Vol. 62 No. 3, July-September 2021

1. Thymolipoma - the frontier between hamartoma and neoplasia?

Cornelia Amalinei, Adriana Grigoras, Raluca Anca Balan, Laura Adriana Riscanu, Simona Eliza Giusca, Irina-Draga Caruntu

Thymolipoma is an uncommon benign thymus lesion, with a partially deciphered etiopathogeny, being most frequently diagnosed in young patients, regardless of gender. Incidentally diagnosed in asymptomatic patients, larger thymolipomas lead to symptoms related to neighboring mediastinal structures compression, with an intensity which is correlated with the mass size. Our review presents the main epidemiological, pathogenic, clinicopathological and morphological characteristics of this rare pathology. Sometimes, thymolipomas may be associated with paraneoplastic syndromes, which are alleviated by the mass complete surgical resection. Imagistics may orientate the diagnosis, which is certified by the microscopic examination of the resection specimens. Extensive thymectomy remains the current therapeutic option and new tools have been developed to increase the accuracy of the surgical procedure to avoid incidental lesions of the important elements of the anterior mediastinum. Although rare, thymolipomas should be considered in the differential diagnosis of mediastinal masses and of paraneoplastic syndromes.

Corresponding author: Raluca Anca Balan, Associate Professor, MD, PhD; e-mail:; Adriana Grigoras, Associate Professor, MD, PhD; e-mail:

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2. Renal oncocytoma with prominent xanthomatous reaction. A rare histopathological variant of oncocytoma

Jose-Fernando Val-Bernal, Maria-Francisca Garijo, Jose-Javier Gomez-Roman

Renal oncocytoma (RO) is a distinctive neoplasm with a well-recognized gross and cytoarchitectural appearance. However, on some occasions, it may show uncommon, atypical, or worrisome gross and microscopic features potentially generating diagnostic difficulties. We herein review the oncocytoma variant characterized by a significant intraneoplastic xanthomatous reaction that produces a variegated macroscopic appearance. This feature may pose a genuine diagnostic problem with conventional (clear cell) renal cell carcinoma (RCC) because this reaction creates a departure from the typical uniform, tan-brown appearance of oncocytoma. The microscopic presence of foamy macrophages in RO may potentially lead to diagnostic difficulties with tumors exhibiting eosinophilic cells and significant infiltration for lipid-laden foamy macrophages such as cystic RCC, unclassified RCC rich in foamy macrophages, the solid variant of papillary RCC with oncocytic features, post-neuroblastoma RCC, succinate dehydrogenase-deficient RCC, mucinous-poor tubular and spindle cell carcinoma, and the oncocytic variant of the epithelioid angiomyolipoma. In conflictive cases, an immunohistochemical panel should help to solve the diagnostic problem. Therefore, the presence of abundant foamy macrophages should not dissuade the pathologist from establishing a diagnosis of RO. Prominent xanthomatous reaction despite its low frequency (4.3%) can be considered an additional feature of RO. Thus, RO should be added to the list of renal tumors that can show a significant reaction of lipid-laden foamy macrophages. Besides, Gamna-Gandy bodies can be present in this tumor.

Corresponding author: Jose-Fernando Val-Bernal, Professor, MD, PhD; e-mail:

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3. Prognostic biomarkers related to tumoral microenvironment in pancreatic ductal adenocarcinoma: a systematic review

Alina Liliana Constantin, Irina Mihaela Cazacu, Cezar Stroescu, Catalin Copaescu, Adrian Saftoiu

Over the past decades, pancreatic ductal adenocarcinoma (PDAC) has been coming into view due to increased mortality, the 5-year survival rate being the lowest of all cancers (around 6%). In PDAC, microenvironmental components possess prognostic relevance. The aim of this article is to perform a review of studies evaluating the composition of the tumor microenvironment to identify tumor microenvironment-related prognostic biomarkers in patients with PDAC. A literature search has been performed in three major databases PubMed, Embase, Web of Science using the search terms: pancreatic adenocarcinoma in combination with one of the following: alpha-smooth muscle actin (alpha-SMA), collagen I, cluster of differentiation (CD)31, CD105, CD3-CD4-CD8, CD68 and CD206. Total number of articles identified through database searching was 1185. After title and abstract review, we have selected 92 articles in which the markers sought were studied. Tumor microenvironment-related biomarkers appear to also possess role in monitoring the response to treatment. Thus, CD105 angiogenetic immunomarker, stromal immunomarkers such as alpha-SMA and collagen I, immune cells markers represented by CD4/CD8 ratio, CD206 and CD68 were correlated with negative prognosis, while CD3+, CD8+ immune cells markers and CD31 angiogenetic immunomarker proved to be correlated with good prognosis. Furthermore, most studies were performed on resected specimens and culture cells, while only a few studies used specimens obtained through endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). To increase the therapeutic response and reduce toxicity, prognostic targets should be determined on a large scale, not only based on resected specimens. EUS-FNB represents a feasible method to provide sufficient tissue for diagnosis and additional immunohistochemistry analysis.

