Primary Gastric Diffuse Large B-cell Research Articles

Primary Gastric Diffuse Large B-cell Lymphoma with Orbital Involvement: Diagnostic Usefulness of 18F-fluorodeoxyglucose Positron Emission Tomography

A 38-year-old man presented to our hospital with abdominal pain and melena. Gastrointestinal endoscopy revealed a large gastric ulcer, and the pathological diagnosis of diffuse large B-cell lymphoma (DLBCL) was made based on immunohistochemical findings. Left diplopia developed soon after commencement of chemotherapy. Despite normal findings from head MRI, orbital involvement in DLBCL was detected with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). The patient was treated with salvage chemotherapy with success. Treatment analysis using FDG-PET for patients with DLBCL, especially for those with clinical symptoms and negative findings on conventional modalities, may be useful for assessing disease status and adjusting treatments.

Clinical analysis of primary gastric diffuse large B-cell lymphoma

To analyze the clinical features and prognostic factors of primary gastric diffuse large B-cell lymphoma (PG-DLBCL) and to evaluate the staging system and treatment modality of PG-DLBCL. The clinicopathological data of 69 patients with PG-DLBCL were retrospectively analyzed. Event-free survival (EFS) and overall survival (OS) were the primary endpoints. The EFS rates at 1, 3, and 5 years were 83.8%, 71.1%, and 69.0%, respectively, with a mean EFS of 91.3 months. The 1-, 3-, and 5-year OS rates were 91.3%, 80.3%, and 72.4%, respectively, with a mean OS of 98.8 months. Univariate analysis revealed that either EFS or OS was significantly prolonged by the following factors (P < 0.05): modified Ann Arbor stage I(E) or II(E1) disease; normal lactate dehydrogenase (LDH) level; normal hemoglobin level; normal albumin level; International Prognostic Index (IPI) of 0 or 1; tumor size < 5 cm; and less depth of invasion. While gender, age, B symptoms at presentation, performance status and treatment modality were not significantly associated with the prognosis (P > 0.05). Cox regression model revealed that only modified Ann Arbor stage and albumin level were independent prognostic factors for EFS and OS. The most accurate staging system and the exact role of different therapeutic options for PG-DLBCL are still debated. Further randomized prospective studies with a large number of patients are still needed to establish an optimal management for this disease.

A liver-metastatic model of human primary gastric lymphoma in nude mice orthotopically constructed by using histologically intact patient specimens

In recent years, incidence and mortality of lymphoma are markedly increasing worldwide. However, the pathogenesis and mechanism of invasion and metastasis for lymphoma are not yet fully clarified. It is mainly due to the lack of ideal animal models, which can precisely simulate the invasion and metastasis of lymphoma in the human body. So, it is very necessary to establish a highly metastatic nude mouse model of human lymphoma. This study developed a liver-metastatic model of primary gastric lymphoma in nude mice by using orthotopic surgical implantation of histologically intact patient specimens into the corresponding organs of the recipient small animals. A histologically intact fragment of liver metastasis derived from a surgical specimen of a patient with primary gastric lymphoma was implanted into the submucosa of the stomach in nude mice. Tumorigenicity, invasion, metastasis, morphologic characteristics (via light microscopy, electron microscopy, and immunohistochemistry), karyotype analysis, and DNA content of the orthotopically transplanted tumors were studied. An orthotopic liver metastatic model of human primary gastric lymphoma in nude mice (termed HGBL-0304) was successfully established. The histopathology of the transplanted tumors showed primary gastric diffuse large B-cell lymphoma. CD19, CD20, CD22, and CD79alpha were positive, but CD3 and CD7 were negative. The serum level of lactate dehydrogenase (LDH) was elevated [(1010.56+/-200.85) U/L]. The number of chromosomes ranged from 75 to 89. The DNA index (DI) was 1.45+/-0.25 (that is, heteroploid). So far, the HGBL-0304 model has been passed on for 45 generations of nude mice. A total of 263 nude mice were used for the transplantation. Both the growth and resuscitation rates of liquid nitrogen cryopreservation of the transplanted tumors were 100%. The transplanted tumors autonomically invasively grew and damaged a whole layer in the stomach of nude mice. The metastasis rates of liver, spleen, lymph node, and peritoneal seeding were 100%, 94.3%, 62.6%, and 43.5%, respectively. The study successfully establishes an orthotopic liver metastatic model of human primary gastric lymphoma in nude mice. The HGBL-0304 model can completely simulate the natural clinical process of primary gastric lymphoma and provides an ideal animal model for the research on the biology of metastasis and antimetastatic experimental therapies of primary gastric lymphoma.

