Background : Controversy exists regarding the topography of lymph vessels in breast cancer, their usefulness as prognostic factors and whether active lymphangiogenesis occurs within the tumour. The goal was to investigate the presence of intratumoural lymphatic vessels, the existence of lymphangiogenesis and their role in tumour dissemination. Materials and methods:  Lymphatic vessel distribution was investigated in 75 specimens of invasive breast carcinoma by immunostaining using a D2-40 antibody. Intratumoural and peritumoural lymphatic vessel density (LVD) was assessed using the Chalkley counting method and correlated with clinicopathologic parameters. Endothelial cell proliferation in lymphatic vessels was analyzed by dual-color immunohistochemistry with D2-40 and Ki-67. Results:  We demonstrated the existence of intratumoural lymphatic vessels in invasive breast carcinoma. Intratumoural LVD was significantly lower (p=0, 0001) compared to peritumoural. Decrease of intra and peritumoural LVD compared to fibrocystic breast disease was observed (p=0,002). The density of intratumoural lymphatic vessels was correlated with the expression of progesterone receptors in breast cancer (p=0,036). Intratumoural endothelial cell proliferation in lymphatic vessels was minimal. Conclusion: Intratumoural lymphatic vessels are present in breast cancer. High intratumoural LVD is correlated with the expression of the progesterone receptor and thereby it may possibly serve as an indicator of a low destructive potential of the tumour, and vice versa. Whether they are tumour induced and newly formed or not is beyond the scope of this study and does not change the fact that they are tumour-associated and do not constitute a risk factor for tumour metastasis. Key words: breast carcinoma, intratumoural lymphatic density, lymphangiogenesis, progesterone

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.

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 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.

Introduction: dermatoscopy is a non-invasive technique which allows us to explore and evaluate the structures of the epidermis, the dermo-epidermal junction and the papillary dermal layer in vivo. Cognition of the specific diagnostic patterns lead to a right clue and proper diagnosis suggestion. Dermatoscopy depends on the timely correct recognizing of dermatoscopic findings and features and is therefore terminated and limited by time input and by experience of a physician. Dermatoscopy gained a great role in general dermatology with its importance in early diagnostics of a malignant melanoma and has become a valuable tool for the diagnosis of a various infectious and inflammatory diseases, nail pigmentations, hair abnormalities and scalp disorders including ectoparasitic infestations, cutaneous/ mucosal infections, psoriasis. Patients and methods: investigations are provided by dermatoscopy equipment – Dermatoscope MoleMax II. Our study included 791 patients (490 women and 301 men), in which we recorded a total of 1670 lesions in the period from May 9, to May 13, 2011. Results: from the total number of lesions analyzed there were 944 melanocytic and 726 nonmelanocytic lesions. Within melanocytic lesions, histopathology confirmed 9 malignant melanomas. From nonmelanocytic lesions present were: seborrheic keratosis 307, actinic keratoses (precancerosis) 118, hemangiomas 77 and bacocelular skin cancer BCC 68. Discussion: dermatoscopy is a method of epiluminiscent microscopy that in the analysis of tumor skin changes has completely replaced the standard magnifying glass. Credibility of dermatoscopy is going from 70-90% and the dermatoscopy became an indispensable diagnostic tool in the analysis of tumor changes on the skin. Conclusion: the dermatoscopy is valuable tool in diagnostics of variety of skin disorders in the field of general dermatology.

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.

