Clinicopathological features of gastric mucosa-associated lymphoid tissue lymphoma: A comparison with diffuse large B-cell lymphoma without a mucosa-associated lymphoid tissue lymphoma component

BACKGROUND AND AIMS: The aim of this study was to clinicopathologically distinguish the pathogenesis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma without a MALT lymphoma component (DLL). METHODS: We investigated clinicopathological features of these gastric lymphomas including age, sex ratio, tumor location and depth, macroscopic appearance, and infection with Helicobacter pylori of these gastric lymphomas and hepatitis viruses in 24 patients with gastric low-grade MALT lymphoma, 10 patients with high-grade MALT lymphoma, and 19 patients with DLL. The frequency of H. pylori infection in lymphoma patients was compared with that in age- and sex-matched control subjects. RESULTS: There was a predominance of females with MALT lymphoma (male to female ratio, 8/16 for low-grade MALT lymphomas and 1/9 for high-grade MALT lymphomas), and there was a predominance of males with DLL (male to female ratio, 13/6); the ratios differed significantly (P < 0.05). Ninety-two percent of low-grade MALT lymphomas and 80% of high-grade MALT lymphomas were confined to the mucosal and submucosal layers, but lymphoma cells invaded the muscular layer or more deeply in 74% of DLL. Helicobacter pylori infection occurred significantly more often in patients with low-grade MALT lymphoma than in age- and sex-matched controls (96 vs 67%, P < 0.01). Conversely, the frequency of H. pylori infection in DLL patients did not differ from that in controls. CONCLUSIONS: These data suggest that H. pylori infection may be associated with the development of gastric MALT lymphoma, but not DLL, and that MALT lymphoma and DLL may have a different pathogenesis.     

Presence of a high-grade component in gastric mucosa-associated lymphoid tissue (MALT) lymphoma is not associated with an adverse prognosis

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B cell lymphoma (DLBCL) show a spectrum of disease characterized by varying proportions of low-grade and high-grade components. While the natural history and optimum treatment for low-grade gastric MALT lymphoma and DLBCL is well established, the prognosis and optimal treatment of patients with both low- and high-grade components is not well established. The purpose of our study was to evaluate the clinical characteristics, survival outcomes, and prognostic factors of patients with gastric MALT lymphoma and gastric DLBCL. A retrospective review of patients with gastric MALT lymphoma, gastric DLBCL, or MALT lymphoma with a high-grade component treated at our centers from 1994 to 2006 was performed. Patients were divided into three categories: “pure MALT lymphoma,” “MALT lymphoma with high-grade component” (mixed), and “pure DLBCL.” Seventy-six patients were included in our study—26 with pure MALT, 22 with MALT with high-grade component (“mixed”), and 28 with pure DLBCL. Pure MALT lymphoma and mixed lymphoma patients had similar clinical characteristics, whereas pure DLBCL patients had less favorable disease characteristics with significantly poorer performance status, higher number of extranodal sites of disease, higher stage, and larger proportion of bone marrow involvement and international prognostic index (IPI) scores compared with mixed lymphoma. The majority of mixed lymphoma (72.7%) and DLBCL patients (71.4%) were treated with chemotherapy. Of patients receiving chemotherapy, a higher proportion of mixed lymphoma and DLBCL patients received anthracycline-based combination chemotherapy regimens compared with MALT lymphoma (73% vs 71% vs 8%) whereas the proportion of mixed lymphoma and DLBCL patients was similar (p = 0.919). At a median follow-up of 37 months, the 5-year overall survival was 66.9%. The 5-year overall survival was 78% for MALT lymphoma, 84% for mixed lymphoma, and 45% for DLBCL. On univariate analysis, DLBCL histology, age, performance status, serum albumin, lactate dehydrogenase, bone marrow, number of extranodal sites, stage, and IPI score were prognostic for inferior survival. On multivariate analysis, DLBCL histology remained significantly prognostic for inferior survival, independent of chemotherapy regimen (hazard ratio (HR) 6.66, 95% confidence interval (CI) 2.01–21.41, p = 0.001). Mixed histology was not prognostic for inferior survival (HR 1.13, 95% CI 0.28–4.54, p = 0.868). Other factors prognostic for inferior survival were serum albumin <37 g/L (HR 3.22, 95% CI 1.11–13.22, p = 0.034) and treatment with non-cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy (HR 4.89, 95% CI 1.67–14.36, p = 0.004). In conclusion, the clinical characteristics of mixed histology MALT lymphoma are similar to low-grade MALT lymphoma and significantly different from pure DLBCL. The prognosis of mixed histology MALT lymphoma is significantly better than pure DLBCL, independent of IPI and chemotherapy regimen, and pure DLBCL histology is independently prognostic of inferior survival outcome.     