Outcomes in patients with primary gastric diffuse large B-cell lymphoma after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy

e19543 Background: The optimal therapy for primary gastric diffuse large B- cell lymphoma (DLBCL) still needs to be defined. The aim of this study was to investigate the patient's outcomes after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) treatment in primary gastric DLBCL in a single institution. Methods: We searched AMC Registry for Non-Hodgkin's Lymphoma and found 26 patients with primary gastric DLBCL, who received R-CHOP as first-line chemotherapy. Ten of 26 patients had localized disease. Remaining patients had disseminated disease. R-CHOP was repeated every 21 days in all patients. Results: Overall, complete response (CR) was observed in 20 of 26 patients (76.9%). Three-year event free survival (EFS) and overall survival (OS) was 76.5% and 75.0%, respectively. After analyses of 10 patients with localized disease, we found that these patients had received a total 38 cycles, with a median of 3 cycles per patient. Of 10 patients, one patient had 2 cycles of R-CHOP, 4 had 3 cycles, and one had 4 cycles, all 6 patients above followed by consolidation radiotherapy. Remaining one patient and 4 patients had 5 cycles and 6 cycles of R-CHOP, respectively. In patients with localized disease, CR was observed in 10 of 10 patients (100%), and both 3-year EFS and OS was 100% (10 of 10 patients). In analyses with 16 patients with disseminated disease, all patients had received a total 91 cycles, with a median of 6 cycles per patient. In these patients, two patients had radiation therapy after R-CHOP, one patient had CR before consolidation radiation therapy, and another had partial response before radiation therapy. CR after R-CHOP treatment was observed in 10 of 16 patients (62.5%), partial response in 3 patients, stable disease in 1 patient, and progressive disease in 1 patient. Three-year EFS and OS was 61.1% and 57.8% in patients with disseminated disease. Conclusions: R-CHOP regimen showed a promising result in primary gastric DLBCL. Combination with rituximab in CHOP regimen showed excellent prognosis especially in patients with localized disease. In localized disease, CR was 100%, 3-year EFS and OS was 100%. In disseminated disease, CR was 62.5%, 3-year EFS and OS was 61.1% and 57.8%. No significant financial relationships to disclose.

Immunohistochemical Expression of Germinal Center and Non-Germinal Center Markers in Primary Gastric Diffuse Large B-Cell Lymphoma

BACKGROUND: Recent studies have shown a correlation between diffuse large B-cell lymphoma (DLCBL) prognosis and molecular features using genome profiles by cDNA microarrays. Later reports have shown that immunohistochemical tests using markers as CD10, bcl-6 and MUM-1 to identify germinal center B-cell (GCB) and non-GCB patterns can have a similar value and are gaining major importance in assessing prognosis in patients with DLBCL. Gastric DLCBL is the most frequent extranodal non-Hodgkin lymphoma.AIM: To evaluate the frequency of GCB and non-GCB subgroups in primary gastric DLCBL and the impact of these tests in prognosis.PATIENTS AND METHODS: Patients older than 18 years with a diagnosis of primary gastric DLBCL were identified in a single institution from January 2002 to December 2005 and included in this analysis. Immunohistochemical stains were performed using antibodies against CD20, CD10, bcl-6 and MUM1 in all cases. Survival curves were obtained using the Kaplan-Meier method.RESULTS: Twenty-nine patients were included in this study. The median age at diagnosis was 68 years (range 40 to 86 years). Thirteen male and 16 female patients were included. All cases received chemotherapy with CHOP regimen. Cases were subclassified in GCB and non-GCB using CD10, bcl-6, and MUM1 expression. Four cases (14%) were considered GCB and 25 cases (86%) non-GCB. There were no statistical differences between both groups in the following variables: age, ECOG performance status, serum LDH levels, clinical stage and International Prognostic Index (IPI) score. No statistical difference in survival was observed between the GCB and non-GCB groups. The 3-year overall survival for the entire group was 30%.CONCLUSION: Immunohistochemical expression of non-GCB pattern is very frequent in primary gastric DLBCL in Peru. However, it does not show an effect in survival, probably related to the small number of cases included in the present study.

