Histologic criteria for the diagnosis of gastric low-grade malt lymphoma

Low-grade B cell lymphoma of the stomach have the features of mucosa-associated lymphoid tissue (MALT) and is characterised by lymphoid hyperplasia and infiltrations of lymphocytes into glandular epithelium or lymphoepithelial lesions. It may be difficult to distinguish low-grade lymphomas from benign inflammatory lymphoid infiltrates. Nine primary gastric lymphomas and 20 benign lymphoid hyperplasia were investigated for the type of tumour cells, lymphoepithelial lesions. Dutcher bodies, cytologic atypia, the density of lymphoid infiltrates, invasion of the muscularis mucosae, germinal centers, reactive epithelial atypia and acute inflammation. Our results suggest that B cells proliferation, lymphoepithelial lesions, cytologic atypia and Dutcher bodies are very important for the diagnosis of low-grade MALT lymphoma. None of these was seen in inflammatory infiltrates. The presence of germinal centers, acute inflammation and reactive epithelial atypia does not exclude a diagnosis of low-grade gastric lymphoma.     

Common clonal origin of lymphocytes and plasma cells in splenic lymphoma with villous lymphocytes

In two-thirds of patients with splenic lymphoma with villous lymphocytes (SLVL) a small amount of M-protein can be detected in association with the presence of plasma cells in the peripheral blood (PB) and/or bone marrow (BM). However, it is not known whether lymphoma cells and plasma cells originate from the same clone. In this report we describe a case of SLVL which was characterized by the presence of marked monoclonal gammopathy (IgG-kappa 90 g/l) and increased plasma cells in the BM. In an attempt to elucidate the origin of lymphoma cells and plasma cells, we performed morphological, cytogenetic and molecular studies on PB mononuclear cells (PBMNC) without plasma cells and BMMNC containing 10% plasma cells from this patient. Immunofluorescence showed that lymphoma cells and plasma cells were positive for cytoplasmic gamma heavy and kappa light chains. Well-developed endoplasmic reticulum was observed in the cytoplasmic organelles of PBMNC using an electron microscope. The mean IgG concentration in the 3 d supernatant cultures of PBMNC was 374 +/- 24 microg/l. More than 50% PBMNC differentiated into plasmacytoid cells in 6 d of liquid culture with IL-3 and IL-6. Analysis by two-colour FISH revealed that karyotypic abnormalities of monosomy X and trisomy 17 existed simultaneously in both lymphoma cells and plasma cells. JH gene rearranged bands from PBMNC and BMMNC by Southern blot hybridization were identical, whereas DNAs from PBMNC failed to hybridize with the Cmu probe. These observations strongly suggest that lymphoma cells and plasma cells originate from the same clone, and that plasma cells, as well as lymphoma cells, which have undergone class switch recombination, could produce IgG type M-protein in this case.     

Clinical features, treatment and outcome in a series of 93 patients with low-grade gastric MALT lymphoma

The purpose of this paper is to report the clinical characteristics and treatment outcome following different therapeutic approaches in a large series of patients with primary low-grade MALT lymphoma of the stomach. A total of ninety-three patients (median age 63 years) were reviewed. The patients were treated by different modalities (local treatment alone, combined treatment, chemotherapy, antibiotics alone); seven patients refused any treatment. The antibiotic-treated group of patients was prospectively followed with regular endoscopic biopsies, and their responses were histologically evaluated. The 5-years projected overall survival is 82% (95% C.I.; 67%-91%) in the series as a whole. Second tumors were observed in 21.5% of the patients in this series (95% CI 14%v to 31%). There was no apparent difference in overall survival and event-free survival between patients who received different treatments. In the antibiotic-treated group histologic regression of MALT lymphoma was documented in 67% of patients (95% CI 51% to 80%). In conclusion the indolent nature of the disease justifies a conservative approach. The use of antibiotics as first-line therapy may avert or at least postpone the indication for surgical resection in the majority of patients.     

