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PubMed2003

Retrospective analysis of sentinel node localization in multifocal, multicentric, palpable, or nonpalpable breast cancer.

UNLABELLED: Multicentric or multifocal breast cancer is considered as one of the limitations for sentinel lymph node (SLN) localization. We did a retrospective analysis to evaluate the success rate, sensitivity, accuracy, and negative predictive values of SLN localization in multicentric or multifocal breast lesions. METHODS: Fifty-nine patients with multifocal or multicentric breast lesions proven by either fine-needle aspiration (19/59), core biopsy (39/59), or lumpectomy (8/59) underwent SLN localization. Of these patients, 46 had SLN localization by both radiocolloid and blue dye, and 13 had SLN localization by radiocolloid alone. Approximately 10 MBq (99m)Tc-labeled unfiltered sulfur colloid in 0.3-0.4 mL were injected intradermally over the 1 or 2 breast tumor locations 2-4 h before surgery. During surgery, vital blue dye was injected intraparenchymally in 4-6 places around the tumor. All lymph nodes with counts of >10 times that of the background counts, whether or not blue dye positive, and all blue dye-positive lymph nodes, whether or not radiocolloid positive, were excised and labeled accordingly. All lymph nodes underwent frozen sectioning and were examined by hematoxylin and eosin and immunohistologic (cytokeratin) staining. RESULTS: Of the 59 patients, 48 had axillary lymph node dissection irrespective of the results of pathologic examination of the SLN. The success rate, sensitivity, negative predictive value, and accuracy were 93%, 100%, 100%, and 100% using the radiocolloid probe, 87%, 100%, 100%, and 100% using blue dye, and 93.5%, 100%, 100%, and 100% using combined methods, respectively. Concordance between blue dye and radiocolloid was 91% (the incidence of the number of sentinel nodes detected was 37.5%, 30.3%, 10.7%, and 21.4% for 1, 2, 3, and 4 or more lymph nodes, respectively). Metastatic lymph node involvement was found in 39.5% of patients. CONCLUSION: The sentinel node localization approach showed a high negative predictive value in breast cancer patients with multifocal or multicentric lesions, contrary to the common belief of significant false-negative results in these patients.

Adult↗
PubMed1992

[Histopathologic studies on whole organ giant section in breast cancer. II. Multicentricity and the chief primary lesion].

From April 1988 to January 1989, histopathologic studies on whole organ serial sections was done in 200 radical mastectomy specimens of female breast carcinoma. Results showed that the chief primary lesion measuring 0.5-1.0 cm or less in diameter had more multiple primary foci. With increasing size of the chief primary lesion, the incidence of multicentricity decreased. No significant relationship was found between the pathologic type of the chief primary lesion and multicentricity. But, in the non-invasive carcinoma, especially in carcinoma arising from the papillomatosis, invasive carcinoma of mucinous type and intraductal carcinoma with early infiltration were prone to develop multicentricity. The multicentricity in the second primary breast cancer was more common than in the first.

Adenocarcinoma, Mucinous↗
PubMedDate not supplied

Histopathologic differentiation of the main nodule determines outcome after hepatic resection for synchronous multicentric hepatocellular carcinomas.

BACKGROUND/AIMS: Clinicopathological features and outcome after surgery in patients with synchronous multicentric hepatocellular carcinoma were examined in relation to the histopathological grade of differentiation of the main nodule. METHODOLOGY: Two hundred and sixty-five patients with synchronous multicentric hepatocellular carcinoma (total, 683 nodules) who had undergone curative hepatectomy from 1988 through 1999 were studied retrospectively. In multicentric occurrences of hepatocellular carcinoma, the tumor with the largest dimension was defined as the main nodule, and the others as accessory nodules. RESULTS: The histopathological grade of differentiation of the main nodule was assessed to be well differentiated in 72 patients (27.2%), moderately differentiated in 160 patients (60.4%), and poorly differentiated in 33 patients (12.4%). Tumor size of the main nodule was significantly smaller in patients with well differentiated hepatocellular carcinoma than in patients with moderately or poorly differentiated hepatocellular carcinoma. Alpha-fetoprotein levels were significantly lower in cases in which the main nodule was diagnosed to be well differentiated hepatocellular carcinoma than in other cases. The 5-year survival rate and recurrence-free survival rate were significantly greater in cases in which the main nodule showed well differentiated hepatocellular carcinoma (78.1% and 33.8%, respectively) than in other cases [moderately differentiated 49.0% (p<0.0001), 11.6% (P=0.0002); poorly differentiated 37.4% (p<0.0001), 8.3% (P=0.0002), respectively]. Multivariate analysis identified the histopathological grade of the main nodule as significant independent prognostic factors. CONCLUSIONS: There were differences in surgical outcome in relation to the histopathological grade of differentiation of the main nodule in patients with synchronous multicentric hepatocellular carcinoma.