Quality of life one year after chemoradiotherapy for localized primary gastric diffuse large B-cell lymphoma

We assessed the quality of life (QOL) at least one year after sequential chemoradiotherapy for the treatment of localized gastric diffuse large B-cell lymphoma (DLBCL). We used the EORTC Quality of Life Questionnaire for Stomach Cancer (EORTC QLQ-STO22). Among the 45 patients available at the one-year follow-up after radiation therapy, 40 patients completed the EORTC QLQ-STO22 questionnaire. Their median age was 54.5 (range, 20-70 years). Social functioning was most adversely affected among the respondents with a score of 59, whereas other functions and the global scales were preserved above a score of 70 by linearly transformed values. Fatigue, the financial impact and specific emotional problems such as "thinking about their illness" (STO-ANX) and "worry about weight loss or future health" (STO-BI) were persistently bothersome for some patients. Other stomach-related symptoms such as dysphagia, pain, or reflux were negligible at 1 year after treatment. Therefore, this organ-preserving combined approach was effective for the maintenance of the QOL and minimization of stomach abnormalities in patients with gastric lymphoma.

High grade B-cell gastric lymphoma with complete pathologic remission after eradication of helicobacter pylori infection: Report of a case and review of the literature

BackgroundTreatment of primary gastric diffuse large B-cell lymphoma is still controversial. The treatment of localized disease was based on surgery alone, or followed by chemotherapy and/or radiotherapy. High-grade gastric lymphomas are generally believed to be Helicobacter pylori (HP)-independent growing tumors. However a few cases of regression of high-grade gastric lymphomas after the cure of Helicobacter pylori infection had been described.Case presentationWe report here a case with primary diffuse large B-cell lymphoma that showed a complete pathologic remission after HP eradication and we reviewed the literature. A computerized literature reach through Medline, Cancerlit and Embase were performed, applying the words: high grade gastric lymphoma, or diffuse large B cell, MALT gastric lymphoma, DLBCLL (MALT) lymphoma and Helicobacter. Articles and abstracts were also identified by back-referencing from original and relevant papers. Selected for the present review were papers published in English before January 2007.ConclusionForty two cases of primary high grade gastric lymphoma that regressed with anti HP treatment were found. There were anedoctal cases reported and patients belonging to prospective studies; four trials studied the effect of eradication of Helicobacter pylori as first line therapy in high grade gastric lymphoma: 22 of a total of 38 enrolled patients obtained complete remission. Depth of gastric wall infiltration and clinical stage were important factors to predict the response to antibiotic therapy. Our case and the review of the literature show that high-grade transformation is not necessarily associated with the loss HP dependence. In early stage, for high-grade B-cell HP-positive gastric lymphomas, given the limited toxicity of anti-HP therapy, this treatment may be considered as one of the first line treatment options.

