CORRELATION OF PERITUMORAL BRAIN EDEMA WITH MORPHOLOGICAL CHARACTERISTICS AND KI67 PROLIFERATIVE INDEX IN RESECTED INTRACRANIAL MENINGIOMAS.

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.

Fine Needle Aspiration Cytology of Lymph Nodes in Metastatic Cancer and Lymphoma: Our Single-institution Experience.

Background: Lymphadenopathy is a common finding in clinical practice. The cause of enlarged nodes on clinical examination alone is challenging and there may be multiple reasons for this enlargement. It may become enlarged due to stimulation by infectious agents or the involvement of metastasis or malignant diseases, such as lymphoma. Objective: The aim of the study was to investigate the diagnostic role of fine needle aspiration cytology of lymph nodes in metastatic cancer and lymphoma. Methods: A total of 48 FNAC lymph nodes suspicious for malignancy were sampled with follow-up biopsy in Clinical Center of University of Sarajevo from 2017 to 2023. Lymph nodes were aspirated using 20-22 G needle with minimally 2 passes, spread on slides, air-dried, stained with May-Grünwald-Giemsa or Papanikolaou and residual material sent for cytoblock. Results: Out of 48 cytological samples, 30 (62.5%) revealed metastatic epithelial cells and 12 (25%) lymphoproliferative neoplasm. Three samples were suspected for malignancies, one sample was unrepresentative, one inconclusive and one falsely negative. Histopathological confirmation had 35 patients, while others were confirmed based on clinical presentation and radiological techniques. Compared to histopathological diagnosis, cytology had a sensitivity of 89.47%, specificity of 93.33%, positive predictive value (PPV) 95.04% and negative predictive values (NPV) 86.13% for epithelial metastatic cancer. The overall diagnostic test accuracy was 91.06%. For lymphoproliferative neoplasms cytology in comparison to histopathology had sensitivity 85.71%, specificity 91.18%, PPV 76.4% and NPV 95.04%. The overall diagnostic test accuracy was 89.81%. In both ways cytology is showing significant possibility to be used as a primary tool in detecting cancers. Conclusion: FNAC is a fast, reliable, and efficient method for diagnosing malignant lymphadenopathy. The cytological diagnosis can sometimes be accepted as the definitive diagnosis without further correlation with histopathology, especially in advanced malignancies and known primary malignancies.

The Impact of BMP-4 Tissue Expression on Progression and Survival in Breast Cancer.

Background: Bone morphogenetic protein -4 (BMP-4) plays important role in many aspects of carcinogenesis but is also involved in progression and metastasis of breast cancer where its precise role is yet to be elucidated. Objective: Since the majority of studies related to BMP-4 expression in breast cancer were conducted on cell lines of mouse models, we aimed to investigate BMP-4 tissue expression in primary human breast cancer and to correlate it with standard pathological factors for breast cancer, progression and survival. Methods: We analyzed immunohistochemical expression of BMP-4 in primary breast cancer tissue of 97 patients, correlated it with standard pathological factors for breast cancer and investigated its impact on progression and survival. Results: BMP-4 expression was positive in 74.23% breast cancer tissue specimens. We found that hormone positive breast tumors are more likely to show BMP-4 strong granular staining pattern (p<0.01; p=0.029, respectively). There was significant association between stage group and BMP-4 expression in order that stage III breast cancer group were predominantly BMP-4 positive tumors (p=0.046). Although the most common site of distant metastases in patients with BMP-4 positive tumors were bones, we found no significant association (p>0.05). Patients with BMP-4 positive breast cancer showed longer overall and progression-free survival, but the results did not reach statistical significance (p>0.05). Conclusion: The results of our study in some extent can confirm the current available data and suggest that the role of BMP-4 in breast cancer is ambiguous, acting both as tumor suppressor and tumor promoter in breast cancer. For final elucidation of its impact on survival and progression in breast cancer, multicentric studies on larger sample size are required.

Serum total prostate-specific antigen (tPSA): correlation with diagnosis and grading of prostate cancer in core needle biopsy.

