Vol. 53 No. 4, October-December 2012

1. Georges Marinesco (1863-1938): neurologist, neurohistologist and neuropathologist

M. Catala, J. Poirier

Gheorghe Marinescu (Georges Marinesco, in French) is a Romanian physician, founder of the School of Neurology in that country. He begins his medical studies in Bucharest, then has the opportunity to reach Paris and join the School of Neurology in La Salpetriere Hospital, lead by Jean-Martin Charcot. This trip will forever imprint the mind of Marinescu, a great friend of France, a respectful student of Charcot and a friendly colleague of many Parisian neurologists. Marinescu's works are multiple and very important. He describes the succulent hand in syringomyelia and the palmar-jaw reflex. Marinescu is also one of the first to use the cinema for medical purposes. His work as an anatomo-clinician, a method developed by Charcot, is important. We denote the description of the locus niger affected by tuberculosis in a case of parkinsonism (this description paving Etienne Brissaud's way to highlight the anatomical origin of Parkinson's disease), the original clinical description of Marinesco-Sjogren syndrome, and that of medullomyoblastoma. Marinescu is also a famous neurocytologist as evidenced by his work, La Cellule Nerveuse, published in 1909. The first volume of the book is devoted to the aspects of the normal nervous tissue: the neurofibrillar network, the chromatophilic elements, and the paranucleolar corpuscles (now known as Marinescu's bodies). The second volume of the book is almost related to features revealed by experimental lesions: chromatolysis and neuronophagia. Furthermore, Marinescu describes with Oscar Blocq, small nodules than are now regarded as the first description of senile plaques.

Corresponding author: Martin Catala, Professor, MD, PhD; e-mail:

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2. Immunohistochemical and morphologic evaluation of primary cutaneous apocrine carcinomas and cutaneous metastases from ductal breast carcinoma

A. Fernandez-Flores

The differential diagnosis between a primary cutaneous apocrine carcinoma (CAC) and a cutaneous metastasis from a breast carcinoma can be a very difficult task if it is only made on morphologic bases. Concerning adnexal tumors (in general), there have been many attempts to define an immunohistochemical panel, and while a definition is useful in certain respects, the series presented often times does not include examples of CAC. Other times, CAC seems to behave in an odd way in an immunohistochemical context; they behave differently than other adnexal tumors, and this in turn adds a grade of confusion to the differential diagnosis of a cutaneous metastasis. In the current study, we include seven cases of primary cutaneous apocrine tumors, including one carcinoma in situ, five infiltrating carcinomas, and one adenoma. Additionally, we examine the expression of estrogen receptors (ER), progesterone receptors (PR), and c-erbB-2. We also study myoepithelial markers, such as p63, D2-40, and SMA in them, as well as the pattern of expression of the following cytokeratins: CK7, CK8, CK18, CK19, CK5/6 and 34betaE12. On the other hand, we examine the expression of six immunohistochemical markers (ER, PR, p63, mammaglobin, CK5/6 and D2-40) in 30 cases of cutaneous metastases from breast carcinoma, ductal type. None of our infiltrating primary CAC expressed ER or PR, while the cutaneous metastasis expressed the markers in 90% of the cases. D2-40 was expressed in 60% of the infiltrating CACs, while the metastases were either negative (93.33% of the cases) or positive with luminal reinforcement. Mammaglobin was a very useful marker, expressed by 66.66% of the metastases, and by only one CAC (and in less than 10% of the cells). None of the metastases were positive for p63, while 60% of the CAC expressed the marker. CK 5/6 was also expressed by a high percentage of our CACs (80%), while it was seen in only 6.66% of the metastases. We found SMA as a very useful tool in diagnosing an invasion in CAC. Regarding the expression of c-erbB-2, all of our cases had a value of either 0 or 1.

Corresponding author: Angel Fernandez-Flores, MD, PhD; e-mail:

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3. Whole-genome DASL gene expression profiling of hepatocellular carcinoma sub-populations isolated by laser microdissection on formalin-fixed and paraffin-embedded liver tissue samples

Corina Gabriela Cotoi, Shirin Elizabeth Khorsandi, I. E. Plesea, A. Quaglia

In the last ten years, a multitude of studies focusing on gene expression profiling have attempted to shed light on the molecular and genomic mechanisms leading to hepatocarcinogenesis. One of the downsides of the technology available until recently was that it was limited to RNA extracted from fresh/frozen tissue or cell cultures. Recent advances have made it possible to obtain good quality RNA from formalin-fixed paraffin-embedded (FFPE) tissue, allowing access to a virtually limitless archival resource to be available for retrospective and long-term prospective clinico-pathological studies. Laser-capture microdissection allows the isolation of specific cell populations or of specific microscopic areas of interest from tissue samples. This allows the selective evaluation of gene expression of targeted cell clusters, especially in a very heterogeneous environment as the malignant tissue. In our study, we demonstrated that by laser microdissecting the areas of interest from FFPE tissue we could obtain gene expression signals by running the purified RNA through the Whole Genome DASL assay. A large number of genes were expressed in both subpopulations of hepatocellular carcinoma (classical HCC and cholangiocellular differentiation) as well as in the cirrhotic and non-cirrhotic liver background.

