ROMANIAN JOURNAL of MORPHOLOGY and EMBRYOLOGY

Vol. 59 No. 1, 2018

1. Microglia morphology in the physiological and diseased brain - from fixed tissue to in vivo conditions

Laura Stopper, Tudor-Adrian Balseanu, Bogdan Catalin, Otilia-Constantina Rogoveanu, Laurentiu Mogoanta, Anja Scheller

First mentioned almost 100 years ago, neuroresearch has linked microglia to the initiation and/or maintenance of most central nervous system pathologies. Since their discovery, we learned that the microglia immune status is often correlated directly to their morphology. However, only recently, have we realized that, in vivo microglia are extremely dynamic cells capable to respond within minutes. Therefore, the name resting microglia is replaced slowly with surveilling microglia. Even more recent, it has been shown that microglia change their morphology and/or immune status depending on the way the tissue is obtained, processed and imaged, making labeling microglia, based on their morphology alone, as active or surveying even more difficult. All these observations correlated with a better understanding of cellular and subcellular process that microglia undergo in pathological conditions, could have profound implications on the time window and/or targets used to ensure the best outcome, when treating brain disease.

Corresponding author: Bogdan Catalin, Lecturer, MD, PhD; e-mail: bogdan.catalin@umfcv.ro; Anja Scheller, PhD; e-mail: anja.scheller@uks.eu

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2. Clinicopathological significance and prognostic value of myoinvasive patterns in endometrial endometrioid carcinoma

Cornelia Amalinei, Anda Maria Aignatoaei, Raluca Anca Balan, Simona Eliza Giusca, Ludmila Lozneanu, Elena Roxana Avadanei, Irina-Draga Caruntu

Endometrioid endometrial carcinoma has an overall good prognosis. However, variable five-year survival rates (92%-42%) have been reported in FIGO stage I, suggesting the involvement of other factors related to tumor biological behavior. These may be related to the role played by epithelial-mesenchymal transition (EMT) and cancer stem cells in endometrial carcinogenesis. In this context, our review highlights the prognostic significance of several types of myoinvasion in low grade, low stage endometrioid endometrial carcinoma, as a reflection of these molecular changes at the invasive front. According to recently introduced myoinvasive patterns, the diffusely infiltrating and microcystic, elongated, and fragmented (MELF) patterns show loss of hormone receptors, along with EMT and high expression of cancer stem cell markers, being associated with a poor prognosis. Additionally, MELF pattern exhibits a high incidence of lymphovascular invasion and lymph node metastases. Conversely, the broad front pattern has a good prognosis and a low expression of EMT and stem cells markers. Similarly, the adenomyosis (AM)-like and adenoma malignum patterns of invasion are associated to a favorable prognosis, but nevertheless, they raise diagnostic challenges. AM-like pattern must be differentiated from carcinoma invasion of AM foci, while adenoma malignum pattern creates difficulties in appreciating the depth of myoinvasion and requires differential diagnosis with other conditions. Another pattern expecting its validation and prognostic significance value is the nodular fasciitis-like stroma and large cystic growth pattern. In practice, the knowledge of these patterns of myoinvasion may be valuable for the correct assessment of stage, may improve prognosis evaluation and may help identify molecules for future targeted therapies.

Corresponding author: Anda Maria Aignatoaei, MD, PhD Student; e-mail: anda_ignt@yahoo.com

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3. The role of tumor microenvironment in development and progression of malignant melanomas - a systematic review

Simona Gurzu, Marius Alexandru Beleaua, Ioan Jung

To reveal the particular aspects of the tumor microenvironment of malignant melanomas, a systematic review including 34 representative papers was performed. The review took into account the aspects related the Wnt/beta-catenin pathway-related epithelial-mesenchymal transition (EMT) versus mesenchymal-epithelial transition (MET) of keratinocytes, fibroblasts and melanoma cells, as possible tools for understanding genesis and evolution of malignant melanoma. The possible reversible features of EMT and the role of tumor microenvironment in the metastatic process were also analyzed. A particular issue was related on the cancer stem cells that include melanocyte stem cells (McSCs) and multipotent mesenchymal stem/stromal cells (MSCs). As the McSCs embryological development in mouse is not similar to human development, the role of stem cells in genesis and development of human melanoma should be proved in human melanoma cells only. For further development of targeted therapy, a better understanding of melanomagenesis pathways and its microenvironment particularities is necessary.

Corresponding author: Simona Gurzu, Professor, MD, PhD, Dr. habil.; e-mail: simonagurzu@yahoo.com

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4. Immunohistochemistry predictive markers for primary colorectal cancer tumors: where are we and where are we going?

Alexandru Barbalan, Andrei Cristian Nicolaescu, Antoanela Valentina Magaran, Razvan Mercut, Maria Balasoiu, Gabriela Bancescu, Mircea-Sebastian Serbanescu, Octavian Fulger Lazar, Adrian Saftoiu

The aim of our study is to highlight and organize the recently published immunohistochemistry (IHC) predictive biomarkers of primary colorectal cancers (CRCs) that could lead to practical implementation. We reviewed articles that examined CRC samples with significant statistic correlation between the IHC marker expression and disease progression over time, relationships with the available clinical features and those who detect the prognosis of drug effects. Our analysis showed that nine markers could correlate with medical treatment response of CRCs in different stages. When using better overall survival (OS) and better disease-free survival (DFS) as a grouping factor, there were 14 markers that could be used in assessing CRC prognosis. By using poor prognostic for the OS and the DFS as a grouping factor, we found 43 markers. Subgroup analysis was also performed based on the 32 markers recently confirmed to predict metastasis evolution or the recurrence risks. Venous invasion could be predictable for tumors, statistically significant metastasis susceptibility was observed for markers and also the capacity to evaluate recurrence. CRCs integrate a variety of localizations and there are proofs that distinguish the sites of tumors. The studies reporting data specifically for rectal cancer separating it from colon cancer contained seven IHC markers. In order to be able to implement a predictive biomarker in clinical practice, it must comply with certain criteria as clinical value and analytical proof. Unique biological signature of CRC can be distinguished by identifying biomarkers expression. Several markers have shown potential, but the majority still need to render clinical utility.

Corresponding author: Razvan Mercut, Assistant Professor, MD, PhD; e-mail: razvanmercut@gmail.com; Octavian Fulger Lazar, Professor, MD, PhD; e-mail: lazarfulger@yahoo.com

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5. The prostatic cellular and molecular kaleidoscope. Starting points for carcinogenesis

Andrei Daniel Timofte, Irina-Draga Caruntu

The prostate cancer is a heterogeneous disorder concealing different phenotypical and functional subtypes of cancer cells. This heterogeneity mirrors the normal prostate cell lineages whose alterations represent the starting points of the carcinogenesis mechanism. The histological structure of the prostate comprises two main types of cells: epithelial and stromal, with a stromal to epithelial ratio of 2:1. The prostate acini are lined by a contiguous layer composed of four different subtypes of epithelial cells: secretory luminal, basal, neuroendocrine, and transit-amplifying. The epithelial component is enclosed in a stromal tissue, consisting of several types of cells: smooth muscle cells (the most numerous cell type), fibroblasts, and myofibroblasts. Despite their quite similar morphological appearance in light microscopy, the molecular markers expressed by the normal epithelial and stromal prostatic components, as well as the stem cells show that the prostatic cells are not equal. Numerous efforts have been made to identify the profile of prostate stem cells, and their role in cellular turnover and morphogenesis of the prostatic tissue, by using experimental and/or human studies. Consequently, several hypotheses regarding the location and the phenotype of these cells were formulated and tested, mainly in animal models. The molecular mapping of normal human prostate tissue might be the key for unlocking the intricate mechanisms of prostate carcinogenesis. Within this context, the prostatic cancer stem cells are thought to play an important role in tumor initiation, progression, recurrence and also therapy resistance. The cancerous phenotype of a stem cell can be reached via multiple genetic trajectories and epigenetic alterations, resulting in different subclonal populations of cancer stem cells, thus explaining the heterogeneity of the prostatic neoplasia. Future efforts should be directed towards better understanding of the relationship and interactions between these cancer stem cells subpopulations, their microenvironments, and also towards characterizing the signaling pathways and molecules involved in the regulation of prostatic cancer stem cells. The results of these studies could offer a different, more comprehensible perspective for a new, molecular classification of prostate cancer, overlapping the existing histological one.

Corresponding author: Irina-Draga Caruntu, Professor, MD, PhD; e-mail: irinadragacaruntu@gmail.com

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6. Mg-Zn alloys, most suitable for biomedical applications

Alexandra Catalina Birca, Ionela Andreea Neacsu, Otilia Ruxandra Vasile, Ion Ciuca, Ion Mihai Vasile, Mohammed Alqasim Fayeq, Bogdan Stefan Vasile

In this review are highlighted the corrosion and biocompatibility of biodegradable Mg alloys for their use in orthopedic applications. It was revealed that mixing with alloying elements, such as Mn and Zn, provides improved corrosion resistance to Mg alloys; this pursuit is built on the fact that Mg and its alloys are degradable through their time in the human body. Furthermore, Mg alloys afford a characteristic profile that is very close or even almost identical to that of human bone. Minimizing the rate of corrosion of Mg is the most adequate method, because a low corrosion rate of an Mg implant involves a decrease in the extent of hydrogen evolution and alkalization, which allow the human body to gradually absorb or consume the corrosion products.

Corresponding author: Bogdan Stefan Vasile, Scientific Researcher, PhD; e-mail: bogdan.vasile@upb.ro

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7. The role of skin and muscle biopsy in the diagnosis of main connective tissue diseases

Sineta Cristina Firulescu, Diana Rodica Tudorascu, Cristina Dorina Parvanescu, Andreea Beatrice Chisalau, Alexandra Eugenia Bastian, Ion Cristian Efrem, Andreea Lili Barbulescu, Mircea Catalin Fortofoiu, Cristina Criveanu, Petronela Ionescu, Stefan Cristian Dinescu, Andreea Daniela Tudorancea, Paulina Lucia Ciurea, Ananu Florentin Vreju

Systemic involvement in autoimmune diseases is often unclear and organ changes are confounding, thus making it difficult to have an early accurate diagnosis. In those situations, both clinical and paraclinical findings might orientate the diagnosis, but only histological or immunohistochemistry changes might be accurate enough. The skin histological changes are relevant and sometimes might have a tremendous role in the accurate diagnosis of autoimmune rheumatic diseases, due to the correlation with the clinical systemic manifestations of the diseases and through the accessibility of biopsy. In the same time, muscle biopsy can provide important support for physicians improving diagnosis and optimizing management of connective tissue diseases.

