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Biomedical subjects

M Bracko

Publications and source records attributed to M Bracko.

103 records · Page 6Linked to original sources

Predictive value of proliferation-related markers, p53, and DNA ploidy for survival in patients with soft tissue spindle-cell sarcomas.

In a retrospective study of 60 spindle-cell sarcomas of peripheral soft tissues, we evaluated the extent of immunostaining with antibodies against Ki-67, proliferating cell nuclear antigen, and p53 protein and flow-cytometric DNA ploidy, their relation to tumor location, depth, histologic type, size, mitotic rate, and extent of tumor necrosis, as well as their influence on survival. Although Ki-67-labeled nuclei were detected in only 41 tumors (68%) and their number varied from 1 to 50%, proliferating cell nuclear antigen immunoreactive nuclei were found in each tumor, with their number ranging from 20 to 99%. p53 Protein was found in 26 cases (43%), and its labeling ranged from 1 to 80%. Although Ki-67 labeling significantly correlated with mitotic rate, no correlation could be found between proliferating cell nuclear antigen or p53 labeling and any other variables studied. Thirty-eight percent of the tumors were diploid, and 64% were aneuploid. Factors that significantly reduced survival in univariate analysis were increasing size and depth of the tumor, the presence of necrosis, the National Cancer Institute grade, and a tetraploid/hypertetraploid DNA pattern. In multivariate analysis of 49 cases with complete information, only DNA ploidy pattern, tumor size, and tumor necrosis retained their independent prognostic significance.

Biomarkers, Tumor↗

Familial occurrence of small-cell carcinoma of the ovary.

To our knowledge, familial occurrence of small-cell carcinoma of the ovary in first-degree relatives has not been described before. We studied two separate cases of small-cell carcinoma in a 21-year-old patient and in her 40-year-old mother, both of whom died of disseminated disease. Both tumors were studied with immunohistochemistry, using a variety of antibodies, and with flow cytometry. Microscopically, the tumor in the daughter was of the usual small-cell type, while that of her mother belonged to a large-cell variety. Immunohistochemically, both tumors showed some degree of epithelial differentiation but also expressed reactivity to some other antigens, most notably to smooth-muscle actin and muscle-specific actin. Both tumors showed a diploid DNA pattern and low S-phase fraction with flow cytometry. Neither of the cases expressed hypercalcemia. Small-cell carcinoma of the ovary may appear as a small-cell or large-cell variety in a familial setting. A diploid DNA pattern appears to be characteristic. Because this tumor was first reported relatively recently, the frequency of its familial occurrence is not known.

Adult↗

Primary bone sarcoma with rhabdomyosarcomatous component.

We present three cases of primary bone sarcoma with rhabdomyosarcomatous component which in one case appeared in a pure form, i.e., as rhabdomyosarcoma; in the other two cases it presented as one of multiple components of the tumor. The first patient was a 70-year-old man with a tumor of the left femur involving surrounding soft tissue of the thigh. Histologically, this was a case of so-called dedifferentiated chondrosarcoma with pleomorphic rhabdomyosarcoma representing high grade malignant component. The second patient, a 31-year-old man, developed a tumor in the left tibia which was a rare, fibrosarcoma-like type of rhabdomyosarcoma. The third patient was a 43-year-old woman with a tumor in the left tenth rib which was shown to be osteo- and chondrosarcoma with a minor rhabdomyosarcomatous component and was classified as malignant mesenchymoma. All patients were treated by surgery and chemotherapy. The first two of them died of metastatic disease 3 months, and 3 years and 4 months following surgery, respectively. Light microscopical diagnosis of rhabdomyosarcoma of hematoxylin-eosin sections was confirmed immunohistochemically in each case using reactions to desmin, muscle specific actin and myoglobin, and ultrastructurally in two cases. Rhabdomyosarcomatous component in primary bone tumors appears to be rarely present but more cases may be diagnosed in the future, if immunohistochemical and ultrastructural examinations are to be employed.

Adult↗

Secretory carcinoma of the breast: light microscopical, immunohistochemical and flow cytometric study.

