PURPOSE: The aim of this study was to evaluate the clinical features, histologic classification and treatment outcomes of patients with malignant lymphoma of the eye. METHODS: The participants included 22 patients with malignant lymphoma of the orbit and ocular adnexa treated at our hospital between May 1994 and September 2001. The authors retrospectively analyzed the sex, age, location of mass, histopathologic type, stage and results of the treatment. RESULTS: Of the 22 patients, 14 cases were male and 8 were female. The age ranged from 26 to 68 years (mean age 43 years). The most common presenting complaint was slowly growing mass of the eye. Histopathologic studies revealed extranodal marginal zone B-cell lymphoma, MALT type in 20 cases (91%). The stages of lymphomas were included I AE in 14 cases (63%), II AE in 3 cases (14%), III AE in 3 cases (14%) and IV A in 2 cases (9%). Patients received radiotherapy and/or chemotherapy. Twenty out of 22 cases (91%) achieved a complete remission. During the mean follow-up of 26 months, two patients died of progression of the disease; one patient had extranodal marginal zone B-cell lymphoma, MALT type of stage III AE and the other patient had diffuse large cell lymphoma of stage II AE. CONCLUSIONS: Radiotherapy can produce durable remission in the majority of the patients with localized primary orbital lymphoma. Chemotherapy should be performed for the patients with highly malignant lymphomas or lymphomas with systemic manifestations.
Classification ; Drug Therapy ; Female ; Follow-Up Studies ; Humans ; Lymphoma* ; Lymphoma, B-Cell, Marginal Zone ; Lymphoma, Large B-Cell, Diffuse ; Male ; Orbit* ; Radiotherapy ; Retrospective Studies

Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Agents ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bleomycin ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Dacarbazine ; therapeutic use ; Doxorubicin ; therapeutic use ; Hodgkin Disease ; drug therapy ; Humans ; Lymphoma ; classification ; drug therapy ; pathology ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; Lymphoma, Large-Cell, Anaplastic ; drug therapy ; metabolism ; Lymphoma, Non-Hodgkin ; drug therapy ; Prednisone ; therapeutic use ; Receptor Protein-Tyrosine Kinases ; metabolism ; Rituximab ; Vinblastine ; therapeutic use ; Vincristine ; therapeutic use

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; therapeutic use ; DNA-Binding Proteins ; metabolism ; Doxorubicin ; therapeutic use ; Female ; Germinal Center ; pathology ; Humans ; Immunohistochemistry ; Interferon Regulatory Factors ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; classification ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Neprilysin ; metabolism ; Prednisone ; therapeutic use ; Prognosis ; Proto-Oncogene Proteins c-bcl-6 ; Vincristine ; therapeutic use

Many predictive models have been proposed for better stratification of diffuse large B-cell lymphoma (DLBCL). Hans' algorithm has been widely used as standard to sub-classify DLBCL into germinal center B-cell (GCB) and non-GCB origins. However, there have been disagreements in the literature regarding its prognostic significance. Here, we retrospectively analyzed Hans' algorithm and the individual immunohistochemical biomarkers at different cut-off values (5%, 30%, 50% or 75%) in 94 Korean patients with DLBCL treated with combination chemotherapy with cyclophosphamide, daunorubicin, vincristine, and prednisone. No significant differences were observed between the GCB (18 patients, 19.1%) and non-GCB (76, 80.9%) groups. Among individual biomarkers, CD10 negativity (cut point: 30%) and bcl-6 positivity (cut point: 5%) were independent good prognostic markers in progression-free survival (PFS), whereas bcl-6 (cut point: 5%) positivity was an independent good prognostic marker in overall survival irrelevant of international prognostic index. The present study showed the lack of predictability of Hans' algorithm in DLBCL patients, and that CD10, Bcl-6 may have diverse prognostic significance at different cut-off values. Our results suggest that the proposed cut-off value may not be applied universally, and that the optimal cut-off value may need to be optimized for individual laboratory.
Adult ; Aged ; Aged, 80 and over ; Algorithms ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cyclophosphamide/therapeutic use ; DNA-Binding Proteins/analysis ; Doxorubicin/therapeutic use ; Female ; Humans ; Lymphoma, Large B-Cell, Diffuse/classification/*drug therapy ; Male ; Middle Aged ; Neprilysin/analysis ; Prednisone/therapeutic use ; Prognosis ; Republic of Korea ; Retrospective Studies ; Tumor Markers, Biological/*analysis ; Vincristine/therapeutic use

<b>OBJECTIVEb>To analyze CD5 expression in diffuse large B cell lymphoma (DLBCL) and to explore its relationship with the clinicopathological characteristics.