Aged↗
PubMed1991

Multicentric gliomas. Report of seven cases.

Multifocal gliomas fall into four main categories: diffuse, multiple, multicentric and multiple-organ. Multicentric gliomas are uncommon lesions of the central nervous system. Even more so are multicentric gliomas lying both above and below the tentorium (16 cases to date, as far we know). We report a clinical series of 7 cases, including 3 supra-infratentorial tumors. The distinctive features of multicentric gliomas are mainly the absence of gross or microscopic connections and absence of seeding along easily accessible routes like the cerebrospinal fluid pathways or the median commissures. We consider the pathogenetic hypotheses and problems of diagnosis, especially differential from other multifocal diseases of the central nervous system.

Adult↗
PubMed1991

Treatment of primary hypercholesterolaemia with simvastatin. New Zealand multicentre evaluation.

OBJECTIVE: To assess the efficacy of simvastatin in a large patient cohort. DESIGN: In an open multicentre study, after a four week placebo phase, patients were treated with simvastatin for 24 weeks; a subgroup continued therapy for a further 24 weeks. Efficacy of simvastatin (a) with prolonged use over three years, and (b) in combination with bezafibrate was assessed in an open single site study. SETTING: Lipid or cardiology specialist hospital outpatient clinics. PATIENTS: For the open multicentre study, 228 patients with primary hypercholesterolaemia (total cholesterol level greater than 6.5 mmol/L) were recruited, of whom 224 met entry criteria and completed the study. Forty-seven of these patients continued therapy for one year. In the open single site study, 22 patients (with low density lipoprotein [LDL] cholesterol levels greater than 4.3 mmol/L) participated in studies of long term use (n = 9) or of combined therapy (n = 13). INTERVENTION: Therapy in the open multicentre study began with 10 mg of simvastatin per day, doubling to 20 mg after six weeks and then 40 mg after 12 weeks of therapy if total cholesterol levels persisted above 5.2 mmol/L. In the study of long term use, simvastatin (40 mg daily) was taken continuously over three years. In the study of combination therapy, bezafibrate (600 mg daily) was taken in addition to simvastatin (40 mg daily) for 10 months. MAIN OUTCOME MEASURES: Plasma lipid and lipoprotein concentrations. RESULTS: In the multicentre study, total plasma cholesterol levels were reduced by 32.8% from 9.11 +/- 1.84 (in mmol/L, mean +/- SD) to 6.12 +/- 1.25 (P less than 0.001), and LDL cholesterol levels by 41.4% from 6.90 +/- 1.92 to 4.04 +/- 0.31 (P less than 0.001). The effect of therapy was sustained in those patients continuing therapy to 48 weeks. The study of long term use found no significant attenuation of effect over three years of monotherapy. Combined simvastatin/bezafibrate therapy reduced the LDL cholesterol concentration by a further 19.9% (P less than 0.001) from levels achieved on simvastatin alone. CONCLUSIONS: Simvastatin is an effective, well tolerated lipid lowering drug, without significant attenuation of effect with prolonged use. Simvastatin plus bezafibrate appears to be a potentially useful drug combination.

Adult↗
PubMed1989

[Multicentric cancer spread in the mouth cavity and oropharynx].

The clinical entity of multicentric cancerisation comprises multiple carcinomas arising from different anatomical sites and widespread carcinomas of multicentric origin. Over a period of 12 years multicentric cancerisation was diagnosed in 42 out of 150 patients (28%) with primary tumours of the oral cavity or the oropharynx. Patients with multicentric cancerisation are younger at the time of diagnosis of their first primary tumour, and their survival rates are worse compared with patients with only primary tumour. We conclude from our results that a routine panendoscopy should be performed in every patient presenting with a carcinoma of the oral cavity or the oropharynx to rule out a synchronous second primary tumour. Furthermore, these patients should be encouraged to stop smoking, to stop drinking spirits and to undergo regular follow-up examination.

