Snail and E-Cadherin Immunoexpression in Clear Cell Renal Cell Carcinoma.

Renal cell clear cell carcinomas (ccRCC) represent 75% of the malignant renal neoplasias. A critical molecular characteristic in the epithelial-mesenchymal transition (EMT) is the loss of E-cadherin expression, as well as the epithelial-mesenchymal transcription factors, one of the most important of which is Snail. In the current study, we analyzed the immunoexpression of the two markers in 46 cases of clear cell renal cell carcinomas, with reference to the most important prognosis histopathological factors. Our results indicated significant associations between the overexpression of Snail, under expression of E-cadherin and high Fuhrman grade. E-cadherin immunoexpression was high in incipient tumoral stages, and Snail was overexpressed in advanced tumoral stages of ccRCC. Our study supports the importance of this antibody panel in the prognosis of ccRCC.

E-cadherin and Snail Immunoexpression in Colorectal Adenocarcinomas.

Epithelial-mesenchymal transition (EMT) is a fundamental process which governs invasiveness. E-cadherin plays a major role in development, organogenesis and tissue formation, but also in tumor progression. Snail is a transcription factor described as a direct repressor of E-cadherin during development and in carcinogenesis. In this study we analyzed E-cadherin and Snail immunoexpression in 47 cases of colorectal adenocarcinoma (CRC) in comparison with some histopathological prognostic factors. The majority of cases were G2 tumors in stages II and III, with vascular and perineural invasion. All cases showed positive cytoplasmic signal for E-cadherin and Snail. E-cadherin reactions were intense with the highest composite score (CS) values in CRC G1. CS values of E-cadherin decreased with the advancement in tumor stage and the association with vascular and perineural invasion was statistically significant. Snail immunoreaction was intense with the highest values of CS in CRC G3, being more evident with the increase of tumor staging, aspect which was statistically significant. CS and Snail association demonstrated a statistically significant aspect related to vascular invasion. We found a negative linear correlation of E-cadherin and Snail expression. The obtained results indicate the implication of Snail and E-cadherin in EMT of CRC, aspect which is useful in the evaluation and stratification of patients with CRC for the targeted specific therapy.

Low Grade Ovarian Serous Carcinoma - A Clinical-Morphologic Study.

Low grade ovarian serous carcinomas (LGSC) are rare tumors, representing only a small part of all ovarian carcinomas. The study included six LGSC cases for which we followed the clinical-epidemiological and morphological parameters depending on the tumoral stages. The tumors corresponded to stage I in four cases, in one case to stage II and in another case to stage III. The majority of the analyzed histopathological parameters were present in all tumoral stages. The accuracy of the diagnostic and the correct staging of the LGSC affected patients is very important, because the grade and stage of the serous ovarian tumors impose the therapy and the prognosis.

Histopathological and Morphometric Study of Fibrosis and Nuclear Pleomorphism in Dilated Cardiomyopathy.

Histopathological changes associated with dilated cardiomyopathy (CMD) are frequently nonspecific and often only present in the terminal stage of the disease. The study followed the histopathological and morphometric quantification of fibrosis and nuclear pleomorphism in CMD. We analyzed left ventricle myocardial fragments harvested during autopsy, from 35 cases with clinical diagnosis of CMD and 5 cases of normal myocardium. Fibrosis was present in all CMD cases, with higher values compared with control cases. Nuclear pleomorphism was identified in 18 cases (45%), two of the analyzed parameters, respectively the ratio of nuclear diameters and roundness of nucleus, revealing significant differences in CMD compared to the control cases. Myocardial fibrosis present in all cases of CMD represents a major feature of the disease. The nuclear pleomorphism due to the nuclei change in diameters and size was more pronounced in the vicinity of fibrosis areas, possibly related to this alteration.

Dermoscopy Patterns and Histopathological Findings in Nodular Basal Cell Carcinoma-Study on 68 Cases.

Basal cell carcinoma (BCC) is the most common skin cancer, with an increasing incidence in Europe particularly in young individuals. Nodular basal cell carcinoma is the most common subtype and accounts for approximately 57.6-78.7% of all BCCs. We performed an observational, morphological study which involved 68 patients with the diagnosis of nodular BCC. The localization and diameter of the lesion, histological subtype of the lesion, dermoscopic patterns, Fitzpatrick skin type and sex of each patient were recorded. The most common dermoscopic pattern seen in nodular BCCs was irregular vascularity and, arborizing vessels (>0.2mm in diameter) being the most frequent irregular vascular pattern. The second most common dermoscopic feature in patients with nodular BCCs was translucency. The most common dermoscopic features of the 12 pigmented BCCs were: pigmented islands (blue-gray globules and blue-gray ovoid nests); the pigmented distribution pattern (with (maple leaf-like structures and spoke wheel-like areas); arborizing vessels and white streaks/white areas. The histopathological analysis of the 68 BCCs revealed that the nodular type was the most frequently identified for 71.7% of cases The differential diagnosis between basal cell carcinoma and other skin lesions and inflammatory skin diseases is very important, since serious morbidity may result from an undiagnosed tumor.