Corresponding author: Alexandra Eugenia Bastian, Lecturer, MD, PhD; e-mail: aleca.bastian@yahoo.com

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8. Correlations between morphological changes induced by curcumin and its biological activities

Laura Stoica, Bogdan Alexandru Stoica, Doinita Olinici, Pavel Onofrei, Emanuela Ana Botez, Carmen Elena Cotrutz

Curcumin is a phytochemical polyphenol extracted from turmeric rhizome, with multiple biological activities, intensively studied in various therapeutic areas. Its effects covers a wide range of specialties, from the neuroprotective to the antimetastatic properties, influencing pathologies from cardiovascular, neuronal and oncological fields, as a part of its broad spectrum of action. These effects are explained by antioxidant, anti-inflammatory and anticarcinogenic simultaneous roles of curcumin and its derivatives. In this review, we selected the information about morphological evidences correlated with the biological effects on the following organ systems: the central nervous system (including neurological pathology, such as Parkinson s and Alzheimer s disease), the cardiovascular system (including disorders like atherosclerosis, endothelial dysfunction and drug-induced myotoxicity), multiple forms of cancer, and metabolic syndromes including diabetes. The central point of this review was to target a variety of morphological changes at microscopic level induced by curcumin, using different microscopy techniques.

Corresponding author: Bogdan Alexandru Stoica, Associate Professor, MD, PhD; e-mail: bogstoica@gmail.com

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9. Hyaluronic acid-based scaffolds for tissue engineering

Cristina Chircov, Alexandru Mihai Grumezescu, Ludovic Everard Bejenaru

Hyaluronic acid (HA) is a natural glycosaminoglycan found in the extracellular matrix of most connective tissues. Due to its chemical structure, HA is a hydrophilic polymer and it is characterized by a fast degradation rate. HA-based scaffolds for tissue engineering are intensively studied due to their increased biocompatibility, biodegradability and chemical modification. Depending on the processing technique, scaffolds can be prepared in the form of hydrogels, sponges, cryogels, and injectable hydrogels, all discussed in this review.

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

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10. Sepsis and identification of reliable biomarkers for postoperative period prognosis

Cristian Adrian Silosi, Isabela Silosi, Vlad Padureanu, Maria Bogdan, Stelian Stefanita Mogoanta, Marius Eugen Ciurea, Manole Cojocaru, Lidia Boldeanu, Carmen Silvia Avramescu, Mihail Virgil Boldeanu, Dragos George Popa

Sepsis is currently defined as the presence of organ dysfunction occurring as the result of a disturbed host response to a serious infection. Sepsis is one of the most common diseases, which cause mortality and a considerable absorber of healthcare resources. Despite progress in technology and improving knowledge of pathophysiology, the disease mechanism is still poorly understood. At present, diagnosis is based on non-specific physiological criteria and on the late identification of the pathogen. For these reasons, the diagnosis may be uncertain, treatment delayed or an immunomodulatory therapy cannot be established. An early and reliable diagnosis is essential to achieve better outcomes on disease progression. The host response to infection involves hundreds of many mediators of which have been proposed as biomarkers. There is a need for new diagnostic approaches for sepsis, new sepsis biomarkers that can aid in diagnosis, therapeutic decision and monitoring of the response to therapy. The differentiation of sepsis from non-infectious systemic inflammatory response syndrome is difficult, and the search for a highly accurate biomarker of sepsis has become one important objective of the medicine. The goal of our review is to summarize the recent advances on the most commonly studied serum biomarkers, evaluated in clinical and experimental studies, for early diagnosis of sepsis and their informative value in diagnosis, prognosis, or response to therapy. In this context, we have tracked the clinical utility of measuring serum biomarkers, such as procalcitonin, pro- and anti-inflammatory cytokines, C-reactive protein, leptin and their combinations. Currently, has not been identified an ideal biomarker to aid in the diagnosis of sepsis. It is hoped that the discovery of new serum markers, as well as their combinations, will serve for the diagnosis and prognosis of sepsis.

Corresponding author: Vlad Padureanu, Teaching Assistant, MD, PhD; e-mail: vldpadureanu@yahoo.com

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11. A morpho-functional study using PEP/LVET ratio and global longitudinal strain in patients with dilated cardiomyopathy

Oana Maria Corici, Cornelia-Andreea Tanasie, Dragos Ovidiu Alexandru, Mihaela Corina Florescu, Maria Victoria Comanescu, Kamal Constantin Kamal, Tiberiu Stefanita Tenea-Cojan, Maria Iancau, Sorin Nicolae Dinescu

Aim: To assess left ventricular (LV) systolic function and morphology in patients with severe dilated cardiomyopathy (DCM), using both conventional and a complex technique, speckle-tracking echocardiography, and evaluate the correlation between pre-ejection period and left ventricular ejection period (PEP/LVET) ratio, global longitudinal strain (GLS), and severity of the condition. Patients, Materials and Methods: Seventeen patients were enrolled after rigorous criteria. Echocardiography was performed in conventional and speckle-tracking mode, in all patients with DCM, in sinus rhythm. LV dimensions, volumes and ejection fraction (LVEF) were measured. PEP/LVET ratio was obtained from apical 5-chamber axis and was defined as the time between QRS onset and LV ejection reported to LV ejection period. Speckle-tracking imaging was performed in offline mode and GLS was obtained from parasternal 4-, 3-, 2-chamber apical view, by averaging longitudinal peak systolic strain of all 17 LV-segments. Results: New York Heart Association (NYHA) functional class correlated significantly with LVEF (-0.82; p=0.0006), PEP/LVET (0.86; p=0.001) or GLS (0.85; p=0.0002). Considerable correlations were between mitral regurgitation (MR) severity and LVEF (-0.65; p=0.01) or PEP/LVET (0.69; p=0.0059), but higher were between MR severity and GLS (0.76; p=0.0018). Tricuspid regurgitation (TR) grading correlated statistically with LVEF (-0.62; p=0.01), PEP/LVET and GLS (0.6; p=0.018; and 0.62; p=0.014, respectively). As opposed to the parameters in conventional echocardiography, GLS correlated with DCM etiology (p=0.0046) and with the gender (p=0.048). Conclusions: This study demonstrates that, in patients with DCM, assessment of cardiac dyssynchrony can be accurately accomplished by combining parameters in conventional and in speckle-tracking echocardiography.

Corresponding author: Dragos Ovidiu Alexandru, Lecturer, MD, PhD; e-mail: dragosado@yahoo.com

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12. Vestibular sensory functional status of cochlear implanted ears versus non-implanted ears in bilateral profound deaf adults

Romica Sebastian Cozma, Lucia Corina Dima-Cozma, Luminita Mihaela Radulescu, Maria Cristina Hera, Cristian Martu, Raluca Olariu, Bogdan Mihail Cobzeanu, Oana Roxana Bitere, Mihail Dan Cobzeanu

Patients with hearing loss who underwent cochlear implantation can present symptomatic or asymptomatic vestibular damages earlier or later after the surgery. The vestibular permanent lesions could be acute, produced by surgical trauma or could be progressive due to local morphological changes made by the presence of the portelectrode in the inner ear (fibrosis related, ossification, basilar membrane distortion, endolymphatic hydrops). Besides histopathological findings in inner ear of cochlear implanted patients, the vestibular permanent damages could be found by assessment of clinical vestibular status. This study reports the sensorial vestibular functional findings for adults in cochlear implanted ears related to the electrode insertion type (cochleostomy or round window approach) and comparing to non-implanted deaf ears. A total of 20 adult patients with 32 cochlear implanted ears (12 patients with binaural cochlear implant and eight with monoaural) were selected for postoperatory vestibular examination by cervical and ocular vestibular myogenic potentials and vestibular caloric tests. The same tests were made for a control group of 22 non-implanted deaf ears. Functional testing results were reported related to the electrode insertion approach. For the cochleostomy group, we found different deficits: in 40% for saccular function, 44% for utricular function, and 12% horizontal canal dysfunction. In round window group, the deficit was present in 14.29% for saccular function, 28.57% for utricular function, and 28.58% for horizontal canal. In 46.88% of implanted ears, the vestibular function was completely preserved on all tested sensors. In conclusion, the vestibular functional status after inner ear surgery presents sensorial damages in 53.12% ears compare with the vestibular dysfunction existing in 50% of deaf non-operated ears. Round window insertion allows for better conservation of the vestibular function.