Corresponding author: Corina Gabriela Cotoi, Clinical Research Fellow; e-mail:

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4. Hypoxia induced VEGF synthesis in visceral adipose depots of obese diabetic patients

Ana Marina Fusaru, Catalina Gabriela Pisoschi, Adriana Bold, C. Taisescu, R. Stanescu, Mihaela Hincu, Stefania Craitoiu, Ileana Monica Banita

VEGF is one the pro-inflammatory adipokines synthesized by the "adipose secretoma" of obese subjects as a response to hypoxic conditions; but the main function of VEGF is angiogenesis, being recognized as the most important factor increasing blood capillaries in the adipose tissue by stimulating endothelial cell growth. In this paper, we propose a comparative study of the vascular response to VEGF synthesis in the subcutaneous and central-peritoneal adipose depots in lean, obese and obese diabetic patients. We used CD31 to label the endothelial cells in order to evaluate the response of the vascular network to VEGF synthesis. Our results showed an increase of VEGF protein synthesis in obese and obese-diabetic patients compared to lean subjects where the protein was absent. The positivity for VEGF in obese diabetic samples was observed in numerous structures from the adipose depots, both in the stromal vascular fraction - blood vessels and stromal cells - as well as in the cytoplasm of adipocytes. Positivity in the vascular wall was observed more frequently in areas of perivascular and intralobular fibrosis. Obese and diabetic patients showed similar incidence of CD31 immunoreactivity with lean subjects in both subcutaneous and peritoneal depots. In conclusion, human adipose depots show a different incidence of VEGF positive cells in relation with their disposal and the metabolic status. VEGF synthesis in visceral adipose tissue is inefficient being not followed by angiogenesis to counterbalance tissue hypoxia. We suggest that may be a pathogenic link between the degrees of intralobular fibrosis in adipose depots and VEGF expression.

Corresponding author: Ileana Monica Banita, Professor, MD, PhD; e-mail:

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5. VEGF and CD31 expression in arthritic synovium and cartilage of human knee joints

R. Melinte, I. Jung, Lia Georgescu, Simona Gurzu

Purpose: To determine the histological differences and the particular aspects of local angiogenesis in knee joint of the patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Materials and Methods: In 10 cases with RA and five OA, immunohistochemical stains were performed with CD31 and VEGF-A (Vascular Endothelial Growth Factor). All surgical samples provided from total knee joint arthroplasty. Angiogenesis was quantified in both synovial membrane and cartilage. Results: In patients with OA, villous proliferation of the synovial membrane was more prominent that in RA. In the last, invasion of the cartilage by the proliferated synovial tissue was more characteristic. The neovascularization was more intense in RA than in OA, in both synovium and degenerated cartilage. In RA, the vessels were immature in the superficial areas and became larger in the deep synovium. The local angiogenesis was characterized by sprouting and splitting (intussusceptions) mechanisms. In OA, the mature vessels predominated in the subintimal zones. Sprouting or non-sprouting mechanisms of local angiogenesis, which can indicate vascular formation from the resident mature vessels, were not identified in OA. Conclusions: Angiogenesis seems to have particular behavior in RA and OA. In RA, local active angiogenesis seems to predominate but in OA up taking of the circulating precursors may be more intensely involved. Intra-articular inhibition of local angiogenesis could have therapeutically impact in RA but not in OA. Finally, we can conclude that there probably are many different pathways leading to the same joint damage having certain therapeutic consequences.

Corresponding author: Simona Gurzu, Senior Lecturer, MD, PhD; e-mail:

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6. Clinical and morphological correlations in acute ischemic stroke

Anca-Stefania Slujitoru, Andreea-Lorena Enache, Irina Lavinia Pintea, Elisabeta Rolea, Cristina Mariana Stocheci, O. T. Pop, Anca Predescu

We studied the clinical and histopathological changes in twenty-seven cases of acute ischemic stroke, aged between 65 and 75 years. All deaths occurred within 30 days after stroke. The aim of our study was to establish the clinical and histological correlations in acute ischemic stroke to detect prognostic factors. Brain lesions after acute stroke were observed in all regions. Our study describes the heterogeneity of brain injury after acute ischemic stroke with the participation of all brain components and the chronology in which these lesions develop and evolve. By histological and immunohistochemical studies, we identified neuronal, glial and vascular damage. The neurons had undergone in the area of lesion a process of necrosis, ballooning or condensation process. In the ischemic penumbra, we observed the presence of red neurons. Vascular lesions were represented by the discontinuity of capillaries, always associated with a marked perivascular edema. The following clinical and morphological correlations were established: liquefactive necrosis, astrocyte gliosis, phagocytosis phenomena are the more intense the later the death of the patient; apoptosis phenomena are the more intense the faster the death of the patient; the entire cerebral microcirculation presented microscopic modifications following the ischemic strokes, regardless of the time since the lesion occurred and the histological examination was made; the major neurological complications of the ischemic stroke - the hemorrhagic transformation phenomena, cerebral edema, were microscopically objectified, regardless of the time since the lesion occurred and the histological examination was made.

Corresponding author: Anca-Stefania Slujitoru, MD, PhD student; e-mail:

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7. The value of the histopathologic examination in the diagnosis and management of the actinic keratosis

Alina Maria Vilcea, I. D. Vilcea, Claudia Valentina Georgescu, V. Patrascu

Actinic keratosis, considered lately as an intraepithelial squamous cell carcinoma in evolution, are powerful predictors of the risk for developing a cutaneous carcinoma and melanoma. The aims of the study were to establish the value of the histopathologic examination as a confirmation method for the actinic keratosis diagnosis, to assess the percentage of these lesions that suffer a malignant transformation, and also the frequency of the association between actinic keratosis and cutaneous carcinomas. This is a retrospective study, performed on 208 patients diagnosed with different types of cutaneous precancers, hospitalized in Dermatology Clinic of Craiova, Romania, between 2006 and 2010. Actinic keratosis represented 37.93% (79 cases) of all cutaneous precancers (the most frequent cutaneous precancer). Patient's age ranged from 17 to 85 years, 54.8% of the patients being from rural environment; 86.07% of the lesions were located on the solar exposed skin (head and face). 72.16% of the actinic keratosis was clinical subdiagnosed. The most frequent form was hypertrophic actinic keratosis (89.06%); in 18.98% of cases, malignant transformation in squamous cell carcinoma was noticed. Actinic keratosis represent 86% of the precancers that associate a carcinoma, basal cell carcinoma being diagnosed the most frequent. In conclusion, actinic keratosis are the most frequent cutaneous precancer, diagnosed in chronic sun-exposed patients, and manifest a tendency to progress into a squamous cell carcinoma without a proper treatment. Pathologic evaluation is mandatory to an accurate assessment of the actinic keratosis prevalence, and for the right management of these lesions.