Assessment of Histopathological Parameters Useful in the Diagnosis of Low Grade Non-Invasive Urothelial Carcinomas.

Urothelial papillary lesions of urinary bladder are frequent lesions in medical practice and sometimes difficult to be histopathologically classified. In this study were included 179 urothelial papillary lesions, represented by low grade non-invasive urothelial carcinomas (LGNIUC), papillary urothelial neoplasms of low malignant potential (PUNLMP) and urothelial papillomas (UP), for which the architectural and cytological histopathological parameters were analyzed in order to determine their usefulness for the classification of lesions. For each parameter, an aggressivity score was set, the sum representing the composite histological score (CHS) for each case. The increase of urothelial thickness, the papillae fusion, the loss of cellular polarity, loss of basal cell palisading and absence of umbelliform cells were commonly associated with diffuse pattern in LGNIUC, were focal/absent in PUNLMP and absent in UP. The nuclear hypertrophy and hyperchromasia, the nucleoli presence and mitotic activity were specific for LGNIUC, rarely associated with PUNLMP and absent/low in UP. CHS values for the three categories of analyzed lesions were superior statistically significant in LGNIUC compared to PUNLMP and UP. The mitotic index and the thickness of cytological atypical epithelial layers support the parameters utility as reproducible criteria for the differentiation of papillary urothelial tumors.

EGFR Immunoexpression in Malignant Serous and Mucinous Ovarian Tumors.

The epithelial growth factor receptor (EGFR) is involved in various stages of cancer growth such as tumor initiation, angiogenesis and metastasis, being an attractive target for oncogenic therapy. The present study aims to evaluate the EGFR expression in 54 cases of serous and mucinous ovarian borderline tumors and carcinomas. EGFR expression was present in more than half of the investigated tumors, more frequently in carcinomas than in borderline tumors, especially in the serous type. The highest values of the final staining score (FSS) were observed only in serous carcinomas in the advanced stages of the disease. As a result of frequent expression of EGFR in ovarian tumors, it is necessary to monitor EGFR inhibitors for ovarian cancer therapy, but probably after establishing more rigorous selection and stratification criteria for patients.

Immunoexpression of Transforming Growth Factor Beta 3 (TGFß3) and Its Receptor Type III (TGFßRIII) in Basal Cell Carcinomas.

Basal cell carcinomas (BCCs) are malignant tumors with particular biological prognosis and behavior, and the biomolecular investigation of these lesions can provide important therapeutic targets for epithelial neoplasia. In this study we analyzed the immunoexpression of transforming growth factor beta 3 (TGFß3) and its receptor type III (TGFßRIII) for 53 cases of BCC in relation to the main histopathological prognostic parameters. The results indicated statistically significant differences of TGFß3 and TGFßRIII expression related to histological type and lesion stage, the both proteins being higher expressed in adenoid and morpheaform advanced stage tumors. In this study, TGFß3 and TGFßRIII immunoexpression analysis indicated their utility for identifying aggressive BCCs with potential for tumor progression.

Histopathological Prognostic Factors for Colic Adenocarcinoma.

The majority of colorectal carcinomas are adenocarcinomas derived from the colic mucosae cell, more frequently moderately differentiated. The purpose of this study was to determine de incidence of CRC and the relationship between histopathological risk factors in patients with colic adenocarcinomas. The study included 144 cases of CRC diagnosed within the Pathology Laboratory of the Clinical County Hospital of Craiova in the year 2017.The biological material consisted in samples from colectomies and hemicolectomies provided from patients admitted within the surgical clinics of the same hospital, then fixed with 10% buffered formalin and afterwards processed using the classic histopathological technique of paraffin inclusion and staining with hematoxylin and eosin. We observed certain histopathological parameters such as: pattern, grading, stage, vascular invasion and neural invasion. The mean age of diagnostic was 68.6 ± 11.2, and it was predominantly male patients (64.6%). Most cases presented with mucinous pattern (31.9%) and cribriform comedocarcinoma type (29.9%). The majority were classified as stage III B (34%), being moderately differentiated (64.6%) and associated with vascular invasion (47.2%) and perineural invasion (25.7%). Statistical analysis indicated significant relationships between tumor stage and differentiation grade (p<0.01, χ²test), as well as between tumor stage and vascular invasion (p<0.05, χ²test), without including perineural invasion (p<0.05, χ²test).