Corresponding author: Catalin Copaescu, Professor, MD, PhD; e-mail:

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4. Morphological aspects of the vasculogenesis and angiogenesis during prenatal edification of the circle of Willis: a review

Ana Maria Dumitrescu, Claudia Florida Costea, Cristina Furnica, Mihaela Dana Turliuc, Andrei Ionut Cucu, Camelia Margareta Bogdanici, Serban Turliuc, Gabriela Florenta Dumitrescu, Anca Sava

In the literature, there are many articles reporting anatomical variations of circle of Willis (CoW), defined as those changes that lead to the inability of this anastomotic structure to maintain adequate brain flow. Because there is such a wide variation in the configuration of the CoW, its anatomical variations affect the hemodynamics of blood flow, thus contributing to the development of aneurysms or stroke. As such, we consider that a good knowledge of the embryological development of the constituent arteries of the CoW can shed some light on the causes of the appearance of its anatomical variants. Reviewing literature, we will present the embryological development of the constituting arteries of the CoW and will begin with vasculogenesis and angiogenesis of the vascular system as a whole. Then, we will focus on the embryological development of the internal carotid artery (ICA) and its branches because, starting with the embryological day 24, these arteries are the first vessels that begin to develop to provide the necessary blood for the primitive brain. As the hindbrain increases its volume, a larger amount of nutrients is needed. Because a larger amount of blood is required to be provided by the primitive ICAs, there is a need for arterial capacity development and thus the posterior circulation begin to take shape. At this stage, the posterior circulation consists of a plexiform arterial network that receives blood from the carotid artery through the carotid-vertebrobasilar anastomoses. At the 5-8 mm embryonic stage, these anastomoses begin to regress, and the basilar artery and vertebral arteries become independent of the ICA. We are pointing out on the process of regression of these primitive vessels, emphasizing the fact that their persistence represents the starting point for the appearance of anatomic anomalies of the CoW, which are identified in the adult individuals. In this review, we also present and illustrate some developmental abnormalities of the anterior and posterior parts of the CoW.

Corresponding author: Claudia Florida Costea, Associate Professor, MD, PhD; e-mail:; Cristina Furnica, Associate Professor, MD, PhD; e-mail:

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5. Changes in skeletal dysplasia nosology

Maria Claudia Jurca, Sanziana Iulia Jurca, Filip Mirodot, Bogdan Bercea, Emilia Maria Severin, Marius Bembea, Alexandru Daniel Jurca

Skeletal dysplasia (SD), also called osteochondrodysplasia (OCD), is a large group of skeletal disorders (over 400 distinct entities) caused by abnormalities in bone development and growth. SDs varies according to different natural histories, prognoses, hereditary patterns to etiopathogenetic mechanisms. At birth, the incidence is low, reported at the level of each entity, but taken collectively; the incidence is estimated at 1:5000 births. Nosology is a branch of medical science. It deals with the systematic classification of diseases and disorders. Thus, combining information about the catalogue of clinically distinct disorders, pending molecular explanations, and genotype-phenotype correlations, the classification of SDs will be more accurate. This is extremely useful for diagnosing patients with genetic skeletal diseases, especially given the expected flow of information with new sequencing technologies. Over the years, various terms and classifications of SD have been used and have attempted to order and classify this group of genetic diseases according to clinical, radiological, and molecular criteria. In 2019, the Nosology Committee of the International Skeletal Dysplasia Society (ISDS) updated the classification of SD. This new classification divides SD into 42 large groups that include 461 entities. Advances in next-generation sequencing techniques have revolutionized the entire field of genetics, with 437 different genes are currently identified in 426 (92.4%) of SDs. Nosology is a real help for the clinician in establishing a diagnosis as accurately as possible, for the recognition of new diseases while serving as a guide for the interpretation of new genetic variants.

Corresponding author: : Emilia Maria Severin, Professor, MD, PhD; e-mail:; Bogdan Bercea, PhD Student; e-mail:

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6. Lung cancer mimickers - a case series of seven patients and review of the literature

Florina Neacsu, Angela Stefania Varban, George Simion, Raluca Surghie, Oana Maria Patrascu, Maria Sajin, Mihai Dumitru, Daniela Vrinceanu

Background: Lung is the third most frequent identified site of malignancy and lung cancer is the most lethal type of cancer in the world. Several benign lung diseases or proliferations may mimic lung carcinoma in its clinical, pathological, and radiological presentation, which makes the differential diagnosis life changing. This case series was designed to describe the main diagnosis encountered in a multidisciplinary emergency hospital during the last years in Romania. Results: The most challenging cases encountered during the recent years were those of lung hamartoma associated with eosinophilic pneumonia because of the multicentricity of the disease and the suspicion for metastasis in the clinical setting, pulmonary aspergillosis that presented as a cystic lesion with a 9 mm mural nodule, actinomycosis discovered as firm nodule showing aspects of false pleural invasion, cryptococcosis - a hilar mass for which a pneumectomy was prepared, pulmonary parasitosis that presented as a nodule with irregular borders, causing pleural retraction, one case of inflammatory myofibroblastic tumor of the lung, one case of tumorlet type neuroendocrine lesion in a patient with history of melanoma and renal oncocytoma, admitted under the suspicion of lung metastasis. Conclusions: These are some of the main mimickers of primary or secondary lung cancers and one must be aware of these similitudes to avoid higher cost procedures, psychological stress for the patient and higher mortality.