Aim To investigate the impact of pre-treatment serum total prostate-specific antigen (PSA) level on prevalence of prostate carcinoma detection in prostate core needle biopsy, and its correlation with established prognostic factors. Methods Prostate needle biopsy samples of 115 patients with available pre-treatment serum total PSA (tPSA) level were analysed. For all cases where morphology alone was insufficient, immunohistochemistry was performed using p63, CKHMW and AMACR antibody panel in order to confirm or exclude the existence of prostate carcinoma. Results Statistically significant positive correlation between serum total PSA values and prevalence of finding prostate carcinoma in needle biopsy specimens was found (p=0.011), as well as in the case when the patients were classified into groups according to tPSA levels (p=0.028). Serum total PSA values and levels (level groups) showed significant positive correlation with Gleason score (p=0.029 and p=0.036, respectively) and Grade Group of prostate carcinomas (p=0.044 and p=0.046, respectively). Sensitivity of the screening test by using 4 ng/mL as cut off value for tPSA was 94.12% (CI: 80.32-99.28%), specificity 8.64% (CI: 3.55-17.00%), positive predictive value 30.19% (CI: 21.65-39.87%) and negative predictive value 77.78% (CI: 39.99-97.19%). Conclusion The increase of serum tPSA value increases the likelihood of finding prostate cancer on needle biopsy specimens. Due to such findings and its positive correlation with a grade of prostate cancer, our study indicates that tPSA can still be considered as a useful tool both in detecting and predicting aggressiveness of prostate cancer.

Correlation between numerical and categorical immunohistochemical score of Ki-67 and HER2 with clinicopathological parameters of breast cancer.

Aim To evaluate the relationship between numerical and categorical immunohistochemical score of Ki-67 and human epidermal growth factor of receptor 2 (HER2) with clinicopathological parameters of breast cancer (BC). Methods The study included 311 patients with invasive BC diagnosed at the Department of Pathology, School of Medicine in Sarajevo, Bosnia and Herzegovina, during the period 2015-2019. The expression level of Ki-67 and HER2 was detected by immunohistochemical analysis. Results The expression of Ki-67, as a numerical variable correlated significantly with tumour grade (p=0.025), progesterone receptor (PR) (p=0.034) and categorical score of HER2 (p=0.028). When Ki-67 was categorized into high (>14%) and low (≤14%) level groups, a statistically significant association was found between Ki-67 level groups and HER2 status (categorical and numerical) (p=0.001 and p=0.043, respectively), as well as significant negative linear correlation with PR (p=0.037). The expression of HER2, as a numerical variable, showed a statistically significant correlation with tumour grade (p=0.038), PR (p=0.025) and categorical Ki-67 (p=0.043). Categorical score of HER2 correlated significantly with age (p=0.025), histologic type (p=0.039), tumour grade (p=0.016), estrogen receptor (ER), (p=0.002) progesterone receptor (PR) (p=0.0001), and categorical and numerical value of Ki-67 (p=0.0001 and p=0.0001, respectively). Conclusion The results demonstrated that the categorical immunohistochemical score of HER2 provided a greater association with clinicopathological parameters than numerical score of BC. Furthermore, a slightly better correlation with clinicopathological parameters was shown by the numerical value than by the categorical score of Ki-67 by applying a cut-off value of 14%.

Immunohistochemical expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in invasive breast carcinoma.

Tissue inhibitor of metalloproteinase-1 (TIMP-1) is a natural inhibitor of matrix metalloproteinases (MMPs). Aim of this study was to assess the immunohistochemical expression of TIMP-1 in invasive breast carcinomas, and to examine its association with classical clinico-pathological parameters, oestrogen receptor, progesterone receptor and Her-2/neu protein expression. Immunohistochemistry was used to determine the expression of TIMP-1 on 38 paraffin-embedded breast tissue specimens - 18 with invasive ductal carcinoma, 10 with invasive lobular carcinoma, and 10 specimens from patients with fibrocystic breast disease. TIMP-1 protein was immunodetected in the carcinoma cells, fibroblasts and inflammatory cells of the stroma in 92,9%, 65,8%, and 65,8% of cases, respectively. TIMP-1 protein expression in carcinoma cells showed positive correlation with TIMP-1 protein expression in peritumoural fibroblasts (p=0,010). Positive peritumoural fibroblast TIMP-1 expression was associated with histological tumour type with higher frequency in ductal carcinomas (p=0,023). Negative association was found between TIMP-1 protein expression in carcinoma cells and HER-2/neu nuclear staining (p=0,005). TIMP-1 may be particularly useful as a predictive marker in breast carcinoma when evaluated along with HER-2/neu protein being a promising indicator of favourable prognosis in breast carcinoma.