p27kip1 expression is inversely related to the grade of gastric MALT lymphoma

Background: Decreased or lost expression of the cyclin-dependent kinase inhibitor p27^kip1 protein has been found to be a poor prognostic factor in many cancers, including gastric cancer. Aim: To evaluate p27^kip1 expression in gastric mucosa-associated lymphoid tissue (MALT) and gastric B-cell lymphoma. Methods: Fifty-two cases of gastric lymphoma, mean age 68.7 yr (range 23–90 yr), 11 of chronic Helicobacter pylori-associated gastritis, and 5 of normal gastric mucosa were studied. Patients were classified into two groups. Stage IE gastric lymphomas were defined as local gastric lymphoma of MALT and more advanced stages as advanced gastric lymphoma. Twenty-three patients diagnosed as stage IE, 13 of these were low-grade and 10 diffuse large B-cell lymphoma (DLBL). Twenty-nine patients were at stage IIE or above, 18 with low-grade and 11 with DLBL. Serial sections were evaluated by immunohistochemistry after staining with antibodies against p27/Kip1 and Ki-67. Results: The proliferative index was higher in gastric DLBL than in low-grade MALT lymphomas, 57.1±31.2 vs 17.3±20.6 (p=0.0001). The mean p27^kip1 expression score for high-grade patients was significantly lower compared with that of low-grade patients, 0.5 ± 0.4 and 1.6±0.8, respectively (p=0.001). Comparative evaluation of p27^kip1 expression in malignant lymphoid cells revealed that B cells of the localized gastric DLBL patients expressed the least p27^kip1, 0.36±0.32. This value was lower than that of malignant lymphoid cells of patients with advanced DLBL, 0.64±0.53, advanced low-grade MALT lymphoma, 1.59±0.79, and localized low-grade MALT lymphoma, 1.59±0.84. In the multivariate model in which all p27^kip1 variables were entered, the expression of p27^kip1 in malignant lymphoid cells was inversely correlated with the grade of the lymphoma irrespective of the stage of the disease (p=0.0001), and significantly predicted grade: OR:0.07, 95% CI 0.07–0.31, p=0.0001. Conclusion: p27^kip1 may be a putative distinct molecular marker to differentiate between low-grade and high-grade gastric lymphoma.     

Expression of CD86 and increased infiltration of NK cells are associated with Helicobacter pylori-dependent state of early stage high-grade gastric MALT lymphoma

AIM: A high percentage of early-stage high-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas remain Helicobacter(H pylori)-dependent.. However, unlike their low-grade counterparts, high-grade gastric MALT lymphomas may progress rapidly if unresponsive to H pylori eradication. It is mandatory to identify markers that may predict the H pylori-dependent status of these tumors. Proliferation of MALT lymphoma cells depends on cognate help and cell-to-cell contact of H pylori-specific intratumoral T-cells. To examine whether the expression of co-stimulatory marker CD86 (B7.2) and the infiltration of CD56 (+) natural killer (NK) cells can be useful markers to predict H pylori-dependent status of high-grade gastric MALT lymphoma. METHODS: Lymphoma biopsies from 26 patients who had participated in a prospective study of H pylori-eradication for stage IE high-grade gastric MALT lymphomas were evaluated. Tumors that resolved to Wotherspoon grade II or less after H pylori-eradication were classified as H pylori-dependent; others were classified as H pylori-independent. The infiltration of NK cells and the expression of CD86 in pre-treatment paraffin-embedded lymphoma tissues were determined by immunohistochemistry. RESULTS: There were 16 H pylori-dependent and 10 H pylori-independent cases. CD86 expression was detected in 11 (68.8%) of 16 H pylori-Adependent cases but in none of 10 H pylori-independent cases (P = 0.001). H pylori-dependent high-grade gastric MALT lymphomas contained significantly higher numbers of CD56 (+) NK cells than H pylori-independent cases (2.8±1.4% vs 1.1±0.8%; P=0.003). CD86 positive MALT lymphomas also showed significantly increased infiltration of CD56 (+) NK cells compared to CD86-negative cases (2.9±1.1% vs 1.4±1.3%; P= 0.005). CONCLUSION: These results suggest that the expression of co-stimulatory marker CD86 and the increased infiltration of NK cells are associated with H pylori-dependent state of early-stage high-grade gastric MALT lymphomas.     

