, Anca Loredana Udristoiu, Dragos Ovidiu Alexandru, Alex Ioan Salan, Andrei Ioan Drocas

Due to complex interplay between host and viral factors, pathogenesis of chronic hepatitis C (CHC) is considered a challenging issue. Infection with hepatitis C virus (HCV) is not confined only to liver but can induce disturbances in many other organs and systems. Our primary aim for this study was to evaluate biological response rates and sustained virological response (SVR) in patients diagnosed with CHC, treated with Interferon-alpha (IFN-alpha), Pegylated (PEG)-IFN-alpha2a or -alpha2b plus Ribavirin. The second aim of the study was the identification of predictive factors for a favorable response to antiviral therapy in patients diagnosed with CHC. We enrolled in this study 210 patients diagnosed with CHC who have accomplished all inclusion and exclusion criteria, treated with PEG-IFN plus Ribavirin. Patients recovery progress has been evaluated by determining: age, gender; biochemical tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST); serological assays - detect anti-HCV antibody and molecular assays - detect, quantify and/or characterize hepatitis C viral load (ribonucleic acid) (HCV-RNA); liver histopathological (HP) examination. According to their response to treatment, they were classified into responders (n=145) and non-responders (n=65). Liver biopsies were histopathologically evaluated for necroinflammatory grade and fibrosis stage according to the modified Ishak and Metavir scoring systems for chronic hepatitis. Demographic, laboratory, and HP results were introduced in statistical analysis. These parameters were included in area under curve (AUC) analysis in order to estimate their degree of influence on getting early virological response (EVR) and SVR. Our study demonstrates that factors connected to treatment failure in CHC are linked to older age, high hepatitis C viral load, and impaired glucose tolerance at beginning of treatment [high fasting glucose and insulin, high homeostatic model assessment of insulin resistance (HOMA-IR) index] and also to liver histology features (high fibrosis score, liver steatosis, iron infiltration, and more or less high necroinflammatory activity). Analyzing results of our study shows that HOMA-IR index, serum insulin levels, baseline HCV-RNA, baseline mean blood glucose and HP score like Ishak fibrosis score, steatosis score and liver iron score may have a predictive value for obtaining an EVR in patients diagnosed with CHC.

Corresponding author: Anca Marilena Ungureanu, Associate Professor, MD, PhD; e-mail: ancaungureanu65@yahoo.com; Eugen Nicolae Tieranu, Teaching Assistant, MD, PhD; e-mail: tieranueugen@gmail.com

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21. Peripheral adenopathies in children - an attempt of clinical morphological profile

Georgeta Ligia Stanescu, Gigi Calin, Iancu Emil Plesea, Catalina Marin, Mircea Ovidiu Ciobanu, George Alin Stoica, Elena Loredana Selaru, Rebeca Cristiana Serban, Cristina Popescu, Razvan Mihail Plesea, Lucian Paul Dragomir

Aim: The authors have proposed to assess peripheral adenopathies in a series of hospitalized children in order to identify and define clinical and morphological profiles of different types of lymph node (LN) diseases. Materials and Methods: The studied group consisted of 58 patients less than 18 years of age. The investigation algorithm included: gender, age, site, involvement, side, extension and histopathological (HP) type of LN lesions. Tissue fragments were processed using classical histological techniques (formalin fixation and paraffin embedment) and stained with Hematoxylin-Eosin (HE). In some cases (tuberculous lesions and lymphomas), special stainings (Ziehl-Neelsen) and immunohistochemistry were used. Stratification scales of cases were defined according to each parameter in order to compare the data. All obtained data were assessed individually, compared to each other and with similar data from the literature with the help of a statistical apparatus [chi2 (chi-squared) test and analysis of variance (ANOVA) test] in some cases. Results: The young patients were slightly more frequently boys, of all ages but with a mean age of 10 and half years. The affected LNs belonged most often to neck region, either on the left or on the right side but sometimes bilateral or even on the midline; usually, more than one LN was involved in the area. In most of the cases, the lesions were localized in only one LN area. HP picture was dominated by the inflammatory processes, firstly the nonspecific ones, followed by tuberculosis. Discussions: Our observations fitted, for each parameter, with the wide ranges found in the literature. Comparisons between parameters variations revealed differences, sometimes significant that we tried to organize in clinical and morphological profiles. Conclusions: The assessment of our data allowed us to define some clinical and morphological profiles of different types of adenopathy that, by improvement on studies including larger series, could be of real use in daily pediatric practice.