Corresponding author: Maria Sajin, Professor, MD, PhD; e-mail:

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7. E-cadherin, fibronectin and Slug immunoexpression in non-melanoma skin cancers

Alexandra Roxana Ciuciulete, Alex Emilian Stepan, Anne Marie Badiu, Bianca Catalina Andreiana, Mirela Marinela Florescu, Cristiana Eugenia Simionescu, Alina Maria Vilcea

Epithelial-mesenchymal transition (EMT) is an essential biological process involved in the initiation and progression of cancer by which epithelial tumor cells lose their differentiated characteristics, such as cell-cell adhesion and apical-basal polarity and acquire a more invasive and/or metastatic mesenchymal phenotype. The present study investigated the expression of immunomarkers with a role in EMT of non-melanoma skin cancers (NMSCs), such as E-cadherin, fibronectin and Slug, for a number of 50 NMSCs, represented by 30 cases of basal cell carcinomas (BCCs) and 20 cases of squamous cell carcinomas (SCCs). For BCC, the statistical analysis of the investigated immunomarkers indicated significantly differences in relation to the depth of invasion, and for E-cadherin and fibronectin with the degree of risk. In the case of SCC, the statistical analysis indicated significant differences of E-cadherin and Slug with the degree of tumor differentiation, and for fibronectin and Slug with the depth of invasion. The analysis of the distribution for the percentage values of the investigated immunomarkers in the case of BCC indicated a significant negative linear relation between E-cadherin/fibronectin and E-cadherin/Slug, and in SCC a significant negative linear relation between E-cadherin/fibronectin, E-cadherin/Slug and a positive linear one in the case of fibronectin/Slug. The study indicates through the statistically significant relation between E-cadherin/fibronectin and E-cadherin/Slug, the EMT intervention in carcinogenesis of NMSC.

Corresponding author: Cristiana Eugenia Simionescu, Professor, MD, PhD; e-mail:; Alex Emilian Stepan, Professor, MD, PhD; e-mail:

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8. Hypertension induces compensatory left ventricular hypertrophy by a mechanism involving gap junction lateralization and overexpression of CD36, PKC and MMP-2

Madalina Dumitrescu, Alina Constantin, Andreea Miruna Nemecz, Emanuel Dragan, Lucia Doina Popov, Gabriela Tanko

Hypertension-induced left ventricular hypertrophy evolves initially as an adaptive response meant to minimize ventricular wall stress. The mechanisms involved in the preservation of the cardiac function during the compensatory phase of the left ventricular hypertrophy are still unclear. Therefore, we aimed at uncovering fine changes that aid the heart to cope with the increased stress in hypertension. Male golden Syrian hamsters were given NG-nitro-L-arginine methyl ester (L-NAME) for 16 weeks, and they became hypertensive (HT), developing left ventricular hypertrophy with no impaired contractility or fibrosis. As compared to age-matched control hamsters, the hypertrophied left ventricles in L-NAME-induced HT hamsters exhibited the following structural and molecular changes: (i) accumulation of lipid droplets (LDs) within cardiomyocytes and relocation of gap junctions to the lateral membrane of cardiomyocytes or close to mitochondria (revealed by electron microscopy); (ii) overexpression of the cluster of differentiation 36 (CD36) fatty acid transporter, protein kinase C (PKC), and matrix metalloproteinase-2 (MMP-2), enhanced activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, and unchanged expression of the connexin 43 (Cx43) and N-cadherin junctional proteins (assessed by Western blot); (iii) increased protein carbonyl content, assessed with a 2,4-Dinitrophenylhydrazine (DNPH)-based spectrophotometric assay, indicative of an enhanced reactive oxygen species (ROS) production; and (iv) augmented MMP-2 activity (determined by gelatin zymography). These changes may participate in an orchestrated adaptive hypertrophic growth response that helps to maintain cardiac performance, in HT hamsters. Together, these findings could provide support for designing future strategies meant to prevent the transition from compensatory left ventricular hypertrophy to decompensated heart failure.

Corresponding author: Gabriela Tanko, PhD; e-mail:

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9. A morphological and immunohistochemical study of the endoscopic ultrasound-fine-needle biopsy samples from solid pancreatic masses: a single center study

Alexandru Constantinescu, Cristina Madalina Ilie-Stan, Vasile Sandru, Bogdan Silviu Ungureanu, Dan Ionut Gheonea, Tudorel Ciurea, Oana Mihaela Plotogea, Christopher Pavel, Valentin Enache, Mihai Alexandru Munteanu, Gabriel Constantinescu

Objective: The purpose of this study was to present the experience of a single center on endoscopic ultrasound-fine-needle biopsy (EUS-FNB) of pancreatic solid tumors amenable to immunohistochemistry (IHC) assay. Patients, Materials and Methods: Inclusion criterion for this prospective study was identifying patients with pancreatic solid tumors, by means of imaging methods, from January 2018 to February 2020, within the Department of Gastroenterology, Emergency Clinical Hospital, Bucharest, Romania. All patients underwent EUS-FNB and the harvested tissue was sent to the Department of Pathology for histopathological (HP) diagnosis and IHC assessment if tumoral origin remained undetermined. Results: A total of 57 patients were ultimately selected to take part in our study. We performed immunohistochemical analysis based on the morphological diagnosis of the pancreatic tumors and assessed cytokeratin (CK)7, CK20, caudal type homeobox 2 (CDX2), MutL homolog 1 (MLH1), MutS homolog (MSH)2, MSH6, postmeiotic segregation 2 (PMS2) for all histopathologically uncertain pancreatic ductal adenocarcinoma (PDAC) and chromogranin A, synaptophysin, pan-CK AE1/AE3 for pancreatic neuroendocrine tumors (pNETs). Cox hazard regression was performed to identify the factors influencing the survival rate. In univariate analysis, patient survival time was significantly associated with stage, location, surgical management and CK7 positivity. Our data show a statistically significant predictive relationship between stage (regional or metastatic) and hazard for survival (p=0.015). Tumoral location in the tail (p=0.015) and radicality surgery (p=0.015) significantly decrease the survival of pancreatic cancer (PAC) patients. The presence of CK7 (p=0.015) significantly increases the survival of pancreas cancer patients. Conclusions: EUS-FNB has opened up a new path for pancreatic tumor diagnosis providing enough tissue for HP examination and IHC. A panel of several immunomarkers might aid in providing new therapies for PAC patients.