Corresponding author: Alina Maria Vilcea, Assistant Professor, MD; e-mail:

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8. Surface characteristics of retrieved coated and nickel-titanium orthodontic archwires

Georgeta Zegan, Alina Sodor, C. Munteanu

Objective: The purpose of this study was to investigate the effects of oral fluids and archwire-bracket friction on the surface characteristics of NiTi alloy orthodontic archwires with/without aesthetic coating, in vivo for 2-3 months. Materials and Methods: Different cross-sections of NiTi Archwires (DENTSPLY GAC International) and Titanol Cosmetic Archwires (FORESTADENT USA Inc.) were examined by electron microscopy with dual-beam and spectroscopy analysis, before and after a collecting protocol from patients with multi-technique. Results: Initially, the orthodontic archwires showed microscopic manufacturing and coating defects in the physiognomic layer. After intra-oral exposure, amorphous organic matter deposits were observed on the surface of the NiTi Archwires and the wire coating presented exfoliation on the oral areas of friction with brackets. X-ray microanalysis revealed changes in all atomic and mass percentages of chemical elements from the surface of all retrieved dental archwires, nickel and titanium ion depletion and the occurrence of additional elements due to interactions with saliva. Conclusions: Intra-oral exposure of NiTi Archwires and the archwire-bracket friction of coated wire altered the morphology and changed the elemental composition of the surface due to the process of corrosion, adhesion of organic matters and ionic exchange with oral fluids.

Corresponding author: Georgeta Zegan, Associate Professor, DMD, PhD; e-mail:

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9. Correlations between intratumoral interstitial fibrillary network and tumoral architecture in prostatic adenocarcinoma

A. Stoiculescu, I. E. Plesea, O. T. Pop, D. O. Alexandru, M. Man, M. Serbanescu, R. M. Plesea

The authors made a preliminary assessment of possible correlations between the amount of intratumoral stromal fibrillary components (ISFC) and the architectural tumoral patterns described by Gleason. The studied material consisted of samples obtained by transurethral resection from 34 patients diagnosed with prostatic adenocarcinoma. Ten fields, five for dominant and five for secondary identified patterns of each case, with no necrosis were selected randomly from Gomori stained sections using x20 objective. ISFC-ratio increased with Gleason pattern both for the entire group but also for "Necrotizing" phenotype patterns and "Solid" phenotype patterns, excepting the subtype "4A" where the stromal compartment was reduced by the expansion of tumoral ducts enlarged by growing tumoral intraductal cribriform masses. These preliminary data showed that stromal microenvironment try to adapt to the loss of tumoral differentiation by increasing the amount of fibrillary components of intratumoral stromal compartment.

Corresponding author: Iancu Emil Plesea, Professor, MD, PhD; e-mail:

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10. The vascular layers on the rostral ventrolateral medulla

M. C. Rusu, Elena Pop, Adelina Maria Jianu, A. G. M. Motoc

There has been a keen interest in assessing the neurovascular anatomy of the rostral ventrolateral medulla oblongata (RVLM). The present study was aimed at documenting the complete neurovascular anatomy of the RVLM, in order to offer a general picture of the possible offending vessels of this area, which seems to be involved in the pathogeny of the essential hypertension. Noteworthy, syndromes of the last cranial nerves could be due to vascular contacts or compressions. The present study was performed on 20 human adult brainstem-cerebellum blocks, dissected out of the posterior cerebral fossa at autopsies. The origins of the inferior cerebellar arteries (anterior - AICA and posterior - PICA) were traced bilaterally (n=40 sides). When present (26/40) AICA most frequently left the basilar artery and PICA (28/40) most frequently left the vertebral artery. At the level of the RVLM, a quadrilateral space delimited by the vertebral artery (VA) and the vertebrobasilar junction, the AICA and the PICA, was defined. Within that space, three vascular layers were identified: a superficial one, formed by the inferior cerebellar arteries, a middle one, consisting of perforating arteries, and a deep, venous one. The RVLM perforating arteries left the VA (31/40), basilar artery (BA) (3/40), anterior spinal artery (ASA) (34/40), PICA (28/40) and AICA (24/40). These perforators had a transverse or oblique course if given off by the VA, BA or ASA, were descendant if given off by the AICA or BA, and were ascending if given off by the VA or PICA. Microanatomical studies of the vascular relations of the RVLM are able to complete the somewhat limited findings of studies based on imaging techniques. The offending vessels of the RVLM could be any of the vessels inside the quadrilateral space. Major vessels, such as the VA, AICA or PICA should not be viewed as the only possible offending vessels at this level. The perforators and the venous layers in the quadrilateral space should also be better evaluated from this perspective.

Corresponding author: Mugurel Constantin Rusu, Senior Lecturer, MD, PhD (Med.), PhD stud. (Biol.); e-mail:

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11. Expression of Epidermal Growth Factor (EGF) and its receptors (EGFR1 and EGFR2) in chronic bronchitis

Andreea-Elena Marinas, Paulina Ciurea, Cl. Margaritescu, O. S. Cotoi

Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of morbidity and mortality in the industrialized and in the developing countries. It is believe, at least in part, that some of the structural changes that occur in COPD would be a result of epidermal growth factors (EGFs) and their receptors. Therefore, our study aims was to examine the expression patterns of EGF and their receptors (EGFR1 and c-erbB2) in the bronchial mucosa from the biopsy specimens harvested from smoking and non-smoking CB patients, compared with their expression in normal controls. The statistical analysis proved that for both EGF and EGFR1 reactivity were significant correlation with smoking status and FEV1% scores. Thus, we found that the highest levels of its expression were recorded in smoker CB patients with higher FEV1% scores. Regarding cellular localization and staining pattern, we noticed a cytoplasmic and nuclear immunostaining for EGF in bronchial epithelium both for control and CB subjects at the level of basal and ciliated cells. For the receptors, reactions were at the membrane level especially at the lower lateral junctions between ciliated cells and their junctions with basal cells. This reactivity proved the pathogenic implication of the EGF and their receptors in patients with CB and suggests that blockade of the EGFR pathway can be an alternative successful therapy.