Corresponding author: Iancu Emil Plesea, Professor, MD, PhD; e-mail: emil.plesea@umfcd.ro

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22. Oral cancer histopathological subtypes in association with risk factors: a 5-year retrospective study

Alexandra Roi, Ciprian Ioan Roi, Nicoleta Ioana Andreescu, Mircea Rivis, Ioana Daniela Badea, Noemi Meszaros, Laura Cristina Rusu, Stela Iurciuc

Background: Oral cancer is a worldwide public health problem, being the sixth most common neoplasm. The high mortality rate of this type of cancer is due to a delayed diagnosis, a fast evolution and metastasis, no primary symptomatology, the multitude of risk factors and the lack of awareness among the population concerning oral malignancy. Aim: The aim of this 5-year retrospective study was to evaluate the incidence of oral cancer patients in the Clinic of Maxillo-Facial Surgery, Emergency County Hospital, Timisoara, Romania and quantify the histopathological (HP) subtypes, localization, age, gender, tumor staging and differentiation, positive loco-regional lymph nodes and risk factors. Patients, Materials and Methods: A number of 129 patients diagnosed with oral cancer were included in the study and their medical records were analyzed. A statistical analysis was performed that included the variables gender, age, tumor staging, differentiation grade, HP subtype, lymph nodes, localization, and risk factors. Results: Our results outlined a high prevalence of oral cancer among males (65.9%), squamous cell carcinoma (SCC) being the most common HP subtype. Tumor staging revealed the fact that the majority of were T3 and T4 tumors with dissemination in the loco-regional lymph nodes. In 52% of the cases, tobacco was identified as a risk factor, and the association of tobacco and alcohol was present in 28.3% of the cases. Conclusions: The early diagnosis is crucial for the improvement of oral cancer survival rate. The oral cavity is permanently exposed to carcinogenic substances that associated with other risk factors have an influence upon the incidence of oral malignancies.

Corresponding author: Mircea Rivis, Senior Lecturer, MD, PhD; e-mail: rivis.mircea@umft.ro; Ciprian Ioan Roi, Associate Professor, MD, DMD, PhD; e-mail: ciprian.roi@umft.ro

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23. The immunoexpression of MMP-1 and MMP-13 in eyelid basal cell carcinoma

Irina-Maria Mercut, Cristiana Eugenia Simionescu, Alex Emilian Stepan, Bianca Catalina Andreiana, Ana-Maria Ciurea, Razvan Mercut, Marius Eugen Ciurea

Basal cell carcinoma (BCC) is the most frequent human malignancy and at the same time the most frequent periocular malignancy, representing almost 80% of all non-melanoma skin cancers and 90% of eyelid cancers. The study included 50 cases of eyelid BCC, out of which 41 were nodular BCC (NBCC) and nine were infiltrative BCC (IBCC), with various Breslow scores (BS) and primary tumor (pT) category. We analyzed the immunoexpression of matrix metalloproteinases (MMPs) 1 and 13 in the tumoral epithelial component (TEC) and inflammatory stromal component (ISC) of BCC in relation to the two histopathological parameters. The immunoreaction for MMP-1 was identified in 41 (82%) cases and for MMP-13 in 46 (92%) cases both in the TEC and ISC of both types of BCC. The statistical analysis revealed that both collagenases had positive/high scores significantly associated with advanced BS. For MMP-1, there were statistical associations in TEC related to IBCC and high pT category, while MMP-13 only revealed statistical association in ISC with high pT. The presence of collagenase MMP-1 and MMP-13 expression in a high number of cases, both in TEC and ISC, confirms their intervention in the tumor progression and proposes these MMPs as potential targets in antineoplastic therapy.

