Histological diagnosis of Bechterew's disease on exhumed female remains in Bosnia and Herzegovina: a case report

Ankylosing spondylitis is a serious ailment that affects people, and the first signs or symptoms usually occurr between the ages of 15 and 45. While the condition is mostly prevalent in men, women are not immune to this disease. This problem is diagnosed with a combination of clinical history and X-rays, pathology and HLAB27 test. The aim of this case study is to demonstrate how macroscopic and microscopic analysis can be used for identification of the disease from a forensic point of view. In April 2018, we exhumed 11 remains near the city Višegrad, twenty-five years after the last war. All the remains were completely skeletonized. The skeleton of a female was specific and shaped like a bamboo branch, with a partial knitting of vertebral bodies in the lumbar region of spine and with total knitting in the thoracic part. The spinous processes were completely knitted. Her son gave informations for verbal autopsy that she had trouble walking and doing normal activities during life. Samples for analysis and pathological diagnostics were used to determine the real bone condition for forensic purposes. To our best knowledge our case is first one in the literature which combines macroscopic and microscopic analysis of AK in exhumed skeletal remains after 25 years of death in modern era of Europe

Lymphangiogenesis in breast carcinoma is present but insufficient for metastatic spread

Introduction: The lymphatic vasculature is an important route for the metastatic spread of human cancer. However, the extent to which this depends on lymphangiogenesis or on invasion of existing lymph vessels remains controversial. The goal of this study was to investigate the existence of lymphangiogenesis in invasive breast carcinoma: by measuring the lymphatic vessels density (LVD) and lymphatic endothelial cell proliferation (LECP) and their correlation with various prognostic parameters in breast cancer, including lymphovascular invasion (LVI).Methods: Lymphatic vessels density was investigated in 75 specimens of invasive breast carcinoma by immunostaining for D2-40 using the Chalkley counting method. Endothelial proliferation in lymphatic vessels was analyzed by dual-color immunohistochemistry with D2-40 and Ki-67.Results: Decrease of intra and peritumoral LVD in invasive breast carcinoma compared to fibrocystic breast disease was detected (p=0.002). Lymphatic endothelial cell proliferation was significantly higher in invasive breast cancer (p=0.008) than in the fibrocystic breast disease. LECP showed a correlation with histological grade of the tumor (p=0.05). Involvement of axillary lymph nodes with metastatic tissue was in strong correlation only with existence of lymphatic vascular invasion (p=0.0001).Conclusion: These results suggest that development of breast cancer promotes proliferation of lymphatic endothelial cells whose level correlates with histological grade of tumor, but in a scope that is insufficient to follow growth of tumor tissue that invades them and destruct them. This might explain the decrease of lymphatic vessels density

The relationship of tumor microenvironment and clinicopathological parameters in different molecular subtypes of breast cancer

Introduction: Tumor microenvironment plays a significant role in tumor progression. Tumor stroma is one of the strongest modifiers of tumor cell response, cancer behavior, and cancer progression. This study aimed to investigate the correlation of matrix metalloproteinase-9 (MMP-9) expression and tumor-stroma ratio (TSR) with standard clinicopathological parameters in different molecular subtypes of breast cancer.Methods: Ninety biopsy samples of primary breast cancer diagnosed at the Department of Pathology, School of Medicine, Sarajevo, were selected for this study. The molecular subtype was determined based on the immunohistochemical expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67. Stromal and tumoral MMP-9 immunohistochemical expression and the TSR were determined for each tumor.Results: Tumoral MMP-9 expression correlated positively with the presence of lymphovascular invasion (p= 0.016). TSR showed significant association and correlation with tumor grade (G) (p= 0.031; p= 0.049) and tumor size (pT) (p = 0.049;p= 0.021, respectively). Stromal MMP-9 expression correlated with histologic type, histologic grade of tumor, and lymphocytic inflammatory infiltrate (p= 0.021;p= 0.047, p= 0.038, respectively). A higher percentage of stromal MMP-9 expression correlated with the strongest lymphocytic response (p = 0.007). Significant correlation was observed between molecular subtypes and histologic grade of the tumor (p= 0.032).Conclusion: Our results, to some extent, confirm the significance of the tumor microenvironment in breast cancer, especially when it is about stromal MMP-9 expression. Although we observed significant association, without linear correlation, we found no significant correlation between molecular subtypes of breast cancer and MMP-9 expression

Is the expression of matrix metalloproteinases (MMP-2, -9) and tissue inhibitors of metalloproteinases (TIMP-1, -2, and -3) associated with angiogenesis and clinicopathological features for breast cancer?