Evaluation of Gastric Carcinomas Histological Patterns in Relation to Tumors Aggressiveness Parameters.

Gastric carcinomas are frequent tumors with variable growth patterns that may interfere with the evaluation of histopathological prognostic parameters of the lesions. In this study we analyzed the incidence and statistical relation of histological growth patterns depending on the prognostic parameters of gastric carcinomas for 95 cases. Pure forms were present in 82.2% of cases, from which more frequent subtypes were low grade tubular carcinomas and poorly cohesive with signet-ring cells carcinomas. Mixed forms were present in 17.8% of cases, with the highest incidence of tumors containing well differentiated tubular carcinoma and poorly differentiated papillary carcinoma areas. Analysis of the identified types and subtypes in relation to the histological prognostic parameters indicated significant differences regarding the tumor stage, the mixed subtypes being more frequent in advanced stages. Although mixed subtypes were more commonly associated with vascular and perineural invasion, the aspects were statistically insignificant. Together with tumor stage, the lymphovascular and/or perineural invasion should be taken into consideration as prognostic indicators in the postoperative management of gastric cancer.

Architectural Histopathological Changes in Ovarian Serous Carcinomas.

Ovarian serous carcinomas have a very large spectrum of growth patterns that contrast with the most primitive ovarian carcinomas, in which the morphology varies very much less. Serous carcinomas growth patterns include papillary and glandular aspects, but also cribriform, solid, microcystic and trabecular, some being common to the both high- and low-grade types of ovarian serous carcinomas, others being distinct. The study included 45 cases of ovarian serous carcinomas out of which five cases with low grade and 40 cases with high grade. High grade serous carcinomas were associated with mixed growth patterns, with large complex papillae, glands with irregular shape lined by stratified epithelia, often with areas of extended necrosis. In the case of low grade ovarian carcinomas we observed the association with more uniform growth patterns, micropapillary or glandular, the presence of optically empty slit-like spaces, psammoma bodies, the absence of necrosis and the association with a borderline or benign component. The recognition of the common histopathological aspects, allows a more accurate diagnosis of the ovarian serous carcinoma types and subtypes, which has a great importance in the actual era of personalized therapy.

Histopathological Patterns of Microinvasion in Ovarian Serous Borderline Tumors.

Stromal microinvasion in ovarian serous borderline tumors can take various aspects, some of which are difficult to identify. Thus, the identification of stromal microinvasion is relatively simple for typical intracystic papillary proliferations such as serous borderline tumors, but may be difficult for tumors with glandular component. The study analyzed 14 cases of ovarian serous borderline tumors diagnosed in patients with mean age of 47,1 years. Histopathologically all tumors corresponded to typical forms in which we identified only two cases of stromal microinvasion. In one case, microinvasion was of eosinophilic type, and in the other case was observed a glandular and micropapillary pattern, being associated with the noninvasive peritoneal implants.

Proliferative Activity in Basal Cell Carcinomas.

Basal cell carcinomas (BCCs) represent one of the most common human neoplasias. The excellent prognosis of the diagnosed early lesions and the low metastasis rate are particularities that required the investigation of the mechanisms of carcinogenesis on these lesions. In this study we analyzed the proliferation rate for 53 cases of BCC in relation to the clinicopathological parameters of the lesions using Ki67, considered a true indicator of cellular proliferation. The results indicated statistically significant differences in Ki67 immunoexpression related to histological type and lesion stage. The highest Ki67 values were observed in the adenoid and morpheaform subtypes, and in advanced tumor stages. This aspects may be useful for stratification of lesions in terms of tumor aggressiveness.

Study of Histopatological Parameters of Gastric Carcinomas with Micropapillary Component.

Micropapillary carcinoma was recently identified as a carcinoma variant characterized by the presence of small clusters of tumor cells located in optically empty spaces. The study included a number of 14 cases represented by surgical excision specimens diagnosed with gastric carcinoma (tubular, papillary and signet-ring) which associated the micropapillary component in variable proportions. Regarding the low-grade tubular carcinomas, the micropapillary component represented less than 25% of the tumor, while in the high-grade tubular carcinomas and papillary carcinomas it represented 25-50%. Among signet-ring carcinomas, the micropapillary component had a percentage of over 50. The depth of invasion was frequently associated with T3 and T4 categories. Lymph nodes metastasis were found in ten cases and distant metastasis were present in three cases. Recognition of the micropapillary component associated with gastric carcinoma represents an aspect of great importance because it is frequently correlated with unfavorable prognosis parameters.