Corresponding author: Maria Cristina Hera, MD, PhD Student; e-mail: cristinahera@yahoo.it; Luminita Mihaela Radulescu, Associate Professor, MD, PhD; e-mail: lmradulescu@yahoo.com

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13. The management of the oropharyngeal anterior wall cancer

Nicolae Constantin Balica, Marioara Poenaru, Caius Ion Doros, Flavia Baderca, Maria-Alexandra Preda, Vasile Ciprian Iovan, Horia Tudor Stanca, Cristina Jana Busuioc, Ioana Cristina Opriscan, Ovidiu Boruga

Introduction: Anterior wall of the oropharynx or the base of the tongue is the site of different types of cancers, most of them usually diagnosed in advanced stages. The most common histological type of cancer diagnosed in these patients is squamous cell carcinoma (SCC). The treatment methods are multiple, but the optimal therapeutic option with best results on outcome and on the patients quality life has not been established. The objectives of our study were to evaluate the tongue base SCCs treated by transhyoid approach and the oncological outcomes of the surgery combined with radiotherapy. Patients, Materials and Methods: The retrospective study was performed over a period of 10 years (2001-2010) on 37 previously untreated patients. All the tumors were biopsied and after histopathological (HP) diagnosis, the tumors were excised. All the specimens were fixed in 4% (v/v) buffered formalin and sent for the HP evaluation. Results: In the study were included only the patient diagnosed on biopsy with different types of SCC. The mean age was 61 years old, most of the patients (94.59%) being males. We performed a tongue base transhyoid tumor resection in 23 (62.17%) cases followed by epiglottectomy in five (13.51%) cases or horizontal supraglottic laryngectomy in nine (24.32%) cases, respectively. Bilateral neck dissections and postoperative radiotherapy were performed in all cases. The postoperative and post-therapeutic evolution was favorable at three years (81.1%) and five years (75.67%). There were no signs of local or regional recurrences. The tumor specific three-year and five-year survival rates were: pT2 100%, pT3 87.5%, pT4a 71.42% and 57.14%, and pT4b 50% and 25%, respectively. The stage specific three-year and five-year survival rates were: stage II 100%, stage III 85.71%, stage IVA 83.33% and 79.16%, and stage IVB 50% and 25%, respectively. Conclusions: The prognosis for the SCC of the tongue base is poor. Cancer resection by transhyoid approach is a feasible procedure, which permits a good tumor control with limited postoperative morbidity, with an important benefit on the life quality of the patients.

Corresponding author: Vasile Ciprian Iovan, Associate Professor, MD, PhD; e-mail: dr.iovan@biostandard.ro; Horia Tudor Stanca, Associate Professor, MD, PhD; e-mail: balica@umft.ro

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14. Mutational status of KRAS and MMR genes in a series of colorectal carcinoma cases

Florina Lucia Cionca, Maria Dobre, Camelia-Marioara Dobrea, Cristina-Ileana Iosif, Maria Victoria Comanescu, Carmen Maria Ardeleanu

Background: The KRAS gene mutation is the most common somatic change in colorectal carcinoma (CRC) and is predictive of resistance to anti-epidermal growth factor receptor (EGFR) therapy in the metastatic forms. Microsatellite instability (MSI), a mismatch repair (MMR) system defect, accounts for 15-20% of all CRCs, more frequent in early stages. CRCs with MSI present better prognosis, a distinct histopathological aspect and a different response to chemotherapy. Patients with both KRAS wild type and MSI have a reduced risk of dissemination and recurrence. Materials and Methods: Our study included formalin-fixed paraffin-embedded tissue samples from 40 patients with metastatic CRCs, aged between 40 and 71 years old, gender (males/females) ratio 2.33:1. The MMR proteins were analyzed using an indirect bistadial immunohistochemical (IHC) technique with monoclonal antibodies. KRAS mutations were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: Of the 40 tumors analyzed, 40% presented KRAS mutations located in codon 12 or codon 13. IHC expression of MMR proteins revealed a microsatellite stable status in 35 cases, including 15 cases with mutated KRAS. MSI status was identified in five cases (four with KRAS wild type). All MSI tumors had a poorer histological differentiation and four cases revealed a mucinous phenotype. Eighty percent of the patients with MSI status were older women. Conclusions: Our study demonstrates a 20% frequency of mutated KRAS in MSI CRCs, the incidence of KRAS mutations being inversely correlated with MSI status in these tumors. MMR protein deficient CRCs tend to occur in older females, have a poorer differentiation and are frequently associated with KRAS wild type.

Corresponding author: Florina Lucia Cionca, MD, PhD Student; e-mail: florinalcionca@gmail.com

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15. The immunoexpression of p53 and Snail in endometrioid endometrial carcinomas

Mihaela Dragomirescu, Alex Emilian Stepan, Claudiu Margaritescu, Cristiana Eugenia Simionescu

Endometrial cancer is one of the most common tumors in women worldwide. P53 has a well-known function as tumor suppressor, but it can also regulate the tissues metabolism, differentiation and development. Snail is a zinc-finger transcription factor, involved in the cell differentiation and survival. We analyzed the immunoexpression of p53 and Snail in 55 cases of endometrioid endometrial carcinoma (EEC), in relation with the histopathological prognosis parameters and tumoral compartments, respectively intratumoral and advancing edge areas. For both markers, we found a statistically significant association with histological grade, in relation with tumoral compartments. P53 and Snail can be used in developing EEC targeted treatment.

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

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16. Highlighting the R1 and R2 VEGF receptors in placentas resulting from normal development pregnancies and from pregnancies complicated by preeclampsia

Mihnea Istrate, Carina Mihu, Sergiu Susman, Carmen Stanca Melincovici, Andrei Mihai Malutan, Rares Buiga, Sorana Daniela Bolboaca, Carmen Mihaela Mihu

Preeclampsia (PE), a pathological entity characterized by hypertension and pregnancy-related proteinuria, is a medical condition of incompletely known etiopathogenesis. Placental defects and placental angiogenesis may be a cause of this condition. The main factor that controls angiogenesis in the early stages of placental development is vascular endothelial growth factor A (VEGF-A) and its two receptors, namely VEGFR-1 and VEGFR-2. This study analyzed the immunohistochemical (IHC) expression of the two VEGF receptors, R1 and R2, in pregnancies complicated by PE compared to pregnancies with a normal evolution. The pregnancies included into the study for the harvesting of placental tissue to be microscopically analyzed were divided into two groups: the group of physiological pregnancies (22 pregnancies) and the group of pregnancies complicated by preeclampsia (13 pregnancies). For the microscopic analysis, we used the Hematoxylin-Eosin (HE), Masson s trichrome and IHC stainings. The microscopic aspects of HE and Masson s trichrome stainings most commonly found in normal development pregnancies underlie the normal process of placental senescence. In the case of pregnancies complicated by PE, the microscopic analysis of the placentas revealed fibrinoid necrosis of the vascular wall, lipid-loaded endothelial cells, diffuse trophoblastic hypertrophy, microinfarctions, calcification areas, fibrin deposits, vascular-syncytial membrane surface reduction, basement membrane thickening. According to the established marker intensity score, the VEGFR-1 and VEGFR-2 receptors were more pronounced in the placentas resulting from pregnancies complicated by preeclampsia. The present study brings arguments that support the major regulatory role of VEGF-A and of the two receptors in the normal or pathological angiogenesis in the placenta, and implicitly in the pathogenesis of preeclampsia. Further studies are needed for a more comprehensive analysis of the stages in which these factors cause alteration of the placental angiogenesis and vasculogenesis processes, so that they can intervene effectively in the treatment or prevention of this disease.

Corresponding author: Carina Mihu, Medical Student; e-mail: carina.mihu@umfcluj.ro

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17. Morphological features of tongue squamous cell carcinoma diagnosed in Dolj County population between 2012-2014

Petre Costin Marasescu, Adina Andreea Turcu, Veronica Mercut, Monica Scrieciu, Claudiu Margaritescu, Nina Ionovici, Alex Ioan Salan, Felicia Ileana Marasescu, Mihaela Cristina Stan

Tongue squamous carcinoma can be found in many forms, having a lot of risk factors, and whose morphological characteristics can be used as a prognostic. The purpose of this study was to histologically characterize a number of 54 patients diagnosed between 2012-2014, with tongue squamous carcinoma. Surgical resection specimens of tongue tumors were processed by paraffin inclusion technique. The diagnose samples were reevaluated according to the World Health Organization (WHO) criteria for head and neck tumors diagnosis, by screening the Hematoxylin-Eosin staining sections. The most common histopathological variety of tongue carcinoma observed in our cases was the non-keratinized form, the basaloid and sarcomatoid types of carcinoma being ranked on the last places. The study outlined the prevalence of non-keratinized forms of tongue squamous carcinoma and all types of tumoral invasion patterns have been observed in different percentages.

Corresponding author: Monica Scrieciu, Professor, DMD, PhD; e-mail: scrieciu_monica@yahoo.com; Nina Ionovici, Associate Professor, MD, PhD; e-mail: ninaionovici@yahoo.com

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18. Adnexal masses in pregnancy: perinatal impact

Nuti Daniela Oprescu, Cringu Antoniu Ionescu, Ioana Dragan, Andreea-Catalina Fetecau, Amira Livia Said-Moldoveanu, Raluca Chirculescu, Simona Vladareanu

The incidence of adnexal masses in pregnancy has increased significantly over the last decades and this is mostly because of the widespread use of ultrasound for pregnancy surveillance. Although a clear majority of adnexal masses found in the first trimester are functional cysts, which have a small diameter and disappear spontaneously, those that do persist into the second and third trimester require ultrasound surveillance for proper management. The presence of a large adnexal mass in the third trimester of pregnancy represents solid grounds for delivery via Caesarean section (C-section) both because of the risk of dystocia and the advantage of one-step approach of cystectomy/oophorectomy at the time of C-section. This is a retrospective study of all the third trimester pregnancy related adnexal masses that delivered in our Hospital in the last 10 years via C-section where cystectomy was also performed. Our aim was to look at the histological type of ovarian mass and to compare our results to those previously published by other authors. We also wanted to see whether the clinical suspicion based on prenatal ultrasound aspect, where this was available, was similar to the postnatal histology report. Secondary outcomes were gestational age at delivery, fetal weight and Apgar score. We found that dermoid cysts are the most common type of adnexal mass with an incidence of 46%, followed by mucous cysts 27%, serous cysts 18% and endometrioses 9%, which is consistent with the data published by other authors in larger series. In terms of prenatal clinical diagnosis, detailed ultrasound assessment of the ovarian mass was available only in less than half of these cases, but in these, the clinical suspicion was confirmed by histology report. In our series, we had no case that required premature delivery because of adnexal mass-related complications and fetal outcome was very good with normal birth weight and high Apgar score. Although this is a small series of cases, it confirms the incidence previously published of the different histological types of ovarian tumors. It also shows that fetal outcomes are very rarely affected by the presence of ovarian masses and premature iatrogenic delivery for maternal well-being is the only note wordy one of them.