Introduction: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in the progression of several tumors, including breast cancer. Our aim was to investigate the association of immunohistochemical expression of protein MMP-2, and -9 and tissue inhibitors TIMP-1,-2,-3 by tumoral cells in the process of angiogenesis and to define their relation with clinicopathological features for breast cancer. Methods: Immunohistochemical analysis of MMP-2,-9, TIMP-1,-2,-3, endoglin/CD105, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status was performed on 79 tissue samples of breast cancer with axillary lymph node dissection. Results: Statistically significant difference was found between mean age of patients and tissue inhibitors of metalloproteinase (TIMP-1) expression status (p=0.008), i.e., women with TIMP-1 negative tumors were on average younger (mean age 46.5) compared to women with TIMP-1 positive tumors (mean age 58.1); TIMP-2 expression status showed association with ER status (p=0.017), while TIMP-3 negative tumors were on average more frequently ER and PR negative (p=0.016; p=0.027). Status of protein expression of MMP-9 was associated with TIMP-1 protein expression status (p=0.033), i.e., breast cancers with overexpression of protein MMP-9 were more frequently TIMP-1 protein positive. Conclusion: Only TIMPs were associated with clinicopathological features for breast cancer. TIMP-2 expression was associated with worse (TIMP-2 positive tumors were frequently ER-negative), while TIMP-3 expression in tumoral cells was associated with better clinicopathological features for breast cancer (TIMP-3 positive tumors were frequently ER and PR positive)

Korelacija peritumoralnog edema mozga s morfološkim karakteristikama i Ki67 proliferacijskim indeksom kod reseciranih intrakranijskih meningeoma

The aim of the study was to analyze correlation between morphological characteristics of intracranial meningiomas and Ki67 labeling index (Ki67 LI), and their influence on peritumoral brain edema (PTBE). There were 41 consecutive patients with intracranial meningiomas surgically treated at the Department of Neurosurgery, Zenica Cantonal Hospital, Zenica, Bosnia and Herzegovina, during the period from January 2010 to December 2015. We reviewed clinical data including patient age, gender, magnetic resonance imaging (MRI) characteristics of the tumor and peritumoral edema, tumor margins, intraoperative characteristics, histopathologic grade and Ki67 LI. In all cases, follow up MRI was obtained at about three months after resection and PTBE was analyzed. Our research showed the tumor volume, tumor margins, and intraoperative signs of arachnoidal and pial invasion to be associated with PTBE in intracranial meningiomas. Ki67 LI expression correlated with PTBE. This study showed the resolution of PTBE to depend on invasive behavior of meningioma and KI67 LI. PTBE, pial/cortical and arachnoidal invasion significantly influence the extent of surgical resection.Cilj studije je bio analizirati korelaciju između morfoloških karakteristika intrakranijskih meningeoma i Ki67 proliferacijskog indeksa, kao i njihovog odnosa s peritumoralnim edemom mozga. U studiju je bio uključen 41 konsekutivni bolesnik s intrakranijskim meningeomom koji su operativno liječeni u Službi za neurokirurgiju Kantonalne bolnice Zenica u razdoblju od siječnja 2010. do prosinca 2015. godine. U svrhu istraživanja analizirali smo kliničke podatke uključujući dob, spol, MRI karakteristike tumora i peritumoralnog edema, margine tumora, intraoperacijske karakteristike tumora, histopatološki gradus i Ki67. Kod svih bolesnika napravljen je kontrolni MRI mozga oko tri mjeseca nakon resekcije tumora. Na tim snimkama se analizirala moguća prisutnost peritumoralnog edema. Naše istraživanje je pokazalo da su volumen tumora, izgled njegovih margina, znaci arahnoidalne i pijalne invazije u korelaciji s veličinom peritumoralnog edema. Također, rezultati su pokazali da je rezolucija peritumoralnog edema ovisna o invazivnom ponašanju meningeoma i veličini Ki67. Peritumoralni edem, invazija pije/korteksa i arahnoideje značajno utječu na obim resekcije tumora

Correlation of the HER-2 protein expression and other clinicopathological features of ductal infiltrative breast cancer

The aim of the study was to investigate the relationship between the expression of the HER-2 membrane protein and other clinical-pathological parameters such as: histological size of the tumor, degree of the tumor's differentiation, presence of vascular invasion and presence of metastases in regional lymph nodes, in cases of ductal infiltrative breast cancer. We have investigated 56 cases of ductalinfiltrative breast cancer. In all patients a mastectomy with a dissection of axillary lymph nodes has been performed. All tissue samples, taken by biopsy, were embedded in the paraffin, stained by hematoxylin-eosin technique and screened, and evaluation was performed by using a semiquantitative method of the immunohistochemical expression of the HER-2 protein. A decrease of the protein HER-2 expression was noticed in cases of an increase of the tumor's diameter above 50 mm. Increased expression of the HER-2 protein was noticed in cases of moderate (grade II) and poor (grade III) differentiation of carcinoma, as well as in cases where there was no metastases in the regional lymph nodes. No relationship has been observed between the expression of HER-2 and occurrence of vascular invasion. In cases of ductalinfiltrative breast cancer the expression of HER-2 protein is in correlation with the size and degree of tumor's differentiation, as well as with the presence of metastases in regional lymph nodes

Immunohistochemical expression and significance of NM23 suppressor protein in primary gastric adenocarcinoma

