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Multicentric plasma cell variant of Castleman's disease with cutaneous involvement.

BACKGROUND: Castleman's disease (CD) is a rare low-grade B-cell lymphoproliferative disorder that can be associated with a variety of antibody-mediated paraneoplastic syndromes. The disease is classified clinically by two forms and three histologic variants. METHODS: We describe the clinical and pathological features of a 44-year-old woman who presented with an autoimmune hemolytic anemia, thrombocytosis, polyclonal gammopathy, axillary lymphadenopathy, hepatosplenomegaly, and several erythematous and violaceous nodules and plaques without scaling involving the trunk and extremities. RESULTS: Histologic examination of the skin lesions revealed a deep dermal and subcutaneous nodular mononuclear infiltrate composed primarily of polyclonal plasmacytoid cells without atypia and an increased vascular proliferation. Additional studies including a bone marrow and lymph node biopsy, serum and urine protein electrophoresis, and computed tomography scans supported the diagnosis of multicentric plasma cell variant of CD with an associated autoimmune paraneoplastic hemolytic anemia. CONCLUSION: Cutaneous involvement in CD is part of the multicentric nature and should be considered in the differential diagnosis of a polyclonal plasma cell-rich lymphoproliferative disorder associated with paraneoplastic autoimmune disease.

Adult↗

Role of increased DNA synthesis activity of hepatocytes in multicentric hepatocarcinogenesis in residual liver of hepatectomized cirrhotic patients with hepatocellular carcinoma.

To examine whether the marked increase in DNA synthesis of hepatocytes in cirrhotic liver might elicit multicentric hepatocarcinogenesis, we examined the relationship between new development of hepatocellular carcinoma (HCC) and the bromodeoxyuridine (BrdU) labeling index (LI) of hepatocytes in the residual liver of hepatectomized patients with liver cirrhosis (LC) and HCC. Eighteen hepatectomized patients with LC and HCC, whose resected liver revealed neither portal nor hepatic vein invasion by histologic examination, were studied (to exclude cases with intrahepatic metastasis). DNA synthesis activity of hepatocytes from the residual cirrhotic liver was measured by a BrdU/anti-BrdU in vitro method. The incidence of HCC recurrence was studied during a 3-year follow-up period. Among 18 patients, 9 patients had recurrence and 9 did not. The average BrdU LI in the recurrent patients was 2.6 +/- 1.3% and was significantly higher than that in patients without recurrence (1.4 +/- 0.5%, P < 0.05). All five patients who had a BrdU LI of 2.4% or above showed recurrence within 3 years, as compared with 4 of 13 (30.8%) patients with BrdU LI of less than 2.4% (P < 0.05). Our data indicate that abnormally high DNA synthesis in hepatocytes in the background cirrhosis might lead to the development of multicentric carcinogenesis in human cirrhotic liver, and in the residual cirrhotic liver of hepatectomized patients with HCC and LC, it may be a predictor of new development of HCC.

Adult↗

Multicentric reticulohistiocytosis and malignant disease.

Multicentric reticulohistiocytosis developed in a 45-year-old woman, who had a 3 year history of untreated breast carcinoma. A review of the literature revealed that malignant disease has been associated with 27% of reported cases. It is considered that, like adult dermatomyositis, the onset of multicentric reticulohistiocytosis should stimulate detailed investigation for an underlying neoplasm.

Adenocarcinoma, Scirrhous↗

Malignancy-associated multicentric reticulohistiocytosis: a clinical, histological and immunophenotypic study.

