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Zoltán Sápi

Publications and source records attributed to Zoltán Sápi.

18 recordsLinked to original sources

[Reclassification of gastrointestinal mesenchymal tumors].

A retrospective (1985-2005) multicentric evaluation of the pathological diagnoses of GIST (gastrointestinal stromal tumor) in Hungary was performed. A large cohort of 463 patients with abdominal mesenchymal tumors was reevaluated with the help of immunohistochemistry for CD117, CD34, desmin and S100. Prognostic groups have been established based on international criteria. Two hundred fifty five GISTs have been found in 245 patients during the evaluated period. Beside GIST, 81 leiomyogenic and 25 neurogenic tumors were the primary pathological diagnosis and in 74/255 cases the primary diagnosis was a benign tumor. In our cohort high-risk GIST cases were found to be the predominant. Based on our experience, in case of abdominal tumors of uncertain localization, immunohistochemical markers of CD117, CD34, S100 and desmin provide a proper tool for precise identification of the tumor entity including GIST.

Adult↗

Divergences in diagnosing nodular breast lesions of noncarcinomatous nature.

Nodular breast lesions of noncarcinomatous origin are often of fibroepithelial origin. They may cause classification problems when they are hypocellular or hypercellular; the latter setting may also raise the differential diagnosis of phyllodes tumors. Thirty equivocal nodular breast lesions were collected and one hematoxylin and eosin slide from each was assessed by six pathologists with special interest in breast pathology. The overall reproducibility of classifying these lesions into categories of fibroadenoma, phyllodes tumor or anything else was moderate (kappa value: 0.48). The lack of a uniform nomenclature was not felt disturbing for hypocellular lesions, but the discordant diagnosis of tumors resembling or representing phyllodes tumors was acknowledged to require intervention, such as more obvious implication of guidelines and quality assurance programs aiming at assessing diagnoses and prognostic parameters.

Adenofibroma↗

Her-2 oncogene amplification, chromosome 17 and DNA ploidy status in synovial sarcoma.

The treatment options for synovial sarcoma (SS) are very limited, though this type of sarcoma seems to be more heterogeneous than it has been traditionally considered. The present study investigates the Her-2 oncogene status of 20 cases of SS, to determine whether Her-2 amplification can be considered as a prognostic factor. Her-2 oncogene amplification was determined on smears (frozen material was used from our tumor bank in each case), using fluorescence in situ hybridization technique (dual color FISH with centromeric probe for chromosome 17 and specific probe for Her-2 oncogene). Moreover, protein expression was assessed by immunohistochemistry, and DNA ploidy status was measured using image analysis. We had 5 biphasic and 15 monophasic SSs, patients' age ranged from 13 to 68 years (mean, 39.8 years). Tumor size was larger than 5 cm in each case. Follow-up time ranged from 6 to 78 months (mean, 38.5 months). For statistical analysis the chi-square test was used. Her-2 oncogene amplification was found in three cases (15.0%) of 20 SSs. These cases proved to be 2+ positive by immunohistochemistry, but massive amplification, characteristic of a subset of breast carcinomas, was not observed. Her-2 oncogene amplification was significantly associated with a lower risk of developing metastasis (P<0.05) (none of the 3 amplified cases had metastases), while no association was found with recurrence. Six cases proved to be aneuploid and 14 were diploid, but no association was found between Her-2 amplification status and ploidy, and between ploidy status and metastasis or recurrence. Our results emphasize and confirm that Her-2 oncogene amplification is a rare event in SS, but the small subset of SS with Her-2 amplification has a better overall prognosis. Furthermore, this may open a theoretically new treatment possibility with Trastuzumab for Her-2-amplified cases of SS.

Adult↗

Gastrointestinal stromal tumors: a clinicopathologic and immunohistochemical study of 136 cases.