Corresponding author: Ioana Dragan, MD, PhD Student; e-mail: dr.ioana.dragan@gmail.com

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19. Vertebral body clinico-morphological features following percutaneous vertebroplasty versus the conservatory approach

Cristian Constantin, Dana-Maria Albulescu, Daniel-Razvan Dita, Claudia-Valentina Georgescu, Andrei-Constantin Deaconu

Most percutaneous vertebroplasty procedures are being performed in order to relieve pain in patients with severe osteoporosis and associated stable fractures of one or more vertebral bodies. In addition, vertebroplasty is also recommended for patients suffering from post-traumatic symptoms associated with vertebral fractures, patients with large angiomas positioned inside the vertebral body, with an increased risk for collapse fracture and also patients presenting with pain associated with vertebral body metastatic disease. On another aspect, it is possible that in isolated cases, an orthopedic surgeon confronted with a vertebra plana presentation will recommend bone cement injection into the vertebral bodies adjacent to the fractured one, in order to have a better and more robust substrate for placement of screws or other fixation devices. The aim of our study is to compare results attained by the Department of Interventional Radiology, in performing this procedure, with results attained by following the classical orthopedic treatment procedure, involving non-operative treatment, using medication and bracing varying from simple extension orthoses in order to limit spinal flexion, light bracing for contiguous fractures, presenting either angulation or compression, and for severe cases standard thoracolumbosacral orthoses (TLSOs).

Corresponding author: Dana-Maria Albulescu, Associate Professor, MD, PhD; e-mail: med73danam@yahoo.com

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20. Modern molecular study of weight gain related to antidepressant treatment: clinical implications of the pharmacogenetic testing

Luminita Stefania Ageu, Codrina Mihaela Levai, Nicoleta Ioana Andreescu, Mirela Loredana Grigoras, Lavinia Maria Hogea, Daniela Veronica Chiriac, Roxana Folescu, Ana Cristina Bredicean, Liliana Maria Nussbaum, Virgil Radu Enatescu, Vladimir Poroch, Viorel Lupu, Maria Puiu, Laura Alexandra Nussbaum

Antidepressant medication influences cellular lipogenesis, being associated with metabolic side effects including weight gain. Due to the increasing use of antidepressants in children and adolescents, their metabolic and endocrine adverse effects are of particular concern, especially within this pediatric population that appears to be at greater risk. Genetic factors with a possible influence on antidepressant s adverse effects include CYP [cytochrome P450 (CYP450)] polymorphisms. We target to evaluate the efficacy of the pharmacogenetic testing, when prescribing antidepressants, in correlation with the occurrence of adverse events and weight gain. Our research was performed between the years 2010 and 2016, in the University Clinic of Child and Adolescent Psychiatry, Timisoara, Romania. We recruited 80 patients, children and adolescents with depressive disorders. Our study sample was divided in two groups: G1 - 40 patients took treatment after pharmacogenetic testing, and G2 - 40 patients without pharmacogenetic testing before the treatment election. Our results show statistically significant differences concerning the weight gain for groups G1 (with pharmacogenetic testing) and G2 (without pharmacogenetic testing). The CYP genotype and the pharmacogenetic testing, for choosing the personalized antidepressant therapy in children and adolescents with depressive disorders, proved to be good predictors for the response to antidepressants and the side effects registered, especially for weight gain. The significant correlations between the CYP polymorphisms for group G2 (without pharmacogenetic testing) and the weight gain/body mass index (BMI) increase, as major side effects induced by antidepressants, proved the fact that the pharmacogenetic screening is needed in the future clinical practice, allowing for individualized, tailored treatment, especially for at-risk pediatric categories.

Corresponding author: Mirela Loredana Grigoras, Assistant Professor, MD, PhD; e-mail: mirela.grigoras@yahoo.com; Viorel Lupu, Associate Professor, MD, PhD; e-mail: violupu14@yahoo.com

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21. Morphological and ultrasound findings in the placenta of diabetic pregnancy

Costin Berceanu, Adrian Victor Tetileanu, Anca-Maria Ofiteru, Elvira Bratila, Claudia Mehedintu, Nicoleta Loredana Voicu, Florin Adrian Szasz, Sabina Berceanu, Simona Vladareanu, Dan-Bogdan Navolan

The purpose of this study is to analyze the morphological, histological, immunohistochemical and ultrasound findings in the placenta of maternal type 1 and gestational diabetes, to compare the pathological changes of the placental structure in the two types of metabolic disruptions, but also to establish correlations with the expression of these findings, influenced by different associated conditions. This multicenter study includes 53 pregnancies, of which 37 with pregestational and 16 with gestational diabetes. All cases undergone specific obstetric ultrasound assessment and detailed placental scan. There were assessed 49 singleton and four twin pregnancies, all of which having live births as fetal outcome. Maternal preexisting hypertension, preeclampsia and obesity were the main associated conditions. Placental ultrasound scan revealed increased placental thickness even from the second trimester, with significant increases in the first half, and placentomegaly at the end of the third trimester. Macroscopic analysis of the placentas and umbilical cords has shown that the placentas of women with diabetes are heavier, and abnormal cord insertion has been also found. Gross analysis of maternal and fetal surfaces of the placentas revealed certain changes in both metabolic conditions. We observed 14 types of placental pathological findings in pregestational and 11 in gestational diabetes. In diabetic placenta, it is not appropriate to discuss about specific changes, but rather about a pathological diabetic pattern, influenced by associated conditions. Preconceptional and first trimester glycemic control is the key element, and euglycemia throughout pregnancy is a purpose whose accomplishment depends the maternal-fetal outcome.

Corresponding author: Claudia Mehedintu, Associate Professor, MD, PhD; e-mail: claudiamehedintu@yahoo.com

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22. Placental abruption: etiopathogenic aspects, diagnostic and therapeutic implications

Anca Daniela Braila, Adrian Gluhovschi, Adrian Neacsu, Cristian Virgil Lungulescu, Mihai Braila, Elena Luminita Vircan, Bogdan-Virgil Cotoi, Alexandru Marian Goganau

The severe form of retroplacental hematoma is a serious accident in the second stage of pregnancy and at birth with frightening for the mother and fetus that often lead to death. The pathological mechanism presumes conditions for a special ground capital for the efficiency of the acute intradecidual vascular accident with the rupture of the uterus-placental arterioles. The complete clinical picture of this severe form of retroplacental hematoma - the placental abruption, observed and mentioned by the classics (vascular drama of Couvelaire) consists of five syndromes, 18 signs and symptoms, four paradoxes, phenomena not fully met in the other forms of retroplacental hematoma (minor and intermediate). The rate of incidence of retroplacental hematoma is in between 0.13-1.38% and depends on the environment, on the socio-economic and medical conditions, on the obstetric education and associated pathology. Our study aims at re-evaluating the clinico-paraclinical phenomenon imposed by the dramatism of the phenomenon of in utero placental apoplexy, the impact on neonatal mortality and on the functional prognosis from the point of view of surgical climax.

Corresponding author: Adrian Neacsu, Associate Professor, MD, PhD; e-mail: adrianneacsu2006@yahoo.com; Bogdan-Virgil Cotoi, Lecturer, MD, PhD; e-mail: bogdan230376@yahoo.ro

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23. The urologist and child hydronephrosis caused by ureteral anomalies

Gheorghe Adrian Bumbu, Mihail-Claudius Berechet, Karim Nacer, Gheorghe Bumbu, Nina Ionovici, Bogdan Andrei Bumbu

Congenital hydronephrosis caused by ureteral anomalies, like ureteral duplicity, megaureter, ureteral ectopy and ureterocele, must be differentiated from ureteropelvic junction obstruction (UJO) hydronephrosis and from the hydronephrosis caused by vesicoureteral reflux. These represent a differentiated branch of congenital abnormalities in children even if not so common, but this fact should not be disconsidered. Over a five years period, from 111 operated children in our Clinic, we performed 13 interventions for congenital hydronephrosis, 11 (84.61%) being caused by ureteral abnormalities. Here, there were described particular cases, with diagnosis steps and treatment decisions. Ureteral ectopy can be manifested by loss of urine drops in cases where ureteral holes are located in the vagina, septum or urethra, inferior to the sphincter mechanism. Incontinence in boys never occurs because the ectopic ureter never opens under the sphincter mechanism. If the ureter opens in the genital tract, patients may clinically present with the epididymitis symptom. From autopsy statistics in the US, the incidence of ureteral duplex is estimated to be less than 1%. When the duplex is associated with urinary infection, the incidence of ureteral duplex increases up to 8%.

Corresponding author: Mihail-Claudius Berechet, MD, PhD; e-mail: berechet.mihail@yahoo.com; Nina Ionovici, Associate Professor, MD, PhD; e-mail: ninaionovici@yahoo.com

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24. Fluorescence influence on screening decisions for oral malignant lesions

Silvana Canjau, Darinca Carmen Marilena Todea, Cosmin Sinescu, Marius Octavian Pricop, Virgil-Florin Duma

Objectives: The aim of the present study was to assess the capability of the low-cost VELscope device to visualize the tissue auto-fluorescence of potentially malignant oral lesions and to establish the diagnostic accuracy, sensitivity, and specificity of this method when validating the retrieved data through the gold standard, i.e., histological examination. Patients, Materials and Methods: Eighteen patients were evaluated by conventional oral examination (COE) followed by direct visual fluorescence evaluation (DVFE) using VELscope. Areas clinically suspicious detected by COE or with positive DVFE (visual fluorescence loss) were further investigated using surgical biopsy. Results: Eight positive biopsies for malignant lesions were detected by COE and DVFE. Only one positive biopsy for a premalignant lesion was not in accordance with COE and DVFE. One lesion identified on the VELscope and COE as a non-malignant lesion was confirmed by the biopsy. Therefore, the VELscope system had a sensitivity of 94.44% and a specificity of 100% in discriminating in situ normal mucosa from carcinoma or from invasive carcinoma, compared with histology. The predictive positive value was 100% and the negative predictive value was 50%, with a 95% confidence interval (CI). Conclusions: DVFE allows for a simple and cost-effective margin determination, in order to perform the detection and screening of oral precancerous and early cancerous disorders. It was found that the VELscope system could not fully replace the histopathology procedure. Nonetheless, the study demonstrated its usefulness for clinical examination, monitoring oral lesions, and guiding the biopsy. Therefore, this method may add sensitivity to the oral tissue examination and be an effective adjunct for high-risk patients.

