Diffuse Axonal Injury-A Distinct Clinicopathological Entity in Closed Head Injuries.

The knowledge about the diffuse axonal injury (DAI) as a clinicopathological entity has matured in the last 30 years. It has been defined clinically (immediate and prolonged unconsciousness leading to death or severe disability) and pathologically (the triad of DAI specific changes). In terms of its biomechanics, DAI is occurring as a result of acceleration forces of longer duration and has been fully reproduced experimentally.In the process of diagnosing DAI, the performance of a complete forensic neuropathological examination is essential and the immunohistochemistry method using antibodies against ß-amyloid precursor protein (ß-APP) has been proved to be highly sensitive and specific, selectively targeting the damaged axons.In this review, we are pointing to the significant characteristics of DAI as a distinct clinicopathological entity that can cause severe impairment of the brain function, and in the forensic medicine setting, it can be found as the concrete cause of death. We are discussing not only its pathological feature, its mechanism of occurrence, and the events on a cellular level but also the dilemmas about DAI that still exist in science: (1) regarding the strict criteria for its diagnosis and (2) regarding its biomechanical significance, which can be of a big medicolegal importance.

Comparison Between HPV DNA Testing and HPV E6/E7 MRNA Testing in Women with Squamous Cell Abnormalities of the Uterine Cervix.

INTRODUCTION: The aim of the study was to compare the results of two human papillomavirus (HPV) diagnostic techniques: human papillomavirus deoxyribonucleic acid (HPV DNA) testing and human papillomavirus E6/E7 messenger ribonucleic acid (HPV E6/E7 mRNA) testing in women with squamous cell abnormalities of the uterine cervix. MATERIAL AND METHODS: Comparative prospective study, conducted in the period from January 2016 to June 2017 of 128 sexually active women, age groups of 20 to 59 years (40.50 ± 10.85) with squamous cell abnormalities on the cervical cytology. All patients were subject to: HPV DNA testing, HPV E6/E7 mRNA testing and colposcopic cervical biopsy with endocervical curettage for histopathologycal analysis. HPV DNA testing was done using multiplex polymerase chain reaction (PCR) and reverse hybridization methods. HPV E6/E7 mRNA testing was done using real-time PCR method. RESULTS: Data analysis showed an association between the results of HPV DNA testing and HPV E6/E7 mRNA testing (p˂0.0001). The concordance between the results of both tests was moderate (55.47%). The results show that HPV E6/E7 mRNA testing had a higer specificity 88.89% and positive predictive value (PPV) 93.59% for HSIL + invasive squamous cell carcinoma compared to HPV DNA testing that had specificity of 55.56% and PPV 84.61%, respectively. CONCLUSION: The results of our study suggested that HPV E6/E7 mRNA testing is more specific and has a higher positive predictive value than HPV DNA testing and that viral oncoproteins E6 and E7 are superior biomarkers for the detection of high-risk HPV-associated squamous intraepithelial lesions of the uterine cervix.

Presentation of the Molecular Subtypes of Breast Cancer Detected By Immunohistochemistry in Surgically Treated Patients.

INTRODUCTION: The detection of estrogen, progesterone and HER-2 neu receptors on the surface of the tumour cell is a significant prognostic factor, alone or in combination. The presence or absence of receptors on the surface of the tumour cell is associated with the conditional gene expression in the tumour cell itself. Based on these genetically determined expressions of the tumour cell, five molecular subtypes of breast cancer have been classified on the St. Gallen International Expert Consensus in 2011 that can be immunohistochemically detected, with each subtype manifesting certain prognosis and aggression. AIM: Analyzing the presentation of molecular subtypes of breast cancer that are immunohistochemically detected in surgically treated patients at the Clinic for Thoracic and Vascular Surgery. MATERIAL AND METHODS: We used the international classification on molecular subtypes of breast cancer which divides them into: Luminal A (ER+ and/or PR+, HER-2 negative, Ki-67 < 14%), Luminal B with HER-2 negative (ER+ and/or PR+, HER-2 negative, Ki-67 ≥ 14%), Luminal B with HER-2 positive (ER+ and/or PR+, HER-2+, any Ki-67), HER-2 enriched (ER-, PR-, HER-2+), and basal-like (triple negative) (ER-, PR-, HER-2 negative, CK5/6+ and/or EGFR+). A total of 290 patients, surgically treated for breast cancer, were analysed during 2014. RESULTS: In our analysis, we found that Luminal A was present in 77 (26.55%) patients, Luminal B HER-2 negative was present in 91 (31.38%) patients, Luminal B HER-2 positive was present in 70 (24.14%) patients, HER-2 enriched was present in 25 (8.62%) patients and basal-like (or triple negative) was present in 27 (9.31%) patients. CONCLUSION: Detecting the subtype of breast cancer is important for evaluating the prognosis of the disease, but also for determining and providing an adequate therapy. Therefore, determining the subtype of breast cancer is necessary for the routine histopathological assay.

Traumatic axonal injury, a clinical-pathological correlation.