The clinical, histopathological, and immunophenotypic characteristics of four cases of malignancy-associated multicentric reticulohistiocytosis (MMR) and one case each of diffuse cutaneous reticulohistiocytosis (DCR) and isolated reticulohistiocytoma (IR), are reviewed. In all four cases of MMR the cutaneous lesions and joint manifestations were judged to be concurrent with the diagnosis of malignancy. Malignancies observed included one case each of pancreatic adenocarcinoma, squamous cell carcinoma of the lung, metastatic melanoma and intraperitoneal grade 4 mucinous adenocarcinoma of uncertain origin. Histologically, all six cases demonstrated the typical changes of a diffuse histiocytic and multinucleated giant cell infiltrate with ground-glass cytoplasm, predominantly in the upper dermis. Immunohistochemical investigation revealed strong cytoplasmic staining with KP-1 (CD68) in all six cases. Prominent membrane staining was noted with leucocyte common antigen (CD45) in four cases (three MMR and one IR), and CD3 in four cases (three MMR and one IR). Weak membrane staining with Leu 22 (CD43) was noted in two MMR cases. UCHL-1 (CD45RO), L26 (CD20), S-100 and BerH2 stains were all uniformly negative. A prominent number of perilesional factor XIIIa-positive dermal dendrocytes were noted in the single case of IR, in contrast with the other five cases. We conclude that MMR, DCR and IR are histopathologically and immunohistochemically similar. The pattern of immunoreactivity observed is consistent with a monocyte-macrophage origin of the infiltrating tumour cells. We emphasize the paraneoplastic association of multicentric reticulohistiocytosis, which we have observed in four of 13 such cases (31%) evaluated at our institution.

Adult↗

Multimarker phenotypic characterization of adult and childhood acute lymphoblastic leukaemia: an Italian multicentre study.

A multicentre phenotypic study was carried out in Italy combining conventional immunological techniques with monoclonal antibody (MoAb) analysis in 190 cases of adult and childhood acute lymphoblastic leukaemia (ALL), in an attempt to define better the lineage relationship of the neoplastic cells. Of the 140 children evaluated, 79.3% expressed the common ALL (cALL) antigen (all analyses performed by MoAb), 11.4% were T-ALL and 9.3% were non-T, non-B, non-common ('null') ALL. The proportion of adult cALL cases was slightly lower (64% of the 50 cases studied) than that of childhood ALL, whilst the incidence of T-ALL was significantly higher in adults than in children (26% v. 11.4%, P less than 0.05). Because of the high proportion of cALL cases, the incidence of 'null' ALL in adult patients was similar (10%) to that of children, and lower than previously reported. The recognition of early pre-T-ALL cases (T1+, RFT2+, T10+, T6-, T11-, E-) contributed to the overall low proportion of 'null' ALL; prior to the use of MoAb, such cases would probably have been classified as undifferentiated acute leukaemia or 'null' ALL. The search for B-cell-related markers showed that the incidence of pre-B-ALL cases (cytoplasmic immunoglobulin positive cases) was similar in adults and in children (25.6% and 32%, respectively). Furthermore, the great majority of cases studied expressed the BA-1 antigen (92.8% of adults and 79% of children), whilst the BA-2 antigen was found in 53% of cases (tested only in children), confirming a hierarchy in the expression of B-cell related markers in cALL: BA-1, BA-2, CyIg. Several of the 'null' cases also expressed the BA-1 antigen on a variable proportion of cells, pointing to a possible B-cell origin of the blasts. This multicentre study shows that both in adult and in childhood ALL the combined use of conventional immunological markers and of a panel of MoAb allows identification of the cell lineage of the great majority of cases, thus reducing the number of 'null' ALL. Furthermore, these findings suggest that practically all cases of ALL belong either to the T or to the B cell compartment and that the neoplastic cells appear blocked at different levels along the lymphoid differentiation pathway.

Acute Disease↗

Cardiac and systemic complications in multicentric reticulohistiocytosis.

A 75-year-old man with a short history of cutaneous lesions of multicentric reticulohistiocytosis, preceded by a few months of a symmetrical polyarthritis is described. Within 5 months of onset of symptoms, he developed congestive cardiac failure secondary to pericardial involvement by the disease and succumbed despite therapy with cyclophosphamide and methylprednisolone. Post-mortem revealed the true extent of the disease, with nodules seen in the epiglottis and aryepiglottic folds, duodenal mesentery, pleura, pericardium and myocardium. Although the hallmarks of the disease are the papulonodular skin lesions, together with a severe, sometimes mutilating polyarthropathy, its widespread systemic nature is not often appreciated. We review five other cases in the literature with pericardial involvement and discuss aids to earlier diagnosis by synovial fluid cytology; gallium scanning is discussed as a potentially useful means of detecting the extent of systemic involvement in multicentric reticulohistiocytosis.

Aged↗

A multicentre study of the management of disorders of defecation in patients with spina bifida.