<b>METHODSb>The clinical data from 160 DLBCL patients who were treated in First Bethune Hospital of Jilin University from January 2001 to December 2010 were retrospectively analyzed. Immunohistochemical staining (SP method) for CD5, CD10, bcl-6 and MUM-1 was performed on the paraffin-embedded tissue. The relationship between CD5 expression and the clinicopathological characteristics was evaluated by Chi-square test. Survival analysis adopted Kaplan-Meier analysis and Log-rank test.

<b>RESULTSb>In the patients aged 60 years or older, the incidence of CD5(+) lymphoma (12/17) was significantly higher than that of CD5(-) ones (39.9%, 57/143); two or more extranodal involvements in CD5(+) patients (11/17) were more commonly found than that of CD5(-)patients (31.5%, 45/143); DLBCL-related death in CD5(+) patients (13/17) was higher than that of CD5(-) patients (37.1%, 53/143). Survival analysis showed that the overall survival (OS) and the event-free survival (EFS) of CD5(+) patients were significantly lower than those of CD5(-) patients. In the condition of different GCB type, different therapy and low IPI (0 ∼ 2), the OS of CD5(+) DLBCL patients was significantly lower than that of CD5(-) patients, while in the condition of high IPI (3 ∼ 5), the OS of CD5(+) and CD5(-) DLBCL patient had no obvious difference.

<b>CONCLUSIONSb>CD5 expression is an adverse prognostic factor in DLBCL and it has more prognostic value in the condition of low IPI (0 ∼ 2).

Age Factors ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; CD5 Antigens ; metabolism ; Cyclophosphamide ; therapeutic use ; Disease-Free Survival ; Doxorubicin ; therapeutic use ; Female ; Humans ; Interferon Regulatory Factors ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; classification ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Neprilysin ; metabolism ; Prednisone ; therapeutic use ; Proto-Oncogene Proteins c-bcl-6 ; metabolism ; Retrospective Studies ; Survival Rate ; Vincristine ; therapeutic use

The gastrointestinal tract is the most common primary extranodal site for diffuse large B-cell lymphoma (DLBCL). However, there is no consensus on the most appropriate staging system for intestinal DLBCL. We evaluated the utility of the modified Ann Arbor system, the Lugano system, and the Paris staging system (a modification of the Tumor, Node, Metastases [TNM] staging for epithelial tumors) in 66 cases of resected intestinal DLBCL. The cases were treated with surgery, plus either cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy alone (n=26) or with the addition of rituximab immunotherapy (n=40). Median follow-up time was 40.4 months (range, 2.1-171.6 months). Fifty-six patients (84.8%) achieved complete remission. The overall 5-yr survival rate was 86.4% (57/66). Of the stage categories defined for each staging system, only the T stage of the Paris classification showed prognostic significance for overall survival by univariate analysis. However, none of the stage parameters was significantly correlated with patient survival on multivariate analysis. In conclusion, the results suggest that the T stage of the Paris classification system may be a prognostic indicator in intestinal DLBCL. The results also imply that in surgically resected intestinal DLBCL, the addition of rituximab to the CHOP regimen does not confer significant survival advantage.
Adolescent ; Adult ; Aged ; Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cyclophosphamide/therapeutic use ; Doxorubicin/therapeutic use ; Female ; Humans ; Immunologic Factors/therapeutic use ; Intestinal Neoplasms/*classification/drug therapy/mortality/surgery ; Lymphoma, Large B-Cell, Diffuse/*classification/drug therapy/mortality/surgery ; Male ; Middle Aged ; Neoplasm Staging/*methods ; Prednisone/therapeutic use ; Retrospective Studies ; Survival ; Survival Rate ; Treatment Outcome ; Vincristine/therapeutic use ; Young Adult

<b>OBJECTIVEb>To evaluate the molecular mechanism and prognostication of bcl-2 protein expression in different subgroups of diffuse large B-cell lymphoma(DLBCL) in Guangxi Zhuang Autonomous Region, China.