We studied five cases of secretory carcinoma of the breast (SC) by light microscopy, by immunohistochemistry, and by flow cytometry. Four cases were retrieved from the series of 7038 cases of breast carcinoma seen in our department during the 20-yr period of 1973 to 1992; one case was seen recently. Histologically, different growth patterns in SC were observed; the most characteristic feature was prominent intra- and extracellular secretion. Immunohistochemically, all tumors showed strong positive reaction for alpha-lactalbumin and S-100 protein, whereas the reactions to carcinoembryonic antigen and gross cystic disease fluid protein were variable. By flow cytometry, four tumors were examined (three of them were diploid and one near diploid), and they all showed low S-phase fraction. Immunohistochemical findings in SC were compared to a group of 13 cases of nonsecretory carcinoma that all showed an appreciable degree of secretion or morphological similarities to SC. In a single case of cystic hypersecretory carcinoma an unequivocal positive reaction for alpha-lactalbumin was demonstrated; S-100 positive reaction was seen in two cases. It was concluded that in an appropriate morphological setting, positive reaction for alpha-lactalbumin is an essential feature in diagnosing SC. S-100 protein positivity and diploid flow cytometric pattern are also characteristics of SC.

Adult↗

Preparation of fine needle aspiration biopsy samples for flow cytometric analysis.

In order to improve the quality of flow cytometric (FCM) DNA histograms, a new preparatory method was tested on samples obtained by fine needle aspiration biopsy (FNAB) of breast tumors. Twenty-four samples were obtained in vivo (group 1), and 20 were obtained from surgically resected specimens (group 2). Tumors from both groups were aspirated twice each. The first sample was injected directly into 70% ethanol, whereas the second sample was pretreated with a mixture of Tween-20 and citric acid solution (Tween-20 CA) before ethanol fixation. The coefficient of variation (CV) of G0-G1 peaks of Tween 20 CA-pretreated samples varied from 1.85 to 5.10 (mean, 3.3) in group 1 and from 1.87 to 3.72 (mean, 2.77) in group 2. The CV of G0-G1 peaks of ethanol-preserved samples ranged from 2.28 to 7.22 (mean, 5.23) in group 1 and from 1.78 to 4.04 (mean, 3.48) in group 2. The CV values of histograms obtained by the new protocol were significantly lower (group 1, P < .05; group 2, P < .01).

Analysis of Variance↗

Familial occurrence of infantile myofibromatosis.

Two brothers with multicentric infantile myofibromatosis (IM) are reported. In both, tumors were present at birth; the tumors regressed spontaneously, but new lesions developed throughout the follow-up periods of 15 and 8 years. Immunohistochemically, the nodules were found to be positive for vimentin and actin, but negative for desmin and S-100 protein; these findings support the myofibroblastic nature of IM. A literature review revealed nine additional families with IM in more than one family member. Although the occurrence of IM in eight sets of siblings, with consanguinity in two of them, favors an autosomal recessive mode of inheritance, the disorder also has been well documented in half-sisters and in successive generations, which makes autosomal dominant inheritance a more plausible explanation.

Actins↗

Metastatic pattern of infiltrating lobular carcinoma of the breast: an autopsy study.

We analyzed the autopsy records and autopsy histological slides of 261 patients with breast carcinoma who died at the Institute of Oncology, Ljubljana, from January 1972 to October 1989, with particular attention to the metastatic pattern of infiltrating lobular carcinoma (ILC) which we compared with infiltrating ductal carcinoma (IDC). In 226 of 261 patients who died with metastatic disease there were 25 cases of ILC, 195 cases of IDC, 4 cases of mixed IDC-ILC, and 2 cases of mucinous carcinoma. There was no statistically significant difference in frequency of metastases to common metastatic sites, such as the liver, bone, and pleura, with the exception of the lungs, in which IDC metastases prevailed (P less than 0.006). By contrast, a statistically highly significant prevalence of ILC metastases to the peritoneum/retroperitoneum, hollow viscera, internal genital organs, leptomeninges, and myocardium was found (P values of less than 0.006- less than 10(-6). The metastases to these sites were characterized by diffuse growth of neoplastic cells that infiltrated in a lymphoma or leukemia-like fashion. Such metastases may remain clinically silent for a long time, in spite of their extensiveness. The difference of metastatic pattern between ILC and IDC is insufficiently appreciated in most of the published studies on ILC.

