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Diagnostic and therapeutic problems in multicentric renal angiomyolipoma.

Multicentric renal angiomyolipoma is a rare form of benign tumor. However, its effective incidence as evaluated in autopsy studies may be as high as 8%. There are 2 main types of renal angiomyolipoma, that is isolated forms and those associated with other diseases, such as phakomatosis, polycystic kidneys and fibromuscular dysplasia. The tumor may also display malignant behavior with local invasiveness and regional lymph node involvement. However, the clinical course is benign and multicentricity is important for prognosis. Histopathological diagnosis often is difficult. Immunohistochemical analysis of surgical specimens using a panel of monoclonal antibodies, including HMB-45 and actin, enabled us to make a definitive diagnosis in 3 cases of multicentric renal angiomyolipoma.

Adolescent↗

Multicentric angiofollicular lymph node hyperplasia: a clinicopathologic study of 16 cases.

A clinicopathologic analysis of 16 cases of multicentric angiofollicular lymph node hyperplasia (MAFH) was performed. Histologically, the disease was characterized by recognizable lymph node architecture that was at least partially intact, by paracortical hyperplasia with prominent vascular proliferation, and by numerous evenly distributed, apparently benign germinal centers of various types, usually including some typical hyaline-vascular centers. At the onset of the disease, 12 patients had the plasma cell (PC) type of MAFH, three patients had the hyaline-vascular (HV) type, and one patient presented with PC and HV types at separate sites. Transitions between the PC and HV types were observed in two cases. Immunologic studies demonstrated polyclonal populations of plasma cells in the lymph nodes of all patients and the absence of suppressor T lymphocytes in the one patient tested. Clinically, the patients had constitutional symptoms, multicentric lymphadenopathy, hepatosplenomegaly in many cases, and abnormal laboratory findings, including anemia, polyclonal hypergammaglobulinemia, and bone marrow plasmacytosis. The 16 patients were placed in four different clinical groups based on presentation and course: stable disease, chronic relapsing disease, aggressive disease, and development of malignant lymphoma. Ten of the 16 patients died (median survival, 26 months; range, eight to 170 months). Multicentric angiofollicular lymph node hyperplasia appears to be a variant of classic angiofollicular lymph node hyperplasia (Castleman's disease) and is associated with significant morbidity and mortality.

Adult↗

Radiographic incidence of multicentric malignant gliomas.

BACKGROUND: Multicentric malignant gliomas are interesting yet uncommon clinical entities with an unknown rate of occurrence. METHODS: We reviewed the computed tomography (CT) and magnetic resonance (MR) images of 100 consecutive patients with malignant gliomas to determine the incidence of multicentricity in malignant glial neoplasms. RESULTS: Five patients had multiple lesions on their initial radiographic study (synchronous lesions) and in four patients multiplicity developed after initial diagnosis (metachronous lesions). MR imaging demonstrated one lesion not seen on CT. CONCLUSIONS: Because synchronous or metachronous multicentricity was found in 9% of patients with malignant gliomas, treatment delivery should not be based on radiographic imaging without attempting to obtain an accurate diagnosis of the ongoing intracranial process.

Adult↗

Sentinel-node biopsy in axillary lymph-node staging for patients with multicentric breast cancer.

Multicentric breast cancer is thought to be a contraindication for sentinel-node biopsy by most clinicians. In a prospective study we took sentinel-node biopsy samples from 19 patients with multicentric invasive breast cancer with use of a blue dye and radiolabelled colloid mapping technique at the subareolar injection site. All patients underwent complete axillary dissection after sentinel-node biopsy. Nine patients had tumour-free and ten had metastatic sentinel nodes. The sentinel-node status was in concordance with the axillary sample in all patients. Sentinel-node biopsy might become an alternative to complete axillary dissection in patients with multicentric breast cancer with clinically negative lymph nodes.

Axilla↗

[Multicentric liposarcoma. Apropos of a case].