Patients with spinal dysraphism may have severe constipation and faecal incontinence. The impact of antegrade colonic enema (ACE) in the management of patients with spina bifida (SB) is analysed. In a multicentre cross-sectional study, constipation, faecal incontinence and faecal management were described. Cases surgically treated were identified. Data were collected from 423 patients, of whom 230 did not use any manoeuvre or laxatives to assist evacuation. Conventional treatment was used in 193 patients, including digital extraction in 39%, retrograde enema in 21% and oral laxatives in 52%. For intractable constipation and overflow of faecal incontinence, 47 patients were treated with ACE, of whom 41 used the method at a mean time of interview of 4.1 +/- 1.9 years after ACE operation; six abandoned ACE for conventional management. With ACE, faecal continence was significantly improved compared with conventional management, and neither retrograde rectal enema nor digital extraction were required. The conduit was fashioned to the right colon in 32 cases and to the left colon in nine cases. This study provides information on a multicentre experience in bowel management in SB patients. Whatever the technique used, ACE has improved faecal status compared with conventional therapy.

Adolescent↗

Multicentric lymphoma involving large granular lymphocytes in a cow.

This case report describes for the first time in the literature a bovine multicentric lymphoma involving large granular lymphocytes (LGL). Clinically, the cow had typical manifestations of multicentric lymphoma with nonspecific signs. Most lymphocytes in cytological specimens from blood and lymph nodes had an LGL-morphology. Histopathologically malignant LGLs were found in the liver, kidneys, and lungs. The azurophilic granules were clearly seen with May-Grünwald-Giemsa stain. The granules were slightly eosinophilic as shown with hematoxylin-eosin stain, and most stained intensively dark with phosphotungstic acid hematoxylin.

Animals↗

Multicentric astrocytomas of the optic chiasm, brain stem and spinal cord.

Autopsy was performed on a 52-year-old man with a 20-year history of neurological symptoms. At autopsy, both a brain stem tumor and a spinal cord tumor were found. These showed the features of pilocytic astrocytoma histologically. A pilocytic astrocytoma was also found in the optic chiasm upon microscopical examination. These three tumors were thought to be multicentric astrocytomas, because there was no continuity among them and no evidence of dissemination or metastasis by any pathway. From a review of the literature, the present case is considered to be an exceedingly rare one because of the multicentric sites of occurrence.

Adult↗

Synchronous and metachronous multicentric squamous cell carcinomas in the upper aerodigestive tract.

A rare case is presented of a 57-year-old Japanese male with synchronous and metachronous multicentric squamous cell carcinomas (SCC) in the upper aerodigestive tract. During a 9-year-period from the appearance of first primary SCC to autopsy, 14 foci of primary SCC and one severe dysplasia developed in succession in the thoracic esophagus, oral floor, soft palate, uvula, lingual radix, piriform recess, hypopharynx, cervical esophagus, trachea and lingual body. The patient died of severe bronchopneumonia due to Gram-negative bacterial infection that developed as a result of recurrent nerve paralysis. Human papilloma virus and Epstein-Barr virus, which are risk factors, were not detected by immunohistochemistry or by the polymerase chain reaction method. Genetic analysis revealed the absence of point mutations in K-ras codon 12. Heavy consumption of alcohol and excessive smoking may have been responsible for the multicentric carcinogenesis. This is the first case report in the literature of the development of so many primary SCC lesions in the upper aerodigestive tract during such a short period.

Carcinoma, Squamous Cell↗

Multicentric angiosarcoma of the gastrointestinal tract.

A case of multicentric gastrointestinal angiosarcoma suffering from severe melena is presented. Endoscopical examination revealed two polyps in the stomach and duodenum. Histological examination showed angiosarcoma. Although a gastroduodenectomy was performed, severe melena continued, and the patient developed respiratory failure and died. At autopsy, multiple hemorrhagic tumors were present from the duodenum to the cecum. Histologically the tumors demonstrated vasoformative structure and were immunohistochemically positive for von Willebrand factor (factor VIII related antigen), CD34, and CD31. Numerous metastases were found in various organs, including the lungs, bones, liver, gall-bladder, and lymph nodes. The patient had received hemodialysis for 21 years due to chronic renal failure. Long-term dialysis had been associated with various malignancies. Multicentric development of angiosarcoma in the present case may also be related to long-term dialysis.