Autopsy↗

Pleomorphic fibroma of tendon sheath.

We report an example of fibroma of tendon sheath with pleomorphic bizarre cells without mitoses. The tumor appears to be morphologically identical to a similar tumor in the skin and represents yet another example of a benign soft-tissue neoplasm with disturbing morphological features.

Fibroma↗

Synovial sarcoma: a clinicopathological study of 36 cases.

Thirty-six cases of synovial sarcoma (13 biphasic and 23 monophasic) were subjected to a clinicopathologic study that included electron microscopy and immunohistochemistry. The group consisted of 21 males and 15 females ranging in age from 2 to 63 years. The majority of tumors (27 cases) were found in the hip and lower extremity. Immunohistochemical study revealed that keratin, which was detected in 92% of the biphasic and 57% of the monophasic tumors, was a more sensitive marker of epithelial differentiation than EMA or CEA. The overall 5-year survival of the patients was 64%. Male sex, older age, presence of tumor necrosis, monophasic pattern, and absence of keratin positivity had an unfavourable effect on survival but lacked statistical significance. Survival was significantly lower in patients with tumors exhibiting more than 15 mitoses per 10 HPF (P less than .02) and in those with tumors showing necrosis and a mitotic rate greater than 5 mitoses per 10 HPF (P less than .005).

Adolescent↗

Accuracy of frozen section diagnosis in soft tissue tumors.

This study was undertaken to analyze the accuracy of frozen section (FS) diagnosis of 118 soft tissue tumors with respect to the reasons for which the intraoperative consultation was indicated. Fifty-seven frozen sections were performed for the diagnosis of an unknown pathologic process. Complete agreement was established in 40.3% and the correct pathologic process in 43.9%, the diagnosis was deferred in 14%, and the remaining 1.8% were diagnosed incorrectly. Examination for determination of the adequacy of resection margin (22 cases), lymph node or skip metastases (23 cases), residual or recurrent tumor after previous surgery (29 cases), viable tumor tissue after previous locoregional or systemic therapy (ten cases), and identification of the specimen (five cases) proved to be 95.5%, 95.7%, 96.6%, 90%, and 100% accurate. Considering the whole series, an erroneous answer to a question posed by a surgeon was given in four cases (two false positive and two false negative), of which two cases were a sampling error made by pathologist. Intraoperative consultation by FS in soft tissue tumors is (a) reliable for general rather than exact diagnosis in defining the previously unknown pathologic process and (b) mandatory in evaluating resection margins and any discrepancies between preoperative cytologic and intraoperative gross impression.

Diagnostic Errors↗

Rhabdomyosarcoma. Cytomorphology, subtyping and differential diagnostic dilemmas.

OBJECTIVE: To identify morphologic characteristics and architectural patterns of rhabdomyosarcoma (RMS), to attempt a subclassification from fine needle aspiration biopsy (FNAB) smears and to point out some differential diagnostic problems. STUDY DESIGN: We reviewed all positive cytologic material from 53 patients with RMS whose diagnoses were histologically and/or immunocytochemically confirmed. We analyzed several morphologic features and identified architectural patterns of smears. RESULTS: Among alveolar RMS, we identified two major architectural patterns: one containing completely dissociated cells and one containing many chance formations. Among the embryonal type, the predominant architectural pattern contained large tissue fragments with abundant eosinophilic material and various numbers of dissociated cells. The pattern of only dissociated cells was similar to the one seen in the alveolar type. The relative proportion of poorly to better and well-differentiated rhabdomyoblasts varied in both types and in all patterns. CONCLUSION: RMS exhibits a variety of morphologic pictures regarding cellular morphology and architectural patterns, even within the same histologic subtype. Therefore, a reliable subclassification into alveolar and embryonal RMS cannot be made from FNAB smears. The embryonal type can be suggested in cases containing large tissue fragments with abundant eosinophilic material and small, tightly packed cells with oval nuclei. However, all cases suspected to be RMS must always be confirmed immunocytochemically since they could be confused with some benign and malignant tumors with similar morphology.

Adult↗