Traumatic axonal injury (TAI) is a distinct clinicopathological entity that can cause serious impairment of the brain function and can sometimes be found as a concrete cause of death. It has been discussed from the perspective of its biomechanical importance, and also from the standpoint of certain criteria for the pathological diagnosis of TAI. However, since the time when DAI (diffuse axonal injury) was initially described, there have been few, if any, discussions about the clinical-pathological correlation in TAI. This paper is an attempt to address this issue. For the purpose of certain pathological diagnoses of TAI, 63 cases with closed head injuries have been subjected to the complete forensic-neuropathological examination, involving immunohistochemistry with antibody against ß-APP. In the diagnosis of TAI strict criteria have been followed. Then, retrograde analysis of the clinical parameters has been performed in order to determine some clinical-pathological correlation. The following two most reliable parameters of the impairment of the brain function have been analyzed: the impairment of the consciousness and the time of survival. Comparing the two groups, the one with TAI and the other without TAI, and using appropriate statistical evaluation, our results show that TAI is not a significant contributing factor to the lethal outcome in the early post injury period (24 h), but it is undoubtedly a contributing factor for the severe impairment of the brain function indicated through the status of the consciousness.

Correlation Between Microvessel Density and Morphological Features in Skin Squamous Cell Carcinoma.

INTRODUCTION: Abnormal angiogenesis is described in tumor growth and it facilitates its metastatic spread. Tumors with high angiogenic activity belong to the category of aggressive tumors with poor prognosis for patients. The aim of this study was to determine the blood vessels density (BVD), i.e. neovascularization at the tumor invasive front in skin squamous cell carcinoma (SCC) in order to determine its possible role in the tumor progression, and to correlate it to the blood vessels density of healthy skin and with the prognostic parameters of the TNM classification: T status, depth of tumor invasion (DI) and tumor histological grade (G), which were also correlated between each other. MATERIAL AND METHODS: The material consisted of surgical specimens obtained from 30 patients with skin SCC, who underwent surgery. Tissue samples were routinely processed by standard paraffin technique stained by Hematoxilin-Eosin and immunohistochemically with antibodies against smooth muscle actin (SMA) and CD34. The BVD in the invasive front of the neoplasms was correlated to the healthy skin, tumor status (pT), depth of invasion and grade of histological differentiation (pG). RESULTS: The histological analysis has shown a high statistical difference in the density of blood vessels in SCC compared to the healthy skin and statistical difference in BVD in neoplasms with different depth of invasion and different grade of differentiation. The density of neovascularzation increased with the deeper invasion and the worse differentiation. CONCLUSION: The increased vascularization at the invasive front of SCC with deeper invasion and worse differentiation has pointed out to its possible role in neoplasm progression.

Superficial leiomyomas of the gastrointestinal tract with interstitial cells of Cajal.

OBJECTIVE: Some authors suggest common origin of gastrointestinal stromal tumors from stem cells, which may show diverse differentiation. There are reports in which cells morphologically identical to the interstitial cells of Cajal are found in deep leiomyomas. The aim of this study was to demonstrate CD117 positive cells in superficial gastrointestinal (GI) leiomyomas and to find other cells that would suggest diverse differentiation in histologically typical leiomyoma. MATERIALS AND METHODS: We analyzed 8 cases of superficial leiomyomas and one deep leiomyoma, received in our institutions as endoscopically or surgically obtained material. The tumor sections were immunohistochemicaly stained with CD117, CD34, NF, S100, αSMA, desmin, caldesmon and mast cell antigen. RESULTS: All leiomyomas showed diffuse positivity for αSMA, caldesmon and desmin. All of them had CD117 and CD34 positive cells morphologically identical to the interstitial cells of Cajal between smooth muscle fibers, 5 had S-100 and NF positive cells and 2 showed positivity for GFAP. The cells were found in different quantity; they were usually diffusely scattered through the tumors without predilection site, forming small groups in some areas. CONCLUSION: CD177, CD34, S-100 and NF positive cells are present in superficial leiomyomas and they may suggest common origin of GI stromal tumors.

Impact of socio-demographic factors on the delayed diagnosis and advanced stage presentation of patients with invasive cervical cancer in Macedonia.

AIM: The study aims to establish certain socio-demographic factors associated with delayed presentation (i.e. advanced stage at diagnosis) in patients with invasive cervical cancer in Macedonia. MATERIALS AND METHODS: The cross-sectional study was conducted with patients already diagnosed and treated for invasive cancer of the uterine cervix who came in for their regular annual check-up at the University Radiotherapy and Oncology Clinic, Medical Faculty, Ss. Cyril and Methodius University in Skopje, Macedonia. The data were collected by interviewing the participants using a standardized questionnaire. RESULTS: A total of 115 patients were recruited in the study. Eight of them were excluded from further analysis due to incomplete data. Close to 72% of the patients analysed presented with advanced stage disease, while 28.04% of the patients were diagnosed with early stage disease. The univariate analysis and Chi-square statistics showed that the patients had a higher probability of being diagnosed with advanced stage disease if they had a low monthly income (p = 0.01), had lower degrees of education (p < 0.001), had an unsatisfactory level of genital hygiene (p < 0.001) and had no family history of invasive cervical cancer in first degree female relatives (p = 0.003). DISCUSSION: The results from the study could be utilized to identify the population at risk which should be targeted for implementation of specialized educational programmes for familiarizing the population with the nature of the disease which in turn would increase the level of consciousness as a step towards implementing a national screening programme.