INTRODUCTION: Though rare, observations of multiple liposarcomas show that the development of secondary tumors occur in sites usually considered as primary locations. This would be more frequent for myxoid liposarcomas than for other subtypes of the disease. Their origin, either multicentric (i.e., coexistence of several primary tumors) or due to metastatic spreading, is still debated. EXEGESIS: We report a case of myxoid-type multicentric (i.e., right popliteal fossa, retroperitoneum and soft tissue of the left arm) liposarcomas of different sizes, without pulmonary, hepatic or osseous involvement. These liposarcomas were simultaneously diagnosed in a patient who presented with pain in the right knee. CONCLUSION: This support the hypothesis that multiple liposarcomas have a multicentric origin. Initial and follow-up staging of such tumors must investigate not only usual metastatic sites but also classical primary locations.

Adult↗

Multicentric glioblastoma multiforme determined by positron emission tomography: a case report.

UNLABELLED: The actual incidence of true multicentric glioblastoma multiforme (GBM) varies between 2.4 and 4.9% of all GBMs. True multicentric tumors are described as widespread lesions in different lobes or hemispheres, which cannot be explained by spreading along the cerebrospinal fluid or blood pathways. We present here a case of multicentric GBM identified with positron emission tomography. CASE REPORT: A 73-year-old woman with sudden onset headaches, balance problems, and one episode of syncope was diagnosed as having an irregular, contrast-enhancing, space-occupying lesion in the left-temporal-parietal region on magnetic resonance imaging (MRI). The tissue diagnosis was confirmed as GBM, and she received stereotactic radiosurgery using the Leksell Gamma Knife (Elekta Instruments, Atlanta, GA). A 3-month, follow-up, MRI scan showed a remarkable decrease in the size of the contrast-enhancing area that was targeted during radiosurgery. A suspicious area of enhancement was detected on the right side, although no surrounding edema was evident. Fluorodeoxyglucose (FDG)-PET scanning revealed a large irregular neoplasm extending from the inferior left-temporal lobe into the deep parietal lobe with extremely intense FDG uptake, suggesting a very aggressive tumor. A smaller lesion was also discovered in the deep right-frontal lobe, representing a second neoplastic focus. The patient refused any further treatment. CONCLUSION: PET scans, in conjunction with MRI scans, allow for the best possible and most comprehensive diagnosis and treatment plans.

Aged↗

Human herpesvirus-8 in lymphomatous and nonlymphomatous body cavity effusions developing in Kaposi's sarcoma and multicentric Castleman's disease.

Human herpesvirus-8 (HHV-8) has been associated with Kaposi's sarcoma, multicentric Castleman's disease and primary effusion lymphoma. Kaposi's sarcoma and multicentric Castleman's disease patients may develop body cavity effusions that, unlike primary effusion lymphoma, are poorly characterized. To better define these effusions, pleural and peritoneal fluids derived from 12 human immunodeficiency virus-seropositive and one seronegative patients affected by Kaposi's sarcoma or multicentric Castleman's disease were analyzed by a combination of morphologic, immunophenotypic, and DNA analyses, including polymerase chain reaction amplification of HHV-8, Epstein-Barr virus, and immunoglobulin heavy-chain (IgH) gene sequences. In addition, HHV-8 serologic status was assessed by using an immunofluorescence assay. All patients were adult men with high antibody titers to HHV-8; 11 of the 13 patients were homosexual/bisexual. Effusions revealed monocyte/macrophage-rich infiltration (10 patients) or large-cell lymphoma with CD45(+)/non-T/non-B phenotype (three of 13 patients); polymerase chain reaction analysis showed the presence of HHV-8 sequences (nine of 13 patients), germline IgH (seven of 12 patients) or clonal IgH rearrangements (four of 12 patients), and rarely Epstein-Barr virus sequences (two of 12 patients). In the setting of HHV-8 infection, two effusion types may occur. One fulfills the criteria for HHV-8-positive PEL (lymphoma-morphology, HHV-8-DNA(+), IgH rearrangement). The other seems more reminiscent of an HHV-8-associated nonneoplastic process (monocyte-macrophage morphology, HHV-8-DNA(+/-), germline IgH). Interestingly, a single case of the latter effusion type harbored a B-cell monoclonal proliferation, which suggests the hypothesis that a prelymphomatous effusion may precede overt body cavity lymphoma.

Adult↗

Treatment of multicentric Castleman's disease complicated by the development of non-Hodgkin's lymphoma with high-dose chemotherapy and autologous peripheral stem-cell support.

