[Angiomyolipoma of the liver]. / Angiomiolipoma pecheni.

Angiomyolipoma of the liver is an extremely rare neoplasm, the number of reported cases of this disease is only about 600 worldwide. Morphological criteria for neoplasm verification present difficulties due to low occurrence and complexity of differential diagnostic search. In this regard, this observation is of interest to pathologists and physicians. A special feature of this tumor is the presence of three components: adipose, vascular and muscular with characteristic epithelioid cells. The article presents the clinical and morphological characteristics of liver angiomyolipoma in a 40-year-old woman. The diagnosis was confirmed by immunohistochemical study: a positive reaction with HMB45, Melan A, SMA, desmin, CD31, CD34; proliferative index was more than 25%.

[Fibromyxoid sarcoma of maxilla]. / Fibromiksoidnaia sarkoma verkhnei cheliusti.

The paper presents literature review and clinical case of patient with fibromyxoid sarcoma of maxilla illustrating diagnostic difficulties and efficacy of multidisciplinary treatment approach.

[ Spectrum of oncogene mutations is different in melanoma subtypes].

Melanoma is the most lethal malignancy of skin, which is comprised of clinically relevant molecular subsets defined by specific "driver" mutations in BRAF, NRAS, and KIT genes. Recently, the better results in melanoma treatment were obtained with the mutation-specific inhibitors that have been developed for clinical use and target only patients with particular tumor genotypes. The aim of the study was to characterize the spectrum of "driver" mutations in melanoma subtypes from 137 patients with skin melanoma and 14 patients with mucosal melanoma. In total 151 melanoma cases, the frequency of BRAF, NRAS, KIT, PDGFRA, and KRAS mutations was 55.0, 10.6, 4.0, 0.7, and 0.7%, respectively. BRAF mutations were found in 69% of cutaneous melanoma without UV exposure and in 43% of cutaneous melanoma with chronic UV exposure (p=0.045), rarely in acral and mucosal melanomas. Most of melanomas containing BRAF mutations, V600E (92%) and V600K (6.0%) were potentially sensitive to inhibitors vemurafenib and dabrafenib. NRAS mutations were more common in cutaneous melanoma with chronic UV exposure (26.0%), in acral and mucosal melanomas; the dominant mutations being Q61R/K/L (87.5%). KIT mutations were found in cutaneous melanoma with chronic UV exposure (8.7%) and mucosal one (28.6%), but not in acral melanoma. Most of KIT mutations were identified in exon 11; these tumors being sensitive to tyrosine kinase inhibitors. This is the first monitoring of BRAF, NRAS, KIT, PDGFRA, and KRAS hotspot mutations in different subtypes of melanoma for Russian population. On the base of data obtained, one can suppose that at the molecular level melanomas are heterogeneous tumors that should be tested for "driver" mutations in the each case for evaluation of the potential sensitivity to target therapy. The obtained results were used for treatment of melanoma patients.

[Immunohistochemical study of adhesive molecules Her-2/neu in nonendometrial carcinoma of corpus uteri].

46 cases of nonendometrial carcinoma of the corpus uteri have been studied. The expressions of E-cadherin, alpha and beta-catenins were detected by immunohistochemical method. The high level of studied markers expression was founded out in clear cell carcinoma, whereas the less expression was detected in the corpus uteri of patients with serous, papillary, undifferentiated and mixed cancer. The absence of E-cadherin, alpha and beta-catenins complex expression correlated with unfavorable clinic-morphological features of carcinoma.

[Clinico-morphological properties and surgical treatment results in retroperitoneal liposarcomas].

The separate clinico-morphological features of nonorganic retroperitoneal liposarcoma (NRL) and their prognostic value were studied in 200 patients. The type of primary NRL is histologically erentiated in 65.5%, myxoid in 16.1%, dedifferentiated in 9.2%, pleomorphic in 4.6% and mixed in 2.3%. There is a positive elation between overall survival, lyposarcoma hystologic type < 0.007) and completeness of tumor resection (p < 0.0008). Differentiated and myxoid NRL with cell volume less than 5.0% are characterized by better prognosis. Myxoid NRL with cell volume more than 5.0%, dedifferentiated and pleomorphic NRL types are unfavorable prognostic factors. Radical surgical resectio leads to 5-year and 10-year overall survival of 57.5% and 7.8%. Palliative surgery lead to worse results with 3-year and 5-year overall survival of 50.0% and 31.8% respectively. Therefore, the most important prognostic factors in NRL are histological type and completeness of resection.

[Morphological characteristics and prognostic criteria for gastrointestinal stromal tumors].

