Amălinei C

Meningiomas – insights into genetics and correlations with histological features

Meningiomas are the most common intracranial tumors. They occur more frequently in women and may be completely asymptomatic. According to the World Health Organization, the ability to invade and to develop recurrences represents the criterion which is used to designate three grades of meningiomas. In the last decade, advanced knowledges in genetics and molecular biology have improved our understanding of the clinical behavior of meningiomas. In addition to mutation or loss of NF2 gene, recurrent mutations of other genes, such as TERT, TRAF7, AKT1, AKT3, SMO, KLF4, SMARCE1, POLR2A, SUFU, BAP-1, PIK3CA, TSLC1, CDNK2A, PTCH1, TP73, PTEN, NDRG2, S6K, and CDNK2B have been identified within subsets of meningiomas. This review provides an overview and updates of the current knowledge of the genetics of meningioma in correlation with its histopathology. The insights into genetics and molecular profile of meningiomas may provide a valuable step towards developing new therapeutic approach for this type of intracranial tumor.

Diagnosis challenges in a uterine leiomyosarcoma

Uterine leiomyosarcoma (LMS) represents a rare tumor, accounting for 1.3% of all uterine malignancies. Although this tumor shares morphological and clinical features with other uterine benign and malignant tumors, the accurate diagnosis is necessary, due to their different biological behavior and prognosis. Therefore, we present a case of LMS in a 48 year-old patient, complaining of a 3-months metrorrhagia. The tumor presented as a poorly defined submucosal nodule, with a soft consistence and measuring 6 cm in diameter. The microscopic examination of this tumor nodule revealed fascicles of spindle cells, with pleomorphic hyperchromatic nuclei exhibiting moderate to severe atypia and areas of tumor necrosis. At least 5 atypical mitoses/ 10 HPF were also found. Immunohistochemistry technique, with a panel of six antibodies, comprising ER, PR, PCNA, SMA, p53, and bcl-2, has been performed for the differential diagnosis. The final histopathological diagnosis was that of uterine LMS. Considering LMS an aggressive tumor, the patient has been recommended a thorough follow-up.

Arrhythmogenic right ventricular cardiomyopathy: an overview and update

Arrhythmogenic right ventricular cardiomyopathy consists in partial or total progressive replacement of cardiac muscle fibers with a fibro-adipose tissue. This is a hereditary disease with an autosomal dominant inheritance with incomplete penetrance and variable expressivity, except two autosomal recessive syndromes. The most frequent abnormal proteins are that of desmosomal intercellular junctions, such as junctional plakoglobin, plakophilin-2, desmoplakin, desmoglein-2, and desmocollin-2, although other types of non-desmosomal components may be also involved. Desmosomal disorders result in myocardial fibers necrosis and their progressive replacement with fibro-adipose tissue. The morphological modifications are usually beginning in the subepicardial layer and develop towards the endocardium, being associated with the ventricular wall degeneration, thinning, and progressive increase of the amount of adipose tissue. The average age of clinical manifestations onset is around 30-40 years old, with ventricular arrhythmia and high risk of sudden death. Currently, the diagnosis is based on the 2010 Task Force Diagnostic criteria. The current review presents an overview on traditional knowledge about this disease, adding updated information regarding molecular and genetic data. The knowledge of this disease is important for medical practice as a possible cause of arrhythmia and sudden death and its prognosis might be improved by appropiate genetic testing as family screening.

Comparative analysis of CD4 and CD8 lymphocytes — evidences for different distribution in primary and secondary liver tumors

INTRODUCTION The impact of tumor cells on tumor-infiltrating lymphocytes (TILs) in cancer development is not yet clarified. Our study analyzed the distribution and prognostic value of CD4+ and CD8+ T lymphocytes in hepatocellular carcinoma (HCC) and liver metastases (LM). MATERIAL AND METHODS Archival tissue specimens of 35 HCC and 39 LM patients were immunohistochemically processed. The number of intratumoral (IT) and peritumoral (PT) CD4+ and CD8+ T cells was quantitatively analyzed. RESULTS We noted large variances of T lymphocyte subpopulations. Similar number of CD4+ and CD8+ lym-phocytes was present in HCC, whereas in LM the number of CD8+ cells was approximately two times higher than CD4+ lymphocytes. A significant prevalence of T cells in PT over IT areas was observed. The prognostic value was demonstrated only for PT CD8+ lymphocytes in LM, their reduced number being associated with shorter survival. CONCLUSIONS The differences between proportions of T lymphocytes within tumor and its environment might be explained by proapoptotic effect of cancer cells on TILs.

Metalloproteinases involvement in liver tumoral pathology- an update

MMPs and TIMPs involvement in tissue destruction may be incriminated in malignant invasion and metastasis, showing correlations between the overexpression, aggressiveness, tumor stage and prognosis. Recent data provide evidence of their complex role in creating an auspicious microenvironment for tumor growth in primary and metastatic sites. The investigation of MMPs and TIMPs functional interdependency is an important direction, useful in carcinogenesis intrinsic mechanisms deciphering, its apparently paradoxical role being incompletely defined. Literature review regarding MMPs and TIMPs study in primary and secondary hepatic tumors allows us to affirm that defining a precise profile of their activities is extremely difficult. The most studied metalloproteinase, in liver tumoral microenvironment, were MMP2 and MMP9 together with their inhibitors TIMP 2 and TIMP1, respectively. The expression variability of both MMPs and TIMPs is associated to promoter or inhibitor action of stromal cells and / or tumor cells, as liver microenvironment has a modulatory action for MMPs and TIMPs. MMPs capacity to intervene in many biological processes is attributed to their ability of ECM proteolysis, as a possible initiator of unrevealed functions. The understanding of biochemical and structural aspects of MMPs, and the capacity to form molecular complexes with TIMPs open the perspectives of design of potent specific inhibitors for MMPs and, thus, the development of new therapies for primary and metastatic liver cancers.

Morphometric approach to pulp fibroblast development in tooth germ.

This paper builds a morphometric framework for the analysis of dental pulp fibroblast evolution during tooth development. We investigated 15 tooth germs (cases) organized, by histological criteria, in three groups corresponding to cap, early bell, and late bell stages, respectively. Each group comprised five cases. The morphometric description used the following parameters: area (A), perimeter (P)—automatically extracted by a color segmentation technique, and form factor (FF)—calculated as 4πA/P 2. The designed framework operated at inter- and intragroup levels. The intergroup analysis quantified the differences between groups, in the sense of a relative distance (RD) adequately defined by mean-value scaling. We showed that the stage of early bell is approximately 5 times closer to late bell than to cap. The quantification procedure required concomitant information about A, P parameters (as P versus A dependences, or FF values), whereas the procedure failed for A or P separately used. The intragroup analysis quantified the similarity of the cases belonging to the same stage. We proved that, unlike the intergroup tests, the individual exploitation of all three descriptors A, P, and FF is effective, yielding highly compatible results. Within any group, most cases presented RDs less than 10% from the group mean value, regardless of the descriptor type.