P058 Modified NHL-BFM-90 program in primary gastric diffuse large B-cell lymphoma (PGDLBCL) with adverse prognostic factors

P058 Modified NHL-BFM-90 program in primary gastric diffuse large B-cell lymphoma (PGDLBCL) with adverse prognostic factors

Identification of cardiac metastasis of primary gastric diffuse large B‐cell lymphoma

A 72-year-old man was admitted to our hospital with a 10-day history of appetite loss. He had been diagnosed with primary gastric diffuse large B-cell lymphoma (DLBCL) 1.5 years prior to this admission. The patient had achieved complete remission after six courses of rituximab and cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy. Although the results of physical examination were unremarkable, laboratory data revealed mild anaemia (haemoglobin, 103 g/l), and elevation of serum lactate dehydrogenase (530 IU/l; normal, 250–450 IU/l) and soluble interleukin 2 receptor levels (1230 U/ml; normal, 220–450 U/ml). Gastroendoscopy showed an ulcerated mass in the inferior gastric corpus and biopsy revealed recurrence of DLBCL. F-Fluorodeoxyglucose positron emission tomography (F-FDG PET) before treatment showed intense uptake in the gastric wall and the heart (left panel). Marked thickening of the atrial septum (arrows) measuring 17 mm was detected on a transoesophageal echocardiography (TEE) (top right panel: LA, left atrium; RA, right atrium). These observations were strongly suggestive of cardiac metastasis of the disease. After two courses of rituximab and ifosfamide, carboplatin and etoposide (ICE) chemotherapy, the patient’s general condition improved. Repeated F-FDG PET scan showed complete disappearance of FDG uptake on whole-body imaging (centre panel). TEE also showed marked regression of atrial septal thickening (arrows), with the septum measuring 6 mm (bottom right panel). The patient entered complete remission and continued to receive additional treatment with rituximab and ICE. Cardiac metastasis of DLBCL is extremely rare, and F-FDG PET scanning appears to be useful for its detection. The incidence of cardiac metastasis in advanced lymphoma may be higher than generally accepted and the increasing use of PETcomputed tomography is likely to lead to a higher rate of detection.

Epstein–Barr virus involvement is a predictive factor for the resistance to chemoradiotherapy of gastric diffuse large B‐cell lymphoma

Primary gastric diffuse large B-cell lymphomas are generally well controlled by non-surgical treatment with combination chemotherapy followed by radiotherapy. We have previously reported that over 90% of patients achieved complete response (CR) with this therapeutic strategy: three cycles of cyclophosphamide, adriamycin, vincristine and prednisone followed by radiotherapy (40.5 Gy). Although the CR rate was very high, some patients still showed resistance to this combination therapy. In order to clarify the factors related to therapy resistance, we examined the relationship between Epstein-Barr virus (EBV), which was examined using an in situ hybridization technique, and the patients' clinical courses. Out of the 50 patients, four were EBV positive; over half of lymphoma cells were positive for EBV by in situ hybridization. Of the three EBV-positive patients, two showed progressive disease and one achieved partial response (PR). Two of the patients died of disease progression. The other patient achieved CR, but the lymphoma recurred with distant metastasis in the cerebellum 3 months after remission. In the present study, eight patients did not achieve CR or they relapsed, four patients showed progressive disease, one patient achieved PR, and three patients achieved CR with recurrence. Therefore, half of these unfavorable patients were EBV positive. This finding strongly indicated that EBV-associated gastric diffuse large B-cell lymphomas frequently show resistance to standard chemoradiotherapy, although some other adverse factors remain unclear.

CHOP followed by involved field radiotherapy for localized primary gastric diffuse large B-cell lymphoma: Results of a multi center phase II study and quality of life evaluation

We aimed to define the role of cyclophosphamide, vincristine, doxorubicin, prednisone (CHOP) followed by involved field radiotherapy (IFRT) for treating localized primary gastric diffuse large B-cell lymphoma (DLBCL). Newly diagnosed patients with localized primary gastric DLBCL were to receive four cycles of CHOP followed by IFRT of 40.0 Gy. At 1 year after the completion of treatment, patients filled out the EORTC Quality of Life Questionnaire specified for stomach cancer (QLQ-C30-STO22). Fifty evaluable patients (25 men, 25 women) were included. The median age was 54.5 years (range, 21 – 73 years. The overall response rate to the CHOP was 94% (95% confidence interval [CI], 87 – 100) in the intent-to-treat population. Forty-one of the 50 patients (82%; 95% CI, 71 – 93) achieved complete remission (CR). After the completion of radiotherapy, five patients who were in PR following chemotherapy eventually attained CR. The overall complete response rate was thus 92% (95% confidence interval, 84 – 99). With a median follow-up period of 30 months, the 2-year progression-free and overall survival rate was 92% and 92%, respectively. The gastric function was well preserved with negligible stomach-related symptoms at 1 year after the completion of treatment. This organ-preserving combined treatment is highly effective and well tolerated for the patients with localized gastric DLBCL.