Corresponding author: Bogdan Silviu Ungureanu, Teaching Assistant, MD, PhD; e-mail:

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10. Clinical and pathological features of upper limb nerve tumors - four years retrospective study

Andreea Grosu-Bularda, Razvan Nicolae Teodoreanu, Flavia Francesca Lita, Florin-Vlad Hodea, Andra-Luana Lazarescu, Valentin Enache, Andreea-Maria Vrancianu, Ioan Lascar

Benign peripheral nerve tumors and malignant peripheral nerve tumors are rarely found in patients with upper limb tumors. A four-year retrospective study was conducted on patients with tumors in the upper limb area admitted to the Emergency Clinical Hospital, Bucharest, Romania. Seventeen patients were admitted within this time range, 15 of which were benign and two malignant. All patients required surgical intervention after thorough clinical and imaging evaluation. Benign masses were removed, follow-up examination revealing no local recurrent, as well as good function recovery. On the other hand, malignant tumors due to their highly aggressive features, both determined local recurrence, one requiring upper limb amputation, the other presenting metastases.

Corresponding author: Razvan Nicolae Teodoreanu, MD, PhD; e-mail:

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11. Immunoexpression of Ki67, p53 and cyclin D1 in osteosarcomas

Stefan Adrian Niculescu, Dan Cristian Grecu, Cristiana Eugenia Simionescu, Elena Carmen Niculescu, Mioara Desdemona Stepan, Alex Emilian Stepan

The main malignant tumor of the bone tissue is represented by osteosarcoma, neoplasia with a reserved prognosis and an unpredictable evolution, often aggressive. Cell cycle disruption is one of the complex biomolecular mechanisms involved in the progression of osteosarcomas. In this study, we analyzed the immunoexpression of Ki67, p53 and cyclin D1 for 18 primitive osteosarcomas in relation to the clinicopathological prognosis parameters of the lesions. The results indicated the predominance of lesions in male young patients, with femoral location, most tumors being represented by the osteoblastic type, with high grade, size <8 cm and in advanced stages. Reactions were present in all cases, the high immunoexpression being associated with osteoblastic/epithelioid types (Ki67, cyclin D1, p53), high grade (Ki67, cyclin D1) and advanced stage (Ki67, cyclin D1). The study revealed a positive linear relation of the investigated immunomarkers expression, which indicates their usefulness in identifying lesions with aggressive progression potential.

Corresponding author: Cristiana Eugenia Simionescu, Professor, MD, PhD; e-mail:; Mioara Desdemona Stepan, Lecturer, MD, PhD; e-mail:

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12. Alimentary tract duplications in children - a 15 years experience

Radu-Iulian Spataru, Mircea-Ovidiu-Denis Lupusoru, Dragos Serban, Monica Ivanov, Dan-Alexandru Iozsa

Duplications of the alimentary tract are a diverse and complex spectrum of congenital malformations and can be found anywhere along the digestive tract. The management depends on multiple factors, such as age, location, size, macroscopic aspect, and the associated anomalies. This study reflects a 15-year single surgical team experience. We reviewed medical records of 35 consecutive patients presenting alimentary tract duplications, evaluated and managed between 2004 and 2019. The anatomical distribution included: oral structures (two cases), esophageal (three cases), gastric (three patients), jejunoileal (seven cases), ileocecal (12 cases), colonic (six cases), anorectal (one case), and one case of complex tubular duplication of the terminal ileum and entire colon with two anal openings at the perineum. Four patients had antenatal diagnosis, initially asymptomatic, were followed, after birth, with repeated ultrasound examinations for a medium period of 3.8 months. All cases were managed with open surgery. Excision of the lesion with preservation of the gut integrity could be performed in 28 of the cases, while in six cases, enterectomy followed by digestive anastomosis was required. In one complex caudal duplication syndrome, the duplicated tubular colon was left in place. The postoperative complications were gastroesophageal reflux disease (GERD) (two cases), Claude Bernard-Horner syndrome (one case), wound infection (one case), and in one case, massive tongue edema. Clinical findings may be misleading, imaging studies may be uncertain, therefore the surgeon remains to complete de picture with intraoperative findings. In complex duplication cases, a multidisciplinary approach is imperative for the best results.