Corresponding author: Alex Emilian Stepan, Professor, MD, PhD; e-mail: astepan76@yahoo.com

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24. Correlations between stones composition, dietary and comorbidities context of the lithiasic patient

Catalin Pricop, Marius Ivanuta, Andreea Stan, Dana-Teodora Anton-Paduraru, George Daniel Radavoi, Viorel Jinga, Tudor-Marian Proca, Dragos Puia

The incidence of nephrolithiasis is in full expansion, its etiology being frequently associated with lifestyle changes. The objective of this retrospective study, carried out between April and December 2019, was to identify the correlations of the known lithogenic factors with the chemical structure of the calculi in the patients from the North-Eastern region of Romania. The results obtained after the data analysis of our LAMPA questionnaire (L - liquids, A - antecedents, M - medication, P - associated pathologies, A - aliments) made in evidence a statistically relevant relationship between the heredocollateral history of lithiasis and calcium oxalate dihydrate (COD) calculi, hypertension and calcium oxalate monohydrate (COM) stones, uric lithiasis and diabetes, COD, and obesity, between predominantly uric lithiasis and meat or meat-derived products consumption, between frequent potato consumption and COD stones and the frequently consume of dairy products and predominantly COM calculi. The authors concluded that the use of a complex questionnaire, like LAMPA, together with Fourier-transform infrared (FTIR) spectroscopic and morphological analysis are essential steps for developing an efficient metaphylaxis.

Corresponding author: George Daniel Radavoi, MD, PhD; e-mail: radadaniel@yahoo.com

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25. Calcium fructoborate coating of titanium-hydroxyapatite implants by chemisorption deposition improves implant osseointegration in the femur of New Zealand White rabbit experimental model

Renata-Maria Varut, Petru Razvan Melinte, Andreea Silvia Pirvu, Oana Gingu, Gabriela Sima, Carmen Nicoleta Oancea, Alina Cristina Teisanu, Gheorghe Dragoi, Andrei Bita, Horia Octavian Manolea, Ioana Mitrut, Otilia Constantina Rogoveanu, Ion Romulus Scorei, Johny Neamtu

Background: The identification of biocomposites that improve cell adhesion and reduce bone integration time is a great challenge for implantology and bone reconstruction. Aim: Our aim was to evaluate a new method of chemisorption deposition (CD) for improving the biointegration of hydroxyapatite-coated titanium (HApTi) implants. CD method was used to prepare a calcium fructoborate (CaFb) coating on a HApTi (HApTiCaFb) implant followed by evaluation of histological features related to bone healing at the interface of a bioceramic material in an animal model. Methods: The coating composition was investigated by high-performance thin-layer chromatography/mass spectrometry. The surface morphology of the coating was studied by scanning electron microscopy (SEM), before and after the in vitro study. We implanted two types of bioceramic cylinders, HApTi and HApTiCaFb, in the femur of 10 New Zealand White (NZW) rabbits. Results: The release of CaFb from HApTiCaFb occurred rapidly within the first three days after phosphate-buffered saline immersion; there was then a linear release for up to 14 days. SEM analysis showed similar morphology and particle size diameter for both implants. Around the porous HApTiCaFb implant, fibrosis and inflammation were not highlighted. Conclusions: Easily applied using CD method, CaFb coatings promote HApTi implant osseointegration in the femur of NZW rabbits.

Corresponding author: Ion Romulus Scorei, Professor, Biochem, PhD; e-mail: romulus_ion@yahoo.com

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26. Histopathological and immunohistochemical aspects of bone tissue in aseptic necrosis of the femoral head

Razvan Marius Vicas, Florian Dorel Bodog, Florin Ovidiu Fugaru, Florin Grosu, Oana Badea, Liviu Lazar, Mariana Lidia Cevei, Carmen Delia Nistor-Cseppento, Gabriela Corina Beiusanu, Gineta Holt, Florica Voita-Mekeres, Calin David Buzlea, Ovidiu Tica, Adina Nicoleta Ciursas, Sorin Nicolae Dinescu