The clinicopathologic features of 136 gastrointestinal stromal tumors were analyzed. The tumors occurred in 60 women and 76 men, ranging in age from 19 to 88 years (median 59 years, mean 59.2 years). Sixty-one cases arose from stomach, 38 from small intestine and 11 from colon or rectum. Abdominal cavity was indicated as tumor site in 10 cases, but the extra-gastrointestinal origin using strict criteria was not proved. Four locally recurrent cases and 12 metastatic samples were also included. The primary and recurrent tumors ranged in size from 0.5 to 30 cm (mean 8.3 cm). The large number of high-grade cases (85 of 112 classifiable) is alarming and emphasize the importance of oncology care. Histologically, ninety-two cases were classified as spindle cell while 11 as epithelioid GIST. Mixed cellularity was seen in 33 cases. Skeinoid fibers were present in 14 and coagulation necrosis in 40 primary cases. Ulceration observed by microscopic examination was common (36 of 110 cases, 32.7%), explaining the clinically frequently observed gastrointestinal bleeding. Unusual histological features such as stromal hyalinization and nuclear palisading were present in 30 and 27 cases, respectively. Immunohistochemical CD117 (c-kit) positivity was documented in 133 cases. Three cases with CD117 negative results were included, because their morphology was most consistent with GIST and immunohistochemical reactions excluded the possibility of other neoplasms. CD34 positivity was seen in 70%, alpha-smooth muscle actin positivity in 39.6% of examined cases. Only one case showed desmin reactivity and seven had S100 positive tumor cells. For h-caldesmon 39 cases proved to be positive (60.9% of the tested cases).

Actins↗

[Chronic necrotizing pulmonary aspergillosis in an immunocompromised patient].

A case with chronic necrotizing pulmonary aspergillosis that was mimicking the radiomorphology of malignant tumor was reported. The patient was admitted to hospital with progression of a left upper lobe infiltrate which was known and under regular observation for 8 years, and haemoptoe. Computer tomography scan showed a spiculated abnormality in the left upper lobe with mediastinal lymphadenomegaly. Based on this finding pulmonary malignancy was suspected and, therefore, the patient was referred to surgical intervention. The post surgical histology revealed aspergillus in the specimen. Since signs of vascular invasion could not be detected microscopically and the disease developed in immunocompromised patient (due to diabetes mellitus and long term steroid treatment) the clinical condition was determined as chronic necrotizing aspergillosis. It is very likely that the pathogen infected the patient during his daily work in a bakery. The present paper also summarizes the clinical aspects, differential diagnosis and therapy of different forms of pulmonary aspergillosis with emphasis on chronic necrotizing pulmonary aspergillosis.

Adrenal Cortex Hormones↗

Partial protection against dextran sodium sulphate induced colitis in histamine-deficient, histidine decarboxylase knockout mice.

OBJECTIVES: Chemically induced mucosal inflammation in animal models is a suitable tool for studying factors in the pathogenesis of inflammatory bowel disease. The aim of this study was to determine whether absence of histamine has an effect on the development of experimental colitis. METHODS: Histamine-deficient, histidine decarboxylase (HDC) knockout Balb/c mice and genetically identical control animals with intact HDC were studied. Colitis was induced by the administration of 2% dextran sodium sulphate in drinking water. Mice were killed after 5 days and disease activity assessed by clinical, histologic, and immunohistologic parameters. Bacterial components of stool were examined. RESULTS: Clinical disease activity was higher in the mice with intact HDC (disease activity index, 2.21) than in the histamine-deficient knock-out mice (1.88). Histologic findings were similar in the two groups. On day 5, the inflammation score of the HDC sufficient group was 5.25 (+/-1.055) and the crypt score was 5.00 (+/-1.128). The scores in the HDC knock-out group were 4.667 (+/- 0.707) and 4.667 (+/- 0.86), respectively. There was a significant difference in the number of interleukin (IL-10)-producing lymphocytes in colon mucosa. Large numbers of IL-10-positive lymphocytes were observed in wild type mice both those with DSS induced colitis and untreated controls. Only sporadic IL-10 positivity was found in histamine-deficient mice. Significant differences were found in the composition of the fecal bacterial flora between the two groups. CONCLUSION: The reduced number of IL-10-positive lymphocytes in the intestinal mucosa of histamine-deficient, histidine decarboxylase knockout mice and the altered fecal bacterial flora in these animals suggest that histamine may play a role in the pathophysiology of inflammation in the colon of normal animals by upregulating local IL-10 production and stimulating a local shift to Th2 response.

Animals↗

DNA ploidy and chromosome (FISH) pattern analysis of peripheral nerve sheath tumors.