Biomarkers, Tumor↗

Multicentric chemodectoma in the head and neck.

A case of a multicentric chemodectoma, with the unusual combination of glomus vagale and glomus tympanicum, is presented. The patient, though asymptomatic, showed elevated levels of urinary catecholamines, suggesting some biochemical activity of the tumour. Multicentricity was unsuspected prior to selective carotid arteriography. Intra-operative haemostasis was assisted by the utilization of pre-operative selective embolization of the tumour mass. Subsequently, the injected Ivalon was confirmed histologically in the specimen. The asymptomatic small glomus tympanicum tumour was treated using embolization alone but only time will determine the effectiveness of this method of management. The vagus nerve was anatomically spared, but complete function had not returned after 2 years of follow-up.

Adult↗

The influence of review pathology on study outcome of a randomized multicentre superficial bladder cancer trial. Members of the Dutch South East Cooperative Urological Group.

OBJECTIVE: To determine whether differences between local and review pathology in a multicentre study influence the results of treatment and results from prognostic factor analysis. PATIENTS AND METHODS: A randomized multicentre study in superficial bladder cancer is reported, in which the influence of local and review pathology on the study outcome was investigated. RESULTS: The conformity between local and review pathology of the pT category was 79.3%, of the grade 70.2%, and the combination of both 59.7%. In local pathology, undergrading was more frequent than overgrading and overstaging more frequent than understaging. However, the risks of recurrent disease in the separate stage and grade groups remained the same after correcting the pathology result. A prognostic factor analysis with regard to the risk of recurrent disease was carried out. The Cox hazard ratios of tumour localization, multiplicity, patient age (significant factors), tumour grade, size, history and gender (not significant) remained almost the same after correction for review pathology. Only the prognostic relevance of tumour stage increased after pathology correction. CONCLUSION: We conclude that, although review pathology caused considerable changes in the pathology results, this did not change the results of treatment, and hardly altered the results of a prognostic factor analysis in this randomized study.

Carcinoma, Transitional Cell↗

Multicentric carcinoma of the female lower genital tract.

The clinical history and treatment of 17 patients with multicentric primary carcinomas of the cervix and vulva is presented. There is a significant association between vulval intraepithelial neoplasia and cervical neoplasia. The concept of multicentricity in relation to invasive and intraepithelial neoplasia of the cervix and vulva is critically reviewed.

Adult↗

Parasuicide in Europe: the WHO/EURO multicentre study on parasuicide. I. Introduction and preliminary analysis for 1989.

The WHO/EURO multicentre study on parasuicide is a new, coordinated, multinational, European study that covers two broad areas of research: monitoring trends in the epidemiology of parasuicide (epidemiological monitoring study); and follow-up investigations of parasuicide populations, with a view to identifying the social and personal characteristics predictive of future suicidal behaviour (repetition prediction project). This article provides background information on the development and organization of the multicentre study, and presents selected findings from the epidemiological monitoring project, based on a preliminary examination of data collected in 15 centres on parasuicides aged 15 years and over treated in health facilities in defined catchment areas during the year 1989. The overall parasuicide incidence varied considerably across the centres, from a high (event) rate of 414 per 100,000 males in Helsinki to a low of 61 among males in Leiden. The highest female event rate was 595 in Pontoise, and the lowest 95 in Guipuzcoa. The mean event rate across all centres was 167 among males and 222 among females. Parasuicide incidence tended to be elevated among 15- to 34-year-olds, with lowest rates among those aged 55 years and over. With one exception (Helsinki), the female parasuicide rate was higher than the male rate, the F:M ratio ranging from 0.71:1 to 2.15:1, with a median of 1.5:1 (events). Short-term repetition rates (as measured by the event:person ratio) differed between centres, from 1.03 to 1.30 (median = 1.12) among males, and from 1.07 to 1.26 (median = 1.13) among females. Although we warn against generalizing from our findings to make statements about differences in parasuicide between countries, we argue that the differences between centres are valid and should be addressed in further research.

Adolescent↗

Patients with schizophrenia treated with aripiprazole, a multicentre naturalistic study.