Deletion analysis of the p16 tumor suppressor gene in gastrointestinal mucosa-associated lymphoid tissue lymphomas

BACKGROUND & AIMS: The molecular mechanisms responsible for initiation and progression of gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphomas are largely unknown. The aim of this study was to analyze the p16 tumor suppressor gene in MALT lymphomas of the stomach and colon. METHODS: Tumor samples were obtained from 28 patients with low-grade (n = 12) and high-grade (n = 14) gastric MALT lymphomas and from 2 patients with colonic MALT lymphomas. DNA was extracted from microdissected areas with at least 80% tumor cells. To detect homozygous p16 deletions, a semiquantitative polymerase chain reaction assay was used, whereby either p16 exon 1 or exon 2 was coamplified with an unrelated sequence as internal control. RESULTS: Homozygous p16 deletions were found in 2 of 14 (14%) cases with high-grade gastric MALT lymphomas. Both patients had Helicobacter pylori-associated gastritis; however, DNA extracted from areas of gastritis showed a normal p16 complement. No deletion was found in any of the low-grade gastric or the colonic MALT lymphoma specimens. CONCLUSIONS: In a subset of gastric MALT lymphomas, homozygous p16 deletions are acquired and may contribute to the transformation from a low-grade to a high- grade malignancy. (Gastroenterology 1997 Jun;112(6):1871-5)     

Treatment outcome of localized Helicobacter pylori-negative low-grade gastric MALT lymphoma

AIM: To investigate treatment outcome of Helicobacter pylori (H.pylori )-negative low-grade gastric mucosaassociated lymphoid tissue (MALT) lymphoma.METHODS: In this study,we retrospectively reviewed the clinical outcome and clinicopathologic factors of stage Ⅰ E H.pylori -negative low-grade gastric MALT lymphoma cases from August 1998 to June 2009.RESULTS: A total of eleven patients with H.pylori -negative low-grade gastric MALT lymphoma were enrolled in the study and received anti-H.pylori eradication tre...     

Gastric Lymphoma

Opinion Statement The approach to the management of gastric lymphoma must begin with a precise pathologic diagnosis based on histologic examination and immunophenotyping, at a minimum. This should be followed by detailed staging procedures that include endoscopic ultrasonography (EUS). Most primary gastric lymphomas are low-grade Mucosa-Associated Lymphoid Tissue (MALT) or large-cell (high-grade) types. The treatments for these differ. For low-grade MALT lymphomas confined to the stomach, an attempt at eradication of Helicobater pylori is the first choice. If the patient does not have H. pylori, if eradication is unsuccessful, or if the disease stage is II1E, radiation therapy is the next approach. Chemotherapy is the best option for disease that is stage II2E or higher and for disease that does not respond to antibiotics and radiation. Surgery should be reserved for patients with localized disease who do not respond to these other therapies. In patients with clinical stage IE large-cell lymphomas, there are valid arguments for and against the use of both surgery and stomach-sparing therapy. Surgery alone (if disease is pathologic stage IE) or surgery followed by chemotherapy (for disease that is pathologic stage II or higher) has more data defining expected outcomes. Recently published experience indicates that chemotherapy plus radiation therapy may be an acceptable alternative to surgery. The entire clinical picture and the patient’s preferences must play a role in this difficult management decision. Chemotherapy is the clear first option in patients with disease that is stage II or higher. Local radiation therapy should be added in selected cases with residual local disease or bulky tumor.     