BACKGROUND AND METHODS: 44 peripheral nerve sheath tumors (PNST) (27 schwannomas, 9 neurofibromas and 8 malignant peripheral nerve sheath tumors (MPNST)) were analyzed to determine DNA ploidy pattern and to clarify the conflicting data in the literature concerning this topic (whether benign PNSTs are aneuploid or not). For further insight we analyzed 6 schwannomas, one atypical neurofibroma and five MPNSTs by fluorescence in situ hybridization (FISH) technique using centromeric chromosome probes (7, 17 and 18) and automatic image analysis station, Metafer 4. RESULTS: Benign schwannomas (including the problematic variants as ancient, cellular, neuroblastoma like and multiplex schwannomas) could be characterized by euploid-polyploidisation and by their 4c peak height value which was usually more than 10% of total cell number measured. These characters were not found among neurofibromas and MPNST-s. FISH analysis revealed and confirmed that the 'normal' euploid-polyploid cells are mainly eusomic-polysomic containing two, four, eight or sixteen signals for each chromosomes examined, but in a small proportion aneusomy was found among tumor cells of benign schwannomas (average: 2.58; range 1.33-3.44). In contrast, the atypical neurofibroma displayed marked aneusomy (18.44%) but it contained normal eusomic and polysomic cells too. Two diploid MPNSTs proved to be clearly aneusomic with trisomy of chromosome 17 and monosomy of chromosome 18. CONCLUSIONS: All these data suggest that ploidy pattern determination combined with FISH analysis may be a very useful supplementary tool for making a right diagnosis (to differentiate benign versus malignant schwannomas in problematic variants) and to understand better the malignant transformation in PNSTs.

Adolescent↗

Measuring telomerase activity in various human tumors in routine histology and cytology.

The aim of this study was to investigate telomerase reactivation, to quantitatively measure the human telomerase reverse transcriptase (hTERT) content and telomerase activity level (TA) in routine histological and cytological samples, and to examine the relationship between these values and morphological factors. We analyzed 86 (35 cytological and 51 histological) lesions which were divided into four main groups: renal tumors, soft tissue tumors, bladder-urine and thyroid gland lesions. The relative expression of mRNA of hTERT was examined by real-time polymerase chain reaction (RT-PCR). Almost all of the renal cell carcinomas showed TA. In soft tissue tumors no correlation was seen between TA and histogenesis, aggressiveness and prognosis. Concerning cytological material a very good correlation was seen between TA and the benign or malignant nature of these tumors (92.3% specificity and 60% sensitivity). Our results indicated that TA can be used beside histology also in cytologic samples, for example in the preoperative differential diagnosis of the thyroid gland lesions and urine samples. Telomerase reactivation may not play an important role in tumorigenesis in STT. Useful observations can be made by concentrating not only on one group of diseases or localization but the unselected analysis of routine diagnostic cases can also be of help both in diagnosis and therapy.

DNA, Complementary↗

[Severe nephrotic syndrome in a young man taking anabolic steroid and creatine long term].

Anabolic steroids and creatine supplementation is one of the current abuse used by body builders. It is less known that this combination beside of many deleterious effects may also cause renal damage. Authors report a case of diffuse membranoproliferative glomerulonephritis type I in a 22-year-old man who had been taking continuously methandion in a large quantity and 200 grams of creatine daily, and was sent to the outpatient nephrologic unit with typical clinical signs of nephrosis syndrome. They also call attention to the role of the continuously consumed creatine in the renal failure.

Adult↗

[Effect of imatinib treatment of gastrointestinal stromal tumors].

INTRODUCTION: Advanced malignant gastrointestinal stromal tumours are practically resistant to further radio- or chemotherapy. These tumours are characterized by the presence of C-KIT (a transmembrane tyrosin kinase) mutation which can be specified by CD117 expression. Imatinib (2-fenilaminopirimidine) is a selective inhibitor of the mutated C-KIT. AIM: The purpose of our study was to determine the potential antitumour effect of imatinib in patients with gastrointestinal stroma tumour patients. MATERIALS AND METHODS: An open, non-randomized trial was performed involving 38 patients each of which had received/metastatic disease associated with CD117 positivity. Consecutively daily doses of 400-600 mg imatinib was administered orally to the patients. The evaluation was carried out on 37 patients in a form of an interim analysis. RESULTS: After a 3-18 months observation period 1 complete, 19 partial remissions and 10 static diseases could be registered (78%), in association of only grade 1-2 toxicity. CONCLUSIONS: The imatinib treatment improved the quality of life of the patients with gastrointestinal stroma tumour and their life expectancy became considerably prolonged. Further follow-up of the patients as well as design of a prospective, randomized trial on a larger patient material is urgently needed.

Adult↗

[FISH diagnostics].

