Background and objectives: In patients with colorectal cancer (CRC), heterogeneous expression of Mismatch repair (MMR) proteins can manifest itself in several different forms and is not such a rare phenomenon. Therefore, it is very important to recognize the nuclear expression of MMR proteins of different MMR status in order to avoid false positive or false negative results. The aim of this study was to determine the frequency and distribution of heterogeneous expression of MMR proteins in patients with stages II and III of the disease as well as its association with clinical, demographic and pathological characteristics of CRC in relation to proficient and deficient expression of MMR proteins. Material and Methods: The study included 104 cases of colorectal cancer obtained from surgical colectomy material in stages II and III of the disease. Results: From a total of 104 patients with colorectal cancer, immunohistochemical analysis of the expression of all four MMR proteins showed that heterogeneous expression of MMR proteins (as well as deficient immunoreactivity of tumor cells) was present in 12 cases, while proficient expression of MMR proteins was detected in 80 tumors. Conclusions: Our study showed that the only independent predictors of the loss of MMR protein expression were younger patient age and right-sided anatomical location of the tumor. The study also established the existence of heterogeneous expression of MMR proteins in a non-negligible percentage of CRCs (11.5%), where heterogeneous nuclear expression of MMR proteins was described in several different forms.

Background/Aim. Mammary phyllodes tumors (MPT) are uncommon fibroepithelial (biphasic) neoplasms whose clinical behavior is difficult to predict on the basis of histological criteria only. They are divided into benign, borderline malignant and malignant groups. Sometimes it appears difficult to distinguish these tumors from other types of soft tissue sarcomas. Because of the relatively scant data on the role of biological markers in MPT histogenesis, we have decided to undertake the following study, trying to shed more light on the issue by investigating the following elements that make up MPT: their histological patterns, biological behavior, enzymohistochemical, histochemical and immunohistochemical characteristics (ICH) together with the mast cell analysis. Methods. We examined the biopsy material of 35 MPT in our laboratory. Enzymohistochemistry was performed on frozen sections (method of Crowford, Nachlas and Seligman). The used methods were classical hematoxylin-eosin (H&E); histochemical Massontrichrome, Alcian-blue, Periodic acid Schiff and immunohistochemical LSAB2 method (DacoCytomation). Ki-67, ckit, vimentin, estrogen receptor (ER), progesterone receptor (PR) and Her-2 oncoprotein immunohistochemistry was performed on all tumors. Results. The patients were ranged per age from 30-62 years (mean 43.3 years, median 39 years). A total of 35 cases of MPT were included: 20 benign (57%), 6 borderline malignant (17%) and 9 malignant (26%). Twenty-two patients (62.8 %) underwent segmental mastectomy, while 13 (37.2%) had total mastectomies. Twenty-eight patients had negative surgical margins at original resection. The mean size of malignant MPT (7.8 cm) was larger than that of benign MPT (4.5 cm). Significant features of the malignant MPT were: stromal cellularity, stromal cellular atypism, high mitotic activity, atypic mitoses, stromal overgrowth, infiltrative tumor contour and heterologous stromal elements. Benign MPT showed strong enzymohistochemical Leucine Amino Peptidase (LAP) activity in both epithelial and stromal components while it was weak or absent in the epithelial parts of the malignant tumors. Acid mucopolysacharides were present in the stromal component of all types of these tumors. Benign MPT had a lower Ki-67 than did borderline malignant MPT (4 versus 28). Malignant MPT had a greater than 8-fold higher Ki-67 activity than did benign tumors (35 versus 4). Intracytoplasmatic c-kit expression was associated with a pathological diagnosis of malignant MPT, correlating with increasing grade (p < 0.05). In hypercellular stroma of borderline malignant and especially malignant forms of MPT, high activity of ER in mast cells was confirmed. Oncoprotein Her-2 activity, mostly in epithelial components, correlated with the degree of malignant progression of MPT (p < 0.05). Conclusion. Besides the well-known malignant features additional parameters have been found to be high Ki-67 and ckit stromal expressions, and weak LAP activity in the epithelial part of malignant MPT, as well as mast cells with a high expression of ER.

