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.

Early detection and treatment of preneoplastic lesions represents an obvious option to reduce morbidity and mortality from lung malignancies. Until now, radiological detection, sputum cytology, and autofluorescence have shown limited effectiveness as screening methods. Novel technologies such as Narrow Band Imaging (NBI) are showing promising results, but new studies are still needed to evaluate their use as screening methods. Together with early detection, adequate methods of lesion treatment, such as argon plasma coagulation, are needed. This case report concerns a 45-year-old man who was referred for bronchoscopy after his annual checkup. Using NBI technology, a preneoplastic lesion was identified, and treated using argon plasma coagulation. Our experience has shown us that both NBI screening and argon plasma coagulation are very promising, easily implemented, methods.

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 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.