Corresponding author: Darinca Carmen Marilena Todea, Professor, DMD, PhD; e-mails: todea.darinca@umft.ro, carmen.todea@gmail.com

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25. Morpho-histological assessment of the periodontal support structures under the action of excessive occlusal forces and under the influence of nicotine

Ana Ispas, Carmen Mihaela Mihu, Antarinia Maria Craciun, Mariana Constantiniuc

Smoking and occlusal trauma are two factors that can interfere with bone homeostasis. The aim of this study was to evaluate the histocellular changes occurring in the periodontal ligament and alveolar bone during the action of excessive occlusal forces, and to assess the influence of nicotine on the alveolar bone loss in teeth subjected to occlusal trauma. Materials and Methods: Fifty-six Wistar rats were randomized into seven groups (n=8). Animals were exposed to nicotine and occlusal trauma for 7, 14 and 30 days. Three groups were exposed to occlusal trauma alone, another three groups were exposed to occlusal trauma and nicotine, and one group was not exposed to any treatment. Results: Periodontal lesions induced in the first stage (7-14 days) manifested by a moderate increase of the periodontal space, a multiplication, thickening and elongation of periodontal fibers, as well as their condensation in the middle area of the periradicular space. Regarding bone changes induced by occlusal trauma, groups 5 and 7 (occlusal trauma and nicotine administration) had higher bone losses compared to groups 1, 2, 3, 4 and 6. This study demonstrated that nicotine significantly affected the alveolar bone. Conclusions: The induced occlusal trauma caused obvious tissue damage. At the same time, it was found that nicotine enhanced alveolar bone resorption, increased tooth mobility and induced an exacerbation of inflammatory processes.

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

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26. Morphofunctional changes in distribution of pressure center in multiple sclerosis

Marius Cristian Neamtu, Oana Maria Neamtu, Denisa Enescu Bieru, Mihnea Ion Marin, Mihai Robert Rusu, Stefania Tudorache, Anca Daniela Braila, Catalina Poiana, Ligia Rusu

Introduction: Gait evaluation and assessment of motor performance are of utmost importance in the clinical management of multiple sclerosis (MS). A new approach to the analysis of static and dynamic balance of MS patients is the use of complex biomechanical analysis that includes an analysis of the distribution of the center of pressure (DCP) and loading, measured by using the pressure and force platforms. Patients and Methods: The study was conducted on a total of 18 patients with MS, with the mean age of 41.2 years old, divided into two groups, according to the presence of clinically detectable gait disturbances. The biomechanical analysis that included the assessment of the loading and DPC was performed using the platform of force distribution. DPC represented the center of all the forces applied and its value could appreciate the mediolateral stability, hence the pronation or, respectively, the supination. Group 1, consisting of 12 patients with MS with clinically detectable gait disorders, including six men and six women, and group 2, of six MS patients without clinically detectable gait disorders, including two men and four women. Results: For group 1, the center of pressure had a left-right asymmetric distribution, and also an anterior-posterior one. There was a predominant distribution at the medial heel, at metatarsals 1-3 and at the hallux. For group 2, the analysis of the plantograms recorded in our study indicated a tendency of the distribution of the pressure center in the metatarsals 2, 3 and less in the heel. Conclusions: The analysis of the loading and distribution of the pressure center was important not only to appreciate the static equilibrium disorders but also to appreciate how these disorders affected the gait initiation, since the patients suffered from anterior-posterior and mediolateral disorders, which produced spatial and temporal distortion preventing gait initiation. In the study of pressure and force, we noticed a predominant distribution on the lateral region of the heel, explained by an attempt of the body to compensate the disorders of balance and orientation of the reaction force of the ground to normalize the gait.

Corresponding author: Oana Maria Neamtu, Assistant Professor, PhD; e-mail: oanacristi_neamtu@yahoo.com

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27. Expression and significance of Ki-67 in lung cancer

Roxana Folescu, Codrina Mihaela Levai, Mirela Loredana Grigoras, Teodora Smaranda Arghirescu, Ioana Cristina Talpos, Ciprian Mihai Gindac, Carmen Lacramioara Zamfir, Vladimir Poroch, Mirella Dorina Anghel

Ki-67 parameter is a proliferation marker in malignant tumors. The increased proliferation activity and the decreased prognosis in lung cancer determined us to investigate different parameters connected to the tumor s aggression, such as cellularity, Ki-67 positivity rate, and proliferating cell nuclear antigen (PCNA). We evaluated the proliferative activity in 62 primary lung tumors by determining the cell s percentage of Ki-67 and immunoreactive PCNA (using MIB-1 and PCNA monoclonal antibodies), classifying Ki-67 and PCNA immunoreactivity into three score groups. The results obtained emphasized a linkage between Ki-67 score with the histological tumor subtype, tumor cellularity and degree of differentiation and with other proliferation immunohistochemistry (IHC) markers, such as p53 cellular tumor antigen. The tumor s cellularity, the Ki-67 positivity rate and PCNA, together with the clinical stage and the histological differentiation bring extra pieces of useful information in order to anticipate the evolution and the prognosis of lung cancer.

Corresponding author: Mirela Loredana Grigoras, Assistant Professor, MD, PhD; e-mail: mirela.grigoras@yahoo.com; Teodora Smaranda Arghirescu, Associate Professor, MD, PhD; e-mail: sarghirescu@yahoo.com

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28. Morphological assessment of the mandibular canal trajectory in edentate subjects

Victor Nimigean, Valentin Daniel Sirbu, Vanda Roxana Nimigean, Daniela Gabriela Badita, Alexandru Poll, Simona Andreea Moraru, Diana Loreta Paun

Background: The mandibular canal and its content represent the vital structure, which can complicate dentoalveolar surgical procedures in the posterior region of the mandible. The purpose of the present study was to determine the path the mandibular canal takes in relation to the horizontal and the vertical anatomical reference planes in edentate subjects, in order to minimize the risk of affecting its neurovascular content during various oral surgery procedures. Materials and Methods: Morphometric evaluations were performed on 12 dried fully edentulous human mandibles and on cone-beam computed tomography (CBCT) cross-sectional images of the mandible, from 20 patients with either partial or complete edentulism. Both methods were utilized, in three target areas (corresponding to the second premolar, to the first molar and to the second molar regions), in order to measure the distance between the mandibular canal and the following reference points: (i) the lateral (buccal) surface of the mandible (MC-BS distance); (ii) the medial (lingual) surface of the mandible (MC-LS distance); (iii) the alveolar surface of the mandible (MC-AS distance). The results were statistically processed in Stata MP/13 software package using analysis of variance (ANOVA) test. Results: The mandibular canal crossed the trabecular bone from the posterior towards the anterior, and from the lingual towards the buccal, reaching the premolar region, distal to the mental foramen, where it was located in the centre of the trabecular bone, main topographic pattern encountered in 27 (84.37%) of the cases. In five (15.63%) of the cases, in the premolar region, the mandibular canal was located near the buccal cortical plate. The mandibular canal descended from the second molar region towards the premolar region, main topographic pattern found in 28 (87.5%) of the cases. In four (12.5%) cases, the mandibular canal had a descending trajectory in the molar regions and it took a slightly ascending course in the premolar region. Conclusions: According to the results, the second molar region represents the highest risk area in the accidental injury to the content of the mandibular canal, during various oral surgery procedures.

Corresponding author: Vanda Roxana Nimigean, Associate Professor, DMD, PhD; e-mail: vandanimigean@yahoo.com

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29. The ultrastructural features of the premalignant oral lesions

Doinita Olinici, Carmen Elena Cotrutz, Ciprian Valentin Mihali, Vasile Bogdan Grecu, Emanuela Ana Botez, Laura Stoica, Pavel Onofrei, Oana Condurache, Daniela Cristina Dimitriu

Premalignant oral lesions are among the most important risk factors for the development of oral squamocellular carcinoma. Recent population studies indicate a significant rise in the prevalence of leukoplakia, erythroplakia/erythroleukoplakia, actinic cheilitis, submucous fibrosis and erosive lichen planus. Since standard histopathological examination has numerous limitations regarding the accurate appreciation of potential malignant transformation, the present study aims to aid these evaluations using the transmission electron microscopy (TEM) technique, which emphasizes ultrastructural changes pertaining to this pathology. Oral mucosa fragments collected from 43 patients that were clinically and histopathologically diagnosed with leukoplakia, erosive actinic cheilitis and erosive lichen planus have been processed through the classic technique for the examination using TEM and were examined using a Philips CM100 transmission electron microscope. The electron microscopy study has confirmed the histopathological diagnosis of the tissue samples examined using photonic microscopy and has furthermore revealed a series of ultrastructural details that on the one hand indicate the tendency for malignant transformation, and on the other reveal characteristic features of tumor development. All the details furnished by TEM complete the overall picture of morphological changes, specific to these lesions, indicating the importance of using these techniques in establishing both a correct diagnosis and prognosis.

Corresponding author: Carmen Elena Cotrutz, Professor, MD, PhD; e-mail: cotrutz@yahoo.com

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30. Effects of moderate exercise and a multiple vitamin and mineral complex on the arterial wall

Cristian Simion Potora, Simona Tache, Adriana Albu, Andras-Laszlo Nagy

Background: Aerobic exercise has favorable effects on vascular structure and function. Its beneficial role may be due to a decrease in oxidative stress. The association of vitamin and mineral supplements to exercise determined contradictory effects on arterial wall and oxidative stress parameters. The aim of this experimental study was to evaluate the effect of moderate aerobic exercise, alone or in association with a vitamin and mineral complex, on aortic wall morphology and oxidant/antioxidant balance. Materials and Methods: Four groups, each of 10 Wistar rats, were included in the study, as follows: (I) sedentary controls, (II) group subjected to physical exercise, (III) group subjected to physical exercise and nutritional supplement, and (IV) sedentary nutritional supplemented group. Aortic wall histological examinations and serum and aortic wall oxidative stress measurements were performed in each group. Results: Moderate aerobic exercise induces vascular smooth muscle cell hypertrophy and transformation in a secretory phenotype. There was a trend for increase in malondialdehyde (MDA) and decrease in thiol (SH) groups in aortic tissue homogenates, together with reduction in serum MDA values and increase in SH groups, after exercise. A reduction in aortic wall lipid peroxidation was found in supplemented trained animals compared to sedentary group, while no influence on aortic structure was noted. Conclusions: Moderate aerobic exercise induces adaptive modifications in the arterial wall and a favorable effect on systemic oxidative response. The association of vitamin and mineral supplement did not influence significantly arterial morphology, while its effects on aortic oxidative stress suggest an increase in local antioxidant defense.