BACKGROUND: Castleman's disease or angiofollicular lymph node hyperplasia is a rare entity with a localized/unicentric or a generalized/multicentric presentation. While surgery is curable for most localized presentations, there is limited information regarding the optimal management of the multicentric type. The latter type is associated with a poor prognoses and can be associated with the development of lymphoma and infections. PATIENTS AND METHODS: In this report we describe a case of multicentric Castleman's disease who failed steroids and chemotherapy and developed a follicular mixed lymphoma. He was treated with high-dose chemotherapy with autologous stem-cell support and remains disease at four years of follow-up. CONCLUSIONS: A long-term durable remission may be possible with high dose chemotherapy with stem-cell support. This treatment modality should be considered an option in the management of multicentric Castleman's disease.

Adult↗

Diagnostic and neural analysis of skin cancer (DANAOS). A multicentre study for collection and computer-aided analysis of data from pigmented skin lesions using digital dermoscopy.

BACKGROUND: Early detection of melanomas by means of diverse screening campaigns is an important step towards a reduction in mortality. Computer-aided analysis of digital images obtained by dermoscopy has been reported to be an accurate, practical and time-saving tool for the evaluation of pigmented skin lesions (PSLs). A prototype for the computer-aided diagnosis of PSLs using artificial neural networks (NNs) has recently been developed: diagnostic and neural analysis of skin cancer (DANAOS). OBJECTIVES: To demonstrate the accuracy of PSL diagnosis by the DANAOS expert system, a multicentre study on a diverse multinational population was conducted. METHODS: A calibrated camera system was developed and used to collect images of PSLs in a multicentre study in 13 dermatology centres in nine European countries. The dataset was used to train an NN expert system for the computer-aided diagnosis of melanoma. We analysed different aspects of the data collection and its influence on the performance of the expert system. The NN expert system was trained with a dataset of 2218 dermoscopic images of PSLs. RESULTS: The resulting expert system showed a performance similar to that of dermatologists as published in the literature. The performance depended on the size and quality of the database and its selection. CONCLUSIONS: The need for a large database, the usefulness of multicentre data collection, as well as the benefit of a representative collection of cases from clinical practice, were demonstrated in this trial. Images that were difficult to classify using the NN expert system were not identical to those found difficult to classify by clinicians. We suggest therefore that the combination of clinician and computer may potentially increase the accuracy of PSL diagnosis. This may result in improved detection of melanoma and a reduction in unnecessary excisions.

Adult↗

Multicentric malignant melanoma in a giant melanocytic congenital nevus 20 years after dermabrasion in adulthood.

BACKGROUND: Dermabrasion is one approach to the treatment of treating giant melanocytic congenital nevi. Treatment is recommended to reduce the risk of spontaneous malignant transformation of giant nevi into malignant melanomas that usually occur in childhood. OBJECTIVE: To describe the development of a multicentric malignant melanoma in a giant melanocytic congenital nevus after dermabrasion. METHODS: We report about a 46-year-old male patient who developed a multicentric malignant melanoma in a giant melanocytic congenital nevus. The nevus was located on his left shoulder extending to his neck and chest. Previously, dermabrasion of the nevus was performed twice at the ages of 26 and 28. RESULTS: To our knowledge, this is the first report of malignant transformation of a giant nevus into a multicentric malignant melanoma diagnosed 20 years after the procedure of dermabrasion. CONCLUSION: We conclude that a close follow-up of such patients is mandatory.

Cell Transformation, Neoplastic↗

Sentinel lymph node drainage in multicentric breast cancers.

Axillary lymph node status is the most important prognostic marker in patients with breast cancer; the presence of axillary metastases impacts prognosis as well as subsequent systemic therapy. Axillary lymph node dissection (ALND) is associated with significant morbidity and psychological distress; the introduction of sentinel lymph node (SLN) biopsy with lymphatic mapping affords the ability to identify those patients most likely to benefit from ALND, sparing node-negative patients. The lymphatic drainage of the breast is poorly understood, and the situation is further complicated by the lack of standardization of the SLN biopsy technique among institutions. Multicentricity has generally been considered to be a contraindication to SLN biopsy due to concerns about potential inaccuracies. Here we report five cases of patients with multicentric breast cancers (two tumors in two distinct quadrants). In each case, injection of one site with technetium-labeled sulfur colloid and the second site with isosulfan blue dye resulted in successful identification of at least one node that was both hot and blue within the axilla. These observations suggest that the lymphatic drainage of the entire breast coincides with drainage of the tumor bed, regardless of the quadrant. However, further studies are needed to validate the accuracy of SLN biopsy in multicentric breast cancers.