Corresponding author: Mircea-Ovidiu-Denis Lupusoru, Lecturer, MD, PhD; e-mail:

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13. CK 8/18: the key to differentiating intracutaneous lesions with pagetoid features

Andreea Catalina Tinca, Iuliu Gabriel Cocuz, Mihaela Cornelia Sincu, Raluca Niculescu, Adrian Horatiu Sabau, Diana Maria Chiorean, Silviu Horia Morariu, Sabin Gligore Turdean, Ovidiu Simion Cotoi

Introduction: Neoplasms with pagetoid features are a category of rare lesions defined by the presence of atypical cells at different levels of the epidermis. The most important diseases within this category are mammary Paget disease (MPD), extramammary Paget disease (EMPD), Bowen s disease, in situ melanoma, and pagetoid reticulosis. Aim: The aim of this analysis was to describe the importance of the cytokeratin 8/18 (CK 8/18) immunostaining in diagnosing MPD and EMPD and differentiating them from other lesions. Materials and Methods: A retrospective study was employed, based on the histopathological and immunohistochemical (IHC) characteristics of 30 cases that presented pagetoid features. The cases were processed and analyzed at the Department of Pathology, Mures Clinical County Hospital, Targu Mures, Romania, from 2017 to 2020. Results: Five MPD cases, one EMPD case, one pagetoid reticulosis case, 10 Bowen s disease cases, and 13 in situ melanoma cases were collected. Under Hematoxylin-Eosin staining, cells presented pale cytoplasm in MPD, EMPD, and in 25% of the melanoma cases. Hyperchromasia with nuclear enlargement was seen in all cases. Immunostaining with CK 8/18 was positive in all MPD and EMPD cases. Tests for CK7, p63, and CK AE1/AE3 were positive in MPD, EMPD, and Bowen s cases. Tests for S100, SRY-box transcription factor 10 (SOX10), human melanoma black 45 (HMB45), and Melan A were positive in melanoma cases, while cluster of differentiation (CD)3, CD4, and CD8 tests were positive in the pagetoid reticulosis case. Conclusions: CK 8/18 is an IHC marker that can help establish the diagnosis of MPD and EMPD and differentiate them from other pagetoid neoplasms, ensuring the proper diagnosis and prognosis are provided.

Corresponding author: Iuliu Gabriel Cocuz, Assistant, MD, PhD Student; e-mail:

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14. Diagnostic and prognostic significance of hepatic steatosis in patients with chronic hepatitis C

Ionelia Sorina Stan, Viorel Biciusca, Patricia Durand, Ana-Maria Petrescu, Dragos Mihai Oancea, Alexandra Roxana Ciuciulete, Mihai Petrescu, Ion Udristoiu, Georgiana-Cristiana Camen, Mara Amalia Balteanu, Cristina Maria Marginean, Suzana Danoiu

Knowing that hepatic steatosis (HS) is a common occurrence in patients with chronic hepatitis C (CHC), it is essential to establish what are the factors that predispose to its occurrence and what is the role of HS in the evolution and prognosis of patients with CHC who develop this feature. To achieve these aims, we performed a retrospective clinical study in 33 patients with CHC hospitalized, diagnosed, and monitored in the 2nd Medical Department of the Emergency County Hospital, Craiova, Romania, in a period of two years (2011-2012). Following clinical, hematological, biochemical, immunological, and pathological investigations of the 33 patients with CHC selected, only 14 patients showed pathological changes of the HS. The appearance of steatosis in patients with CHC results from a complex interaction between the particularities of the host and viral factors. The main risk factors of the host, which contributed to the appearance of HS were sex, age, body mass index (BMI), body weight, and personal history of pathology (obesity, metabolic syndrome). Virus-related factors involved in HS were viremia and viral genotype. In conclusion, HS is a common finding (42.42%) in patients with CHC, particularly genotypes 1 and 2. Early detection of HS by invasive or non-invasive methods is an important objective of monitoring patients with CHC, because HS is correlated with a high degree of fibrosis. Therefore, early correction of metabolic factors and early introduction of antiviral therapy are important targets for treating of patients with CHC.

Corresponding author: Viorel Biciusca, Associate Professor, MD, PhD; e-mail:; Ionelia Sorina Stan, MD, PhD Student, Resident Physician; e-mail:

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15. Clinical and morphological outcomes after percutaneous needle fasciotomy in Dupuytren s disease according to the contracture severity

Cristian Trambitas, Alina Dia Trambitas-Miron, Andrei Marian Feier, Octav Marius Russu, Dorin Constantin Dorobantu, Klara Brinzaniuc

Background and Objectives: Dupuytren s disease (DD) is a chronic progressive disorder causing contractures in the palmar and digital fascia. The primary aim of management is to correct the deformity while reducing the risk of recurrence and avoiding complications. The purpose of our retrospective study was to validate the efficacity, safety and the rate of recurrence of DD after percutaneous needle fasciotomy (PNF). Patients, Materials and Methods: We present results for a population of 40 patients, divided into three groups, based on the severity of the contracture according to Tubiana staging. We analyzed patient demographic data, encountered complications and the degree of release achieved both post-procedure and at one-year follow-ups. Results: From a total of 98 joints we treated, we obtained satisfactory release [passive extension deficit (PED) <=10 degrees] in 85% of joints, while full release was obtained in 70% of joints. Full release was obtained mostly in metacarpophalangeal (MCP) joint (95%) rather than proximal interphalangeal (PIP) joint (50%) or distal interphalangeal (DIP) joint (60%). Our patient preferred PNF in comparison to open fasciectomy because of its minimum invasive approach and the quick recovery time. Conclusions: The study shows that PNF has great short-term results and it is suitable for patients who prefer minimally invasive care.