Femoral head osteonecrosis, also known as avascular necrosis, is a disease with a multifactorial etiology, characterized by a profound change of bone architecture, which leads to the diminishing of bone resistance and femoral head collapse. The main causes that lead to femoral head necrosis are represented by the decrease of local blood perfusion and increase of intraosseous pressure, because of an excessive development of adipose tissue in the areolas of the trabecular bone tissue in the femoral head. The histopathological and immunohistochemical (IHC) study performed by us showed that most of bone trabeculae were damaged by necrotic-involutive processes, their sizes being reduced, both regarding their length and their diameter; generally, the spans were thin, fragmented, distanced among them, which led to the occurrence of some large areolar cavities, full of conjunctive tissue, rich in adipocytes. Some of the residual bone spans even presented microfractures. In the structure of the trabecular bone tissue, numerous cavities showed lack of content, which indicates the death of osteocytes inside, while the endosteum appeared very thin, with few osteoprogenitor, flattened, difficult to highlight cells. The IHC study showed a low reaction of the bone reparatory processes and a reduced multiplication capacity of bone cells involved in the remodeling and remake of the diseased bone tissue. Nevertheless, there were identified numerous young conjunctive cells (fibroblasts, myofibroblasts), positive to proliferating cell nuclear antigen (PCNA), cells that have a high capacity of multiplication, participating in the formation of a fibrous conjunctive tissue (sclerous) instead of the damaged bone trabeculae. The formation of fibrous conjunctive tissue causes the reduction of mechanical resistance of the femoral head and its collapse. The IHC study of the microvascularization in the femoral head damaged by aseptic osteonecrosis showed the presence of a very low vascular system, both in the residual bone trabeculae and in the sclerous conjunctive tissue. Of the inflammatory cells present in the spongy bone tissue of the femoral head affected by osteonecrosis, the most numerous ones were the macrophages. Both macrophages and T- and B-lymphocytes had a heterogenous distribution.

Corresponding author: Florin Grosu, MD, PhD; e-mail: drfloringrosu@gmail.com; Adina Nicoleta Ciursas, MD, PhD; e-mail: adina.ciursas@gmail.com

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27. Analysis of the distribution and expression of some tumor invasiveness markers in palate squamous cell carcinomas

Adrian Patru, Valeriu Surlin, Claudiu Margaritescu, Eduard Mihai Ciuca, Marius Matei, Mircea-Sebastian Serbanescu, Adrian Camen

Oral cancer remains an important global health issue and despite recent diagnostic and therapeutic advances, it continues to have an unfavorable prognostic and decreased survival. Although palatal tumors represent one of the rarest locations of oral squamous cell carcinomas (SCCs), they are among the most aggressive local tumors, leaving behind important morpho-functional disabilities. In order to explain such local aggressiveness, the present study aims to investigate the immunohistochemical expression in palate SCCs of some markers known to be involved in the process of tumor invasiveness, such as Wiskott-Aldrich syndrome like (WASL), Claudin-1 (CLDN1), Integrin beta-6 (ITGB6) and c-Mesenchymal to epithelial transition protein (c-Met). We have found here a higher tumor WASL and CLDN1 reactivity in well-differentiated (G1) palate SCCs, and regardless the histological type, degree of differentiation or tumor topography, an overexpression at the invasion front, and in those palate SCC cases with muscular invasiveness and with lymph node (LN) dissemination. ITGB6 and c-Met had a higher reactivity in moderately differentiated (G2) palate SCCs, especially at the periphery of tumor proliferations, at the invasion front and in those high invasive cases and as well as in those that associated LN dissemination. All four investigated markers were also positive at the level of LN metastatic proliferations. None of the markers could statistically stratify on age group and pain, and on bone and perineural invasion while all of them statistically stratified on survival and grading. We concluded that these markers have a prognostic role allowing the identification of those cases with an unfavorable clinical evolution and decreased survival.

Corresponding author: : Claudiu Margaritescu, Professor, MD, PhD; e-mail: c_margaritescu2000@yahoo.com; Mircea-Sebastian Serbanescu, Lecturer, MD, PhD; e-mail: mircea_serbanescu@yahoo.com

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28. Contribution of the cyto-histopathological diagnosis and ultrastructural parameters to the evaluation of maxillary cysts - a 10-year multidisciplinary approach

Mircea Rivis, Ciprian Ioan Roi, Alexandra Roi, Ovidiu Alexandru Mederle, Diana Florina Nica, Doina Chioran, Laura Cristina Rusu, Stela Iurciuc, Adina Valeanu