Biopsy↗
PubMed1994

[Value of cytological analysis of the synovial fluid in multicentric reticulohistiocytosis. A case].

The authors report the case of a patient who had both multicentric reticulohistiocytosis--a systemic disease characterized by symmetric polyarthritis and papulonodular skin lesions--and an ovarian adenocarcinoma. Synovial fluid analysis found histiocytes with a ground-glass cytoplasm, binucleate giant cells, and undifferentiated cells undergoing mitosis. PAS-positive, diastase-resistant cells similar to the synovial fluid histiocytes were seen in the synovial and cutaneous biopsy specimens. These findings established the diagnosis of multicentric reticulohistiocytosis and suggested an underlying malignancy. Whether or not multicentric reticulohistiocytosis is a paraneoplastic syndrome remains unsettled. However, our report provides evidence that synovial fluid analysis can be helpful not only for the early diagnosis of multicentric reticulohistiocytosis but also for suggesting the presence of an underlying tumor, especially when arthritis is the presenting symptom.

Adenocarcinoma↗
PubMed1994

Possible multicentric occurrence of hepatocellular carcinoma: a clinicopathological study.

To assess the features of multicentric occurrence in hepatocellular carcinoma, we analyzed 10 of 72 patients (14%) who had undergone hepatic resection for hepatocellular carcinoma from May 1989 to October 1992 both clinically and pathologically. The multicentric occurrence of hepatocellular carcinoma was defined among the simultaneously detected small tumors as (a) at least one tumor consisting of extremely well-differentiated (grade I) hepatocellular carcinoma growing in a replacing pattern or (b) one of a group of hepatocellular carcinomas growing in an area of adenomatous hyperplasia. Of the 10 patients, the tumors in 9 were diagnosed as synchronous multicentric hepatocellular carcinomas, whereas the tumor in 1 was considered metachronous. All patients had cirrhosis; one of them had hepatitis B virus infection and nine patients had HCV infection. The inflammatory findings in the parenchyma were determined on the basis of serum enzyme values (AST, 89 +/- 27 IU/L; ALT, 96 +/- 43 IU/L). One or two tumors in 9 of 10 patients had thin trabecular or trabecular patterns showing replacing growth. In addition, one of the two tumors in two of nine patients was observed growing in areas of adenomatous hyperplasia. Recurrences were found in 4 of 10 patients. The 3-yr disease-free survival rate was 23%. Multiple recurrences were recognized in the two patients, and in the patients who underwent repeat surgery, grade I tumors were also found. Even though these tumors were small and well-differentiated, the recurrence rate was high. Therefore to detect the recurrence of metachronous multicentric hepatocellular carcinoma at an earlier stage, careful follow-up after surgery should be carried out.

Carcinoma, Hepatocellular↗
PubMed1993

Multicentric Castleman's disease in a child with prominent thymic involvement: a case report and brief review of the literature.

A fatal case of multicentric Castleman's disease (giant lymph node hyperplasia) with prominent thymic involvement in a 12-yr-old girl is presented. Multicentric Castleman's disease is a poorly understood lymphoproliferative disorder generally occurring in elderly individuals. To our knowledge, this is the first case in the English literature of multicentric Castleman's disease in a child. Thymic involvement has not been described previously in the multicentric variant or in a child. Besides the characteristic findings of Castleman's disease (CD), such as hyaline-vascular follicles and a prominent plasmacytic infiltrate, the thymus was also marked by prominent epithelial hyperplasia in the medulla. The clinical and pathologic findings are presented with a review of the literature, particularly thymic involvement in CD and CD in the pediatric population.

Biopsy↗
PubMed1996

Multicentric giant cell tumor of bone.