Japanese multicenter phase II study of CHOP followed by radiotherapy in stage I–II1, diffuse large B‐cell lymphoma of the stomach

CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) followed by radiotherapy is regarded as standard care for localized aggressive lymphoma; however, prospective confirmation of its applicability to localized primary gastric lymphoma is inadequate, and most patients in Japan have been initially treated with gastrectomy. We conducted a multicenter phase II study to evaluate the feasibility and efficacy of the non-surgical treatment. Eligibility criteria required primary gastric diffuse large B-cell lymphoma, stage I-II(1), age 20-75, performance status 0-1 and adequate organ function. Treatment consisted of three cycles of CHOP followed by radiotherapy 40.5 Gy. Fifty-five patients were enrolled between December 1999 and February 2003, and 52 eligible patients were analyzed. Patient characteristics were as follows: median age, 61 years; 28 men, 24 women; 36 with stage I, 16 with stage II(1); 47 with a low International Prognostic Index (IPI) and five with a low-intermediate IPI. All but one patient completed planned treatment. No serious complications including massive hemorrhage or perforation were observed. A complete response was achieved in 48 of the 52 patients (92%, 95% confidence interval: 82-98%) and progressive disease in three. Two patients underwent salvage gastrectomy due to disease persistence or recurrence. With a median follow-up period of 28 months, 2-year progression-free and overall survivals were 88 and 94%, respectively. CHOP followed by radiotherapy is safe and highly effective in localized gastric diffuse large B-cell lymphoma. This organ-preserving treatment should be considered as a very reasonable therapeutic option.

FAS (CD95) Mutations Are Rare in Gastric MALT Lymphoma but Occur More Frequently in Primary Gastric Diffuse Large B-Cell Lymphoma

A loss of FAS (CD95) function has been proposed to constitute an important step in early mucosa-associated lymphoid tissue (MALT) lymphoma development and FAS mutations have been recognized in malignant lymphomas, in particular at extranodal sites. Since primary gastric lymphomas frequently exhibit resistance to FAS-mediated apoptosis, we investigated whether FAS is mutated in 18 gastric MALT lymphomas and 28 diffuse large B-cell lymphomas (DLBCL). We detected seven mutations in five lymphomas, one MALT lymphoma and four DLBCL; two DLBCL had two mutations. The MALT lymphoma exhibited a point mutation in the splice donor region of intron 3. Three DLBCL had missense mutations in exon 2, which encodes a signal peptide and a portion of the extracellular FAS ligand-binding domain. One DLBCL carried a point mutation in the splice donor region of intron 8, which would result in exon skipping. Two DLBCL harbored a missense mutation in exon 9, which encodes the intracellular death domain. The two death domain mutations inhibited FAS ligand-induced apoptosis in a dominant-negative mode, when transiently expressed in human T47D breast carcinoma and Jurkat T cells. A signal peptide and an extracellular domain mutation, however, failed to inhibit apoptosis in these transfection assays. They are likely to reduce apoptosis in lymphoma cells solely by a loss of function. In summary, our data show that FAS mutations are rare in primary gastric MALT lymphomas (5.6%) but occur in a subset of primary gastric DLBCL (14.3%) and suggest that these mutations contribute to the pathogenesis of gastric lymphomas by rendering lymphocytes resistant to apoptosis.

Diffuse large B-cell lymphoma of the stomach: assessment of microsatellite instability, allelic imbalance, and trisomy of chromosomes 3, 12, and 18.