Diagnostic and treatment plans in cystic jawbone tumors are often difficult to address. The etiopathogenic links involved in cell-matrix differentiation disorders are complex. Quantification of the inflammatory process in the evolution of cystic odontogenic lesions highlights a particular reactivity of the host, especially age-dependent and the endodontic-periodontal space interrelation, drawing attention to the difficulties of etiopathogenic, evolution, prognostic and treatment of these lesions. Difficulties in histopathological (HP) diagnosis are reported by the lack of morphofunctional integration of dental tissues, both topographically and evolutionarily, especially when odontogenic epithelial remains in the cystic wall, reactive bone condition, appearance and condition of the reactive epithelium are overlooked. In this study, we developed an interdisciplinary approach for the dynamics of tissue morphology found in the walls of maxillary cysts. Failure to recognize the tissues that form the cystic lesion leads to misinterpretations of pathology and to the wrong classification in the group of maxillary cysts. We analyzed by different techniques 564 biopsy fragments from maxillary cystic lesions, most of which are clinically classified as inflammatory or odontogenic ones. From our experience, we reevaluated the lesions with cystic changes and completed the diagnosis in 10-12% of cases. The most common maxillary cystic lesion encountered by us was the root cyst, an inflammatory dental cyst, which has been over diagnosed clinically, radiologically and histopathologically. Recognition and selection of embryonic remnants from odontogenesis is crucial for the HP diagnosis of maxillary cysts, allowing the clinician to monitor treatment or to develop evolutionary-prognostic perspectives of odontogenic cystic lesions.

Corresponding author: Ciprian Ioan Roi, Associate Professor, MD, DMD, PhD; e-mail: ciprian.roi@umft.ro; Stela Iurciuc, Lecturer, MD, PhD; e-mail: stela_iurciuc@yahoo.com

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29. Gingival proliferative growth - stress and cytoarchitecture related with fixed and mobile orthodontic therapy

Catalin Petru Simon, Andrei Gheorghe Marius Motoc, George Alexandru Simon, Diana Brezovan, Florin Muselin, Romeo Teodor Cristina, Dana Cristina Bratu

The fixed orthodontic measures taken induce significant stress to the gingival growth process during arch wire maneuvers of aligning and leveling. We observed, for a period of one to four years, fixed orthodontic devices in 80 human subjects. From these, we selected 44 subjects (22 women and 22 men) where the inflammatory process exhibited following the orthodontic fixed treatment, and with vacuum-formed orthodontic retainers (VFR) succeeding to fixed treatment. Samples were collected from each patient and histological and immunohistochemical (IHC) methodology was made to analyze the cytoarchitecture. Statistics were made after one-way analysis of variance (ANOVA), with the Bonferroni s correction. The IHC examination performed in the early stage revealed the presence in the inflammatory infiltrate of CD8-type T-lymphocytes, and of dendritic cells in large numbers. The examination performed in the late stage revealed the presence in the inflammatory infiltrate of CD20-type B-lymphocytes, which are mature cells capable of immunoglobulin synthesis, their activation being an important step in the maturation of the antibody response. The stress generated by arch wires in both genders was significantly higher than in the case of VFR. This observation was pointed out also by the cytohistological investigation outcome but was also based on an original scale conceived by our research team, following gingival hyperplasia evaluation. Also, with statistical significance, the comparative obtained values for men (p=0.01) and for women (p=0.001) illustrate clinical observations, allowing to affirm that, in our case, men were more stressed in bearing arch wire devices (AWD) and VFR, in comparison with women.

Corresponding author: Romeo Teodor Cristina, Professor, DVM, PhD; e-mail: romeocristina@usab-tm.ro

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30. Evaluation of the incidence of inflammatory and tumor pathology of nose and nasal sinus region

Salah Nassrallah, Cristian Mircea Neagos, Simona Liliana Mocan, Adriana Neagos

Inflammatory and nasal-sinus tumor pathology is a field of great interest in rhinology worldwide. The aim of the paper is to determine the prevalence of nasal and nasal-sinus inflammatory diseases, as well as nasal and nasosinusal rhinosinusitis tumors, in association or not with inflammatory diseases, using histopathological (HP) examination. It is also desired to identify the association of chronic inflammatory pathology with the tumor one, considering inflammation and immunodeficiency as local susceptibility factors. A retrospective study was performed on a group of 254 patients hospitalized between 2018-2019 in Department of Otorhinolaryngology, Emergency County Hospital, Targu Mures, Romania. Based on the clinical and HP examination, the distribution by inflammatory pathologies was made as follows: 175 nasal polyposis, 108 chronic rhinitis, 39 sinusitis - strictly affecting the sinus and 28 chronic polyposis rhinosinusitis - nasal and sinus association. Considering the evaluation of the incidence of benign tumor pathology, the following were found: out of the total examined cases, 4% squamous papilloma, 4% exophytic papilloma, 44% Schneiderian papilloma, 4% benign fibrous histiocytoma, 18% hemangioma, 4% hamartoma, and 4% osteoma were identified. The incidence of malignant tumors is 26% squamous cell carcinoma, 12% intestinal adenocarcinoma, 2% nonintestinal type adenocarcinoma, 2% large B-cell lymphoma, 2% plasma cell, 2% olfactory neuroblastoma, 7% malignant melanoma, 16% basal cell carcinoma. The paper draws attention to the increased incidence of tumor and inflammatory pathology both individually and in combination, considering the involvement of the clinical correlation with the HP result completed, if necessary, with immunohistochemical examinations, for a precise diagnosis.