Corresponding author: Claudiu Margaritescu, Associate Professor, MD, PhD; e-mail:

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12. The immunohistochemical expression of p53 and Ki67 in ovarian epithelial borderline tumors. Correlation with clinicopathological factors

Luminita Nicoleta Giurgea, Carmen Ungureanu, Maria Sultana Mihailovici

Background: Borderline tumor of the ovary is an epithelial tumor with a low rate of growth and a low malignant potential to invade or metastasize. This tumor often is associated with a significantly better prognosis than epithelial ovarian cancer. Most of these tumors are either serous or mucinous in histology. Aim: Assessment of p53 and Ki67 immunohistochemical expression in 52 epithelial ovarian tumors, correlation with clinicopathological factors, and comparison between results in benign, borderline, and malignant tumors. Materials and Methods: From the total number of 125 patients diagnosed with epithelial ovarian neoplasms in the period 2002-2010, 52 operated patients were selected, with serous and mucinous tumors. There were 26 (50%) malignant cases, 15 (28.8%) borderline and 11 (21.15%) benign. We used the monoclonal antibody DO7 and Ki67-MM1. Results: P53 immunoreactions were positive in 41.66% of malignant serous tumors, most of them (90%) high-grade carcinomas; 6.66% of borderline and none benign tumors were positive. Ki67 was positive in 61.53% of malignant cases, with higher percents in advanced clinical stages. Ki67 immunoreactions were also positive in borderline and benign tumors, with lower percents, 13.3% respectively 9.09%. Conclusions: We found almost similar frequency of immunostaining in borderline tumors and low-grade invasive serous carcinomas in contrast to the significantly higher frequency of p53 mutations in high-grade serous carcinomas. Proliferative activity as assessed by Ki67 staining does not explain any possible relationship of serous borderline tumors to epithelial ovarian cancer.

Corresponding author: Luminita Nicoleta Giurgea, MD, PhD candidate; e-mail:

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13. Immunohistochemical expression of MMP-9, TIMP-2, E-cadherin and vimentin in ameloblastomas and their implication in the local aggressive behavior of these tumors

Alma Florescu, Cl. Margaritescu, Cristiana Eugenia Simionescu, A. Stepan

Among the benign epithelial odontogenic tumors, the ameloblastoma occupies a special place because of their local aggressive behavior with devastating jaw destructions, which lead to a high recurrence rate, even following the radical surgery. In an attempt to clarify the mechanisms underlying this behavior we immunohistochemically investigated the reactivity of different histological variant of ameloblastoma to MMP-9, TIMP-2, E-cadherin and vimentin. A semiquantitative assessment of their reactivity in the epithelial neoplastic compartment was done and statistical correlation was attempt with histological variant and between them. The MMP-9 and TIMP-2 reactivity was observed with variable intensity both in the neoplastic epithelium and in the stroma that surround the ameloblastic proliferations. Only for MMP-9, the statistical tests proved the existence of significant differences within major ameloblastic histological variants, with the highest reactivity acanthomatous type. The stroma independent of the histological variant had the highest reactivity at the invasive front adjacent to the tumoral islands. Immunoreactivity for E-cadherin was more obvious in the follicular type at the level of stellate-reticulum like cells, and decreased in the peripheral columnar cells, as they are closer to the invasion front. Vimentin reactivity was present in the neoplastic epithelium only in the peripheral columnar cells at the invasion front but at this site, the stroma had the highest expression. Statistical analysis proved the existence of inverse relationship between MMP-9 and E-cadherin scores, while vimentin score had an inverse relationship both with TIMP-2 and E-cadherin scores. Our results proved the implication of these four markers in the growth of ameloblastomas and as a consequence their utility in monitoring of local aggressiveness of these tumors.

Corresponding author: Claudiu Margaritescu, Associate Professor, MD, PhD; e-mail:

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14. Heterogeneity of malignant non-Hodgkin lymphoma-associated blood vessels

Adina Octavia Duse, Raluca Amalia Ceausu, Anca Maria Cimpean, Hortensia Ionita, M. Raica, Pusa Gaje

The present study described for the first time a high heterogeneity of blood vessels in non-Hodgkin lymphomas (nHL). The tumor blood vessels were highlighted with CD105/smooth muscle actin (SMA) and CD34/SMA double immunostaining. For both follicular and diffuse types of lymphomas, more than 85% of CD34/SMA positive vessels were of immature and intermediate type. A percent of 96.54 from CD105/SMA assessed blood vessels were of activated and mature activated types with high expression of CD105 on endothelial cells of newly formed blood vessels. Our results suggest that these types of vessels are potential therapeutic targets for antivascular therapy.

Corresponding author: Pusa Gaje, Lecturer Assistant, MD, PhD; e-mail:

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15. The role of cytology in the diagnosis of fluid collection syndromes associated with liver cirrhosis. Clinical, epidemiological, cytological and biochemical study of pleural effusion

Mihaela Dinu, Ana Claudia Georgescu, Raluca Niculina Ciurea, Mirela Stefan

Cirrhosis, end-stage of many liver diseases, presents many complications during its evolution. One of these is the presence of pleural fluid collection syndrome. This may be a direct consequence of liver disease (hepatic hydrothorax) or may be a random association. A formidable complication due to its consequences is spontaneous pleural empyema. The present study aimed to assess the incidence, the factors that influence its occurrence, and the frequency of the infectious complication.