Corresponding author: Adriana Albu, Associate Professor, MD, PhD; e-mail: adriana.albu@umfcluj.ro

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31. Factors influencing the pathological quality of the surgical specimen in rectal cancer - a retrospective single-centre study

Dragos-Viorel Scripcariu, Cristian Dumitru Lupascu, Ionut Hutanu, Bogdan Filip, Maria-Gabriela Anitei, Dan Ferariu, Mihaela Moscalu, Viorel Scripcariu

Aim: The pathologist s role in the multidisciplinary treatment of rectal cancer is to evaluate and stage the tumor according to the latest standards, as well as indicate the quality of the surgical act. This study aims to evaluate circumferential and distal resection margins as well as quality of mesorectal resection and correlate them with different clinical, pathological and therapeutic factors. Patients, Materials and Methods: Four hundred ninety-eight patients treated radically for mid and low rectal cancer within one Clinic of Oncological Surgery in Iasi, Romania, were included in this study. Results: The distal resection margin showed significant correlations with the type of surgical intervention, chemotherapy in the neoadjuvant treatment plan and pathological node staging. The circumferential resection margin depended mostly on pathological node staging and the length of the interval between neoadjuvant treatment and surgery. Finally, the aspect of the mesorectum varied according to neoadjuvant treatment and the type of surgical intervention performed. Conclusions: The study reached its aim in providing important data for the expected outcome of the specimen after curative treatment for rectal cancer.

Corresponding author: Dragos-Viorel Scripcariu, MD; e-mail: dscripcariu@gmail.com

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32. Scanning electron microscopy evaluation of the root canal morphology after Er:YAG laser irradiation

Darinca Carmen Marilena Todea, Ruxandra Elena Luca, Cosmin Anton Balabuc, Mariana Ioana Miron, Cosmin Locovei, Daliana Emanuela Mocuta

The current limits of the endodontic disinfection strategies are not only a result of bacterial biofilm growth mode inside the root canals, they are equally due to the anatomical complexity of the root canal system, of its structure, of the dentin composition and of the factors associated with chemical disinfectants. One of the major problems is the fact that a great part of the endodontic anatomy remains uninstrumented after conventional treatment and even the accessible parts of the root canals are covered in smear layer, which results as a by-product of the instrumentation and acts as a barrier for irrigants, medication and even influencing the quality of the endodontic filling. Therefore, strategies in advanced disinfection in endodontics are developed and tested in order to meet these challenges. The present study aims to assess the possibility of improving the debridement of the root canals by using erbium-doped yttrium-aluminum-garnet (Er:YAG) laser radiation. We used extracted teeth, which were subjected to the conventional treatment protocol and then divided into three study groups: the negative control group and two other groups, which were exposed to laser radiation using two energy levels. Scanning electron microscopy (SEM) revealed the efficiency of the laser aided treatment versus the conventional methods of cleaning and disinfection of root canals.

Corresponding author: Ruxandra Elena Luca, Assistant Professor, DMD; e-mail: dr.ruxandraluca@gmail.com

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33. Femtosecond-LASIK outcomes using the VisuMax-MEL 80 platform for mixed astigmatism refractive surgery

Horia Tudor Stanca, Mihnea Munteanu, Dragos Catalin Jianu, Andrei Gheorghe Marius Motoc, Cristian Radu Jecan, Bogdana Tabacaru, Simona Stanca, Maria Alexandra Preda

Aim: To evaluate the predictability, efficacy and safety of Femtosecond-laser-assisted in situ keratomileusis (LASIK) procedure for mixed astigmatism. Patients, Materials and Methods: We prospectively evaluated for 12 months 74 eyes (52 patients) with mixed astigmatism that underwent Femtosecond-LASIK treatment. The preoperative mean refractive sphere value was +1.879+/-1.313 diopters (D) and the mean refractive cylinder value was -4.169+/-1.091 D. The anterior corneal flap was cut using the VisuMax femtosecond laser and then the stromal ablation was done using the MEL 80 excimer laser. Results: Mean age was 30.22+/-6.421 years with 61.53% female patients. Postoperative spherical equivalent at 12 months was within +/-0.5D of emmetropia in 75.8% of eyes and within +/-1D in 97.3% of eyes. Postoperative uncorrected distance visual acuity was equivalent to or better than the preoperative corrected distance visual acuity in 91.9% of eyes. Compared to the preoperative corrected distance visual acuity (CDVA), 8.1% of eyes gained one line, 2.7% gained two lines and 2.7% gained three lines of visual acuity. Conclusions: Femtosecond-LASIK using the VisuMax-MEL 80 platform appears to have safe, effective and predictable results in mixed astigmatic eyes. The results are impressive for high refractive error treatment and for improvement of both uncorrected and corrected distance visual acuity.

Corresponding author: Dragos Catalin Jianu, Professor, MD, PhD; e-mail: dcjianu@yahoo.com

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34. Surgical reconstruction of post-tumoral facial defects

Camelia Tamas, Catalina Teodora Pintilie, Ionut Vivi Atanasoae, Andreea Mioara Corduneanu, Iulia Dabija, Florin Stefan Olaru, Irina Mihaela Hreniuc, Angela Tecuceanu, Ioana Munteanu, Costel Dobre, Dan Cristian Moraru, Victor Ianole, Ioana Tamas, Victor Vlad Costan

Purpose: The face is an unfortunate location for any type of tumor - malignant or not - with significant esthetic and functional outcomes. To reconstruct a facial defect may seem simple, but can be rather complicated. The aim of this study is to analyze and discuss our results in order to conclude with specific surgical strategies correlated with the morphopathological results. The most important objective for us is to offer the highest level of expertise to our patients and to prove that the symbiosis between the surgical treatment and the work of the Department of Morphopathology is essential in order to maximize the quality of medical care provided for our patients. Patients, Materials and Methods: A retrospective study was conducted on 116 patients diagnosed with facial malignant tumors, 70 of which were confirmed as basal cell carcinomas (BCCs), 35 confirmed as squamous cell carcinomas (SCCs) and 11 malignant melanomas (MMs). Most BCC cases (57) showed ulceration, with a long clinical evolution (more than 10 years) in 48 cases. Only in 12 SCC cases, patients showed inflammation and ulceration, with a shorter evolution period (2-5 years). For complete microscopic diagnosis, immunohistochemical (IHC) examination was necessary in 46 cases. The BCC deceiving clinical behavior and the generally aggressive character of the MM were found in our patients as well. Results: The most frequent sites were the orbital region (27 cases) and the nasolabial sulcus (26 cases). In order to reconstruct the postexcisional defects, we had to perform local flaps in 62 cases (14 frontal flaps for orbital defects, 32 glabellar flaps for medial epicanthus, lower lid and nasal region, 15 nasolabial flaps for lower lid or nasal alae and one Z-plasty for the submental region). Oncological follow-up was performed in all patients and in 15 cases re-excision was necessary (11 BCCs, two SCCs and two MMs). Cervical lymph node metastasis occurred in six cases (three BCCs, one SCC and two MMs). Conclusions: The cooperation between surgeons and pathologists allowed for good outcomes and the pathology examination can guide the surgical approach towards better results both functionally and esthetically.

Corresponding author: Ionut Vivi Atanasoae, Assistant Lecturer, MD; e-mail: ionutatn@yahoo.com; Dan Cristian Moraru, Assistant Lecturer, MD; e-mail: morarudc@gmail.com

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35. An unusual digital neural loop in a cadaver with bilateral high branching median nerves - case report

Logan Bale, Natasha Brandt, Naomi Enos

Digital neural loops are present in the palms of most individuals. They can arise within the common palmar digital nerves (CPDNs) or proper palmar digital nerves (PPDNs). Typically, common palmar digital arteries (CPDAs) pass through digital neural loops, however there are reports of loops forming around the superficial palmar arch or proper palmar digital arteries (PPDAs). We describe an unusual digital neural loop that involved both a CPDN and a PPDN. To our knowledge, this is the first documented case of a digital neural loop of this type and therefore anatomists and surgeons may benefit from an awareness of its existence. A modification to a current classification system for digital neural loops is presented to include this novel loop. Interestingly, the cadaver documented in this report featured a high division of the median nerve in each forearm. On both sides, the ulnar component of the bifid median nerve followed an intramuscular course in which it pierced the flexor digitorum superficialis and then continued into the palm as the 3rd CPDN. A brief review of the literature is provided for both digital neural loops and the high division of the median nerve variant. Documented muscle associations noteworthy to the bifid median nerve are discussed. Developmental connections, if any, that exist between the unique digital neural loop and the high division of the median nerve are not speculated upon.

Corresponding author: Logan Bale, Instructor, MS; e-mail: lbale@uws.edu

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36. An extremely rare case of distal common bile duct adenocarcinoma in a 65-year-old male patient

Lucian Mihai Florescu, Ioana Andreea Gheonea, Dragos Ene, Dan Nicolae Florescu, Natalia Braia, Daniel Pirici, Vasile Sandru, Mircea Catalin Fortofoiu, Tudorel Ciurea

Cholangiocarcinoma is an extremely rare and highly aggressive primary malignancy of the biliary tract. The current report illustrates a rare case of distal common bile duct adenocarcinoma encountered in a 65-year-old male patient who was thoroughly investigated after presenting with a two weeks history of pain in the right hypochondrium, jaundice and unintentional weight loss (6 kg in two weeks). The medical team opted for a pancreaticoduodenectomy (Whipple procedure) managing to obtain negative resection margins of the tumor with a favorable immediate postoperative evolution. However, the surgical team was forced to reintervene twice due to complications caused mainly by the patient s disregard.