<b>METHODSb>Immunohistochemical stains for CD10, bcl-6, MUM-1, bcl-2 and NF-κB were performed in 214 cases of DLBCL. The Hans immunologic classification was applied to classify DLBCL into GCB and non-GCB subgroups. Using a dual-probe fluorescence in-situ hybridization (FISH) assay, IgH/bcl-2 gene translocation and bcl-2 amplification were analyzed.

<b>RESULTSb>In 214 cases of DLBCL, 30.8% (66/214) of cases were GCB and 69.2% (148/214) were non-GCB. Twenty-seven point three percent (18/66) of GCB subgroups and 59.5% (88/148) of non-GCB subgroups had bcl-2 protein expression, with a significant difference (P < 0.01). IgH/bcl-2 translocation was positive in 3.7% (8/214) of cases, even majority of them (6/8) was found in GCB subgroup, while represented only 9.1% of GCB case. There was a significant difference (P = 0.02) in bcl-2 gene amplification between GCB (27/66, 40.9%) and non-GCB subgroup (86/148, 58.1%). Among non-GCB cases, the expression of bcl-2 was correlated with that of NF-κB expression and bcl-2 gene amplification (r = 0.216 and 0.219, respectively, P < 0.05). No similar correlation was observed in GCB cases. The overall survival time of bcl-2-positive patients (31.4 ± 3.8) months was shorter than that of bcl-2-negative patients (40.2 ± 4.2) months. In conjunction with immunophenotypes and clinical stages, the bcl-2 positive patients had a 1.89 times higher risk than that of the bcl-2 negative patients.

<b>CONCLUSIONSb>Majority of the cases were prognostically unfavorable non-GCB subgroups among DLBCL, which were characterized by high frequency of bcl-2 gene amplification and low frequency of IgH/bcl-2 translocation. The anti-apoptotic gene bcl-2 was frequently expressed in non-GCB subgroups and closely related to the gene amplification and NF-κB activation. bcl-2 positive patients had more short overall survival times, would face significant higher risk of death, these results suggested that bcl-2 could be a prognostic marker independent to clinical staging and immunophenotyping.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Genes, bcl-2 ; Humans ; Immunoglobulin Heavy Chains ; genetics ; In Situ Hybridization, Fluorescence ; Lymphoma, Large B-Cell, Diffuse ; classification ; drug therapy ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; NF-kappa B ; metabolism ; Prednisone ; therapeutic use ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Survival Rate ; Translocation, Genetic ; Vincristine ; therapeutic use ; Young Adult

<b>OBJECTIVEb>To study the immunophenotype and prognostic significance of primary gastrointestinal diffuse large B-cell lymphoma, with reference to Hans, Choi and Tally algorithms.

<b>METHODSb>The clinicopathologic features and follow-up data in 90 cases of primary gastrointestinal diffuse large B-cell lymphoma were analyzed by Kaplan-Meier method, Log-rank test and Cox regression model. Immunohistochemistry was carried out using EliVision and EnVision methods for CD20, CD3ε, CD10, bcl-6, MUM-1, CD5, bcl-2, GCET1, FOXP1, LMO2, BLIMP1 and Ki-67.

<b>RESULTSb>The age of patients ranged from 27 to 83 years (mean = 58 years). The male-to-female ratio was 1.31:1. Amongst the 90 cases studied, 64.4% (58/90) involved the stomach and 35.6% (32/90) involved the intestine. The immunohistochemical findings were as follows: 100% positivity for CD20, 0% for CD3ε and CD5, 17.8% (16/90) for CD10, 75.6% (68/90) for bcl-6, 52.2% (47/90) for MUM-1 (cut off was 30%), 43.3% (39/90) for MUM-1 (cut off was 80%), 50.0% (45/90) for GCET1, 45.6% (41/90) for FOXP1, 23.3% (21/90) for LMO2, 42.2% (38/90) for bcl-2 and 8.9% (8/90) for BLIMP1. The Ki-67 index ranged from 20% to 95% (median = 80%). According to Hans algorithm, 51.1% of the cases belonged to germinal center B-cell (GCB) subtype and 48.9% belonged to non-GCB subtype. In contrast, Choi algorithm classified 55.6% cases as GCB subtype and 44.4% as activated B-cell (ABC) subtype. According to Tally algorithm, 34.4% were of GCB subtype and 65.6% of non-GCB subtype. Most of the patients (67.8%, 61/90) received chemotherapy and 68.9% (62/90) underwent surgical resection. The overall 2, 3 and 5-year survival rates were 58.5%, 52.8% and 49.8%, respectively. The overall 2, 3 and 5-year survival rates in the CHOP therapy group were 68.5%, 61.2% and 52.9%, respectively.