Corresponding author: Raluca Ciurea, University Assistant, MD, PhD; e-mail:

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16. Correlations between Her2 oncoprotein, VEGF expression, MVD and clinicopathological parameters in gastric cancer

Alina Badescu, Claudia Valentina Georgescu, C. C. Vere, Stefania Craitoiu, Diana Grigore

Introduction: Gastric carcinoma is one of the most common malignancies worldwide and is the second most frequent cause of cancer deaths. Several molecular factors are studied as prognostic and predictive factors for gastric cancer, VEGF and Her2 being currently in the spotlight. The aim of the study was to estimate the expression of Her2, VEGF and the MVD in gastric carcinoma and its relationship to clinicopathological and biological features of the tumors. Materials and Methods: In this study were included 28 patients with gastric carcinoma, of which 16 patients underwent total gastrectomy, which provided the TNM stage, and 12 patients with gastric biopsy. The gastric biopsies and the surgical samples were processed immunohistochemically using anti-Her2, anti-CD31, anti-CD34 and anti-VEGF antibodies. Results: Her2 oncoprotein was overexpressed in 85.71% of intestinal type gastric cancer cases and 14.29% in diffuse type (p=0.01), and also more in stage I an II comparatively with stage III and IV (p=0.13). Her2 positive tumors were significant low grade (G1/G2) (p<0.01). MVD is higher in Her2 positive tumors than in the negative ones but not statistically significant (p=0.29 for CD31 and p=0.52 for CD34). Positive immunoreaction of VEGF was observed in 55.5% of the intestinal type carcinomas and in 80% of diffuse type. The correlation between expression of VEGF and TNM stage showed that this angiogenic factor is more frequent positive in the first two stages comparative with the IIIrd and IVth stages. The expression of VEGF is more frequent in G1-G2 tumors (p=0.003).There was a close relationship between tumor vascularity detected with CD34 and two main histological parameters: tumor type according to Lauren's classification (diffuse type; p=0.04) and tumor grade (well and moderately differentiated tumors; p=0.01). There was also a significant correlation of mean CD34 MVD value and the TNM stage being more expressed in stage III/IV than in I/II stages (p=0.004). The mean CD34 MVD value of VEGF positive tumors was 30.8 and was a significantly higher MVD than that of VEGF negative tumors (p<0.05). Conclusions: Overexpression of Her2, the selecting factor of patients that benefit from a specific therapy, occurs at a significant frequency in gastric carcinomas, especially in intestinal type. The correlation between VEGF expression and CD34 MVD suggest that two molecular biomarkers play a major role in the biological tumor behavior and are able to be used as important prognostic parameters, which predict the aggressiveness of gastric carcinomas.

Corresponding author: Alina Badescu, MD, PhD candidate; e-mail:

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17. Thyroid cancer profile in Mures County (Romania): a 20 years study

Ramona Catana, Adela Boila, Angela Borda

The aim of the present study was to present data on frequency of thyroid cancer in Mures County (Romania) and border counties, a goiter endemic area, and to analyze its histopathological characteristics, over a 20 years period (1990-2009). Materials and Methods: Demographic, clinical and pathological data were obtained from database registries. Histological subtypes of thyroid cancer were classified according to the WHO criteria (sixth edition, 2004) in the following categories: papillary thyroid carcinoma with its histological subtypes, follicular thyroid carcinoma, poorly differentiated thyroid carcinoma, undifferentiated thyroid carcinoma, medullary carcinoma, lymphoma, metastatic tumors. Results: Our analyze included 524 cases of thyroid cancer of the 3460 surgical thyroid specimens resected between 1990-2009: 410 (78.2%) cases of papillary carcinoma, 19 (3.6%) cases of follicular carcinoma, 24 (4.6%) cases of poorly differentiated carcinoma, 33 (6.3%) cases of undifferentiated carcinoma, 22 (4.1%) medullary carcinomas, eight (1.6%) lymphomas, and eight (1.6%) metastatic tumors. Papillary thyroid carcinoma is the most common histological form (78%) and an increasing incidence of this form was observed. A statistical significant increase in the incidence of the follicular variant of papillary carcinoma was noticed between 2000-2009, compared to 1990-2000. An increased incidence of small tumors was also found (6.66%, 1990-1999 vs. 23.5%, 2000-2009). The undifferentiated thyroid cancer had a marked decreasing trend (20%, 1990-1999 vs. 3.45%, 2000-2009). Conclusions: Our study demonstrates an increasing trend in the incidence of thyroid cancer in the last 20 years. This increase is mainly due to the small papillary cancers, by contrast to the undifferentiated thyroid cancers that have a decreasing trend. A better understanding and description of the morphological criteria could explained the increasing incidence of the follicular variant of papillary carcinoma.

Corresponding author: Ramona Catana, MD; e-mail:

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18. Deciphering caudal embryonic defects: embryological analysis and reviewing literature data

Sunita Arvind Athavale

Background: A number of syndromes/associations involving the caudal region have been described in the literature. Each of them is characterized by a set of morphological features. Reports on difficulties in delineation and an ever-increasing constellation of defects in recent past call for a comprehensive study into the morphologic presentations and pathogenesis of caudal embryonic defects. Materials and Methods: The present article describes a case of the OEIS complex - a combination of omphalocele, exstrophy of bladder, imperforate anus and spinal defects. Literature search was performed and morphologic presentations, as described in literature, of all syndromes and associations affecting the caudal region of the embryo have been compared. Morphologic presentations were analyzed embryologically. Results: A remarkable overlap of symptom complex was observed. Embryological analysis of the phenotypic presentations of all these syndromes points towards a common pathogenesis, early in the embryonic life. The embryologic analysis suggests that these defects are a result of defects in proliferation, migration or subsequent differentiation of any of the three subdivisions of intra-embryonic mesoderm. Conclusions: Based on the analysis a new hypothesis for the causation of caudal defects is proposed. This hypothesis suggests that a local internal environmental imbalance, at the site of implantation, can cause nutritional insult to the embryo during gastrulation, during the third and the early fourth week of embryonic life.