Corresponding author: Dragos Ene, MD, PhD; e-mail: dragoshene@yahoo.com

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37. Cutaneous microcystic/reticular schwannoma: case report and literature review of an exceedingly rare entity with an unusual presentation

Tiberiu Augustin Georgescu, Adrian Vasile Dumitru, Ana Maria Oproiu, Adriana Elena Nica, Diana Costache, Oana Maria Patrascu, Anca Mihaela Lazaroiu, Alina Elena Chefani, Maria Sajin, Mariana Costache

Conventional schwannoma represents a benign peripheral nerve sheath tumor derived from Schwann cells, which usually arises in the fourth or fifth decade of life, in the subcutaneous tissue of the distal extremities, or in the head and neck region of adult patients, with no gender predilection. In addition to the classic type, at least 11 different histopathological subtypes have been described and unawareness of these uncommon histopathological entities may lead to diagnostic pitfalls and risk of mistreatment. Recently described in the scientific literature, microcystic/reticular schwannoma is still relatively unknown to both surgeons and pathologists. The purpose of this paper is to highlight its existence by describing an additional case that occurred in the retroauricular area, and to further characterize its clinical, histopathological and immunohistochemical features. We reviewed the literature and compared the current case with others that have been documented thus far, discussing all possible differential diagnoses.

Corresponding author: Adriana Elena Nica, Lecturer, MD, PhD; e-mail: adriana.nica@suub.ro; Ana Maria Oproiu, Lecturer, MD, PhD; e-mail: anamariaoproiu@gmail.com

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38. A rare case of signet-ring cell carcinoma associated with poorly differentiated adenocarcinoma of the non-ampullary duodenum

Cosmin Carasca, George Simion, Adela Corina Nechifor-Boila, Alina Mioara Boeriu, Ecaterina Daniela Dobru

Primary duodenal cancer is a rare entity accounting for only 0.3% of all gastrointestinal cancers. Histopathologically, most duodenal cancers are mucin-producing adenocarcinomas, 34% being poorly differentiated. Signet-ring cell (SRC) carcinoma is extremely uncommon in the duodenum. Herein, we report a rare case of SRC carcinoma associated with poorly differentiated adenocarcinoma of the non-ampullary duodenum in a 74-year-old woman. The patient was admitted to the hospital for persistent epigastric pain, significant weight loss and hypochromic microcytic anemia. Esophago-gastro-duodenoscopy revealed a protruded lesion, with ulceration in the second portion of the duodenum, above the papilla. The patient was referred to surgery and pancreatico-duodenectomy with lymph node dissection was performed. The tumor consisted predominately of SRCs, Periodic Acid Schiff (PAS)-Alcian blue positive. The tumor cells were CDX2, cytokeratin (CK) 7 and CK 18/8 positive, which suggested a primary upper gastrointestinal tract site of origin. Immunostaining for mucin (MUC) 2 and MUC5AC was also positive demonstrating the duodenal goblet cells differentiation with a mixed gastric-foveolar and intestinal phenotype. Based on the morphological features and the immunohistochemical profile, a diagnosis of SRC carcinoma associated with poorly differentiated adenocarcinoma of the non-ampullary duodenum was set.

Corresponding author: Alina Mioara Boeriu, Associate Professor, MD, PhD; e-mail: aboeriu@gmail.com

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39. Conjunctival melanocytic tumors in children - a challenge in diagnosis and treatment

Roxana Elena Ciuntu, Gabriel Martinescu, Nicoleta Anton, Mihai Danciu

Conjunctival melanocytic lesions are very diverse pigmented tumors that include benign, premalignant and malignant tumors. The aim of this article is to highlight the clinical and histopathological aspects of conjunctival melanocytic tumors at children. This study is a retrospective case series study of three patients selected from fifteen cases with melanocytic conjunctival tumors who were operated in the Department of Ophthalmology, St. Spiridon Emergency Hospital, Iasi, Romania. A systematic review of the literature was undertaken, using an electronic search of PubMed/MEDLINE, Google Scholar and ISI Web of Knowledge, to identify original English or French articles and reviews on this subject. Patients were diagnosed by the same doctor between 2004 and 2016, in ambulatory of Department of Ophthalmology of the same Hospital. The age of patients was between 7 and 17 years old. Three cases (boys) were treated by surgery - one patient with conjunctival malignant melanoma (histologically confirmed) derived from a pre-existing benign conjunctival nevus (diagnosed 1.5 years before), a patient was operated for aesthetic reasons (with histological diagnosis of compound conjunctival melanocytic nevus) and one boy was diagnosed of melanocytic conjunctival nevus. All cases operated had normal visual acuity and fundoscopy. There was no regional lymph node present in any case studied. The traditional method for clinical diagnosis of suspected pigmented conjunctival lesions was to remove these lesions surgically and to examine architectural and cytological features with light microscopy. We recommend an immunohistochemical staining for the detection of specific cellular antigens in conjunctival melanocytic tumors in children. The diagnosis, treatment and the follow-up of the patient were challenges for the ophthalmologist.

Corresponding author: Gabriel Martinescu, MD, PhD Student; e-mail: g.martinescu@yahoo.com

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40. Morphological and functional renovascular changes as cause of resistant arterial hypertension - case report and literature review

Irina Iuliana Costache, Claudia Florida Costea, Vasile Fotea, Victor Laurian Rusu, Viviana Aursulesei, Razan Al Namat, Dan Alexandru Costache, Nicoleta Dumitrescu, Catalin Mihai Buzduga, Gabriela Florenta Dumitrescu, Anca Sava, Camelia Margareta Bogdanici

Resistant hypertension is defined by the inability to maintain within normal limits the blood pressure values of an individual, while he is under treatment with maximal tolerated doses of three antihypertensive agents. One of the most common types of resistant hypertension is renovascular hypertension (RVH), which is caused by the narrowing of the renal arteries, in the context of existing atherosclerotic plaques at that level. We are presenting the case of a hypertensive 56-year-old man admitted in the Clinic of Cardiology for a sudden rise of his blood pressure values, despite undergoing the scheduled treatment. The abdominal bruit discovered at the clinical examination and the hypokalemia, together with the mild impairment of the renal function raised the suspicion of an existing stenosis of the main renal blood vessels. Simple grey scale kidney ultrasound, Doppler ultrasound of the renal arteries, abdominal computed tomography and magnetic resonance angiography of the renal arteries, along with invasive renal angiography demonstrated a smaller right kidney, adrenal incidentalomas, reduced vascular diameter of renal arteries due to atheromatous lesions, thrombosis of the infrarenal segment of the abdominal aorta, and reduced vascular hemodynamics in the same territories. After the renal arteries revascularization and with minimal antihypertensive treatment, the patient had a favorable outcome, with normalization of blood pressure and renal function. Atherosclerotic disease causing renal artery stenosis is essential to be taken into consideration in the etiopathogenesis of resistant hypertension especially because RVH is a potentially curable disease.

Corresponding author: Claudia Florida Costea, Assistant Professor, MD, PhD; e-mail: costea10@yahoo.com; Victor Laurian Rusu, MD; e-mail: rusu.victorl@gmail.com

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41. The cardiac tumors - some exceptional heart conditions

Ana-Maria Cristian, Oriana Elena Moraru, Viorel Constantin Goleanu, Marian Butusina, Florina Pinte, Bogdan-Virgil Cotoi, Gabriel Cristian

Cardiac tumors are exceptional cardiac conditions, since they have a minimal occurrence, according to statistics. The cardiac myxoma cases are the most dominant for the representative examples for these clinical situations. Those tumors being benign, the patients enjoy a reasonable life expectancy provided they receive an early diagnosis. In the absence of potential complications, the symptoms can vary very much and they may often be non-specific, a fact which makes it more difficult to establish a proper diagnosis and to quickly tailor the optimal therapeutic solutions. Surgery is, in the most cases, a comfortable solution, allowing the cases to be permanently healed. Nowadays, cardiac surgery provides all the needed facilities to diagnose cases at an early stage, when diagnosis is quick and accurate. This paper illustrates, by the means of two suggestive cases, how difficult it is to establish a quick positive diagnosis, which is vital for healing this condition with an evolutionary risk frequently worsen by major complications.

Corresponding author: Ana-Maria Cristian, MD, PhD Candidate; e-mail: preda_anamaria25@yahoo.com; Bogdan-Virgil Cotoi, Lecturer, MD, PhD; e-mail: bogdan230376@yahoo.ro

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42. Immunohistochemical mismatch in a case of rhabdomyoblastic metastatic melanoma

Adrian Vasile Dumitru, Mircea Stefan Tampa, Simona-Roxana Georgescu, Stana Paunica, Clara Nicoleta Matei, Adriana Elena Nica, Mariana Costache, Ion Motofei, Maria Sajin, Ioana Paunica, Tiberiu Augustin Georgescu

Melanomas can exhibit a wide range of unusual morphologies due to the neural crest origin of melanocytes. Several authors have documented variations in size and shape of cells, cytoplasmic features and inclusions, nuclear features and cell architecture. Metastatic melanoma with rhabdomyoblastic differentiation is an extremely rare condition with poor prognosis. Few studies concerning rhabdoid or rhabdomyoblastic differentiation in melanoma are currently available and the current report highlights some of the most important immunohistochemical features of this rare entity. We report on a case of a rhabdomyoblastic metastatic melanoma showing intense positivity for both melanocytic and rhabdoid markers in two cell populations dissociated within the tumor with multiple mismatches in immunomarker expression. Improved recognition of this rare morphological pattern may provide the means for developing new techniques to identify novel therapeutic targets, which would improve the prognostic outlook for these patients.