Histopathological Prognostic Factors in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (CCRCC) are the most frequent type of renal cell carcinoma. Fuhrman grade and tumor stage are prognostic factors with great importance in survival rate. This study was performed on 75 cases of CCRCC diagnosed by the Anatomical Pathology Laboratory of the County Clinical Emergency Hospital of Craiova between 2014 and 2017. The biological material was represented by pieces of nephrectomy. The cases were analyzed on two criteria: epidemiology (age, sex) and histopathology (Fuhrman grade, tumor stage, architectural pattern, sarcomatoid transformation, and necrosis). Statistical analysis was done using Chi Square tests in IBM SPSS software. Average diagnosis age of CCRCC was 58.8±10.2 years, predominantly in male patients (66.7%). Tumor sizes were between 2 and 14cm, with an average of 6.7±2.9cm. Most cases were determined to be tumor stage III (60%) and Fuhrman grade 2 (56%), followed, in order of frequency, by tumor stages I and II (28% and 10.7%) and Fuhrman grades 3 and 1 (21.3% and 20%). High Fuhrman grade CCRCC were significantly associated with advanced tumor stage (p<0.05, χ2 test). Most cases presented a mixed pattern, significantly associated with advanced tumor stages (p<0.05, χ2 test). Even though the presence of sarcomatoid transformation was more frequent in advanced tumor stages, it wasn't significantly linked to them (p<0.05, χ2 test). Conclusions: Analyzed histopathological parameters are useful for determining CCRCC aggressiveness. CCRCC in advanced tumor stages is associated with high Fuhrman grade and mixed architectural pattern.

Iridociliary melanoma - Clinical case.

Iris and ciliary body melanoma is an aggressive tumor, which, unfortunately, presents symptoms only in advanced stages and is often discovered accidentally during a routine eye examination. There are several treatment options, ranging from in time monitorization in order to observe the tumor's evolution to more aggressive methods such as radiotherapy and enucleation. We present a case of iridociliary melanoma, who underwent conservative surgery, iridocyclectomy under scleral flap, with good results, and maintenance of the function and integrity of the eyeball.

Fetal Kidneys Ultrasound Appearance in the First Trimester - Clinical Significance and Limits of Counseling.

OBJECTIVE: The objective of this study was to determine the visualizing rate of fetal kidneys at various gestational ages in late first trimester (FT) and to establish the clinical significance of their two-dimensional ultrasound (2DUS) appearance in the FT. METHODS: In a prospective cross-sectional study, 1456 women from an unselected population underwent a detailed assessment of fetal anatomy at 11+0 -13+4 weeks of gestation with the use of transabdominal sonography. Information on the ultrasound findings, antenatal course and perinatal outcome was obtained in 1331 cases. RESULTS: 44 cases in which a congenital kidney disease was detected by ultrasound in the prenatal period were identified. The renal pathology was suspected in the FT in 8 cases, and confirmed by a standard test (postmortem autopsy or second-trimester scan) in 4 cases. The standard detailed second-trimester scan at 18-22 weeks diagnosed another 23 cases but refuted suspicion in 4 FT positive cases. The third trimester added another 17, all confirmed by the postpartum scan. For FT presence or absence of congenital renal anomalies, sensitivity, specificity, +LRs and -LRs of 2DUS were 9.09%, 99.69%, 29.25, and 0.91. CONCLUSION: FT prenatal kidneys' visualization is critically dependent on the gestational age. FT diagnosis holds uncertainty. An early diagnosis carries a risk of providing a false-positive or a false-negative result, because the differentiation of the renal system is delayed or the diagnosis is not amenable yet to prenatal ultrasound. No FT findings can exclude the mid-trimester follow-up ultrasound scan. Second and third trimester scan are relevant for congenital kidney diseases.

Histopathological Prognostic Factors for Endometrial Carcinoma.