Gastrointestinal stromal tumors (GISTs) represent a distinct and the most important subset of mesenchymal tumors of the gastrointestinal (GI) tract GISTs occur throughout the GI tract but are usually located in the stomach and small intestine. The cellular origin, differentiation, nomenclature and prognosis of GISTs are controversial. Because GISTs, like the interstitial cells of Cajal, the GI pacemaker cells, express CD117 (c-kit protein), the origin of GISTs from the Cajal cells has recently been suggested. GISTs are also known for their wide variability in clinical behavior and for the difficulty to determine their malignant condition The most reproducible predictors of malignancy are mitotic count >1-5 per10 high-powered fields (HPF), size >5 cm, tumor necrosis, infiltration and metastasis to other sites. However, some tumors with mitotic activity <1/10 HPF may metastasize indicating some uncertainty in malignant potential of GISTs, especially those larger than 5 cm. Recently, mutations in c-kit gene (exon 11) preferentially occur in malignant GISTs and may be a clinically useful adjunct marker in evaluation of GISTs. In conclusion, the strong CD117 expression mostly defines primary GI mesenchymal tumors as GIST. Specific identification of GIST may become clinically important if therapies targeting the c-kit tyrosine kinase activation become available.

Background. We presented an unusual case of adenoid cystic carcinoma (ACC) of the breast with multinucleated stromal giant cells (MSGCs). To the best of our knowledge, the occurrence of ACC with MSGCs has not been reported previously. MSGCs should be distinguished from other multinucleated giant cells in breast tumors. The histogenesis of MSGCs still remains obscure. In hope to elucidate the histogenesis of MSGCs, we used a broad range of antibodies. Case report. A 40-year-old woman presented with a palpable lump in the subareolar location of her right breast. Excision of the tumor was performed. At gross pathologic examination the tumor was 20 ? 15 ? 15 mm in size, redbrown and well circumscribed. The surgical margins were positive for carcinoma and skin-sparing mastectomy with axillary dissection was complited. Eighteen lymph nodes examined were uninvolved. Patohistological examination showed ACC with numerous MSGCs scattered within tumor stroma. Immunohistochemical studies indicated that MSGCs are probably derived from stromal fibroblasts. These cells showed strong reactivity only for vimentin. Staining for histiocytic marker (CD68), as well as for epithelial marker (cytokeratin), myoepithelial markers (S-100, ?- smooth muscle actin), vascular marker (CD34), hormonal receptors (ER, PR) and HER2 in MSGCs were negative. Conclusion. The presence of MSGCs should not alter the prognosis of an otherwise typical breast ACC.

Salivary gland tumors are neoplasms characterized by a high level of pleomorphism and histological overlap. One tumor may contain several cell types; therefore, it is necessary to include immunohistochemical staining, as well as morphometric analysis of tumor cells as prerequisites for an appropriate diagnosis. Our research included 120 tumors, such as pleomorphic adenoma, Warthin tumor, basal cell adenoma, myoepithelioma, adenoid cystic carcinoma, mucoepidermoid carcinoma, salivary duct carcinoma, polymorphous low-grade carcinoma and myoepithelial carcinoma. The aim of the study was to differentiate benign and malignant tumors based on the characteristics of nuclei. The expression of Ki67 and the morphometric nuclear parameters ? area, perimeter, Feret diameter, integrated optical density, circularity, and roundness, were analyzed. It was observed that the Ki67 proliferative index was statistically significantly higher in malignant tumors (P<0.001). Adenoid cystic carcinoma exhibited the highest value, whereas the lowest value was exhibited in basal cell adenoma. Morphometric analysis showed statistically significantly increased values of integrated optical density (P<0.001) and nuclear size parameters (P<0.05) in malignant tumors. The determination of the Ki67 proliferative index and morphometric analysis of the integrated optical density and area can differentiate benign from malignant tumors with high precision. The presented values suggest the obtained results as cut-off values.