Expression of Ki-67 and Estrogen Receptor Beta in Primary Cutaneous Melanoma as a Potential Indicator of Regional Lymph Node Positivity.

In the early stages of cutaneous malignant melanoma (MM), it is extremely difficult to predict adequately the risk from hematogenic and lymphatic metastasis. We investigate whether the immunohistochemical expression of Ki-67 and estrogen receptor beta (ERß) in cells of MM could predict the status of regional lymph nodes. A total of 55 tissue samples of primary cutaneous melanomas with known status of regional lymph nodes were retrospectively evaluated for Ki-67 and ERß expression by quantitative immunohistochemistry and then correlated with the status of regional lymph nodes and relevant clinicopathologic parameters. The ERß-positive expression was detected in 38 of 55 tumors (69.09%). The Clark level showed a strong correlation with ERß expression, as well as pT stage. All cases of MM showed Ki-67-positive expression and an elevated Ki-67 expression was strongly associated with increased Breslow thickness, Clark level, ulceration, lymphovascular invasion, number of mitosis, and pT stage. Logistic regression analysis showed that when ERß levels increase by 1%, the risk of positive lymph nodes decreases by 7% (odds ratio=0.930; 95% confidence interval, 0.87-0.99; P=0.036), and, when the Ki-67 expression increases by 1%, the risk of lymph nodes' positivity increases by 10% (odds ratio=1.108; 95% confidence interval, 1.02-1.19; P=0.009). Correlation between expression of Ki-67 and ERß and the status of lymph nodes has better prognostic significance than the relationship between melanoma thickness and the status of lymph nodes. Our study showed a significant prognostic value of Ki-67 expression in predicting the behavior of MM and the potential prognostic significance of ERß.

Dermal squamomelano-cytic tumor: neoplasm of uncertain biological potential.

We report a case of exceedingly rare cutaneous neoplasm with histological features of malignancy and uncertain biological potential. The nodular, darkly pigmented facial tumor with central exulceration, size 12 x 10 x 7 mm, of the skin 61-year-old man preauricular left was completely exised. Histologically tumor consists of atypical squamous cells, which express signs of moderate to significant pleomorphism, mitotically active, with foci forming of parakeratotic horn cysts ("pearls"). Characteristically tumor also consists of large number of atypical melanocytes with multifocal pattern, inserted between atypical squamous cells, and which contain large amount of dark brown pigment melanin. Immunohistochemically, squamous cells stain positively with keratin (CK116), melanocytes were stained with S -100 protein, HMB 45, and vimentin, but failed to stain with CK 116. To our knowledge this is the sixth reported case in world literature. The follow-up time of four years no evidence of recurrence or metastasis, similar all reported cases, but it is too short period in estimation to guarantee a benign course. However, it appears that this group of neoplasm may have different prognosis from pure squamous carcinoma or malignant melanoma.

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 (p<0,01), as well as combination of dosage and interval (p<0,001), while gender had no statistically significant influence on tested parameter (p>0,05). 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.

Testicular metastasis of gastrointestinal stromal tumor of the jejunum.

Gastrointestinal stromal tumors (GIST) are neoplasm of mesenchymal origin that usually begins in cells of the wall of the gastrointestinal tract. It can be benign or malignant. In this report, we have presented a case of malignant GIST with uncommon site of metastasis. This is of interest because of three reasons. Firstly, metastases to the testis are extremely rare. However, metastases to distally localized organs are not commonly associated with GIST, and finally, to our knowledge this is the first case of malignant GIST metastasis to the testis reported in the world.

Non-small cell lung carcinoma: cyclin D1, bcl-2, p53, Ki-67 and HER-2 proteins expression in resected tumors.