Cure of Helicobacter pylori infection and duration of remission of low-grade gastric mucosa-associated lymphoid tissue lymphoma

BACKGROUND: Low-grade B-cell lymphomas arising in mucosa-associated lymphoid tissue (MALT) are most frequently localized in the gastrointestinal tract. More than 90% of gastric MALT lymphomas are diagnosed in patients with chronic, Helicobacter pylori-associated gastritis. High remission rates for these lymphomas have been observed after the cure of H. pylori infection. Data are lacking, however, with regard to the duration of the remissions. To address this question of remission duration, we have followed 50 patients in whom H. pylori infections were eradicated, and we determined whether the patients in complete remission displayed evidence of residual monoclonal B cells during follow-up. METHODS: Patients were treated with amoxycillin and omeprazole for 2 weeks in an attempt to cure H. pylori infections. Follow-up included endoscopic investigations with biopsy sampling. Monoclonal B cells in biopsy specimens were detected by means of a polymerase chain reaction (PCR)-based assay. RESULTS: H. pylori infections were cured in all 50 patients. The median follow-up for the 50 patients is currently 24 months (729 days; range, 135-1411 days). Forty patients achieved complete remission of their lymphomas, but five have subsequently relapsed. The median time of continuous complete remission for the 40 patients was 15.4 months (468 days; range, 0-1198 days). Among six patients whose Iymphomas did not respond to H. pylori eradication, four revealed high-grade lymphomas upon surgery. PCR indicated the presence of monoclonal B cells during follow-up in 22 of 31 assessable patients in complete remission. CONCLUSIONS: Complete remissions of low-grade gastric MALT Iymphomas after the cure of H. pylori infection appear to be stable, although most patients display evidence of monoclonal B cells during follow-up. Whether these patients are truly cured of their Iymphomas remains to be determined.     

Frequency of vacA genotypes and cytotoxin activity in Helicobacter pylori associated with low-grade gastric mucosa-associated lymphoid tissue lymphoma

The vacA genotypes s1,m1 and s1,m2 were detected in 44 and 30% of Helicobacter pylori isolates, respectively, from patients with gastric mucosa-associated lymphoid tissue lymphoma, compared to 26 and 56% of isolates, respectively, from individuals with gastritis. The vacA s1 genotype was significantly associated with, but not predictive of, the presence of vacuolating cytotoxin activity.     

添加剂对低品位菱铁矿制备高品位碳化铁的影响

低品位菱铁矿作为一种典型的难处理铁矿目前难以应用于钢铁行业.为了促进低品位菱铁矿的利用,提出了渗碳-磁选-酸浸制备优质电炉原料(碳化铁)的新工艺,并探究了添加剂对菱铁矿球团渗碳产物中碳化铁和脉石分离的作用机制以及对酸浸过程中碳化铁提纯效果的影响规律.结果 表明,添加剂能显著促进碳化铁颗粒长大、改善碳化铁与脉石的嵌布关系...     

Minimally invasive management of low-grade and benign gastric tumors

BACKGROUND: Benign gastric tumors and tumors of low-grade malignancy can be safely removed laparoscopically. METHODS: Seven patients were considered candidates for laparoscopic resection of gastric tumors. Inclusion criteria included small tumor size (less than 6 cm), exophytic or endophytic tumor morphology, and benign characteristics. Indications for surgical intervention included bleeding, weight loss, and need for tissue diagnosis. Patients ranged in age from 38 to 70. There were five female and two male patients. All patients underwent preoperative upper GI endoscopy. The procedures were performed using a four- or five-port technique. An Endo-GIA (US Surgical Company, Norwalk, Connecticut) was used to amputate those tumors located on the serosal surface of the stomach. Tumors on the mucosal surface were exposed via a gastrotomy, then likewise amputated using an Endo-GIA. The gastrotomy closure was then either hand sewn or stapled. Operating time ranged from 95 to 225 min. RESULTS: Final pathologic diagnoses included lipoma, lymphoma, leiomyoma, and leiomyosarcoma. There was a 28% conversion rate. There were no complications. Length of postoperative stay ranged from 4 to 7 days. There have been no tumor recurrences in 6-38-month follow-up. CONCLUSIONS: Minimally invasive management of benign and low-grade gastric tumors can be performed safely with excellent short- and long-term results.     

Ongoing somatic mutations and clonal expansions after cure of Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue B-cell lymphoma