For over two decades banding has remained the "gold standard" of cytogenetic analysis, providing the first genome-wide screen for abnormalities. However, conventional cytogenetic banding techniques are limited to the detection of rearrangements involving more than 2 Mb of DNA. In addition,the identification of de novo unbalanced chromosome rearrangements provides a particular challenge for chromosome banding to decipher. In recent years a number of techniques based on FISH have evolved, all of which complement the conventional banding approaches and which have steadily increased the accuracy of cytogenetic diagnosis. FISH is now the method of choice because of the increased sensitivity, and speed with which it can be applied to a variety of cellular targets. In this article we try to highlight the technical aspects of FISH and the practical application of this technique on different tumors (soft tissue tumors, breast carcinomas, renal cell carcinomas, bladder tumors and germ cell tumors).

Breast Neoplasms↗

Expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tissue in correlation with adipocyte cell volume, serum TNF-alpha, soluble serum TNF-receptor-2 concentrations and C-peptide level.

OBJECTIVE: The aim of the study was to evaluate the expression of tumor necrosis factor (TNF)-alpha protein in the subcutaneous and visceral adipose tIssue in correlation with adipocyte cell Volume, serum TNF-alpha, soluble TNF-receptor-2 (sTNFR-2) and indirect parameters of insulin resistance in overweight/obese and lean healthy persons. DESIGN: A cross-sectional case-control study was used. PATIENTS: Twenty-eight overweight/obese probands with normal glucose tolerance (BMI>27 kg/m(2)) and 15 lean people (BMI<25 kg/m(2)), all of them undergoing planned surgical operation, participated in the study. METHODS: Two to four grams of subcutaneous and visceral adipose tIssue were removed and studied using semi-quantitative immunohistochemical staining of the TNF-alpha protein. Serum TNF-alpha, sTNFR-2 (ELISA) and fasting C-peptide (RIA) were measured. RESULTS: TNF-alpha protein was expressed in adipocytes of both depots. The expression was evaluated visually and found to be greater in the obese patients. Significantly higher serum TNF-alpha (5.58+/-0.87 pg/ml vs 4.21+/-0.55, mean+/-s.d., P<0.01, Mann-Whitney) and sTNFR-2 levels (7.84+/-3.56 ng/ml vs 4.59+/-1.35, P=0.005) were found in the obese subgroup in correlation with the fasting C-peptide level (r=0.49, P=0.003; and r=0.74, P=0.001) and the C-peptide/ blood glucose ratio (r=0.47, Spearman, P=0.005; and r=0.70, P=0.001). The cell Volume of both adipocyte depots was found to have a significant positive correlation with serum TNF-alpha and sTNFR-2 levels in the total group of patients (subcutaneous: r=0.52, P=0.0003; r=0.69, P<0.0001; visceral: r=0.65, P<0.0001; r=0.63, P<0.0001) and in both subgroups. CONCLUSIONS: Adipocyte cell Volume of both the subcutaneous and visceral fat depots may be determinants of TNF-alpha, sTNFR-2 production and obesity-linked insulin resistance.

Adipocytes↗

The investigation of galectin-3 in diseases of the thyroid gland.

OBJECTIVE: Malignant tumors of the thyroid gland exhibit a variety of histopathologies and clinical behavior. Immune markers are gaining more and more importance in diagnostic pathology, especially in the differential diagnostics and in the grading of thyroid gland tumors. DESIGN: The Authors investigated the immunohistochemical reaction of galectin-3 (gal3) in patients with various thyroid gland diseases. They tested the diagnostic value of gal3 in determining the benign or malignant nature of various lesions, especially in lesions of follicular origin, because previous results have indicated nearly 100% specificity and sensitivity in this regard. METHODS: Gal3 immunoperoxidase reaction was carried out on 91 sections of thyroid gland samples fixed in formalin and embedded in paraffin. RESULTS: While gal3 expressed itself strongly and diffusely in papillary carcinomas (19 of 20 cases), in other malignant lesions it showed weaker, focal or variable positivity. Focal positivity was found in four of 19 follicular adenomas, and negativity was found in three of 10 follicular carcinomas. In all cases of inflammation a focal positivity was observed (eight of eight cases). All nodular goiter and normal thyroid tIssue were negative (25 of 25 cases). CONCLUSIONS: Based on our results, the gal3 immunohistochemical reaction seems to be reliable in the diagnosis of papillary carcinomas. However, in the case of solitary thyroid nodules and follicular lesions, although it is still a useful supplementary marker, it is not of absolute value (as stated in previous studies) in determining whether a tumor is benign or malignant.