Early stage gastric MALT lymphoma with high-grade component cured by Helicobacter pylori eradication

A 68-year-old woman was diagnosed with gastric lymphoma of the mucosa-associated lymphoid tissue (MALT) type with a high-grade component. Surgical treatment was recommended because of the presence of the high-grade component, but she refused surgery. As an alternative, she received Helicobacter pylori eradication treatment, which successfully induced regression of the lymphoma. She shows no sign of recurrence endoscopically and histologically, as of 29 months after the eradication treatment. Moreover, the B-cell monoclonality and Helicobacter pylori infection demonstrated at diagnosis has disappeared. This is one of the rare cases of gastric lymphoma of the MALT type with a high-grade component cured by Helicobacter pylori eradication alone. Received: October 7, 1999 / Accepted: May 26, 2000     

High frequency of t(11;18) in gastric mucosa-associated lymphoid tissue lymphomas in Taiwan,including one patient with high-grade transformation

t(11;18)(q21;q21), the most frequent chromosomal aberration of mucosa-associated lymphoid tissue (MALT) lymphoma, occurs in 30% of gastric patients.Although the translocation is often associated with an 'aggressive' course, it has not been described in transformed MALT lymphomas. We screened 15 gastric MALT lymphomas [three with concurrent or subsequent high-grade transformation and 11 diffuse large B-cell lymphomas (DLBCLs)] in Chinese patients for t(11;18). t(11;18) was found in 9/15 (60%) MALT lymphomas, but not in any DLBCLs. One patient, with subsequent high-grade transformation, showed the translocation in low- and high-grade lesions. t(11;18) was frequent in Chinese gastric MALT lymphomas and unusually one transformed lymphoma carried the translocation.     

Regression of low-grade gastric mucosa-associated lymphoid tissue lymphoma after eradication of Helicobacter pylori: possible association with p16 hypermethylation

Background. Many reports have stated that the cure of Helicobacter pylori infection can induce a complete remission of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Although p16 hypermethylation was frequently found in MALT lymphoma, the association between this finding and the remission of MALT lymphoma has not been clarified. We performed a prospective study to evaluate the outcome of patients with low-grade gastric MALT lymphoma and the expression of p16 hypermethylation. Methods. We prospectively enrolled 20 patients with H. pylori-positive low-grade gastric MALT lymphoma (stage I E₁). After the eradication of H. pylori, the patients were regularly followed-up with endoscopic and histological assessment. The methylation-specific polymerase chain reaction (PCR) (MSP) method was used for the serial detection of p16 hypermethylation. Results. Eighteen patients (90%) achieved complete remission, with a median duration of 15.7 months. The initial detection rate of p16 hypermethylation was 58% (7 of the 12 patients in whom p16 hypermethylation was evaluated successfully). In a serial investigation, 3 patients who were followed-up for a median 28 months showed that the p16 hypermethylation had disappeared. Conclusions. Complete remission of low-grade gastric MALT lymphoma after the eradication of H. pylori infection can be maintained for more than 1 year. Further studies are warranted to investigate the role of p16 hypermethylation in the pathogenesis of gastric MALT lymphoma. Received: November 24, 2000 / Accepted: May 25, 2001     

Gemcitabine, vinorelbine and prednisone for refractory or relapsed aggressive lymphoma,results of a phase II single center study