Several types of genetic aberrations including microsatellite instability (MSI), allelic imbalance (AI), and chromosomal trisomies have been reported in low-grade (LG) mucosa-associated lymphoid tissue (MALT)-type gastric lymphomas. Presence of such genetic alterations could be a discriminator between de novo large cell lymphoma and high-grade (HG) MALT-type lymphoma. We investigated 17 primary gastric large B-cell lymphomas with and without features of MALT-type lymphoma for MSI, AI, and presence of trisomy of chromosomes 3, 12, and 18. We studied resection specimens from 17 primary gastric extranodal diffuse large B-cell lymphomas. Cases classified as HG MALT-type lymphoma, based on either the presence of LG MALT-type lymphoma component in the background (L/H MALT) or large cell lymphoepithelial lesions (HG MALT), and diffuse large B-cell lymphoma (DLBCL-NOS) when no features of MALT were present. MSI was analyzed using fluorescently labeled polymerase chain reaction primers (D3S11, D6S262, D3S1261, D3S1262, D3S1265). Paired tumor and normal DNA samples were amplified, and PCR products were analyzed on a DNA sequencer (ABI PRISM 373XL) with GeneScan (Applied Biosystems, Foster City, CA). MSI was defined as a gain of a novel-length allele compared with the corresponding normal tissue. AI was assessed at locus 3q27 (D3S1262 and D3S1265). The cases were analyzed for the presence of trisomy of chromosomes 3, 12, and 18 using interphase fluorescence in situ hybridization. MSI was detected in 4 out of 15 (27%) cases from which DNA was amplifiable with all primers and all MALT-type lymphomas. In two cases (13%), MSI was present at two loci sufficient to be classified as high-frequency MSI (MSI-H); this was seen exclusively in HG MALT lymphomas (P = 0.04). In the remaining two cases, MSI was detected at a single locus (low-frequency MSI). Allelic imbalance at the locus D3S1262 was detected in 4 out of 17 (24%) cases. It occurred more commonly in stage IE lymphomas when compared with higher stages (P = 0.03), regardless of lymphoma subtype. Trisomy 12 was detected in 3 out of 17 cases (18%) exclusively in stage IE lymphomas (P = 0.08). MSI was uncommon and was found exclusively in MALT-type lymphomas. MSI-H was even less common but occurred in HG MALT lymphomas only. Allelic imbalance at 3q27 (D3S1262) and trisomy 12 were found more commonly in low-stage disease. The latter two findings are in concordance with the recent suggestion that the published variation in gain of chromosomal material in high-grade gastric lymphomas may be related to stage rather than to the subtype of lymphoma. Because of the relatively low frequency of MSI in the high-grade B-cell lymphomas of the stomach, this feature cannot be used to reliably discriminate between the histologic types of extranodal diffuse large B-cell lymphoma.

Regression of primary gastric diffuse large B-cell lymphoma after eradication of Helicobacter pylori

Primary gastric high-grade mucosa-associated lymphoid tissue (MALT) lymphoma is generally considered refractory to eradication therapy for Helicobacter pylori and therefore is usually treated by surgical resection or by chemotherapy with or without irradiation as for malignant lymphoma.1,2 There are several reports of regression of primary gastric high-grade MALT lymphoma after eradication therapy of H pylori alone.3-5 This is a description of a case of gastric diffuse large B-cell lymphoma that regressed after eradication therapy for H pylori, and a discussion of the potential use of this form of treatment.