Corresponding author: Alina Dia Trambitas-Miron, Lecturer, PhD; e-mail:

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16. In vitro study of the orthodontic mini-implants influence on the growth of human osteoblasts

Andreea Moldoveanu, Mihnea Ioan Nicolescu, Mirela Veronica Bucur, George-Gabriel Moldoveanu, Cristian Funieru, Ionela-Victoria Neagoe, Gina Manda, Tamara-Rahela Ioana, Lucian Toma Ciocan

This study aimed to assess the in vitro biocompatibility of titanium (Ti) alloy orthodontic mini-implants by correlating human osteoblasts (HOb) response with chemical composition and surface morphology of mini-implants. HOb were cultivated with or without custom-made and commercial mini-implants, discs and filings. The surface morphology and chemical composition of the implants were assessed under the scanning electron microscopy (SEM) with energy-dispersive X-ray (EDX) microanalysis system. Cell viability, adhesion and proliferation were analyzed by optical microscopy and flow cytometry. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) reduction and lactate dehydrogenase (LDH) release tests were used to assess the cytotoxicity of discs and filings-treated culture medium. Shape, adhesion, and multiplication of HOb were not significantly altered by the presence of mini-implants, discs or filings in culture, even though Ti alloy may exert in vitro a low cytotoxic effect on HOb adhered to discs. Morphology analysis by SEM demonstrated that custom-made mini-implants surface differs from that of commercial mini-screws in terms of surface finish and roughness, whilst EDX analysis showed largely similar percentages of Ti, aluminum and vanadium for the two types of implants. No major differences were noticed regarding the effect exerted in vitro on HOb by the investigated implants. The new mini-implants have a convenient in vitro cytotoxicity profile on HOb.

Corresponding author: Mihnea Ioan Nicolescu, Lecturer, MD, DMD, PhD; e-mail:; Mirela Veronica Bucur, Assistant Professor, DMD, PhD; e-mail:

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17. Endodontic fillings evaluated using en face OCT, microCT and SEM

Marius-Mihai Togoe, Emanuela-Lidia Craciunescu, Florin-Ionel Topala, Cosmin Sinescu, Luminita Maria Nica, Ciprian Ionita, Virgil-Florin Duma, Mihai Rominu, Adrian Gheorghe Podoleanu, Meda-Lavinia Negrutiu

Objectives: The goal of endodontic therapy is mechanically cleaning and shaping the root canal system, the removal of organic and inorganic debris followed by sealing with permanent filling materials. Materials and Methods: Therefore, the aim of this in vitro study was to engage three imagistic methods: (i) en face (ef) time domain (TD) optical coherence tomography (OCT), (ii) micro-computed tomography (microCT), and (iii) scanning electron microscopy (SEM), in terms of their efficiency in assessing the quality of endodontic fillings. So far, is settled that efOCT images can identify defects/voids in several of the investigated root canal fillings and identify gaps of 50 micro-m. Results: The results delivered by microCT technology also showed several imperfections of the endodontic filling but also at the interfaces formed by the sealer and the root canal walls. SEM investigations highlights the complex form of the interface formed the endodontic filling material and the walls of the root canal, as well as shortcomings of the materials from several samples. Gaps of 50 micro-m are identified with efOCT. Conclusions: The net advantage of OCT technology, in respect to the other two technologies consists in its non-invasiveness. The OCT axial resolution is also sufficient to see the material gaps. Another advantage of efOCT investigations is that they allow real-time imaging of complex arrangement at the interfaces of the filling material with dentinal root.

Corresponding author: Emanuela-Lidia Craciunescu, Lecturer, MD, PhD; e-mail:

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18. In vitro and in ovo experimental study of two anti-VEGF agents used in ophthalmology

Madalina-Casiana Palfi, Ovidiu Musat, Edward Paul Seclaman, Mihnea Munteanu, Adina-Iuliana Milcu, Andreea Iordache, Alina Dolghi, Sinziana Luminita Istrate, Ileana Ramona Barac, Veronica Madalina Boruga

Anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibodies can inhibit neovascularization and also to block the growth of several tumor cell lines. Treatment with anti-VEGF drugs like Bevacizumab (Avastin) and Aflibercept has proven optimistic results in various malignant diseases. The present study was aimed to investigate Bevacizumab and Aflibercept in vitro effects on two human melanoma cell lines (A375 and SK-Mel-28), as well as on a healthy cell line (HaCaT human keratinocytes), followed by characterization of the in ovo effects on the chorioallantoic membrane (CAM). Our data indicated that Bevacizumab and Aflibercept decreased human melanoma cells viability in a dose-dependent way, a more significant effect was obtained for Aflibercept. Regarding the safety profile of the active compounds tested, they showed a low-moderate irritation score. In the case of the tested samples, the vascular capillaries were not majorly affected. In both cases, the only notable change was the appearance of a slight vascular coagulation. The viability of the embryos after application was good, they survived more than 24 hours after testing the compounds on the CAM.

Corresponding author: Ileana Ramona Barac, Lecturer, MD, PhD; e-mail:; Sinziana Luminita Istrate, Teaching Professor, MD, PhD; e-mail:

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19. Neurobiological and pharmacological arguments for customization of cognitive behavioral psychotherapy in the treatment of major depressive disorder

Silvia Ristea, Ramona Adriana Schenker, Puiu Olivian Stovicek, Mihail Cristian Pirlog, Dragos Marinescu