The purpose of our study was to determine the incidence and the relationship between prognostic factors (age at diagnosis, pTNM stage, histological grade, lymph vascular and myometrium invasion) in patients with endometrial carcinoma. We evaluated in terms of diagnosis 50 cases of endometrial carcinomas that were hospitalized during 2011-2014 in the Obstetrics, Gynecology and Surgery clinics of the Emergency County Hospital Craiova. The procedure consisted in fixation in 10% buffered formalin, followed by processing with usual technique of paraffin embedding and finally staining in hematoxylin and eosin. The histological analysis of the 50 endometrial carcinomas revealed well-differentiated carcinomas (G1) in 24 cases (48%), moderately differentiated carcinomas (G2) in 17 cases (34%) and poorly differentiated carcinomas (G3) in further 9 cases (18%).The myometrium invasion was present in the internal half of the myometrium in 12 internal cases (24%) and in the external half of myometrium in further 36 cases (72%). In 2 cases (4%) the myometrium invasion was absent. We achieved significant association between histological grade and invasion of myometrium, also between histological grade and lymphovascular invasion, as well as tumor stage and myometrium invasion. We are also able to report significant association between lymphovascular invasion and tumor stage or tumor stage and presence of lymph nodes. The results of this study emphasize the importance of pathological parameters as prognostic factors in endometrial carcinoma.

Clinical, Histological and Prognosis Correlations in Diagnosis and Treatment of Gastric Cancer.

Purpose The study authors have proposed to highlight the main epidemiologic and prognostic aspects of digestive malignancies in the Dolj county population, justifying the need for permanent and detailed estimate of this phenomenon. Methods The authors of the study have proposed to outline a descriptive epidemiological panel, characteristic for the population groups at risk of developing gastric cancers and establishing clinical factors (tumor location, disease stage, type of surgery) and histological factors (histopathological type, degree of tumor differentiation) with prognostic significance having as landmark, survival rate at 5 years or disease-free survival of 5 years. Results The study was conducted on a sample of 458 patients with gastric tumors endoscopically detected, histologically confirmed and treated between 2000-2010. The epidemiological study allowed us to outline the descriptive epidemiological panel characteristic for the group of patients at risk of developing gastric cancer. Analysis of correlation between clinical parameters and histopathological parameters reached statistical threshold in multivariate statistical analysis of the localization of tumor, disease stage and histological type (p <0.0001) and the degree of differentiation of gastric carcinomas (p <0.005). Multivariate statistical analysis has detected statistically significant differences in terms of survival rate at 5 years (p> 0.001) and free interval of disease at 5 years (p> 0.001), depending on the location of the tumor, correlated with other clinical factors (disease stage, type of surgery) and histological factors (histopathological type, tumor differentiation grade), which allowed us to outline clinical, histological and prognostic groups. Conclusions Defining the clinical, histological and prognostic groups, allows an accurate assessment of patient prognosis from the time of randomization and initiation of treatment, type of surgery in advanced loco-regional, reconverted to operability, after neoadjuvant polychemotherapy being dictated by the location of the tumor (1/3 superior vs. 1 / 3 medium vs. 1/3 lower stomach).

The Role of Podoplanin in the Lymphangiogenesis of Oral Squamous Carcinomas.

Oral squamous cells carcinoma (OSCC) mortality rate ranges between 29-40/100,000 inhabitants. Regional lymph node metastases occur in 30-40% cases and are associated with unfavorable prognosis and decreased survival. Recentely it was suggested that the tumor-associated lymphatic vessels formation plays an active role in metastasis proces of several human malignancies, including OSCC. In the present study we investigated comparatively podoplanin immunoexpression in OSCC in both the tumor cells and lymphatic vessels reported to clinicopathological prognostic parameters. Material and methods The study included a total of 25 cases of OSCC. We investigated clinico-pathological parameters as age, gender, tumor site, and degree of differentiation, size and depth of invasion (pT), lymph node status (pN). Histologic classification was done according to the WHO criteria. For immunohistochemical (IHC) analysis we used podoplanin (Dako, clone D2-40). As visualization system it was used LSAB2 (Dako, Redox, Romania, code K0675) and chromogen DAB (Dako, Redox, Romania, code K3468). Negative controls were obtained by omitting the primary antibodies. IHC quantification was done intensity score and by lymphatic microdensity (LVD), intratumoral and on the advancing edge. For the statistical analysis we used Student's t-tests, ANOVA, chi square and Pearson, using SPSS 10 software. Results Podoplanin immunoexpression in tumor parenchyma presented with an average of 43%, varying intensity. We found a higher intensity in weak and moderately differentiated SCC then in well differentiated ones and no difference intratumoral aand advancing edge. In relation to the degree of tumor differentiation the mean LVD D2-40 was higher in the advancing edge. SCC who presented lymph node metastasis mean values for LVD D2-4 was higher then at advancing edge and higher than those of non-metastatic carcinomas. Conclusions Podoplanin immunoexpresion suggests the involvement both in tumor growth and the acquisition of an lymphangiogenic phenotype invasive by autocrine mechanisms.