Adult↗

Multicentric reticulohistiocytosis in a 14-year-old girl.

Multicentric reticulohistiocytosis is a rare multisystem disorder in which an infiltration of histiocytic cells causes papulonodular skin lesions and potentially a destructive polyarthritis. The active disease typically resolves spontaneously after 5-8 years, but the articular destruction can lead to permanent joint deformities. We present a case of multicentric reticulohistiocytosis in a 14-year-old girl. The number of papules on her hands decreased in number and her arthritic symptoms improved after 4 months of oral naproxen. Thirty months later her joint symptoms remained inactive and only six very small papules remained on her hands. Small flexor deformities were present in the distal interphalangeal joints of both index fingers. This case is an example of how multicentric reticulohistiocytosis can be a relatively stable and self-limited disease but still cause permanent joint deformities.

Adolescent↗

The impact of an end-point committee in a large multicentre, randomized, placebo-controlled clinical trial: results with and without the end-point committee's final decision on end-points.

BACKGROUND: A multicentre study permits rapid recruitment of a large number of patients. However, there is a risk of heterogeneities in end-point evaluations, as complex definitions of criteria are interpreted by several local investigators from different hospitals. Reports discussing end-point evaluation are sparse. The TRIM trial was a multicentre trial of a thrombin inhibitor in patients with unstable angina or non-Q myocardial infarction. In this study, an independent end-point committee evaluated all the reported events of death, acute myocardial infarction and refractory angina pectoris in order to obtain uniform judgements of major end-points. STUDY AIMS: To describe the work of the end-point committee, to analyse its possible effect on the final study results and to discuss the impact on the design of future trials. METHOD: The end-point committee consisted of four members, one from each participating country. After the data were processed by the study monitors, completed case record forms and patient files for patients with reported end-points were mailed to the national member of the end-point committee for judgement. The end-point committee met regularly and made final decisions about the end-points. The work of the end-point committee was documented on a separate case record form. RESULTS: The end-point committee assessed 246 events of death, acute myocardial infarction and refractory angina pectoris in 187 of the 1209 patients (15.5%) in the TRIM trial. Misinterpretation of the index event, an inclusion myocardial infarction, as an early cardiac event was found in 12 patients. After end-point committee judgements, the number of patients with acute myocardial infarction or refractory angina pectoris during 30 days of follow-up was reduced from 177 to 153 (13. 6% reduction). The classification of events was changed in 53 of 187 patients (28.3%) with death, acute myocardial infarction or refractory angina pectoris. The data assessed by the safety committee was significantly different from the final database after end-point committee judgements. CONCLUSION: The end-point committee corrected misinterpretations in such a high proportion of cases that the final results differed significantly from the preliminary results delivered to the safety committee. End-point judgements by an end-point committee should be performed in multicentre clinical trials to improve the quality and reliability of study results.

Anticoagulants↗

Interphase cytogenetics of multicentric renal cell tumours confirm associations of specific aberrations with defined cytomorphologies.

To demonstrate associations of certain chromosomal aberrations with defined renal cell tumour (RCT) subtypes, we analysed 239 tumour nephrectomy cases for specimens with multicentric tumours. Chromosomal in situ hybridization was then performed on 15 cases with 34 foci (16 conventional renal cell carcinomas (RCCs), and 18 papillary RCTs (11 carcinomas and seven adenomas) for specific chromosomal aberrations, using alpha-satellite probes for chromosomes 3, 7 or 17. Particular preference was given to cases which had separate foci with different cytomorphologies. Furthermore, we compared aberrations in relation to tumour size, stage, grade and between different foci in a specimen. Thirty-four cases had multiple tumours. Forty-seven per cent of the multicentric tumours were conventional RCCs and 53% papillary RCTs (against 83% solitary conventional RCCs and 5% solitary papillary RCTs). Three conventional RCCs sized 8 mm (G3), 13 cm (pT2, G2) and 15 cm (pT3b, G3), respectively, revealed monosomy 3, and 13 were disomic. Seventeen papillary RCTs (11 carcinomas and six adenomas) displayed trisomy 17, irrespective of size or grade. Four papillary carcinomas and six papillary adenomas had trisomy 7, and the rest (seven papillary carcinomas and one papillary adenoma) revealed disomy 7. In conclusion, papillary RCTs were tendentially multicentric. Although specific for conventional RCCs heedless of size, monosomy 3 was only observed in high-grade and/or advanced tumours. Trisomy 17 was only detectable in papillary RCTs irrespective of tumour state, showing increased copies with tumour growth. Papillary RCTs also appeared to lose some copies of chromosome 7 with tumour progress, possibly reflecting malignancy.