PURPOSE: Although most patients with primary gastric low-grade mucosa-associated lymphoid tissue (MALT) B-cell lymphoma experience complete endoscopic and histologic remission after the cure of Helicobacter pylori infection, in many patients, the polymerase chain reaction (PCR) still detects monoclonal B cells in the gastric mucosa. The present study asked whether the lymphoma immunoglobulin VH (IgVH) sequences remained stable in patients with gastric MALT lymphoma after H pylori eradication. PATIENTS AND METHODS: Eight patients with stage EI disease treated with H pylori eradication were analyzed before and at different time points after the cure of the infection. After the amplification of IgVH genes from DNA extracted from gastric biopsy specimens, monoclonal PCR products were cloned and multiple clones (43 to 105) were sequenced per patient. RESULTS: Mutations were detected in all lymphoma VH sequences, which suggested germinal center or postgerminal center origin of the lymphoma B cells. In five of the eight patients, clonal heterogeneity was observed at diagnosis or during follow-up. Genealogical analysis of shared and unshared mutations showed that the process of somatic mutations was ongoing after H pylori eradication in four of the five patients who showed clonal instability. Ongoing mutations were observed in three of the four patients who completely responded to H pylori eradication, but in only one of the four patients who did not respond or who partially responded. CONCLUSION: In low-grade gastric MALT lymphomas, an ongoing process of somatic hypermutation and antigen selection can be detected after the therapeutic removal of the underlying stimulus H pylori. These data point to the relevance of yet unknown antigens that drive this disease. In addition, they challenge the view that these lymphomas may be cured solely by the eradication of H pylori.     

Multifocal renal cell carcinoma: evidence for a common clonal origin

The reported incidence of satellite tumor lesions in kidneys resected by radical nephrectomy for renal cell carcinoma (RCC) is 7-25%; however, genetic analyses of satellite tumors in comparison with those of main tumor lesions have not been performed well. In the present study, we investigated the incidence of loss of heterozygosity (LOH) at chromosome arms 3p, 6q, 8p, 9p, 9q, and 14q using 18 microsatellite markers in 10 nonpapillary RCCs of 50 mm or less in diameter and the accompanying satellite tumor lesions to evaluate the genetic alterations in main and satellite tumors. LOH was detected in 10, 3, 5, 3, 2, and 3 cases at chromosome arms 3p, 6q, 8p, 9p, 9q, and 14q, respectively. In addition, primary and satellite tumor lesions in 8 of 10 cases exhibited identical patterns of LOH on the 18 loci examined. In the remaining two cases, both main and satellite tumors demonstrated LOH on the common seven and three loci, respectively, whereas for another locus, LOH was observed only in the satellite tumor lesions. The similarity of LOH patterns detected in main and satellite tumor lesions indicates that the presence of satellite tumors might be the result of intrarenal metastasis from the main tumor lesion. These findings strongly suggest that even in case of small nonpapillary RCC, nephron-sparing surgery might carry the risk of failing to prevent postoperative local recurrence due to the incomplete resection of unrecognized satellite tumors with genetic alterations similar to those of the main tumor.     

Transformation of mycosis fungoides: T-cell receptor beta gene analysis demonstrates a common clonal origin for plaque-type mycosis fungoides and CD30+ large-cell lymphoma

We investigated the consequences of Sr2+ binding to the transport sites of sarcoplasmic reticulum (SR) Ca(2+)-ATPase for two fluorescent conformational probes located in different regions of the ATPase. Using SR vesicles in which Lys-515 in the ATPase had been previously labeled with fluorescein 5'-isothiocyanate (FITC), we found that the Sr(2+)-induced a drop in the fluorescein fluorescence of this FITC-labeled ATPase shifted toward lower Sr2+ concentrations than the Sr(2+)-induced rise in Trp fluorescence for the same FITC-labeled ATPase. The curve describing the Sr(2+)-dependent rise in Trp fluorescence had a characteristic asymmetric shape, and the changes in Trp fluorescence occurred in parallel with the activation by Sr2+ of pNPP hydrolysis by the ATPase. Analysis of these results in terms of the simplest scheme describing the sequential binding of the two Sr2+ ions suggests that under the conditions of these experiments, i.e. at neutral pH in the presence of potassium, the Sr(2+)-induced rise in the Trp fluorescence mainly reflected the formation of ATPase with two ions bound to the transport sites, whereas the binding of a single Sr2+ ion was virtually sufficient to reduce the fluorescence of bound FITC to its minimal level.     

Quality of life in patients with low-grade non-Hodgkin's lymphoma

Low-grade non-Hodgkin's lymphoma (NHL) is an indolent form of the disease with a generally slow course of progression. Although still usually incurable, low-grade disease has shown responsiveness to some of the newer chemotherapeutic and nonchemotherapeutic treatment options. However, since cure remains elusive, and since many patients with lowgrade NHL may have few or even no symptoms initially, the decision about whether or not to initiate treatment logically must include quality-of-life (QOL) issues. This paper summarizes clinical and diagnostic characteristics of low-grade NHL that have some bearing on QOL considerations. Adverse effects of the more common treatment approaches are discussed according to their QOL implications, illustrating the relevance of QOL to the clinical management of low-grade disease. Finally, data from an ongoing study using the Functional Assessment of Cancer Therapy (FACT) measurement system are presented. These data offer a basis for comparing the QOL of patients with NHL to that of individuals with other solid tumors, and also illustrate the effects of chemotherapy on QOL.     