OBJECTIVE: The purpose was to carry out a naturalistic study on efficacy, safety and tolerability of aripiprazole during treatment of schizophrenia. Fifty-one patients with an ICD-10 diagnosis of schizophrenia and partial responders to prior antipsychotic medication were offered treatment with aripiprazole as monotherapy or in combination their prior medication. Inclusion criteria were lack of therapeutic effect or adverse events on former antipsychotic treatment. METHOD: Six-month open multicentre naturalistic study with prospective assessments including Body Mass Index (BMI), Clinical Global Impression-Severity (CGI-S), Clinical Global Impression-Improvement, Global Assessment of Functioning Scale (GAF) and adverse events. RESULTS: A statistically significant improvement in the different measures of psychopathology and global functioning (CGI-S reduction 34.7%; GAF improvement 14%) was shown in combination with a statistically significant reduction in BMI of 2.9%. Nine patients (17.6%) did not complete the 6-month treatment. CONCLUSION: In an open multicentre naturalistic study, aripiprazole showed to improve the severity of psychotic symptoms and the global level of functioning. However, many of the patients (47%) were also given another antipsychotic drug at the same time. Also, high compliance and few side effects were reported. However, because of the study design, the results must be interpreted conservatively.

Activities of Daily Living↗

The achievement and maintenance of inter-examiner consistency in the assessment of plaque and gingivitis during a multicentre study based in general dental practices.

This study set out to demonstrate that it was possible to train general dental practitioners (gdps) to achieve and maintain high levels of inter-examiner consistency in the use of simple periodontal indices over a 12-month period. The gdps were trained by one trainer in the use of the plaque index (PII) and a modified version of the gingival index (mGI) which assessed gingival bleeding only. All the gdps underwent intensive training and employed a technique, when assessing inter-examiner consistency in the use of the PII, such that the 1st examiner did not disturb in situ plaque from 50% of the circumference of a tooth. The problem of variation due to repeat probing, when assessing inter-examiner consistency for mGI, was overcome by one examiner lightly probing gingival margins and both examiners scoring the results. The problems relating to the multicentre nature of the study included: distance between the centres, the need for strict adherence to the study protocol, consistency in the use of forms and instruments, in the application of periodontal indices, and of inclusion and exclusion criteria. Techniques for overcoming these problems included: the planning and application of a coherent study design, which employed simple indices, a detailed protocol, the recruitment of very well-motivated gdps of similar age and experience as examiners, the recruitment of an experienced trainer who trained the gdps thoroughly and monitored their performance throughout the study, and repeat visits to the practices involved to explain the nature of the study to all their staff members. Initially, the gdps achieved inter-examiner kappa scores of 0.78-0.85 (mean 0.81) for PII and of 0.73-0.94 (mean 0.87) for mGI when assessing 168 sites for each variable. During the following 12 months, individual kappa scores, assessed every 3 months at 42 sites, ranged from 0.51-0.90 for PII and from 0.73-1.00 for mGI. Mean kappa for PII scores achieved by the five gdps fell during the study from 0.81 to 0.76, whereas that for mGI rose from 0.87 to 0.92. It is concluded that it is possible to train gdps to achieve high levels of inter-examiner consistency in the use of PII and mGI and for these high levels to be maintained during a 12-month multicentre study.

Calibration↗

Efficacy and toxicity of doxorubicin/cyclophosphamide maintenance therapy in dogs with multicentric lymphosarcoma.

Doxorubicin/cyclophosphamide were evaluated as maintenance drugs for dogs with multicentric lymphosarcoma (n = 28). Median remission time of all dogs was 173 days. Remission duration was shorter, however, in dogs with stage IV/V disease, in dogs with pretreatment hypoalbuminemia, and in dogs that had received glucocorticoids before initiation of chemotherapy (P less than 0.04). Nineteen dogs were evaluable for toxicity. Dose-limiting gastrointestinal toxicosis was observed in three dogs, neutropenia was observed in three dogs, and cardiomyopathy was observed in three dogs. The doxorubicin/cyclophosphamide protocol described in this report is safe and effective in treating canine multicentric lymphosarcoma. Clinical stage, pretreatment steroid therapy, and hypoalbuminemia are prognostic factors for response to this protocol.

Animals↗