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Papers accepted for publication

1. 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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2. Microglial morphology determined with confocal and two-photon laser scanning microscopy

Smaranda Ioana Mitran, Emilia Burada, Cornelia-Andreea Tanasie, Nicolae Catalin Manea, Mihai Calin Ciorbagiu, Cecil Sorin Mirea, Tudor-Adrian Balseanu

Microglia are the first and main form of active immune defense in the nervous system. The immune status of microglia is directly correlated to their morphology. Therefore, microglia morphology is used to distinguish between active and surveilling microglia. For the actual paper, we used confocal laser scanning microscopy (cLSM) and two-photon laser scanning microscopy (2P-LSM), to investigate microglia morphology of 14-16 weeks old male, transgenic mice (n=6). After obtaining, in vivo and fixed tissue, single cells images, we manually tracked individually branch segments of normal microglia. The total number of branches and their overall length were analyzed. Additionally, the number and mean length of each branch order were measured. The overall microglia branching morphology was not different between the two acquisition methods. However, a higher number of fifth branches was observed using cLSM and 2P-LSM, in both fixed and in vivo tissue. Although results from the two methods are mainly comparable, small differences between them should be taken in consideration when formulating an activating/surveilling conclusion that is purely based on pure microscopic findings. Furthermore, in our opinion, due to their highly dynamic nature, microglia should be carefully labeled as resting or active, taking also into consideration the imaging method used to obtain the data.

Corresponding author: Tudor-Adrian Balseanu, Associate Professor, MD, PhD; e-mail: adrian.balseanu@umfcv.ro; Cecil Sorin Mirea, Lecturer, MD, PhD; e-mail: mirea_cecil@yahoo.com

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3. 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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4. 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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5. 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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6. 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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7. 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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8. 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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9. 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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10. 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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11. 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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12. 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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13. 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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14. 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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15. 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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16. 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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17. 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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18. 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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19. 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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20. Letter to the Editor: Corrigendum to the paper Precursor and interstitial Cajal cells in the human embryo liver

Mugurel Constantin Rusu

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

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21. 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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22. 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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23. Letter to the Editor: Desquamative interstitial pneumonia revisited half a century later

Vitorino Modesto dos Santos

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

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