The optimum therapy for patients with relapsed or refractory aggressive non-Hodgkin’s lymphomas (NHL) not qualifying for platinum-based and/or high-dose chemotherapy is not known. We conducted a prospective phase II study evaluating a regimen consisting of gemcitabine (1 g/m², days 1 and 8), vinorelbine (30 mg/m², days 1 and 8) and prednisone (100 mg/day, days 1–8) (GVP) given every 21 days. Fifteen patients with a median age of 68 years and a median of three previous therapies were enrolled. Diagnoses included B lymphoblastic (n=1), diffuse large B cell (n=10), anaplastic large T cell (n=2) and peripheral T-cell NHL (n=2). The median international prognostic index score was 3 (six patients with a score of 4 or 5). Five patients achieved a complete remission and three patients a partial remission. The median overall survival was 13.8 months, and the median time to next treatment was 4.4 months. Haematological toxicities of World Health Organisation grades 3/4 were leucopenia in 58%, thrombocytopenia in 33% and anaemia in 17% of all courses. Three patients had grade 3 infections. There was no treatment-related mortality. GVP shows substantial activity in poor prognosis relapsed or refractory aggressive lymphomas and is generally well tolerated, but haematological toxicity is dose limiting.     

Prognosis and outcome of non-Hodgkin lymphoma in primary Sjögren syndrome

Sj?gren syndrome (SS) has been associated with the development of non-Hodgkin lymphoma (NHL). From a cohort of 584 SS patients followed in our department from 1980 to 2010, we retrospectively analyzed 53 consecutive NHL cases. Considerations included histologic type, clinical manifestation and NHL staging, treatment, response rate and overall survival (OS), event-free survival (EFS), and standardized mortality ratio (SMR).Mucosa-associated lymphoid tissue (MALT) lymphomas constituted the majority (59%) of NHL subtypes, followed by nodal marginal zone lymphomas (NMZLs) (15%) and diffuse large B-cell lymphomas (DLBCLs) (15%). Six lymphoma patients died during the median follow-up of 40.8 months. The corresponding age/sex-adjusted SMR of SS with and without NHLs versus the general population was 3.25 (95% confidence interval [CI] 1.32-6.76) and 1.08 (95% CI, 0.79-1.45), respectively. A "watch and wait" policy was adopted for 9 patients with asymptomatic localized salivary MALT lymphomas. Eight patients with limited-stage MALT lymphomas and extraglandular manifestations were treated with rituximab. Ten MALT lymphoma patients with disseminated disease received chemotherapy with or without rituximab. The 3-year OS and EFS in patients with MALT lymphomas was 97% and 78%, respectively. Rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) was the chosen therapeutic intervention for patients with DLBCLs. A successful outcome was recorded for this group, with 100% OS and EFS at 3 years. Patients with NMZLs had a less favorable outcome, with a 3-year OS of 80% and EFS of 53%. Our results describe the course and prognosis of SS-associated NHL and highlight the need for a risk-stratified treatment approach.     

Additional neoplasms and HCV infection in low-grade lymphoma of MALT type

Several chronic inflammatory conditions and genetic alterations are likely to be involved in the pathogenesis of low-grade lymphoma of MALT type. In a well-characterized series of 27 patients with low-grade lymphoma of MALT type, we studied: (1) the incidence of other neoplasms, which might be indicative of genetic instability, apparently a characteristic of this disease; (2) the prevalence of serologic and molecular markers of HCV infection, which has been found in association with other lymphoproliferative disorders. Three patients had one or more additional cancers; a total of eight tumours, five of which occurred in the same patient, suggests the presence of some genetic instability in at least some cases of the disease. Rather unexpectedly, anti-HCV antibodies and HCV RNA sequences were documented in 50% of the patients examined, without elevation of serum transaminases. Of interest, the two patients with parotid and conjunctival MALT lymphomas, respectively, with a previous history of Sjögren's syndrome, were HCV positive. We suggest, for the first time, that HCV may be considered, in addition to Helicobacter pylori, as another potential infectious co-factor in the multistep pathogenesis of low-grade lymphomas of MALT type.     