Value of radiotherapy in disseminated high-grade non-Hodgkin''s lymphoma]

The usefulness of immunohistochemical demonstration with anti-bromodeoxyuridine (BrdU) monoclonal antibody for estimating proliferative activity was evaluated in experimental meningeal carcinomatosis model. The experimental model was developed by inoculation of 1 x 10(4) Walker 256 carcinosarcoma cells into the cisterna magna of female Wistar rats. Every consecutive day after tumor inoculation, the rat was perfused by saline and then sacrificed 30 min after intravenous BrdU (200 mg/Kg) injection. The brain was removed, fixed in 80% ethanol and embedded in paraffin. Coronal sections of the brain 6 mu in thickness were obtained and stained immunohistochemically using the indirect immunoperoxidase (ABC) method with anti-BrdU monoclonal antibody (Becton-Dickinson). The sections were counterstained by hematoxylin. Labeling index (LI) which represented the percentage of tumor cells in synthetic phase was obtained by counting immunoreactive cells under the microscope. LI was as low as 10.8% to 16.9% in the first 3 days after tumor inoculation. Four to 6 days after tumor inoculation when tumor cells grew several layers in the subarachnoid space, LI was 24.0% to 40.1%. LI increased to reach a plateau around 40.7% to 48.2%, 7 to 9 days after tumor inoculation. Ten days after inoculation when necrosis appeared in the tumor, BrdU-positive cells declinded and LI was between 29.1% to 35.0%. It is a useful method to estimate the proliferative activity of the experimental brain tumors, design treatment modalities and evaluate the effect of chemotherapeutic agents by using immunohistochemical demonstration with anti-BrdU monoclonal antibody. Therefore, we suggest that chemotherapy against malignant leptomeningeal tumors shall be carried out in early or intermediate stage before the proliferative activity reaches its plateau stage.     

Primary hepatic high-grade non-Hodgkin's lymphoma and chronic hepatitis C infection

Little is known about the coincidence of hepatitis C virus infection (HCV) and non-Hodgkin's lymphoma, although there is an increased incidence of chronic HCV infection with cryoglobulinemia type II and, interestingly, low-grade non-Hodgkin's lymphoma (NHL) in a few patients. We therefore report on a 74-year-old white male with known chronic hepatitis C virus infection who was admitted to the clinic due to weight loss and pain in the right upper quadrant. Ultrasound examination was performed for suspected hepatocellular carcinoma since a lesion in the left lobe of the liver was seen. X-ray of the lungs showed a few scattered lesions, suggestive of metastases. The ultrasound-guided fine-needle puncture revealed a high-grade malignant B-cell NHL While alpha-fetoprotein was normal, both cryoglobulin type II and the polymerase chain reaction (PCR) for HCV were positive. After six cycles of chemotherapy consisting of CHOP, the patient showed complete remission over three years. Ultimately, he died due to a sudden myeloic blast crisis. In summary, we discuss the possible etiopathologic role of the hepatitis viruses in the occurrence of non-Hodgkin's lymphoma. As we and others showed that HCV infects peripheral mononuclear blood cells (PBML), the infected PBML not only may be a source for reinfection after orthotopic liver transplantation, but also could be the cause for transformation and monoclonal propagation of lymphomatous tissue.     

AMOPLACE treatment of intermediate-grade and high-grade malignant lymphoma: a Cancer and Leukemia Group B study

To address the question of whether complete seizure relief has a positive effect on psychosocial functioning in patients with temporal lobe epilepsy, a follow-up study was conducted at the Montreal Neurological Institute. The approach was one of "before-after" study, with focus on the successfully operated patients, those in whom complete seizure relief was obtained. The Washington Psychosocial Seizure Inventory, specifically developed and validated for use with epilepsy patients, was used for psychosocial assessments. Of 30 surgically treated patients screened for the study, 15 gained complete relief from seizures. At 1-year postoperative follow-up, they showed reductions in their problems scores on all but one of eight psychosocial scales; the average reduction ranged from 24% in Vocational Adjustment to 60% in Adjustment to Seizures. In the areas of Emotional Adjustment and Interpersonal Adjustment reductions were 37 and 48%, respectively. Among the component items, improvement was greatest in ability to concentrate and make decisions, confidence in interpersonal skills, ability to express personal opinions, and perception by others. No appreciable changes occurred in the 15 patients who did not gain complete relief of seizures; indeed, on six of the eight scales they showed a modest increase in their problem scores. This study provides evidence that complete relief from seizures leads to appreciable improvements in psychosocial well-being, manifest as early as 1-year postoperatively, in young adult patients.     