Introduction: Depression represents a public health issue because it significantly increases the risk of disabilities and premature mortality, decreases the quality of life, and increases the costs of care. The incomplete remissions favor the aggravation of neurobiological dysfunctions and pathogenesis of severe somatic comorbidities. The etiopathogenic mechanisms of depression are complex and involve multisystemic risk factors (genetic, neuroanatomic, neurobiochemical, neuroendocrine and psychosocial). Cognitive behavioral therapy (CBT) is used in all the stages of depression, as independent therapeutic method or as support of pharmacotherapy. Patients, Materials and Methods: This study has evaluated the therapeutic response of depression in M (medication) group with 136 patients under pharmacotherapy, compared with P (psychotherapy and medication) group with 137 patients treated simultaneously with medication and CBT, and the factors that can improve therapeutic management. Results: Patients with depression had predominantly a reactive onset, recurrent evolution of at least four episodes, and frequent somatic comorbidities. After treatment, a significant improvement of depressive symptomatology was recorded especially in M group (72.06%), compared to P group (88.32%), p<0.01, as well as a significant difference in regaining functional skills (69.12% - M group, 93.43% - P group; p<0.001). The therapeutic response was significantly correlated with age (p<0.01), social-economical involvement and education level. Conclusions: CBT demonstrated efficiency in the treatment of major depressive disorder in association with pharmacotherapy. The therapeutic approach should rely on the pathogenic biological models that would highlight the prediction indicators for the therapeutic response and for the evolution of depression, as well as considering the psychological profile of each patient.

Corresponding author: Ramona Adriana Schenker, MD, PhD Student; e-mail:; Puiu Olivian Stovicek, Lecturer, MD, PhD; e-mail:

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20. Hepatic injuries resulting from chronic alcohol abuse identified by forensics

Dragos-Valentin Crauciuc, Cristinel Ionel Stan, Laura Adriana Riscanu, Octavian Ion Predescu, Diana Bulgaru-Iliescu

Alcohol intake is largely spread all over the world, although it is well-known that it causes important changes of the liver, from liver steatosis, hepatitis to liver cirrhosis. The study we performed on 93 patients deceased in suspicious circumstances and brought to the Institute of Forensic Medicine, Iasi, Romania, confirmed through the determination of Ethyl glucuronide, that these were alcohol consumers. The macroscopic analysis during necropsy highlighted the presence of alcoholic liver disease (ALD), while microscopy studies confirmed the macroscopic observations. The immunohistochemical studies showed the existence of a chronic liver inflammation, the transdifferentiation of stellate hepatic cells, the activation of Kupffer cells, important changes of the hepatic vascular network, hepatocyte necrosis, lipid loadings and the progression of liver fibrosis process.

Corresponding author: Dragos-Valentin Crauciuc, Assistant, MD; e-mail:; Octavian Ion Predescu, Lecturer, MD, PhD; e-mail:

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21. The procoagulant status. Hypercoagulability as a risk factor of primary and secondary infertility

Simona-Daniela Neamtu, Liliana Stanca, Mirela Anisoara Siminel, Adela-Valeria Neamtu, Adrian Gluhovschi, Garofita-Olivia Mateescu, Anda-Lorena Dijmarescu, Maria-Sidonia Sandulescu, Anca-Maria Istrate-Ofiteru, Magdalena Rodica Traistaru

Thrombophilia is a disorder that makes patients susceptible to intravascular thrombosis that may increase the risk of developing a pregnancy on a known pathology. The female patient diagnosed with hypoplastic uterus and hereditary thrombophilia had a favorable evolution under properly administered anticoagulant treatment. The homozygous status for the C677T mutation may lead to an increase in plasma homocysteine levels, especially in pregnant women, being an associated risk factor for thrombosis. The risk of developing intravascular thrombosis requires primary prevention measures by adding D-dimers in the early diagnostic algorithm, being the most accurate marker of hypercoagulability and endogenous fibrinolysis. The corroboration of the hypercoagulability status with the results of genotyping, the frequencies of the minor/major alleles studied, single mononucleotide polymorphisms (SNPs) and the establishment of preventive therapy, aims to prevent intravascular thrombosis and thromboembolic phenomena.

Corresponding author: Liliana Stanca, Lecturer, MD, PhD; e-mail:; Mirela Anisoara Siminel, Lecturer, MD, PhD; e-mail:

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22. Sarcomatoid renal cell carcinoma with clear cells and eosinophilia: a case report and short review of the literature

Alexandru Nesiu, Carmen Neamtu, Cristian Mircea Nicolescu, Bogdan Dan Totolici, Horia Dan Muresanu, Mihai Catalin Rosu, Andrei Ardelean, Vlad Constantin Silivestru, Loredana Alina Stanis, Teodora Daniela Marti

Sarcomatoid renal cell carcinoma (SRCC) is an aggressive form of de-differentiated renal cell carcinoma. We report a case of a 79-year-old male who presented himself to the Department of Emergency complaining of macroscopic hematuria for the last two days and a back pain located in the lumbar region persisting for around a month; there were no major changes in the initial laboratory tests. Abdominal ultrasonography identified a renal mass located in the lower pole of the left kidney. The computed tomography (CT) scan with iodine-based contrast revealed the left kidney had a complete deletion of corticomedullary differentiation and a large renal mass located in the lower pole with inhomogeneous iodophilia, which measured around about 15 cm in transversal diameter and 13.6 cm in craniocaudal diameter. Nephrectomy of the left kidney was performed. Histopathological and immunochemistry tests diagnosed a SRCC with clear cells and eosinophilia. We present these findings along with a short review of the literature.