Corresponding author: Sunita Arvind Athavale, Associate Professor, MD; e-mail:

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19. The study of p53 and p16 immunoexpression in serous borderline and malignant ovarian tumors

M. C. Marinas, D. G. Mogos, Cristiana Eugenia Simionescu, A. Stepan, Florentina Tanase

The study assessed p53 and p16 immunoexpression in 20 cases of ovarian serous carcinomas and four cases of serous borderline tumors, the results being statistically analyzed in relation to clinicopathological data of the cases. The p53 immunoreaction was observed in 85% of cases, the medium percentage of positivity being 15% for borderline tumors, 45% for low-grade carcinomas and 60% for high-grade carcinomas. The p16 immunoreaction was observed in 75% of cases, the medium percentage of positivity being 30% for borderline tumors, 25% for low-grade carcinomas and 62% for high-grade carcinomas. The p53 and p16 reaction was also identified at the tubal epithelium in cases of invasive carcinomas. Statistical analysis indicated significant differences in p53 expression depending on tumor type and for p53 and p16 expression compared to the degree of tumor differentiation. The study indicated a diffuse immunostain for p53 and p16 in high-grade serous ovarian carcinomas. The presence of "p53 signature" and areas with variable tumor differentiation and reactivity, in the case of high-grade carcinomas, supporting the existence of multiple mechanisms of their occurrence and progression.

Corresponding author: Marius Marinas, MD, PhD candidate; e-mail:

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20. Macrophage response in experimental third-degree skin burns treated with allograft. Histological and immunohistochemical study

Florina Carmen Popescu, G. D. Mogosanu, Cristina Jana Busuioc, H. Parvanescu, I. Lascar, L. Mogoanta

Macrophages are some of the innate immune cells with a central role in inflammatory and immune responses. Studies in the last 20 years have shown that these cells have a particular influence in the reparative processes also. Our aim in this study was to evaluate the macrophage response in third-degree skin burns treated with allograft in an experimental model. Macrophages were specifically highlighted by immunohistochemical staining with anti-CD68 antibody. In the first evolutive part of the reparatory process, macrophages rapidly increased both numerically and as a relative area with about 300%, and then decreased progressively along with the granulation tissue maturation. Macrophage overall response curve was similar in animals treated with allograft and in the control group (untreated), which leads us to believe that the allograft does not induce a more ample immune response that could be regarded as pathological.

Corresponding author: Laurentiu Mogoanta, Professor, MD, PhD; e-mail:

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21. Immunoexpression of alpha-SMA and CD68 in native kidney biopsies

Ofelia Jercan, M. Penescu, D. Gh. Malaescu

Introduction: The role for inflammation and fibrosis as predictive histopathological markers for renal function has been discussed in several studies. Aim of our investigation was to evaluate the clinico-pathological correlation of myofibroblasts expression as markers for initial development of fibrotic processes and macrophagic infiltration in a population with impaired renal function, in order to better understand their value in diagnostic biopsies. Materials, Methods and Results: We evaluated 20 consecutive native kidney biopsies performed for diagnostic purposes. Material remaining after routine light microscopy and immunofluorescence, was stained for alpha-SMA as myofibroblast marker and CD68 as macrophage infiltration marker. Quantitative evaluation was conducted by electronic image analysis on consecutive low power fields, avoiding glomeruli, and estimated as percentage of the total area or as number of positive cells/field for macrophage infiltration. The renal biopsies were also evaluated for histological characteristics such as percentual area of inflammation infiltration and fibrosis. Clinical and laboratory data were recorded at biopsy moment and followed-up on a period of 17+/-11 months after the renal biopsy. Interstitial alpha-SMA immunoexpression proved to be related with interstitial fibrosis (r=-0.47, p<0.001) and macrophage infiltration (r=0.21, p=0.03). Higher immunoexpression of alpha-SMA was related with renal function assessed by creatinine level at biopsy moment (r=0.32, p=0.002). Conclusions: In this study, detection of myofibroblast infiltration using alpha-smooth-muscle actin (alpha-SMA) proved to be a good marker in describing the initial phases of interstitial fibrosis development in early stages of chronic kidney dysfunction.

Corresponding author: Ofelia Jercan, MD, PhD student; e-mail:

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22. Histological and immunohistochemical aspects of cerebral vessels of the elderly

Andreea-Lorena Enache, Anca-Stefania Slujitoru, Irina Lavinia Pintea, Cristina Mariana Stocheci, Garofita Olivia Mateescu, Irina Gheorghisor

The central nervous system is considered the most complex morphological structure of the human body. Between nervous tissue and cerebral circulation is a very close relationship, so transient vascular meningocerebral disturbances cause changes in neuronal function clinically expressed as various neurological signs and symptoms, especially in the elderly. In this study, we examined from the histological and immunohistochemical point of view encephalon fragments collected from 24 patients aged between 46 and 85 years. All patients exhibited changes in meningocerebral vessels, ranging from atheromatous plaques to vascular rupture. Immunohistochemical techniques have shown changes in the vascular endothelium, smooth muscle fibers of arterial walls and blood-brain barrier disruption.

Corresponding author: Andreea-Lorena Enache, MD, PhD student; e-mail:

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23. Anatomical analysis of azygos vein system in human cadavers

T. Kutoglu, M. Turut, N. Kocabiyik, H. Ozan, M. Yildirim

The azygos system veins vary greatly in their mode of origin, course, tributaries, anastomoses and termination. Therefore, we aimed to investigate the types of azygos system in this study. Our research was made in Anatomy departments on 48 conserved cadavers aging between 27-70 years, of which 35 were males and 13 females. In the research, the diameters and levels of the azygos vein, the hemiazygos vein, the accessory hemiazygos vein and the superior intercostal vein were investigated. The subjects were classified in Anson's system with a basis of vertical and horizontal connections in the azygos venous system the classification included primitive or embryological types, transient type, unicolon type as three basic types and their eleven subgroups. According to this classification (amongst 48 cadavers), one (2.1%) of our subjects was found to be Type I, 44 (91.7%) of them were found to be Type II, and one (2.1%) was found to be Type III. These values were similar to those in the literature, however two (4.2%) subjects did not fit in any otherwise defined groups and were named as atypic group. It is very important to identify the variations of the azygos system in the computed tomography and magnetic resonance imaging of mediastinum. The abnormal azygos venous system may easily be confused with aneurysm, lymphadenopathy and other abnormalities like tumor. It is important to keep these kinds of variations in mind while performing the mediastinal operations or surgery of large vessels.