Giant cell tumor of bone accounts for 4% to 5% of primary bone tumors in the United States. Multicentric giant cell tumors occur in < 1% of all patients with giant cell tumors, and only 43 patients with multicentric giant cell tumor have been reported on in the literature. This series presents 3 additional cases of multicentric giant cell tumor, includes updated data for 2 patients previously reported on in the literature, and reviews 24 cases previously reported on in detail in the literature. The mechanism by which giant cell tumor involves multiple locations is not known. Multicentric giant cell tumor, in contrast to unifocal giant cell tumor, has a tendency to involve the hands, feet, and metaphysis/diaphysis of long bones and to occur in a slightly younger population. In 15 of the 29 patients reviewed, a second lesion did not develop for > 2 years after their initial presentation. Eighteen of those 29 patients had > 2 sites of tumor involvement, 1 of whom had 11 lesions. Two of the 5 patients in the authors' series presented with a spectrum of disease activity, with latent, active, and aggressive lesions present throughout the observation period.

Adolescent↗
PubMed1996

[Multicentric histiocytosis with hematological involvement].

INTRODUCTION: The aim of this work was to present a case of multicentric histiocytosis with haematologic involvement. CASE REPORT: A 68-year-old man presented with poor general health and a nodular eruption of the skin and larynx. On clinical examination there was an enlarged spleen and laboratory results revealed an inflammatory syndrome, platelet count 60,000 and myelemia with 10 p. 100 immature elements in a white cell count of 14,000. Pathology and ultrastructure examinations led to the diagnosis of multicentric histiocytosis. Bone marrow aspiration was normal. Pancytopenia then developed with bone marrow hypoplasia without infiltration. Corticosteroids then cyclophosphamide were uneffective for either the skin disease or the hematologic disorder. The patient developed severe buccal aphthosis which responded well to thalidomide. This treatment reduced the size and the number of skin nodules. Finally, renal failure of unknown origin was observed. DISCUSSION: Electron microscopy is essential for positive and differential diagnosis of atypical multicentric histiocytosis. Hematological disorders associated with multicentric histiocytosis may either be specific or totally independent.

Aged↗
PubMed1997

Genetic evidence for the multicentric origin of synchronous multiple gastric carcinoma.

Multiple gastric cancers, which constitute 4% to 10% of all gastric cancers, occur in older people and are associated with more extensive intestinal metaplasia. With regard to the genesis of multiple gastric cancers, multicentricity (independent origin) rather than multifocality (local or lateral spread of one cancer) has been the favored theory. Conventional morphologic study, however, has not been able to provide convincing evidence in support of multicentricity. The purpose of this study was to verify the multicentric origin of multiple gastric cancers at a genetic level. For this purpose, immunohistochemical and molecular techniques were used to define the mutation pattern of APC, MCC and p53 in multiple lesions of synchronous multiple gastric cancers. The study was based on a total of 30 gastric tumors from 13 patients, including 10 double tumors, 2 triple tumors, and 1 quadruple tumor. Single-strand conformation polymorphism and polymerase chain reaction direct sequencing were carried out for exons 5 to 8 of p53, and loss of heterozygosity was detected on the basis of polymerase chain reaction amplification of polymorphism in exon 10 of MCC and in exon 11 of APC. Twelve of 13 cases showed alteration in one or more genetic markers. Of these, three demonstrated a discordant mutation pattern of p53 in individual lesions, and another two revealed allelic loss of MCC in one lesion and p53 mutation in the other. In six other cases, only one lesion showed alteration of APC, MCC, or p53, and in the remaining case, one lesion carried p53 and MCC mutations and the other carried MCC loss of heterozygosity only. The results of this study showed discordance of the mutation pattern of APC, MCC, and p53 in individual lesions of multiple gastric cancers, providing genetic evidence for a multicentric origin of synchronous multiple gastric carcinomas. Collectively, these findings supported the theory of field cancerization in gastric carcinogenesis.

Adenocarcinoma↗
PubMed1997

Multicentric reference values: shared reference limits.