Deep infiltrative low-grade MALT (mucosal-associated lymphoid tissue) colonic lymphomas that regressed as a result of antibiotic administration: endoscopic ultrasound evaluation

Since 1997 we have experienced three cases of low-grade colonic mucosal-associated lymphoid tissue (MALT) lymphomas. The depth of tumor invasion was evaluated by endoscopic ultrasonography (EUS) and the mass lesions were all diagnosed as having extended beyond the deep region of the submucosal layer. Although all of these patients tested negative for gastric Helicobacter pylori, their tumor lesions regressed after antibiotic treatment in accordance with H. pylori eradication therapy. In general, consensus has been reached regarding antibiotic therapy for gastric MALT lymphomas. However, as a prerequisite for antibiotic therapy, the therapy has been deemed effective against these gastric tumors if the extent of infiltration, as evaluated by EUS, is limited to the mucosal layer or the superficial region of the submucosal layer. Based on the therapeutic outcomes seen in the three patients studied here, it is suggested that antibiotic therapy might be useful in treating MALT lymphomas of the colon, even in patients with advanced invasive tumors, in contrast to the extent of the lesions in the stomach suitable for antibiotic treatment. The success of the antibiotic treatment also suggests that MALT lymphomas may be caused by unknown luminal microorganisms, other than H. pylori.     

Clonal relationship in multifocal non-Hodgkin’s lymphoma of mucosa-associated lymphoid tissue (MALT)

To elucidate the progression of gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type, we analyzed a case presenting simultaneously with MALT lymphoma of the stomach and lung, and a gastric high-grade diffuse large lymphoma. The rearranged immunoglobulin heavy chain (IgH) variable regions were analyzed using a polymerase chain reaction (PCR)-based assay. Clonal relationship was shown between the gastric high-grade and the pulmonary low-grade lymphoma. The gastric MALT lymphoma was not related to the other manifestations. Translocation t(11;18) was not detected in the gastric high-grade lymphoma. MALT lymphomas at various locations and with different histologies may derive from a common precursor cell. Lymphomas at identical sites may have different stem cells.Supported in part by Deutsche Krebshilfe (70–2251-Ne1) and the Kempkes Stiftung     

Early-stage gastric MALT lymphomas: eradication of H. pylori and outcome.

BACKGROUNDS AND OBJECTIVE: Lymphomas of mucosa-associated lymphoid tissue are special because of their indolent course. Low-grade early-stage tumors resolve after Helicobacter pylori (HP) eradication in a high percentage of cases. The aim of this study was to evaluate this regression in our patients with EI1 stage-low-grade B gastric lymphomas after eradication therapy since the introduction of echoendoscopic examinations in the Gastroenterology Department of 'Juan Canalejo' Hospital. MATERIAL AND METHODS: A retrospective study of all cases of low-grade MALT gastric lymphomas in EI1 stage, diagnosed by histological and echoendoscopic examination, from June 1997 to December 2001. After eradication of HP with triple therapy, patients have been followed-up with endoscopic examinations at 2, 3 and 6 months, and yearly afterwards. RESULTS: There were 14 patients in this period with low-grade EI1 stage gastric MALT B cell lymphoma. The median age was 65 years, and 57% were females. HP was eradicated in all cases with first- or second-line (2 patients) antibiotic treatment. Complete remission was observed in 10 patients (71.4%) in a median time of 4.5 months. The other 4 patients needed chemotherapy because of non-remission or early relapse, and also as initial treatment. Complete remission was also obtained in these patients. Only 9 patients have been followed up in our unit for a median time of 20 months, period after which all remain free of disease. CONCLUSIONS: Low-grade early-stage MALT gastric B-cell lymphomas have a high rate of response to HP eradication therapy. Echoendoscopic staging helps in distinguishing the group of patients who will benefit from conservative treatment. These patients must be followed up as it remains unclear whether remission is maintained in the long term, and to know what factors could be associated with lymphoma relapse.     

Rapid development of diffuse large B-Cell lymphoma after successful eradication of Helicobacter pylori for gastric MALT lymphoma

Primary low-grade mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach has a potential to transform to high-grade diffuse large B-cell lymphoma (DLBCL). However, the clonal relation between MALT lymphoma and de novo DLBCL is still controversial. We report here three patients with Helicobacter pylori (H. pylori)-positive gastric MALT lymphoma rapidly progressing to DLBCL at the same site after successful eradication of H. pylori. Although MALT lymphomas in our cases did not possess t(11; 18)(q21;q21), sequence analysis of the rearranged immunoglobulin heavy chain gene showed no clonal relation between preceding MALT lymphoma cells and de novo DLBCL cells at the same site. These findings question the scenario of direct clonal progression of low-grade MALT lymphomas without t(11; 18)(q21;q21) to DLBCL and serve as a reminder of the risk of the progression of DLBCL with a distinct clonality immediately after H. pylori eradication for low-grade MALT lymphoma.     