Corresponding author: Stana Paunica, Associate Professor, DMD, PhD; e-mails: spaunica@yahoo.com, stana.paunica@umfcd.ro

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43. The curious case of a forehead metatypical basal cell carcinoma

Ioan Petre Florescu, Eugen Gabriel Turcu, Andrei Mircea Carantino, Laurentiu Catalin Cocosila, Valentin Enache, Tiberiu Paul Neagu, Cristian Radu Jecan

The risk of developing basal cell carcinoma (BCC) during lifetime varies between 29-55%, while for squamous cell carcinoma (SCC) varies between 7-11%. Between them, considered to be a BCC, there is a particular histological type, named metatypical basal cell carcinoma (MTC) or basosquamous cell carcinoma (BSCC). In this paper, we presented a rare case of metatypical carcinoma of the forehead with an interesting history of unexpected recurrences, underlining the clinical, therapeutic and histological essential aspects that may come in use to other clinicians in managing this type of cancer. In this case, the last recurrent tumor invaded the external layer of the frontal bone and needed a temporo-parietal flap to cover the large defect, which was previously covered in 2014 using skin grafts. Using Hematoxylin-Eosin (HE) staining, the histological assessment revealed a basosquamous carcinoma (IDO-O 8094/3, according to World Health Organization). In addition to the histological aspects revealed using HE staining, in this case, diffused tumor cells were p63 nuclear positive, which according to Bircan et al. (2006), it is strongly and diffuse reactive in 82.1% differentiated, in 77.8% of superficial and in 72.3% of solid undifferentiated BCCs. The aggressive behavior was revealed by tumor s dimension, local invasion of the frontal bone with high mitotic rate as seen in the van Gieson and HE staining, also by the number of recurrences. The prognosis of this case is reserved due to the number of recurrent tumors, immunohistochemistry anomalies, involvement of the external layer of the frontal bone, tumor site, gender, poor remaining reconstructive procedures in case of a relapse, thus, close follow-up is to be recommended for a period of minimum five years. Recurrent tumors raise treatment difficulties regarding the reconstruction procedure of the defect after wide surgical excision. Therefore, the aggressive behavior of the MTC should be taken into consideration in clinical practice.

Corresponding author: Tiberiu Paul Neagu, Assistant Professor, MD, PhD; e-mail: dr.neagupaul@gmail.com

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44. An anomalous origin of the gastrosplenic trunk and common hepatic artery arising independently from the abdominal aorta: a case report using MDCT angiography

Nicoleta Iacob, Agneta Maria Pusztai, Gratian Dragoslav Miclaus, Elena Pop, Petru Matusz

The authors describe a case of a 61-year-old female patient, which presented on multidetector computed tomographic (MDCT) angiography a gastrosplenic trunk (GST) and common hepatic artery (CHA) arose independently from abdominal aorta (AA). The GST arose from the anterior wall of the AA, at the level of upper edge of the L1 vertebral body. The left gastric artery (LGA) arose from the superior wall of the GST. The splenic artery (SA) continuous the path of GST. The CHA arose from the anterior wall of the AA, at the level of upper one third of the L1 vertebral body, at 15.3 mm above the origin of superior mesenteric artery (SMA). The incidence and developmental and clinical significance of this vascular variation is discussed with a detailed review of the literature.

Corresponding author: Elena Pop, Associate Professor, MD, PhD; e-mail: alexandra_2987@yahoo.com

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45. A rare case diagnosed as dentin dysplasia type II

Paula Perlea, Cristina Dragomir, Andreea Bodeanu, Anca Nicoleta Temelcea, Alexandru-Andrei Iliescu

According to their phenotypic features, the hereditary dentin defects in humans are categorized in two major classes: dentinogenesis imperfecta and dentin dysplasia. At its turn, the dentin dysplasia is subdivided in dentin dysplasia type I and dentin dysplasia type II, a milder clinical manifestation of the condition. Here we report the clinical and radiographic findings of dentin dysplasia type II in two members of a family, a young adult female and her mother. Except a mild shade change of the incisal margins in upper central incisors and left upper canine of the daughter no abnormal occlusal wear or crown shape change of the teeth were disclosed in both patients. However, confluent large pulp stones in the thistle-tube shaped pulp chambers and pulpal obliteration were a common finding. The condition was diagnosed as dentin dysplasia type II.

Corresponding author: Anca Nicoleta Temelcea, Lecturer, DMD, PhD; e-mail: anca@temelcea.ro

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46. Neurosurgical rare disease: solitary plasmacytoma of the skull - case report and literature review

Radu Eugen Rizea, Mihai Popescu, Karina Lidia Gheorghita, George Popescu, Marius Cristian Neamtu, Cristina Jana Busuioc, Alexandru Vlad Ciurea

Solitary extranevraxial plasmacytoma (SEP), as a clinical entity without signs of systemic myelomatosis, is extremely rare; it is difficult to find literature on the issue of patient management and proper course of action in the presence of associated pathology. The authors present a rare case of plasmacytoma of the skull vault associated with severe cardiac pathology, which made surgery extremely difficult and possible only through temporization of the interventions, as presented. We discuss our findings and opportunities for treatment in this case, which seemed unapproachable at presentation, in connection with the associated cardiac pathology. The case was followed-up for eight years with no recurrences.

Corresponding author: Mihai Popescu, Professor, MD, PhD; e-mails: mihai.popescu@upit.ro, mihaipopescu2000@yahoo.com; Cristina Jana Busuioc, Associate Professor, MD, PhD; e-mail: dr_cristinab@yahoo.com

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47. Conjunctival invasive poorly differentiated squamous cell carcinoma in a 91-year-old female patient

Adina Ioana Todireasa, Victor Vlad Costan, Mihaela Roxana Popescu, Manuela Ciocoiu

The invasive conjunctival squamous cell carcinoma (SCC) of the eyeball is a malignant tumor that invades only the conjunctiva and rarely the eyeball and the tissue of the orbit. We presented the clinical case of a 91-year-old patient, hospitalized at the 2nd Ophthalmology Clinic of the Prof. Dr. Nicolae Oblu Emergency Clinical Hospital of Iasi, Romania, due to a solid tumor mass of approximately 1x2 cm, which was noticed under the bulbar conjunctiva of the right eye in the nasal sector. The magnetic resonance imaging (MRI) examination showed an adherent tumor of the right eye sclera, presenting invasion into the tissue of the orbit. The right eyeball was enucleated en bloc with the adherent tumor and the partial exenteration of the nearby orbital tissue was carried out as well. The pathological examination revealed that the immunohistochemical (IHC) reactions turned positive for the anti-cytokeratin AE1/AE3 antibody and showed a relatively high Ki67 labeling index, but it did not show immunoreactivity for human melanoma black-45 (HMB-45) marker and S100 protein. The histopathological (HP) diagnosis was poorly differentiated SCC of the right ocular conjunctiva with infiltration of cornea, sclera and orbital connective and adipose tissues (pT4N0M0). The invasive conjunctival SCC requires an early diagnosis for elderly patients in order to prevent the ocular and orbital invasion and the appearance of metastases. This tumor rarely occurs during the ninth life decade, the literature reporting only three cases. HP examination of the lesion is the gold standard for diagnosis, especially when IHC stainings are added.

Corresponding author: Victor Vlad Costan, Lecturer, MD, DMD, PhD; e-mail: victorcostan@gmail.com

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48. Empty sella associated with growth hormone deficiency and polydactyly

Maria Claudia Jurca, Marius Bembea, Kinga Kozma, Mircea Ioan Sandor, Rodica Anamaria Negrean, Luciana Dobjanschi, Emilia Albinita Cuc, Codruta Diana Petchesi, Alexandru Daniel Jurca

Empty sella means the absence of the pituitary gland on cranial computed tomography or magnetic resonance imaging. Empty sella syndrome is the pathological variant of the imaging-described empty sella. We present the case of a male Caucasian child, aged four years and two months, for short stature and diagnosed by imaging procedures as empty sella. The cause of short stature was isolated growth hormone (GH) deficiency. Associated he presented left hand postaxial polydactyly. In connection with this particular case, we propose a review of current knowledge in empty sella syndrome. The particularity of reported case consists of association empty sella with GH deficiency and polydactyly. The association of empty sella with polydactyly is not reported yet in the medical literature and is probably coincidental.

Corresponding author: Maria Claudia Jurca, Lecturer, MD, PhD; e-mail: claudiajurca70@yahoo.com; Kinga Kozma, Assistant Professor, MD, PhD; e-mail: kozmaki@gmail.com

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49. Low-fat, plexiform spindle cell lipoma of the lip expressing S100 protein: a neural tumor simulator

Jose-Fernando Val-Bernal, Maria Luisa Cagigal, Remigio Mazorra

The plexiform variant of spindle cell lipoma is very uncommon. In fact, as far as we are aware only seven cases have been previously reported. We describe herein the case of a 49-year-old man with a smooth nodule of the mucosa of the lower lip that was gradually increasing. Surgical excision of the lesion was done and the study revealed the histological and immunohistochemical features of a plexiform spindle cell lipoma (PSCL). Peculiar to this case was the location in the lip, the presence of abundant S100-positive dendritic cells, and scarce mature lipogenic cells. S100 protein reactivity has rarely been observed in classical and plexiform spindle cell lipoma. To our knowledge, no case of PSCL displaying abundant S100-positive dendritic cells has been described. This feature may lead to a diagnostic pitfall. The main differential diagnosis includes the neuroma group, plexiform intraneural neurofibroma (PIN), plexiform schwannoma and plexiform hybrid tumor of perineurioma and cellular neurothekeoma. It is imperative correctly diagnose and differentiate PSCL from neural tumors because they may show syndromic associations, have different prognosis, including malignant transformation in PIN, and the management of all these lesions differs.

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

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50. Letter to the Editor: Desquamative interstitial pneumonia revisited half a century later

Vitorino Modesto dos Santos

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Corresponding author: Vitorino Modesto dos Santos, Professor, MD, PhD; e-mail: vitorinomodesto@gmail.com

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51. Letter to the Editor: Corrigendum to the paper Precursor and interstitial Cajal cells in the human embryo liver

Mugurel Constantin Rusu

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Corresponding author: Mugurel Constantin Rusu, MD, Dr.Med., Dr.Biol., Dr.Hab.; e-mail: anatomon@gmail.com

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