Corresponding author: Cristian Mircea Nicolescu, MD, PhD; e-mail:

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23. Ectopic liver in a five-week-old embryo

Jose-Luis Carrasco-Juan, Hugo Alvarez-Arguelles Cabrera, Carmen Martin-Corriente, Celeste Gonzalez-Garcia, Ricardo Gutierrez-Garcia, Lucio Diaz-Flores

The first case of a placental tumor composed of benign hepatic tissue was published in 1986 and considered a placental benign hepatocellular adenoma. Since then, this lesion is better known as ectopic liver, and a total of 12 cases have been published. The ectopic liver located in the umbilical cord is an even rarer alteration, with only nine cases described to date. We report another case of ectopic liver, this time in an embryo of only five weeks of gestational age.

Corresponding author: Jose-Luis Carrasco-Juan, Professor, MD, PhD; e-mail:

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24. Cystic hygroma of the neck - case report

Veronica Madalina Boruga, Diana Nadina Szilagyi, Mihaela Prodea, Carmen Aurelia Mogoanta, Vlad Andrei Budu, Cornelia Marina Trandafir, Sorin Dema, Ovidiu Musat, Gheorghe Iovanescu

Cystic hygromas (CHs) are benign congenital malformations of the lymphatic system mainly diagnosed in small children aged less than two years old. They may give a multitude of local, sometimes severe complications. The most used method of treatment is surgical removal. In this paper, we present the case of a CH of a 13-year-old boy, localized in the right lateral region of the neck, diagnosed through magnetic resonance imaging (MRI), with excellent results of the surgical treatment.

Corresponding author: Carmen Aurelia Mogoanta, Senior Lecturer, MD, PhD; e-mail:; Sorin Dema, MD, PhD; e-mail:

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25. Intranodal palisaded myofibroblastoma expressing DOG1: focusing on the potential diagnostic pitfalls

Andreas Kontosis, Evripidis Valanikas, Theodosis Papavramidis, Triantafyllia Koletsa

Intranodal palisaded myofibroblastoma (IPM) is a rare, benign mesenchymal neoplasm of the lymph nodes with a broad differential diagnosis. We report a case of an 82-year-old woman presenting with a slow growing, right inguinal mass. The tumor arose as a circumscribed neoplasm inside a lymph node and consisted of bland spindle cells with nuclear palisading and intervening areas of amianthoid-like fibers among interstitial hemorrhage and hemosiderin-laden histiocytes in the stroma, typical histomorphological characteristics of IPM. Immunohistochemically, the neoplastic cells were positive for vimentin, smooth muscle actin (SMA), beta-catenin, cyclin D1 and discovered on gastrointestinal stromal tumor (GIST) 1 (DOG1) immunostainings. A literature review and differential diagnosis of IPM are discussed. To the best of our knowledge, this is the first case of DOG1 immunoexpression in a case of IPM.

Corresponding author: Triantafyllia Koletsa, Associate Professor, MD, PhD; e-mail:

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26. A rare case of placental mesenchymal dysplasia - case report and literature review

Adrian Vasile Dumitru, Sorin Liviu Vasilescu, Daniela Catalina Meca, Octavian Munteanu, Ana Maria Ciongariu, Maria Sajin, Mariana Costache, Antoine Edu, Monica Mihaela Cirstoiu

Described as a rare anomaly of the placenta, with a reported incidence of 0.02%, mesenchymal dysplasia is a benign condition characterized by placentomegaly, grape-like vesicles and by microscopic features resembling those of a molar pregnancy, such as hydropic villi, cistern formation and dysplastic blood vessels. We report a rare case of placental mesenchymal dysplasia diagnosed in a pregnancy with early symmetric fetal intrauterine growth restriction and a normal karyotype. Based on this case report, we discuss the particularities of this condition, emphasizing the ultrasonography and histopathological findings.

Corresponding author: Octavian Munteanu, Lecturer, MD, PhD; e-mail:; Antoine Edu, Associate Professor, MD, PhD; e-mail:

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27. A rare case of situs inversus totalis associated with sigmoid diverticulitis and appendicular agenesis. Embryological, clinical considerations and literature review

Alin Florin Mihetiu, Dan Georgian Bratu, Oana Maria Popescu, Ciprian Juravle, Iulia Emanuela Dumitrean, Radu Chicea

The revelation of situs inversus totalis by a peritoneal syndrome is an extremely rare event. The association of this condition with sigmoid diverticulitis and agenesis of the vermiform appendix has not been described in the literature. This paper aims to present the first case of this type while screening the literature on this topic. The authors present the case of a sigmoid diverticulitis associated with situs inversus totalis and agenesis of the vermiform appendix, in a 44-year-old male patient. Because of abdominal pain located in the right iliac fossa, elevated temperature (38.2 degrees C) and biological examinations, acute appendicitis was rather simulated and considered as a presumptive diagnosis. Diagnostic accuracy was achieved during laparoscopic exploration of the peritoneal cavity, which proved the coexistence of visceral transposition, appendiceal agenesis and sigmoid diverticulitis, usually noted as a rare finding. Secondly, we performed a systematic search on PubMed and Google Scholar databases introducing the following terms: situs inversus totalis, acute appendicitis. Given the time span of the last 30 years, we have obtained a small number of cases in which symptoms that are specific to acute appendicitis have been found in patients with situs inversus totalis. Due to the rare number of cases, it is difficult to establish a preoperative diagnosis. Usually, this diagnosis is revealed as an intraoperative surprise. A careful clinical examination and a set of standardized paraclinical examinations can guide the diagnosis. The patient s evolution was favorable, without any other changes at the subsequent examinations.

Corresponding author: Dan Georgian Bratu, Assistant Professor, MD, PhD; e-mail:,

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