Corresponding author: Adriana Neagos, Senior Lecturer, MD, PhD; e-mail: neagos.adriana@gmail.com

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31. The quality of colorectal polypectomy. Is it enough to have just a visual assessment of the site?

Mihaela Calita, Dan Nicolae Florescu, Costin Teodor Streba, Andreea Doriana Stanculescu, Mirela Marinela Florescu, Petrica Popa, Dan Ionut Gheonea, Carmen Nicoleta Oancea, Adrian Saftoiu

Introduction: Performing a colonoscopy allows the examination of the entire colon and the assessment of polyps. Patients, Materials and Methods: We performed a retrospective analysis of prospectively collected data from January 2018 until February 2020 (two years), in which we enrolled a number of 210 patients performing colonoscopy in the Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy of Craiova, Romania. We performed 326 polypectomies. Results: We classified the polyps into diminutive (n=169), small (n=103) and large polyps (n=54). Regarding the polypectomy technique, our results indicated that 40 out of 48 (83.3%) polypectomies with the biopsy forceps were complete, as well as 27 out of 31 (87.1%) cold snare polypectomies and 12 out of 14 (85.7%) hot snare polypectomies. The differences were not statistically significant (p=0.116). Regarding the number of incomplete polypectomies, our data suggests that the high expertise endoscopist had two incomplete resections (5.1% of total), the medium expertise endoscopist 1 had also two incomplete resections (11.1% of total), the medium expertise endoscopist 2 had three incomplete resections (15% of total), the limited expertise endoscopist 1 had three incomplete resections (27.27% of total) and the limited expertise endoscopist 2 had four incomplete resections (30.76% of total). Analyzing the data, the differences were statistically significant (p=0.006). Conclusions: Our study is able to suggest that high-definition white-light endoscopy (HD-WLE) macroscopic visualization of the polyp resection site is not enough to assess complete polyp resection and follow-up colonoscopy should be performed for cases with incomplete margins of resection.

Corresponding author: Dan Nicolae Florescu, MD, PhD; e-mail: nicku.dan@gmail.com

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32. Prenatal diagnosis of syndromic alobar holoprosencephaly associated with digynic triploidy fetus

Cristina-Crenguta Albu, Dinu-Florin Albu, Anca Patrascu, Stefan Dimitrie Albu, Ion Cristian Efrem, Alexandru Marian Goganau

Holoprosencephaly (HPE) is a dramatic human brain malformation sequence with an extreme variable phenotypic spectrum and genetic heterogeneity, variable degree of severity and unknown etiology, in many cases. HPE is classified into syndromic, chromosomal, and non-syndromic, non-chromosomal. The most cases of HPE are syndromic. We present an atypical case of syndromic alobar HPE associated with digynic triploidy fetus, prenatally diagnosed, early at 18 weeks of gestation, by ultrasound (US) and complex genetic investigations. The US examination was performed with a specialized US machine, General Electric Voluson E10 OLED BT18, using two-dimensional (2D) scanning, three-dimensional (3D) image reconstruction, four-dimensional (4D) spatiotemporal image methodology and the highest power Doppler US technology. A detailed US examination of the fetus revealed several major abnormalities of the fetal head and severe facial malformations. Based on the antenatal US findings, the fetus was diagnosed with alobar HPE. After a careful examination and genetic counseling, additional cytogenetic investigations and molecular genetic analyses were performed, which revealed an abnormal number of 69 chromosomes, digynic triploidy (69,XXY). Two days later, the parents choose to interrupt the current gestation because of major fetal malformations. The pathological examination of the embryo reaffirmed the antenatal diagnostics.