The aim of this study was to investigate expression of cyclin D1, bcl-2, p53, Ki-67 and HER-2 proteins in 14 cases of non-small cell lung cancer and to establish their correlation to classical clinico-pathological findings, and alleged prognostic value to estimate biological potential of tumor. Retrospective pilot study of the surgically treated non-small cell lung cancer biopsy specimen, paraffin embedded, used immunohistochemical method to demonstrate expression of cyclin D1, bcl-2, p53, Ki-67 and HER-2. Protein quantification was performed by the semi-quantitative method. Achieved results were correlated with classical clinico-pathological parameters, like tumor size, histological type, differentiation level, presence of vascular invasion and metastasis in regional lymph nodes. Out of 14 cases of non-small cell lung cancer, squamous cell carcinoma was found in 7 patients, giant cell carcinoma in 3, adenocarcinoma in 2, and 1 case of pleomorphic and mucoepidermoid carcinoma. Expression of cyclin D1 was not found, while expression of HER-2 and bcl-2 protein was established in one cases each. p53 expression was noted in 8 cases (57,1%). Statistically positive significant correlation (p<0,05) was found among: presence of lymphovascular invasion to tumor tissue and appearance of nodal metastasis; proliferation Ki-67 index and level of tumor differentiation, i.e. size of tumor. Other investigated parameters showed no significant statistically dependence. p53 expression was not correlated to any of the investigated parameters what might imply the possibility that there is an independent pathway of this protein expression. Negative expression of bcl-2 protein points out to possibility that it is not included into process of tumor apoptosis, as well as that proteins cyclin D1 and HER-2 are not included into processes of the tumor genesis. Since the proliferative activity of the tumor, measured by the expression of Ki-67, is correlated to the gradus and size of the tumor mass, Ki-67 protein can be of a prognostic value to determine biological potential of non-small cell lung cancer.

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 ductal infiltrative 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 ductal infiltrative 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 value. 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<0.0001). NM23 protein expression did not correlate with gender (p=0.115), tumour size (p=0.844), tumour grade (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.

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.

Immunohistochemical evaluation of the HER-2 protein in the infiltrative lobular breast cancer.

AIM OF THE STUDY: To investigate the correlation between the expression of HER-2 membrane protein and basic pathohistological parameters in cases of infiltrative breast cancer. MATERIAL AND METHODS: Sixty-nine cases of lobular infiltrative breast cancer were investigated. Mastectomy with a dissection of axillary's lymph nodes was performed in all cases. Upon standard procedure of formalin fixation, embedding in paraffin and examination of slides stained with hematoxillin-eosin, a semiquantitaive method of evaluation of immunohistochemical expression of the HER-2 protein has been performed in all tissue samples of the tumor. RESULTS: Majority of patients (91,3 %) were above 41 year-of-age. In the majority of cases (44,9 %) cancer's diameter ranged from 20-50 mm (pT2), with a moderate degree of differentiation (46,4 %), no signs of vascular invasion (50,7 %) and no metastases in axillary's lymph nodes (65,2 %). Evaluation of immunohistochemical expression of the HER-2 protein revealed that only the degree of tumor differentiation has been in statistically significant (p=0, 037) correlation with the intensity of the HER-2 protein expression. CONCLUSION: In cases of lobular infiltrative breast cancer, oncogenic effect of the HER-2 protein was associated with the degree of cellular differentiation, while it was not in correlation with other pathological parameters of poorer prognosis, such as the size of tumor, presence of vascular invasion and occurrence of metastases in regional lymph nodes.

Giant cell fibroblastoma in a 4-year-old boy: a case report and review of the literature.

Giant cell fibroblastoma (GCF) is a rare type of fibroblastic tumor, first described as a juvenile form of dermatofibrosarcoma. Although recurrences are common after local surgical resection, metastasis is not reported.We report a case of a 4-year-old boy with giant cell fibroblastoma, in which the neoplasm was characterized histologically by a proliferation of spindle-shaped cells intermixed with pseudovascular channels called "angiectold spaces". The spaces were lined by large cells with pleomorphic nuclei intermixed with multinucleated cells. Immunohistochemically, the tumor stained diffusely for vimentin and CD34, but negative for S 100 protein. Since the initial description in 1982, less than 100 cases of GCF have been reported. This patient's presentation is particularly interesting because present the first case reported in Bosnia and Herzegovina.