Tissue inhibitor of metalloproteinase- (TIMP-) is a natural inhibitor of matrix metalloproteinases (MMPs). Aim of this study was to assess the immunohistochemical expression of TIMP- in invasive breast carcinomas, and to examine its association with classical clinico-pathological parameters, oestrogen receptor, progesterone receptor and Her-/neu protein expression. Immunohistochemistry was used to determine the expression of TIMP- on  paraffi n-embedded breast tissue specimens  with invasive ductal carcinoma,  with invasive lobular carcinoma, and  specimens from patients with fi brocystic breast disease. TIMP- protein was immunodetected in the carcinoma cells, fi broblasts and infl ammatory cells of the stroma in ,, ,, and , of cases, respectively. TIMP- protein expression in carcinoma cells showed positive correlation with TIMP- protein expression in peritumoural fi broblasts (p=,). Positive peritumoural fi broblast TIMP- expression was associated with histological tumour type with higher frequency in ductal carcinomas (p=,). Negative association was found between TIMP- protein expression in carcinoma cells and HER-/neu nuclear staining (p=,). TIMP- may be particularly useful as a predictive marker in breast carcinoma when evaluated along with HER-/neu protein being a promising indicator of favourable prognosis in breast carcinoma.

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.

The aim of the study was to define the distribution of p53, bcl-2 and Ki-67 proteins in the inflammatory-regenerative and dysplastic lesions of the colon mucosa. The relationship between the presentation of p53, bcl-2 and Ki-67 proteins and the intensity of the inflammatory-regenerative and dysplastic lesions in the colon flat mucosa was investigated as well. Biopsy specimens from 270 patients were examined: 74 were classified as inflammatory-regenerative and 196 as dysplastic lesions (108 mild, 58 moderate, and 30 severe dysplasia). The expression of all three proteins was assessed on the basis of location, quantity, and intensity of immunostaining, by counting antigen positive cells, in comparison with normal mucosa and adenocarcinoma. p53 protein appears only in sporadic cases (6.6%) of severe dysplasia. Bcl-2 expression appears significantly (p<0.005) more often in cases of mild dysplasia (61.1%) compared to inflammatory-regenerative mucosa (14.8%). In cases of mild dysplasia, bcl-2 positive cells were spreading from the lower third to the middle third of the crypts. Bcl-2 expression was maintained through the stadiums of moderate and severe dysplasia (75.8%), where antigen positive cells were found all along the crypts. A significant increase (p<0.005) in the expression of nuclear protein Ki-67 was noticed in the stadiums of moderate (labelling index =26.3) compared to mild dysplasia (labelling index=16.7), and severe (labelling index=36.7) compared to moderate dysplasia, where the zone of cellular proliferation was widen along the whole crypt length. In the process of the development of epithelial dysplasia in the flat mucosa of colon a degree of the gene p53 alteration is low and appears only in sporadic cases of severe dysplasia. Mutation of the bcl-2 gene is involved in the genesis of the lesion but not in its progression to carcinoma. Increased expression of Ki-67 protein speaks in favour of an increased cellular proliferation which, together with the above mentioned mechanisms, is involved in the process of occurrence and progression of epithelial dysplasia in the flat mucosa of colon.

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.

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.

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.

Haemangiopericytoma is an uncommon tumour of vascular origin. We report a case of one of the rarer sites of this tumour in man: pelvic paravesical site. We report case of 47 years old man with pelvic hemangiopericytoma and discuss imaging studies and pathohystological findings. Although modern imaging techniques have provided useful information concerning the hypervascular and clearly demarcated appearance of this tumour which displaces but does not invade adjacent organs, its diagnosis can only be established by histology. Its degree of malignancy and its invasive potential are unclear. The risk of local recurrence and metastases in more than one half of cases justifies wide surgical excision, possibly combined with adjuvant radiotherapy, and long-term follow-up. That is to say, that hemangiopericytoma malignum pelvis is the very rare sites of this tumour and till now it is not reported in Bosnia and Herzegovina.

The complex craniofacial surgery of solitary bone plasmacytoma (SBP) of the skull base with excellent postoperative outcome was presented. This surgical management was result of the team approach and strategy of neurosurgeon (KD) and maxillofacial surgeon (TM). SBP of the skull base is very rare condition which should be treated by radical microsurgical resection and postoperative radiotherapy.

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.