NM 23 protein was originally identified as a metastasis suppressor protein. The expression of NM23 has been correlated with tumour metastatic potential in various human carcinoma, mostly in ductal breast and colorectal carcinomas. Evidence for their expression in gastric cancer is rather contradictory, both for protein expression status and prognostic vale. This study was done to analyze the immunohistochemical expression of NM23 in gastric carcinoma, and correlation of the degree of staining with clinicopathological parameters was investigated. In a retrospective immunohistochemical study specimens obtained from 56 gastric cancer patients who had undergone gastrectomy with perigastric lymphadenectomy were analysed, in correlation with classical clinical-pathological parameters of tumours, WHO-, Lauren-, Goseki-, and Ming- classification. NM 23 gene expression was compared in gastric adenocarcinoma and tumour-adjacent non-neoplastic gastric mucosa. A semiquantitative immunostaining evaluation (score 0-3) was used, counting the percentage of stained cells. Statistical analysis was performed using Kolmogorov-Smirnov test, and Spearman rank correlation test. The investigated group consisted of 40 males and 16 females (2.5:1) with a mean age of 63 years (range: 48-81 years). The percentage of positive expression of NM23 (score 3) were in 30 (53.5%) specimens in non-neoplastic mucosa in adjacent gastric carcinoma, and negative (score 0-2) in all 56 (100%) specimens of gastric adenocarcinoma. NM23 expression was higher in non-neoplastic mucosa than in adjacent gastric adenocarcinoma tissue (p=0.172), lymphovascular invasion (p=0.606), lymph node metastases (p=0.311), Lauren classification (p=0.426), Goseki classification (p=0.458) and Ming classification (p=0.212). Our series did not show a significant correlation between NM23 expression and analysed clinico-pathological variables, but these results suggest that protein NM23 may have a role in gastric carcinoma pathogenesis

Zearalenone-induced Lymphophagocytosis (T Cell Apoptosis) on the Rat’s Thymus

The effects of nonsteroidal mycotoxin zearalenone on the lymphoid tissue of thymus in a sense of investigating the subacute toxicity Wistar-albino rats have been examined in the course of the study. We analyzed 42 rats' specimens of both gender, treated with three dosage levels: 0,5; 2 and 4 mg/kg of body weight, after oral submission of the compound, and observed during three different time intervals: 10, 20 and 30 days. Microscopically was semiquantitatively determined lymphophagocytosis (apoptosis) and cortical thymic cellularity. It was percepted statistically significant growth of lymphophagocytosis compared to a dosage (p0,05). Changes in cortical thyme cellularity were not percepted. Effects of applied doses of zearalenone on the lymphoid tissue of thymus were very mild and in correlation with estrogenicity. They are probably the result of interaction with estrogenic receptors

Oral acute toxicity of HEPALIP FORTE in rats

he main active component of preparation HEPALIP FORTE is EPL--essential phospholipids. Their chemical structure corresponds to that of endogen phospholipids, but they have functional superiority because of the content of unsaturated fatty acids. Essential phospholipids in combination with the vitamins have been used in the treatment of liver diseases, dyslipoproteinaemias and intoxications with consequent liver failure. Acute toxicity study on HEPALIP FORTE was performed on Wistar rats. The main aim of toxicology studies for the drug registration process is evaluation of the toxic potential and risks of human exposition to the substance (Gelbke et al., 1999). Acute toxicity is an orientation point of the test substance toxicity and represents a starting test for the toxicological evaluation. Study included one oral dose of the substance, applied with oesophageal intubations. There were three dose-levels: 300, 500 and 1000 mg/kg. No lethality was recorded and statistical analysis of body weight variations failed to show any significant difference between the groups. Reversible tremor was more frequently recorded in females and was not present in control animals. After the planed sacrifice, no changes related to the test substance were recorded. We noticed a statistically significant difference in the liver weights between males of 3M and 2M groups in comparison to the control. Similar (not significant) tendency was noticed in females. Significant differences in organ weights might be suggestive of a toxic effect that experimental animal managed to recover from in partial manner. The histopathological analysis detected no changes in the structure and morphology of liver parenchyma

Interdigitating dendritic cell sarcoma of the liver and lung: a case report with morphohological and immunohistochemical features of tumor

Interdigitating dendritic cell sarcoma is extremely rare neoplasm that mainly occurs in the lymph nodes. Only 45 cases have been reported in the literature to date. We report a case of this sarcoma arising from the liver and lung, a previosly unreported site for this neoplasm. An 19-year-old girl deteriorated rapidly after artificial abortion and died 4 weeks later. Autopsy showed markedly enlarged liver and lung with numerous nodules up to 0.5 centimeters in diameter. Microscopically, nodules was composed of large pleomorphic cells that were immunohistochemically positive for proteins S-100 and vimentin, some of them expressed positivity to fascin and CD 68, with a rich small CD3 positive T lymphocytic infiltrateite around them. Based of these findings, the present case was diagnosed as interdigitating dendritic cell sarcoma, a neoplasm that remains a diagnostic and clinical challenge, because it can mimic a wide variety of other malignant tumors and tumor-like lesions