In order to obtain shared reference limits, three laboratories in the same geographical area with a homogeneous population have developed a proposal to produce multicentric reference values. The strategy simulates a virtual laboratory, actually formed by the laboratories involved; the reference limits produced in the virtual laboratory are in fact derived from the blend of reference values obtained by each laboratory. Each laboratory has chosen its own reference sample and has measured the biochemical quantities under study. Reference individuals (n = 171) and 15 biochemical quantities among the most measured in clinical laboratories were selected. The reference values obtained in each laboratory were blended when permitted by the Harris & Boyd test (Clin Chem 1990; 36:265-70). The multicentric reference limits obtained by the virtual laboratory for each quantity were estimated according to the recommendations of the International Federation of Clinical Chemistry. For each quantity, each laboratory, with the results observed in their reference sample, estimated the diagnostic specificity, using as cut-off values the corresponding multicentric reference limits. Each observed value of diagnostic specificity was compared with the theoretical diagnostic specificity value, equal to 0.975, that should be observed when a reference limit is used as cut-off value. The multicentric reference limits obtained by the virtual laboratory are valid in all cases with the exception of the upper reference limit for the concentrations of calcium(II) and urate in serum in one of the laboratories.

Adult↗
PubMed1986

Pathologic findings from the National Surgical Adjuvant Breast Project (protocol 6). II. Relation of local breast recurrence to multicentricity.

One hundred ten local breast recurrences were observed in 1108 pathologically evaluable patients enrolled in NSABP protocol 6 who were treated by lumpectomy and followed for 5 to 95 months (average, 39 months). Eighty-six percent and 95% of all local breast recurrences were noted within 4 and 5 years, respectively, following lumpectomy. Life table analysis revealed their incidence to be 24% for those not and 6% for those receiving lumpectomy and breast irradiation. One hundred four (95%) of the breast recurrences involved the mammary parenchyma and the remaining 6 (5%) involved the skin and/or nipple only. Eleven (10%) of the former were noninvasive. The most common (86%) presentation of breast recurrence appeared to be a localized mass within or close to the quadrant of the index cancer. In 14% the recurrence not only involved the same quadrant, but was more diffuse within the breast extending to remote areas as well. This type was characterized pathologically by marked intralymphatic extension as well as involvement of the overlying skin and/or nipple after the fashion of so-called inflammatory or occult inflammatory breast cancer. The recurrences noted in the skin and/or nipple only were also pathologically characterized by intralymphatic involvement at these sites in the majority of instances. These two forms of breast recurrences appear to reflect the localized growth of highly aggressive invasive breast cancers. The concordance of histologic types and grades of the index and recurrent cancers implies that such events represent growth of overlooked tumor, a deficiency attendant with lumpectomy due to the extreme multifocal nature (not multicentricity) of some breast cancers and/or inadequacies in evaluating the lines of resection of lumpectomy specimens. Sources of error in regard to this latter are identified and guidelines for the examination of such specimens, as well as the assessment of margins, are presented. The observation that local breast recurrences noted following lumpectomy occurred within or close to the same quadrant as the index cancer, despite the presence of multicentric noninvasive cancers in 10% of the patients treated by total mastectomy, minimizes the biological and clinical significance of multicentric foci of cancer present in some breast cancers. Cancer measuring greater than or equal to 2.0 cm, having high histologic and nuclear grades, or intralymphatic extension, were found to have a statistically significant association with local breast recurrence in all patients following lumpectomy. A converse relationship was noted with tubular and scar cancers of types 1 and 4.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗
PubMed1992

Adenocarcinoma of the proximal small intestine. A marker for familial and multicentric cancer?

BACKGROUND: Adenocarcinoma of the small intestine is uncommon. The Hawaii Tumor Registry (HTR) has identified 49 of these tumors since 1960, and the Japan-Hawaii Cancer Study (JHCS) has identified only four of these tumors among a cohort of 8006 Hawaiian-Japanese men followed up for a period of 22 years. Each of the four men reported by the JHCS had multicentric gastrointestinal cancers. METHODS: Newly diagnosed cancers are recorded separately by the HTR and JHCS, and linkage is maintained between the two files. Family histories are available from the JHCS, and these are supplemented by a state population file maintained by the Department of Genetics, University of Hawaii. RESULTS: Five men, all Japanese, were found to have carcinoma of the proximal small intestine. Each had multicentric carcinomas of the gastrointestinal tract. Carcinoma of the stomach and colon was found in the primary relatives of each of four men whose families lived in Hawaii. CONCLUSIONS: The familial clustering of uncommon neoplasms (small bowel carcinoma and multicentric large bowel carcinoma), and the concurrence of gastric and colonic carcinoma suggests that these subjects have a genetic trait that increases susceptibility to a broad range of carcinogens.