Low-grade primary central nervous system lymphoma in immunocompetent patients

Primary central nervous system lymphomas (PCNSL) are usually diffuse large B-cell non-Hodgkin's lymphomas (NHL). Here we characterize the clinical presentation, course and outcome of patients with low-grade PCNSL. Records of 332 patients screened for inclusion in three multicentre prospective trials were reviewed. Ten patients (3%) with a median age of 59 years and a median Karnofsky performance status of 70% were identified. Seven patients had B-cell and three had T-cell lymphoma. The median growth fraction was 4%. The radiological morphology was unusual for PCNSL in eight patients. Three patients underwent complete tumour resection, combined with chemotherapy in one patient and with chemotherapy plus local radiotherapy in another. Four patients received chemotherapy and three received chemotherapy plus whole-brain irradiation, resulting in four complete remissions, two no-change situations and one progressive disease. Patients had an overall survival (OAS) of 2-58+ months with a 2-year OAS of 67%. Low-grade PCNSL may differ from classical high-grade PCNSL in its clinical features and radiological morphology. The clinical course may be variable and frequently more indolent than in classical PCNSL.     

Long-term results of treatment of malignant non-Hodgkin's lymphoma of the stomach.

Our experience with 66 endoscopic-bioptic diagnosed malignant non-Hodgkin's lymphomas (NHL) showed that in most of them (57 of 66 patients) a tumor stage IE or IIE was present. All 57 primary gastric lymphomas were B-cell-lymphomas arising from the mucosa-associated lymphoid tissue (MALT). After curative primary gastric resection in stage IE and IIE the 5-year survival rate was 81%, and the 5-years lymphoma-related survival rate was 88%. These results are superior to those reported in the literature. The following two points are probably of importance for improving the prognosis: early diagnosis made possible by better knowledge of the infiltrative-flat type of tumor growth (38 out of 57 patients, including 23 cases in which infiltration was limited to mucosa and submucosa = "early lymphoma"), and extensive preoperative staging. The infiltrative-flat type, which is difficult to diagnose endoscopically, usually shows low-grade malignancy on histology (76%; in early lymphoma 83%) and has an excellent prognosis when submitted to surgery. In our experience the question as to whether additional treatment by chemotherapy and/or radiotherapy improves the prognosis of NHL of the stomach remains unanswered and further studies are needed.     

Peripheral T-cell non-Hodgkin's lymphomas of low malignancy: prospective study of 25 patients with pleomorphic small cell lymphoma,lymphoepitheloid cell (Lennert's) lymphoma and T-zone lymphoma

Peripheral T-cell lymphomas comprise a heterogenous group of low- and high-grade malignancies differing in their histopathological appearance and also in clinical and prognostic aspects. We prospectively studied 25 patients with low-grade peripheral T-cell lymphomas: pleomorphic, small cell lymphoma (PSC) (n = 9), lymphoepitheloid (Lennert's) lymphoma (LEL) (n= 12) and T-zone lymphoma (TZL) (n= 4). The median patient age was 55 years (range 19-75 years); the male to female ratio was 1.5. 13 patients (52%) had limited stages (I + II), 12 patients (48%) had advanced disease (stage III + IV). 21 patients received the COPBLAM/IMVP-16 regimen. Two patients received more intensive treatments; two received less intensive therapy. Complete remissions were achieved in 16/25 patients (64%). The median observation time of surviving patients was 30 months (range 5-72 months). The actuarial overall survival and event-free survival at 2 years of 21 patients receiving COPBLAM/IMVP-16 were 69% and 35%, respectively. Intensive chemotherapy led to complete remissions in about 60% of the patients and to long-term disease-free survival for one-third. The observed clinical courses illustrate the aggressive nature of PSC, LEL and TZL.