Corresponding author: Necdet Kocabiyik, Associated Professor, MD, PhD; e-mail:

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24. Non-Hodgkin lymphomas of Waldeyer's ring

D. Salplahta, Maria Victoria Comanescu, F. Anghelina, Elena Ionita, Carmen Aurelia Mogoanta, Liliana Anghelina

Lymphomas represent malignant lymphoproliferative diseases and they are generally classified as Hodgkin's (HL) or non-Hodgkin malignant lymphomas (NHML). Head and neck lymphomas represent one of the most common sites of extranodal lymphomas, second after the gastrointestinal tract. Waldeyer's ring structures include the palatine tonsils, the nasopharyngeal lymphatic tissue, and the lingual tonsil. We investigated 38 patients with malignant lymphoma with ages ranging from 21 to 95 years, all localized in the Waldeyer's ring. Good knowledge of the clinical characteristics of these lymphomas and the methods to establish the differential diagnosis are essential for a correct therapy of the disease.

Corresponding author: Daniel Salplahta, MD, PhD student; e-mail:

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25. Histological and immunohistochemical study of cutaneous angiogenesis process in experimental third-degree skin burns treated with allograft

Cristina Jana Busuioc, Florina Carmen Popescu, G. D. Mogosanu, H. Parvanescu, Liliana Streba, L. Mogoanta

Skin burns are a rather high incidence lesions which, depending on their depth and extension, can severely affect not only the skin but the entire organism. Third-degree skin burns extended on over 20% of the body surface often require skin graft. Skin allograft is a therapeutic alternative when autograft cannot be used. We investigated the allograft influence on the angiogenesis process in third-degree skin burns, using an experimental model. We noticed that the allograft induces a stronger inflammatory reaction associated with intense angiogenesis process by about 10-15% compared to control group.

Corresponding author: Laurentiu Mogoanta, Professor, MD, PhD; e-mail:

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26. Spinal involvement with spinal cord compression syndrome in hematological diseases

M. Popescu, Viola Popov, G. Popescu, Camelia Dobrea, Aurelia Sandu, V. T. Grigorean, V. Strambu

Primary spinal involvement in hematological diseases is rare. Purpose: The purpose of this article is studying diagnostic and treatment strategies in patients with spinal cord primary hematologic tumors causing spinal cord compression syndrome. Patients and Methods: We report two cases with spinal cord primary hematologic tumors causing spinal cord compression syndrome. One patient had a diffuse large B-cell non-Hodgkin's lymphoma located in the thoracic spine and the second patient had a plasmocytic plasmacytoma located in the thoraco-lumbar spine. Results: Both patients underwent surgery, with resection of the intracanalar tumor and spinal cord decompression and adjuvant systemic and intrathecal chemotherapy. Neurological outcome was favorable with partial remission of spinal cord compression syndrome. Finally, patients developed secondary dissemination and succumbed due to progression of the hematological disease. Conclusions: Clinical onset and radiographic evaluation is uncharacteristic in early stages. Spinal MRI is mandatory in cases with rebel pain, unresponsive to conservative treatment. Surgery is indicated in all patients with spinal cord compression syndrome. Early diagnosis is associated with better prognosis. Recommended treatment is surgical resection and systemic and intrathecal chemotherapy adapted to histological form of each tumor. In selected cases, if indicated radiotherapy can also be associated.

Corresponding author: Valentin Titus Grigorean, Associated Professor, MD, PhD; e-mail:,

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27. Secondary plasma cell leukemia

Ionela Rotaru, G. Gaman, Daniela Dumitrescu, Camelia Foarfa

Plasma cell leukemia (PCL) is a rare disease and is the least common variant of multiple myeloma accounting for 2-3% of all plasma cell dyscrasias. We report a patient who was diagnosed with multiple myeloma, 12 months earlier; he was treated with VBCMP, VCMP regime, and after 12 months he presented of high grade fever, weakness, palpitations, loss of appetite, bone pains, dyspnea. Initial evaluation revealed plasmacytosis with blood plasma cell count of 13 860/mm(3). His hemoglobin (Hb) was 8.4 mg/dL, platelets were 45 000/mm(3) and total leukocyte count (TLC) was 23 100/mm(3) (60% plasma cells). Bone marrow examination revealed 90% plasmablastic cells. Serum LDH was high at 3117 U/L and serum calcium was also elevated at 9.1 mg/dL. A diagnosis of PCL was made and the patient was started on treatment with VAD regime along with supportive care. Patient condition deteriorated very quickly, despite treatment and he died on the third day. A detailed report of this case and a review of PCL is presented here.

Corresponding author: Ionela Rotaru, Assistant Professor, MD; e-mail:

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28. Multiple disseminated glomuvenous malformations: do we know enough?

C. Solovan, Elena Chiticariu, Doina Beinsan, Sabina Zurac, Flavia Baderca

Multiple glomuvenous malformations (GVMs), also known as glomangiomas, are uncommon entities with histological features of both glomus cells proliferation and venous malformation. A 14-year-old boy was admitted to our clinic with multiple dermal blue nodules, disseminated in different segments of the body. The patient's family history was positive for similar lesions; his mother and maternal grandmother had some asymptomatic blue nodules on their body. Histological examination showed a tumor composed of multiple caveronous vessels surrounded by glomus cells, positive for alpha smooth muscle actin, HHF35 (pan-actin), and h-caldesmon. This is a case of multiple GVMs, a rare disease caused by mutations in glomulin gene, with an autosomal dominant pattern of inheritance. The clinical and histopathological features are briefly discussed.