Adenocarcinoma↗
PubMed2000

Multicentric reticulohistiocytosis: case report with immunohistochemical analysis and literature review.

This report describes the case of a patient with multicentric reticulohistiocytosis. Immunohistochemical analysis revealed prominent markers of monocyte/macrophage origin, as well as the presence of tumor necrosis factor alpha, interleukin-1beta (IL-1beta), and IL-12; the occurrence of the latter in this disease has not previously been reported. Clinical, laboratory, radiographic, and histologic findings in multicentric reticulohistiocytosis are reviewed. In addition, all published cases of multicentric reticulohistiocytosis which included reports of cytokine and immunohistochemical analysis are reviewed, and evidence for a monocyte/macrophage origin and role in disease pathogenesis is provided.

Adult↗
PubMed2005

Successful hematopoietic stem-cell transplantation in multicentric Castleman disease complicated by POEMS syndrome.

A 39-year-old male presented with pedal edema, pleural effusion, splenomegaly, and generalized lymphadenopathy. Serum protein electrophoresis demonstrated the presence of a monoclonal protein. Histological examination of the spleen following splenectomy showed multifocal vascular proliferation and angiovascular lesions consistent with multicentric Castleman disease. He was treated with steroids and rituximab, but without improvement. The patient was found to have portal venous thrombosis and lower extremity arterial thrombosis. He then received combination chemotherapy with cyclophosphamide and mitoxantrone but developed a severe inflammatory polyneuropathy that left him disabled and wheelchair-bound. A diagnosis of multicentric Castleman disease with POEMS syndrome was made, and he then received high-dose chemotherapy with melphalan followed by autologous peripheral blood stem-cell transplantation. Following transplantation, his nerve conduction studies improved and his serum protein electrophoresis normalized. He is currently ambulatory and does not need wheelchair assistance. Hematopoietic stem-cell transplantation may be a treatment option for patients with multicentric Castleman disease and POEMS syndrome.

Adult↗
PubMed2002

Close association between high serum alanine aminotransferase levels and multicentric hepatocarcinogenesis in patients with hepatitis C virus-associated cirrhosis.

BACKGROUND: Multicentric development of hepatocellular carcinoma (HCC) is a characteristic feature of hepatitis C virus (HCV)-associated cirrhosis (HCV-LC). In this study, the objective was to determine whether the persistent elevation of the serum alanine aminotransferase (ALT) level, which represents the inflammatory necrosis of hepatocytes, is correlated with the multicentric development of hepatocellular carcinoma (HCC) in patients with early-stage HCV-LC. METHODS: Ninety-three consecutive patients with biopsy proven HCV-LC (Child Stage A) who had been followed for > 5 years for the development of HCC were studied. They were subdivided into three groups according to their serum ALT level: Group A included 33 patients with annual average serum ALT levels that were persistently high (> or = 80 IU; high ALT group), Group B included 41 patients with annual average serum ALT levels that were persistently low (< 80 IU; low ALT group), and Group C included 19 unclassified patients. The patients had been studied prospectively with frequent ultrasonography and magnetic resonance imaging or computed tomography (CT) scans for > 5 years. When the development of HCC was suspected, angiography, infusion of lipiodol into the hepatic artery, and lipiodol-CT scans were performed in all patients to determine the number of HCC nodules. RESULTS: In Group A, 27 patients (81.8%) developed HCC. Seventeen of 27 patients (63.0%) had multiple nodules. In contrast, in Group B, only 12 patients (29.3%) developed HCC, and only 1 of these 12 patients (8.3%) had multiple nodules. There was a significant difference between Groups A and B in the incidence of developing HCC (P < 0.001) and developing multiple nodules (P = 0.006). In addition, among the male patients, the incidence of developing multiple HCC nodules in Group A (12 of 19 patients; 63.2%) was significantly higher (P < 0.05) compared with the incidence in Group B (0 of 6 patients; 0%). The same tendency was observed among the female patients. CONCLUSIONS: These results showed a close correlation between multicentric hepatocarcinogenesis and sustained necroinflammation of the liver in patients with HCV-LC.

Aged↗