Corresponding author: Cristina-Crenguta Albu, Associate Professor, MD, PhD; e-mail: crenguta.albu@yahoo.com; Stefan Dimitrie Albu, DMD, PhD Student; e-mail: stevealbu@yahoo.com

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33. Replaced right hepatic artery originated from splenic artery, in association with gastrosplenic trunk: a case report

Laura-Andreea Bolintineanu, Nicoleta Iacob, Agneta Maria Pusztai, Horia Ples, Petru Matusz

The authors report a case of a 74-year-old woman found to have an extremely rare case highlighted by multidetector computed tomography (MDCT) angiography, with the presence of a replaced right hepatic artery (RRHA) arising from the splenic artery (SA). In this case, the SA arose from a gastrosplenic trunk (GST). The GST had an endoluminal diameter of 9.2 mm at its origin and a length of 9.3 mm. It arose directly from the anterior abdominal aortic wall, at the level of the T12-L1 intervertebral disc. The SA branched off from the GST and travelled in front of the abdominal aorta (AA) for 18.2 mm up to the level of the L1-L2 intervertebral disc. The SA then continued along an upward and tortuous path towards the splenic hilum. The inflection point of the SA trunk was located above the origin of superior mesenteric artery (SMA). The RRHA arose from the right of this inflection point. The RRHA had an endoluminal diameter of 3.0 mm at its origin and a length of 96.0 mm; it had a downward trajectory towards the hepatic hilum. The common hepatic artery (CHA) had an endoluminal diameter of 6.2 mm at origin and arose directly from the anterior wall immediately to the right of the mediosagittal plane of the AA. Knowledge of this rare anatomical variation is important for interventional radiologists, oncologists, hepatic and abdominal surgeons.

Corresponding author: Agneta Maria Pusztai, Senior Lecturer, MD, PhD; e-mails: pusztai.agneta@umft.ro, agipusztai@yahoo.com

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34. Giant pleomorphic sarcoma of the tongue base - a cured clinical case report and literature review

Daniela Vrinceanu, Mihai Dumitru, Anghelus-Adrian Stefan, Carmen Aurelia Mogoanta, Maria Sajin

Pleomorphic sarcoma of the tongue base is an extremely rare pathology finding. Our review of current databases returned fewer than 10 articles available free full text on this subject. We review the current state of art management guidelines for this type of tumor. Our case presented surprisingly a favorable evolution despite the huge dimensions, the tumor type, and associated pathology. The patient received radiation therapy and oncological treatment followed by revision surgery consisting of partial glossectomy for the residual tumor. Histological examination of the operatory specimen showed a residual tumor of pleomorphic sarcoma type, with clear margins. The evolution was without relapse after 18 months.

Corresponding author: Daniela Vrinceanu, MD, PhD; e-mail: vrinceanudana@yahoo.com; Carmen Aurelia Mogoanta, Lecturer, MD, PhD; e-mail: carmen_mogo@yahoo.com

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35. Management of an old woman with cavernous sinus thrombosis with two different mechanisms: case report and review of the literature

Traian Flavius Dan, Silviana Nina Jianu, Nicoleta Iacob, Andrei Gheorghe Marius Motoc, Georgiana Munteanu, Adelina Baloi, Nicolae Albulescu, Dragos Catalin Jianu

Cavernous sinus thrombosis (CST) usually produces a characteristic clinical syndrome. Septic CST represents a sporadic, but severe complication of infection of the cavernous sinuses, which can bring high mortality and morbidity rates if not treated right away. Case presentation: The current research is a case report of a 64-year-old woman with inherited thrombophilia who developed an acute mastoid infection that resulted in septic right CST. The clinical diagnosis was verified by laboratory studies and evidence from high-resolution computed tomography (HRCT), magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA). Clinical medical care resulted in the patient being successfully treated with low-molecular-weight heparin and broad-spectrum intravenous antibiotics, which avoided severe complications.

Corresponding author: Andrei Gheorghe Marius Motoc, Professor, MD, PhD; e-mail: amotoc@umft.ro; Georgiana Munteanu, MD; e-mail: isfan_georgiana@yahoo.com

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