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract. Analysis of GIST morphology is necessary for selection of primary patients with the high risk of tumor progression for adjuvant treatment with gleevek following complete gross resection of KIT (CD 117)-positive GIST. In this study we've analyzed morphological parameters and survival of 120 GIST patients before target therapy. According to risk stratification of primary GIST by tumor location, size and mitotic index (mitoses per 50 visual fields) 44% of gastric GISTs, 87,5% of small bowel GISTs and 100% of rectum GISTs have been classified as high risk group. There was no significant difference between survival of patients with different type of GIST, Ki-67 proliferative index and presence of necrosis.

[Gastrointestinal stromal tumours: clinico-morphological features, pathogenesis and modern treatment strategies].

Gastrointestinal stromal tumours (GIST) are the commonest mesenchymal tumours of gastrointestinal organs accounting for 1-3% of all gastrointestinal neoplasms and almost 5% of all soft tissue sarcomas. Most GIST (95%) express transmembrane receptor KIT or CD117, CD34 (70%), vimentin (80%), specific smooth muscle and neurogenic markers (with different frequency). Up to 85% of the stromal tumours have mutations in the KIT gene (exones 9, 11, 13, 17) and 3-18% in the PDGFRA (platelet-derived growth factor receptor-alpha) gene (exones 12, 14, 18). Mutations are absent in 5% of KITand PDGFRA genes. Mutational status, mitotic index, size and location of the tumour are the most informative criteria for the choice of treatment strategy and prognosis of the disease.

[Unilateral renal tumor in a child: nephroblastoma concurrent with a rare form of (translocation?) renal-cell carcinoma].

The paper describes a rare case of a renal composite tumor in a two-year-old girl who has nephroblastoma and renal-cell carcinoma of alveolar-tubular structure with focal expression of pancytokeratin AE1/AE3, cytokeratins 7 and 20, EMA, vimentin, CD10, MELAN A, p 504 S, E-cadherin, most likely, carcinoma with Xp.11.2 translocation.

[Study of a role of the expression of a transmembranous CD117/C-Kit receptor in the progression of uveal melanomas].

The authors studied the expression of the protooncogen receptor involved in the regulation of major cell cycle processes in uveal melanoma. The studies performed by a highly sensitive immunohistochemical technique. The findings have allowed the authors to state that the membranous CD117/C-Kit receptor plays an important role in the progression of uveal melanomas. It is suggested that the use of the new drug Glivec is promising in treating uveal melanoma.

[Study of the expression of embryonal choroidal tissue-specific markers].

The authors used the human embryonal eye to conduct immunohistochemical studies employing the tissue-specific markers of the melanocytic series (HMB45, tyrosinase, melanin A, and MITF) and neuronal differentiation (S100), as well as the markers of intermediate and muscular filaments (vimentin, desmin, smooth muscle actin). The nature of antigen expression was analyzed in different structures and portions of the vascular tract of the eye. The findings unveil the possibility of differentiating the vascular tract tumors of various genesis and their sites, by applying a plate containing the above markers.

[Diagnosis of pigment-free optic tract tumors: clinical and morphoimmunohistochemical aspects].

The authors present the results of comparison of clinical, instrumental and histological, immunohistochemical and electron microscopic data on two pigment-free ciliochoroidal tumors. Differential diagnosis was made at each of the above stages of diagnosis. There is evidence that despite the similarity of the clinical syndrome, the spindle-cell type of the histological structure of both tumors, the latter were of various histogenesis. This was confirmed by the results of immunohistochemical and electron microscopic studies. Retrospective analysis of the data of immunohistochemical and echographic studies revealed the distinctive signs that could differentiate these two types of tumors at the stage of clinical and instrumental diagnosis.

[c-Kit and PDGFRA mutations and clinico-morphological features of gastrointestinal stromal tumors].

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the digestive tract. Inherent overexpression of receptor tyrosine kinase KIT (CD117) and mutations in c-Kit or PDGFRA genes are highly significant prognosticators. A first Russian investigation of c-Kit and PDGFRA mutations in GIST was carried out in 60 patients. c-Kit mutations were identified in 83.3% (50/60), the most frequent being mutations in c-Kit exon 11 (73.4%, 44/60). Among them, different mutations were identified in the 5'-end of c-Kit exon 11 in 37 GISTs. Duplications in the 3'-end of c-Kit exon 11 were reported in 7 tumors. Mutations in c-Kit exon 9 (73.4%, 44/60) were found in 5 tumors (8.3 3%, 5/60) while mutations in c-Kit exon 13 (0%, 44/60) and 17 (1.7%, 1/60) were rare. PDGFRA mutations in exon 18 were identified in (8.3 3%, 5/60). Substitution D842V occurred only in one gastric epithelioid-cell GIST. The remaining PDGFRA mutations contained deletions with aminoacids 842-846. There were no c-Kit and PDGFRA mutations in five tumors. Our findings point to a significant correlation between c-Kit and PDGFRA mutations, on the one hand, and tumor site and histological pattern, on the other. Hence, c-Kit and PDGFRA mutation detection should be used as an additional prognosticator for efficacy of target therapy.