Carcinoma, Papillary↗

[Development of a database system for multicentric ENT tumor documentation].

BACKGROUND: Multicentric clinical studies have a great impact on progress in diagnostics and therapy in oncology. However, multicentric retrospective clinical trials require a common documentation standard. METHODS: A network enabled tumor documentation program based on a relational database system was developed for the management of multicentric clinical studies. This system is designed for the documentation of treatment and follow-up. CONCLUSION: The use of a computer-supported documentation system minimizes documentation effort and error frequency. However, communication with cancer registries is still an unsolved problem.

Clinical Trials as Topic↗

Multicentric quality assurance in cardiac surgery. QUADRA study of the German Society for Thoracic and Cardiovascular Surgery (QUADRA: quality data retrospective analysis).

A method for initiating quality assurance in cardiac surgery was developed multicentrically by a commission of the German Society for Thoracic and Cardiovascular Surgery (QUADRA Study). To appraise the quality of cardiosurgical action, variables were compiled from the preoperative, intraoperative, and postoperative treatment course. The data collection was carried out at the same time as treatment. On the basis of unicentric data profiles, multicentric hospital profiles, and problem profiles, a quality comparison could be carried out and the variability of cardiosurgical action which may occasion interventions could be identified. A reduction of perioperative blood consumption during the study period could be observed in four out of five hospitals as the first result. The data collection also revealed epidemiological features. On average, women were older than men at the time of the heart-valve and coronary operations. To ensure data validity and the organization of quality assurance, a documentation assistant and a specially trained physician are necessary at every cardiovascular surgery center. The multicentric external comparison is indispensable and must be carried out by means of a central data collection, for which intrumental and staff capacities are also to be provided. With modern methods of data processing, an additional and new approach to the improvement of quality in cardiac surgery can thus be made.

Blood Transfusion↗

Prospective multicentre trials in developing countries: willingness of surgeons to participate.

OBJECTIVE: To assess the feasibility of conducting a multicentre study among surgeons in Turkey. DESIGN: Prospective open multicentre study. SETTING: Teaching hospitals in Turkey. SUBJECTS: Surgeons working in 23 university and 15 state hospitals. INTERVENTIONS: Surgeons willing to participate were asked to look for the presence of Meckel's diverticulum in all patients undergoing laparotomy. MAIN OUTCOME MEASURES: To find out the number of surgeons willing to participate in the study and once they agreed to see how they fulfilled the requirements. RESULTS: 14 agreed to participate (12 from universities and 2 from state hospitals) and completed the study. A total of 2781 patient records were collected. University hospitals were more willing to participate than state hospitals (52% compared with 13%) but state hospitals contributed 20% of the patients. The number of patients contributed in the first and second halves of the study did not differ, reflecting no diminution of the enthusiasm. CONCLUSION: This study, with no financial support, showed that it is possible to conduct multicentre studies among surgeons in developing countries such as Turkey. Increased awareness of the importance of publication may have helped to obtain this result.

Adult↗

New electron microscopic findings in a case of multicentric reticulohistiocytosis. Long spacing collagen inclusions.

The case of a 68-year-old woman with polyarthropathy and skin nodules is presented. Histologic findings of histiocytes with ground-glass cytoplasm favored the diagnosis of multicentric reticulohistiocytosis. In this article we report new electron microscopic findings of intra- and extracytoplasmic long spacing collagen (type VI). Type VI collagen inclusions are usually found in lymphohistiocytic neoplasms. We believe our findings support the concept of a proliferative rather than inflammatory etiology for multicentric reticulohistiocytosis. It may also give support for the argument of production of collagen by the histiocytic cells of multicentric reticulohistiocytosis.

Aged↗