Bronchioloalveolar adenocarcinoma of lung: monoclonal origin for multifocal disease

In an attempt to understand the histogenesis and molecular pathogenesis of multifocal bronchioloalveolar lung carcinoma (BAC) we studied 28 cases of BAC using a topographic genotyping approach for the presence of K-ras exon 1 mutations and p53 loss of heterozygosity (LOH). This analytical approach demonstrated K-ras exon 1 mutations in 12.5% of solitary BACs, 40% of BACs with microscopic or macroscopic satellite lesions, and 60% of BACs with intrathoracic metastases. In all cases with K-ras mutations, the identical point mutation was present in the primary, satellite, and intrathoracic metastatic lesions. When p53 LOH was demonstrated in the primary lesion, it was also detected in the satellites and intrathoracic metastases. No significant association was noted between the presence of K-ras mutations and p53 LOH. The results strongly support a monoclonal origin of multifocal BACs. Furthermore, the findings support the theories explaining the origin of multifocal BAC by intraalveolar route of spread, intrapulmonary lymphatic spread, or aerosolization leading to implantation at different sites. A trend toward an increased frequency of K-ras mutations and p53 LOH in BACs with satellites or metastases compared to solitary BACs was noted.     

A clinicopathologic study of primary gastric lymphoma of B-cell type among the Japanese with special reference to low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT)

The most common primary site of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is the gastrointestinal tract, particularly the stomach. The relationship of MALT lymphomas, however, with the more commonly occurring large B-cell gastric lymphoma has not been directly discussed except in the report of Chan et al. (1990), which lacked clinical information regarding the behavior of these tumors. To elucidate the relationship between high-grade large-cell lymphoma and MALT lymphoma, we studied in detail the histopathological and clinicopathologic features with the survival date of 77 Japanese cases of primary gastric lymphoma (PGL) of B-cell type. Based on degree of morphologically recognizable low- or high-grade components of the tumor, PGL was divided into four types: 18 cases of pure MALT lymphoma (type I); 13 cases of MALT lymphoma with small area of high-grade lymphoma (type II); 22 cases of high-grade lymphoma with small areas of MALT lymphoma (type III); and 24 cases pure high-grade lymphoma (type IV). Corresponding to the differences in the histologic pictures of each type, there were differences in the gross appearance, pathologic stage (including depth of invasion) and prognosis. These data suggests that both MALT and high-grade lymphomas of the stomach belong to the same cell lineage and constitute a pathological spectrum and that the histological grouping of PGL is clinico-pathologically useful.     

Distinct patterns of chromosomal alterations in high- and low-grade head and neck squamous cell carcinomas

Comparative genomic hybridization was performed on 30 primary head and neck squamous cell carcinomas. Fractional or entire DNA loss of chromosome 3p was a basic finding that occurred in 29 cases (97%). Additional DNA underrepresentations were observed in more than 50% of the cases on chromosomes 1p, 4, 5q, 6q, 8p, 9p, 11q, 13q, 18q, and 21q. Deletions on chromosomes 3p, 13q, and 17p were confirmed by loss of heterozygosity analysis. Entire or partial DNA copy number increases were identified for chromosome 3q in 26 cases (87%) with high-level amplifications at 3q24 and 3q27-qter. Overrepresentations were found in decreasing order of frequency at 11q13 (70%), 8q (57%), 19q (50%), 19p (47%), and 17q (47%). The use of comparative genomic hybridization superkaryograms of the group of well-differentiated carcinomas (G1) indicated that the deletions on chromosomes 3p and 9p along with the overrepresentation of 3q are associated with early tumor development. Accordingly, the undifferentiated tumors (G3) were characterized by additional deletions on chromosomes 4q, 8p, 11q, 13q, 18q, and 21q and overrepresentations on 1pter, 11q13, 19, and 22q, suggesting that these changes are preferentially associated with tumor progression.