Corresponding author: Flavia Baderca, Assistant Professor, MD, PhD; e-mail:

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29. A rare case of basaloid squamous cell carcinoma of the maxilla

Luminita Stanciulescu, Oana Vermesan, Ioana Grintescu, V. Enache, C. Creanga, D. Slavescu, D. Zamfirescu, I. Lascar

Basaloid squamous cell carcinoma (BSCC) is a rare and aggressive variant of squamous cell carcinoma (SCC) that occurs preferentially in the upper aerodigestive tract. Since the first description by Wain SL et al., in 1986, only 21 cases with BSCC in the nasal cavity or in the paranasal cavity have been reported in the English literature. We present here a case of BSCC arising in a paranasal sinus. The case was a 51-year-old male patient with four months history of right cheek swelling and unilateral nasal obstruction, who received operation and postoperative radiotherapy. Clinical, surgical and pathological findings in this case, including immunohistochemistry is presented along with brief discussion of literature.

Corresponding author: Dragos Zamfirescu, MD, PhD; e-mail:

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30. Degenerative alterations of the cementum-periodontal ligament complex and early tooth loss in a young patient with periodontal disease

S. A. Petrutiu, Petronela Buiga, Alexandra Roman, Theodora Danciu, Carmen Mihaela Mihu, D. Mihu

Premature exfoliation of primary or permanent teeth in children or adolescents is extremely rare and it can be a manifestation of an underlying systemic disease. This study aims to present the histological aspects associated with early tooth loss in a case of periodontal disease developed without local inflammation and with minimal periodontal pockets and attachment loss. The maxillary left second premolar was extracted together with a gingival collar attached to the root surface. The histological analysis recorded the resorption of the cementum in multiple areas of the entire root surface with the connective tissue of the desmodontium invading the lacunae defects. The connective tissue rich in cells occupied the periodontal ligamentar space and the resorptive areas. No inflammation was obvious in the periodontal ligament connective tissue. This report may warn clinicians about the possibility of the association of cemental abnormalities with early tooth loss.

Corresponding author: Alexandra Roman, Professor, PhD; e-mail:

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31. Atypical adenomatous hyperplasia of the prostate mimicking adenocarcinoma lesion: case report and literature review

Manuela Enciu, Mariana Aschie, Madalina Bosoteanu, Anca Chisoi

The diagnosis of prostate cancer is challenging because of the existence of lesions that mimic adenocarcinoma. Such a lesion is atypical adenomatous hyperplasia (AAH) or adenosis, which represents a proliferation of crowded, small to medium glands with basal cell layer invariably present, but often inconspicuous on routine stains. The importance of the lesion lies in the potential for being misdiagnosed as low-grade adenocarcinoma (Gleason 1 or 2). We present the case of a male patient, who suffered a transurethral prostatic resection surgery. Histopathological examination showed benign prostatic hyperplasia with a focus of crowded glands with a nodular appearance. The presence of basal cell was assessed using high molecular-weight cytokeratin (HMWCK), clone 34betaE12 and p63 immunostaining, which revealed discontinuous positive immunostaining. In adenocarcinomas, the basal cell layer is absent. This case highlights the usefulness of 34betaE12 antibodies, avoiding a false positive diagnosis of cancer, with negative consequences on the patient's psychological condition and treatment costs. We recommended the follow-up of the patient.

Corresponding author: Mariana Aschie, Professor, MD, PhD; e-mail:

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32. Trigeminal nerve: MRI anatomy and case presentation of trigeminal neuralgia due to arterial compression

Anca Sava, Cristina Furnica, T. Petreus, Raluca Ozana Chistol, A. G. M. Motoc

Trigeminal neuralgia (TN), also known as tic douloureux is a chronic neuropathic pain disorder characterized by sporadic episodes of extreme, sudden burning or shock-like face pain that last from a few seconds to 2 minutes. Trigeminal neuralgia has a reported incidence of 5.9/100 000 women and 3.4/100 000 men in USA. The exact pathophysiology is still unclear, but demyelization leading to abnormal discharge in fibers of the trigeminal nerve is a probable cause. In the majority of cases, no structural lesion is detected but in almost 15% of patients medical imaging methods like MRI, CT or angiography can identify a vein or artery that compresses the nerve which results in focal demyelization. The authors present a case of trigeminal neuralgia investigated by MRI, which identified a vascular compression of the nerve 9 mm after emerging the pons by the superior cerebellar artery (SCA) and one of its branches. The authors also realize a review of the MRI anatomy of the trigeminal nerve.

Corresponding author: Anca Sava, MD; e-mail:

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33. Atypical primary tuberculosis mimicking an advanced penile cancer. Can we rely on preoperative assessment?

Carmen Savu, C. Surcel, C. Mirvald, C. Gingu, Monica Hortopan, I. Sinescu

Tuberculosis of penis is a very rare clinical entity. There are isolated reports of its presentation as a subcutaneous nodule with or without superficial ulcers and can be interpreted as advanced penile cancer. We present a case of penile tuberculosis that presented in our Center with a bulky penoscrotal formation treated in other center for the suspicion of Fournier gangrene.

Corresponding author: Cristian Surcel, MD, PhD; e-mail:

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34. Mandibular second molar impaction treatment using skeletal anchorage

Aurelia Magdalena Enache, I. Nicolescu, Carmen Elena Georgescu

The mandibular second molar impaction is a rare dental anomaly with a very challenging treatment. Although there are some treatment modalities, often the proper option is surgical exposure and orthodontically assisted eruption with a high rate of success depending on the appropriate appliance design, which assures a good control of the tooth movement with minimum side effects. A case report of a severe bilaterally impaction of the mandibular second molar in an adolescent female patient is presented, successfully treated using a miniplate, as skeletal anchorage.

Corresponding author: Magdalena Enache, Assistant, DDS, PhD; e-mail:

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