Primary intestinal diffuse large B-cell non-Hodgkin's lymphoma: Clinical features, management, and prognosis of 66 patients

In Saudi Arabia, primary gastrointestinal non-Hodgkin's lymphoma (NHL) is common. Recently we have reported one of the largest series of primary gastric (PG) diffuse large B-cell lymphoma (DLCL). This has prompted the analysis of another series of patients with primary intestinal DLCL to depict the clinical features and the outcome of that disease and to compare those with that for PG involvement. The data of 66 adult patients with primary intestinal NHL having DLCL histology were retrospectively reviewed. Patients had a median age of 45 years. Of 64 treated patients, 16% and 84%, received single and multiple modality treatment, respectively. Seventy-six percent, ten percent, and fourteen percent attained complete remission (CR), partial remission (PR), and no response/progressive disease, respectively. Multivariate analysis failed to identify any variable that predict the likelihood of attaining CR. Over a median follow-up of 81 months for all 66 patients, 32 (48%) were alive and disease-free, 5 (8%) were alive with evidence of disease, and the remaining 29 (44%) were dead. The median overall survival (OS) was 101 months and it was 58% (+/- 6%) and 48% (+/- 7%) at 5- and 10-year, respectively. Of the 54 patients who achieved CR or PR, the median event-free survival (EFS) was not reached, but the predicted 5- and 10-year EFS was 61% (+/- 7%) and 52% (+/- 7%), respectively. Only low serum albumin (<30 g/l) was associated with adverse OS and EFS in a univariate analysis, however, multivariate analysis was not possible. Our analysis showed that compared with single-modality management, multi-modality strategy attained significantly higher CR, and advantageous EFS, but without a significant superior effect on OS. In comparison with patients with PG DLCL, those with primary intestinal disease demonstrated more adverse prognostic features, but had an equivalent survival. This series characterized the clinico-pathologic features and outcome of patients with primary intestinal DLCL. While surgical resection in primary intestinal NHL seems beneficial, only prospective randomized studies can ascertain its precise role. Compared with patients with PG NHL, patients with primary intestinal disease had more prevalence of adverse prognostic features.

Stage-modified international prognostic index effectively predicts clinical outcome of localized primary gastric diffuse large B-cell lymphoma

The definition of prognostic parameters in early stages of gastric lymphoma is still controversial. The aim of this retrospective analysis was to assess the value of the stage-modified international prognostic index (IPI) in predicting the outcome of a large, consecutive series of patients with PGL of diffuse large B-cell histology (DLCL). Three hundred twelve consecutive, newly-diagnosed, patients with localized PGL (stages I-IIE according to the 'Lugano staging system for GI lymphomas') referred from April 1972 to December 1997 to eight Italian and one Swiss centers were reviewed and their outcomes updated to June 1998. One hundred three patients were treated with single-modality therapy, while two hundred four received combined-modality treatment, most of which included surgery and short-term chemotherapy. After a median follow-up of 66 months (range 0.6-300 months), 195 (64%) were alive in first continuous complete remission (CCR). The five-year estimates of overall survival (OS) and event-free survival (EFS) were 75% and 67%, respectively. OS and EFS varied according to IPI, from, respectively, 90% and 82% for patients with 0-1 risk factors, to 40% and 35% for patients with > or = 3 risk factors (P = 0.00001). Cox regression analysis showed that IPI was the strongest predictor of survival. This study shows that stage-modified IPI is an effective predictive model in patients with primary DLCL of the stomach, enabling identification of patients with significantly different outcomes.

Interstitial Deletion of 8(q13q22) in Diffuse Large B-Cell Gastric Lymphoma

An interstitial deletion in the long arm of chromosome 8 as the sole structural anomaly was detected in a primary gastric diffuse large B-cell lymphoma, high-grade mucosa-associated lymphoid tissue (MALT) type, from a 74-year-old man. Low-grade MALT lymphoma was not seen in the sections submitted for examination. Helicobactor pylori organisms were found in a biopsy performed prior to resection of the tumor. The karyotype was described as 45,X, −Y,del(8)(q13q22). No rearrangement between chromosome 8 and others was detected with fluorescence in situ hybridization using a whole chromosome 8 painting probe. Fluorescence in situ hybridization with the C-MYC gene showed its normal location at 8q24 on both chromosomes 8 without rearrangement. Amplification of C-MYC was not detected in interphase cells. Deletion of 8q may represent a unique genomic alteration in this particular subtype of primary gastric lymphoma.