Adenoma↗

Diagnosis of soft tissue tumors by fine-needle aspiration with combined cytopathology and ancillary techniques.

The diagnosis of mesenchymal neoplasm by fine-needle aspiration biopsy (FNAB) has presented a diagnostic challenge. Most reports claim an accuracy approaching 95%, but while they distinguish benign and malignant lesions, the most problematic group, the intermediary malignant group, is omitted. The purpose of this study was to determine whether rapid cytologic diagnosis of soft-tissue tumors could guide surgeons in therapeutic decisions without the need for a tissue biopsy. Ninety-four FNA cytologic specimens were examined by the National Soft Tissue Consortium of Hungary and compared with the corresponding histology. Ordinary lipomas were excluded. Morphologic evaluation was supplemented by ancillary techniques such as fluorescence in situ hybridization (FISH), DNA cytometry, and immunocytochemistry. From a practical clinicopathological point of view, the cases were grouped in the following categories: 1) tumors with definitive diagnosis: a) high-grade malignant neoplasms (high-grade sarcomas, metastatic carcinomas, lymphoma), b) tumors with precise histogenetic origin by cytogenetics, c) benign tumors; 2) tumors of questionable nature. In the first group there were 74 tumors: 22 high-grade sarcomas, six metastatic carcinomas, one malignant lymphoma, 16 malignant tumors in which the precise histogenetic origin could be established by cytogenetic studies, and 29 benign soft-tissue tumors other than lipomas. In the second group there were 20 tumors comprising benign and malignant soft tissue tumors of low grade, wherein the precise nature of the neoplasm could not be established with confidence on cytologic study, even using ancillary techniques. FNAB of soft-tissue tumors combined with ancillary techniques should be considered a viable diagnostic technique for therapeutic protocols. Although the second group is fairly large, we have reliable, well-characterized categories which provide great freedom for preoperative and surgical treatment, thus providing the best chance for healing.

Adolescent↗

Sarcomatoid renal cell carcinoma with foci of chromophobe carcinoma.

Both chromophobe carcinoma and sarcomatoid carcinoma of the kidney are rare. The former is characterized by a relatively good prognosis, while the latter is a highly aggressive tumor. Coexistence of the two components in one renal tumor, which has been reported only rarely, is therefore paradoxical. Both sarcomatoid and chromophobe renal carcinoma were diagnosed in a 52-year-old woman following nephrectomy and resection of metastases in the right lobe of the liver. She died of the disease two months after the first operation; only the sarcomatoid component of her tumor was seen in the liver metastasis and the recurrent carcinoma. Differences in phenotype, immunophenotype and DNA-ploidy patterns of the two components are reported. The intensive p53 staining observed only in the sarcomatoid area supports the role of the TP53 gene in the transformation of chromophobe renal carcinoma to sarcomatoid carcinoma.

Adenoma, Chromophobe↗

Spontaneously curing anaplastic carcinoma in the lymph node.

A well documented case of a spontaneously curing anaplastic carcinoma in lymph node is presented with a 16 year follow up. Reevaluation and detailed immunohistochemical examination confirmed the original diagnosis of anaplastic carcinoma. This is the first report of a spontaneously curing anaplastic carcinoma which raises the following questions: Was the tumor in the axillary lymph node a metastasis or a primary tumor? Does the anaplastic carcinoma demonstrate the same spontaneous regression characteristics as for example the neuroblastoma?

Journal Article↗

DNA Ploidy Pattern in Pure Seminomas.

Nuclear extract and image cytometry was used to determine the DNA ploidy pattern of 31 pure seminomas. At least 5-year but usually 10-year follow-up was available to compare the clinical outcome to the DNA ploidy pattern. In 24 cases (77.4%) the DNA indexes (DI) showed tetraploid (1,8 < DI < 2,2) pattern confirming the recent cytogenetic and flow cytometric DNA studies of others. However, in 7 cases (22,6%) the tumors were aneuploid. Out of these aneuploid cases 2 had two subpopulations and 2 had less than 1,8 DI. These latter cases (providing the loss of chromosomal DNA) had elevated AFP levels in serum that raises the question of nonseminomatous transformation without any morphological evidence. Usually, the aneuploid cases had worse prognoses but there was no significant difference. Because of the small number of aneuploid cases wider clinicopathologic studies are required to confirm our results.

Journal Article↗