[Gastrointestinal stromal tumor of the esophagus].

The paper describes a rare case of a stromal tumor of the esophagus in a 68-year-old male who was initially diagnosed as having esophageal leiomyoma after biopsy and study of a surgical material. Stromal tumour could be diagnosed by immunohistochemical (positive expression of oncomarkers; CD117, CD34, vimentin, CD99, and GFAP) and molecular genetic (real-time PCR) studies. This case confirms that it is necessary to use an immunohistochemical study in patients with spindle-cell tumors of the gastrointestinal tract.

[Female genital tract polyneoplasia: primary multiple neoplasms or metastases?].

The analysis of 49 cases of synchronous and metachronous malignant mucinous tumors of the colon (rectum) and ovaries in the patients treated in 1990 to 2004 again has confirmed the data that metastatic ovarian cancer occurs from a primary focus in the colorectal region. Immunohistochemical studies (using cytokeratin 7 and cytokeratin 20) may be used in the differential diagnosis of ovarian mucinous ovarian carcinoma from metastatic colonic mucinous tumors.

[Immunohistochemical diagnosis of metastases of small round cell carcinomas with undetected primary focus].

17 small round cell tumors of unkown primary site were studied. The main location was lymph nodes and brain. Immunohistochemical study was performed. One of the following diagnosis was obtained in 14 cases (82.4%): small cell carcinoma, Merkel cell carcinoma, melanoma, Ewing sarcoma family tumor. In other three cases (17.6%) tumor histogenesis was not determined definitively.

Phosphorylated Akt1 in human breast cancer measured by direct sandwich enzyme-linked immunosorbent assay: Correlation with clinicopathological features and tumor VEGF-signaling system component levels.

Protein kinase B (Akt) plays a major role in the regulation of breast cancer growth, survival, hormone, drug and radiosensitivity, but the clinical value of its expression and activation in human tumors is unclear. Activated Akt1 (pAkt1) expression was quantified in a series of 46 breast cancer and adjacent mammary gland samples by a direct Path-Scan PhosphoAkt1 (Ser473) sandwich ELISA kit. VEGF, sVEGFR1 and sVEGFR2 levels were measured simultaneously by standard ELISA kits. Forty-nine percent of the tumors had an increased pAkt1 level as compared to adjacent tissue. pAkt1 levels were significantly higher in stage IIb than in stage I-IIa tumors. The frequency of pAkt1 elevation was positively associated with tumor size and malignancy grade. pAkt1 was also twice as frequently increased in PgR-negative as in PgR-positive tumors, while its mean level was significantly higher in ER-positive than in ER-negative tumors. VEGF, sVEGFR1 and sVEGFR2 were increased in 73-85% of the tumors, but no associations with most clinicobiological factors and pAkt1 level were found. In conclusion, activation of Akt1 is not associated with VEGF signaling protein expression in breast cancer but is related to tumor size, grade of malignancy, and steroid receptor status.

[Morphological characteristics of stromal gastrointestinal tumors].

Stromal tumors are singled out from smooth muscle and neurogenic neoplasms into a special group due to differences in CD117 expression caused by mutation of c-kit gene. Out of 57 stromal tumors, 37 (64,9%) located in the stomach, 17 (29,8%) in the small intestine and 3 (5,3%) in the colon. Immunohistochemically, all the tumors expressed CD117 and vimentine. Smooth muscle actin was found in 82% tumors, S-100 protein in 75%, neuron-specific enolase in 66% cases. Malignant tumors were in 93% cases, and in 7% benign. Metastases were observed in 47.7% cases, recurrences in 14%. The liver was most frequent site of metastases (88.9%), peritoneum (51.9%). 21% patients died of progression of the underlying disease during the follow-up of 6-60 months.

[Tentative results of using 99mTC-methoxyisobutyl isonitrile in predicting the effect of preoperative chemotherapy for locally advanced breast cancer].

The investigation was concerned with use of 99mTc-methoxyisobutyl isonitrile (99m Tc-MIBI)-assisted prognosis for chemotherapy of locally-advanced breast cancer based on the assessment of 99m Tc retrieval from primary tumor in 26 patients. 99mTc was administered in the course of two-phase scintigraphy of the breast prior to chemotherapy. The dynamics of accumulation and withdrawal from tumor was identified. In view of the absence of any correlation between accumulation and chemotherapy efficacy, one was established between high rates of label withdrawal, on the one hand, and lack of pathomorphosis, on the other, while medium and low rates were associated with marked pathomorphosis in 44 and 50%, respectively (p < 0.05).