<b>CONCLUSIONSb>There is no significant difference in ratio between the GCB and non-GCB/ABC subtypes by Hans and Choi algorithms. The non-GCB subtype seems to be more prevalent according to Tally algorithm. Although there is no significant difference in survival between GCB and non-GCB/ABC subtypes by the 3 algorithms, GCB subtype tends to show a better survival. In univariate analysis, LDH level, international prognostic index, chemotherapy, surgical resection, B symptoms, number of involved sites and clinical stage are found to have prognostic significance. In multivariate analysis, Choi algorithm, Tally algorithm, chemotherapy, surgical resection, LDH level and clinical stage are independent prognostic factors.

Adaptor Proteins, Signal Transducing ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD20 ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; therapeutic use ; DNA-Binding Proteins ; metabolism ; Doxorubicin ; therapeutic use ; Female ; Forkhead Transcription Factors ; metabolism ; Germinal Center ; pathology ; Humans ; Immunophenotyping ; Interferon Regulatory Factors ; metabolism ; Intestinal Neoplasms ; classification ; drug therapy ; metabolism ; pathology ; surgery ; Kaplan-Meier Estimate ; LIM Domain Proteins ; Lymphoma, Large B-Cell, Diffuse ; classification ; drug therapy ; metabolism ; pathology ; surgery ; Male ; Metalloproteins ; metabolism ; Middle Aged ; Neoplasm Proteins ; metabolism ; Neprilysin ; metabolism ; Prednisone ; therapeutic use ; Proportional Hazards Models ; Proto-Oncogene Proteins ; Proto-Oncogene Proteins c-bcl-6 ; metabolism ; Repressor Proteins ; metabolism ; Serpins ; metabolism ; Stomach Neoplasms ; classification ; drug therapy ; metabolism ; pathology ; surgery ; Survival Rate ; Vincristine ; therapeutic use

<b>OBJECTIVEb>To investigate the clinical significance of bcl-2 protein expression and three classification algorithms including Hans model, Chan model and Muris model in patients with diffuse large B-cell lymphoma (DLBCL).

<b>METHODSb>Two-hundred and thirty-seven cases were collected. Standard two-step EnVision method of immunohistochemical staining was used to assess the expression of Ki-67, CD3, CD45RO, CD20, CD79a, bcl-2, bcl-6, CD10, MUM-1, GCET-1, and FOXP-1. The phenotypic classifications were assessed according to the standard of the three models.

<b>RESULTSb>The male (131 cases) to female (106 cases) ratio was about 1.24:1, the average age was 52.6 years. Seventy-five cases (31.6%, 75/237) showed primarily lymph node involvement. Gastrointestinal tract (71 cases) was the most commonly involved extra-nodal organ. All cases expressed one or more pan B cell markers such as CD20 (99.1%, 231/233). All patients with complete clinical follow-up data survived from 1 - 120 months. The expression of bcl-2 protein indicated an adverse prognosis (P = 0.019). Two-hundred and thirty cases were classified according to Hans model, with ninety five GCB cases and one-hundred and thirty five non-GCB cases. Survival analysis showed no difference between GCB and non-GCB subtypes (P = 0.102). According to the Chan's algorithm, sixty eight case of one-hundred and eighty one were belong to GCB group, with one-hundred and thirteen non-GCB cases. GCB subtype showed much better prognosis than non-GCB subtype according to survival analysis (P = 0.031). Additionally, bcl-2 protein expression in non-GCB subtype showed the worst survival. In Muris' model, 154 of 218 cases were classified as Group 1, while 64 cases were classified as Group 2. Group 1 showed better prognosis than Group 2 (P < 0.05).

<b>CONCLUSIONSb>Non-GCB group is the more common type of DLBCL in China. High expression of bcl-2 protein is detected in the non-GCB group. Not all subgroups classified with different classification models indicate different prognosis. Bcl-2 expression combined with Chan's algorithm may be the best tool to predict outcome.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Algorithms ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Germinal Center ; pathology ; Humans ; Immunophenotyping ; Lymphatic Metastasis ; Lymphoma, Large B-Cell, Diffuse ; classification ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Prednisone ; therapeutic use ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Retrospective Studies ; Survival Rate ; Vincristine ; therapeutic use ; Young Adult