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PubMed1993

Detection of occult lymphoma in the peripheral blood and bone marrow of patients with untreated early-stage and advanced-stage follicular lymphoma.

PURPOSE: The object of this study was to compare the relative sensitivities of morphologic, immunophenotypic, gene rearrangement, cytogenetic, and polymerase chain reaction (PCR) analyses in the detection of lymphoma cells in the bone marrow and peripheral blood of patients with follicular lymphoma. PATIENTS AND METHODS: Bone marrow and peripheral-blood samples from 28 newly diagnosed patients with follicular lymphoma referred from several different medical centers were assessed. Routine morphologic assessment was performed initially and the remainder of the sample was aliquoted for DNA extraction to be used for gene rearrangement and PCR analyses and for immunophenotypic and cytogenetic analyses where a sufficient amount of sample remained. RESULTS: Morphologic assessment of the bone marrow was positive for lymphoma cells in 11 of 28 patients. PCR amplification of t(14;18) breakpoint DNA detected lymphoma cells in 17 of 24 patients assessed. Morphologic assessment detected lymphoma cells in three bone marrow samples that were negative by PCR. PCR analysis was the only method able to detect circulating lymphoma cells in peripheral blood at diagnosis and was positive in 15 of 24 samples. The other methods of assessment did not show lymphoma in any samples in which lymphoma was not detected by morphologic or PCR analysis. Lymphoma cells were found in the bone marrow and/or peripheral blood as frequently in early-stage patients as in advanced-stage patients. CONCLUSION: PCR amplification of t(14;18) breakpoint DNA together with morphologic assessment had the highest yield of detecting lymphoma cells in the bone marrow and/or peripheral blood of our population of newly diagnosed patients with follicular lymphoma. The clinical significance and prognostic importance of lymphoma cells detected by PCR in the bone marrow and/or peripheral blood of newly diagnosed follicular lymphoma patients awaits long-term follow-up data of these and additional patients.

Base Sequence↗
PubMed1992

[Comparative study of the survival of gastric B-cell lymphoma of mucosal origin with respect to lymph node lymphoma of similar histology].

BACKGROUND: The differences in clinical presentation, morphology, phenotype and genetic changes between lymphomas originating in the gastrointestinal tract and the lymph nodes justified the proposal of a system of specific classification for lymphomas originating in lymphoid tissue associated to mucosa (MALT). Nevertheless, there is no conclusive evidence that the types of lymphoma defined as such have a different clinical evolution with respect to the lymph nodes lymphomas. METHODS: With the aim of analyzing this problem a clinical follow up of 33 patients with primary gastric lymphomas (high and low grade) was compared with the results of a group of 99 lymphomas of the lymph nodes was carried out with classification according to the criteria of Kiel classification and the proposal by Isaacson et al for MALT lymphomas. Survival obtained by the Kaplan-Meier method was compared by the Mantel-Haenzel test. RESULTS: The results obtained showed that all gastric lymphomas have a less aggressive evolution than those of lymph node origin (p < 0.01). This significant statistical difference was also observed when lymphomas of similar histology were compared. Similarly, the subgroups of large cell lymphoma (p < 0.05) and small cells (p < 0.01) differ with respect to lymphomas of similar histology and of lymph node origin. In contrast with the results expected, no significant difference was observed between the two main groups of lymphomas of high and low grade mucosal origin. CONCLUSIONS: The analysis of the results supports the convenience of a system of specific classification for lymphomas of mucosal origin. Nevertheless, the specific existence of groups of high and low grade lymphomas is questioned since the probability of survival between both subgroups does not show statistically significant differences.

Gastric Mucosa↗
PubMed1993

[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.

Adult↗
PubMed1995

Primary cutaneous medium and large cell lymphomas other than mycosis fungoides. An immunohistological and follow-up study on 54 cases. French Study Group for Cutaneous Lymphomas.

Primary cutaneous medium and large cell lymphomas (MLCL) other than mycosis fungoides (MF) are rare, and their prognosis and treatment are controversial. The clinical, immunohistological and follow-up data of 54 well-documented cases of primary cutaneous MLCL other than MF, seen in our institutions over a 14-year period, were retrospectively reviewed, in order to determine the prognostic factors related to these lymphomas, and to analyse the results obtained with different treatment regimens. Forty-six patients presented with a solitary tumour or with localized lesions, and eight had disseminated cutaneous lesions. According to the updated Kiel classification, 45 cases (83%) corresponded to B-cell lymphomas: centroblastic lymphomas, 32 cases; centroblastic-centrocytic lymphomas, 11 cases; immunoblastic lymphomas, two cases. Nine cases (17%) were classified as T-cell lymphomas: pleomorphic medium and large cell lymphomas, eight cases; anaplastic large cell lymphoma, one case. Four of eight patients with disseminated skin lesions had a T-cell lymphoma, whereas 41 of 46 patients with a solitary tumour had a B-cell lymphoma. Patients with disseminated skin lesions and elevated serum lactate dehydrogenase (LDH) levels had a poor prognosis. Comparison of patients' overall survival, depending on immunohistological subtype, showed that the median survival of patients with pleomorphic T-cell lymphoma was 2.5 years, whereas it was not reached at 12 years for patients with centroblastic-centrocytic and centroblastic lymphoma. The eight patients with disseminated skin lesions were treated with polychemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2003

Lymphoma subtypes in patients with rheumatoid arthritis: increased proportion of diffuse large B cell lymphoma.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have an increased risk of developing malignant lymphoma. It is not clear whether the increase is confined to certain subtypes of lymphomas. Immunosuppressive therapy and Epstein-Barr virus (EBV) have been linked to the development of these lymphomas. To gain information about the baseline pattern of lymphoma subtypes in RA before the current widespread use of immunosuppressive drugs, we examined the distribution of lymphoma subtypes and the presence of EBV in a cohort of RA patients with a low frequency and duration of treatment with immunosuppressive drugs. METHODS: By linking data from the Swedish Hospital Discharge Register and the Swedish Cancer Register, 42 cases of lymphoma were identified among 11683 patients with RA in the Uppsala Health Care Region between 1964 and 1984. The medical records and paraffin-embedded lymphoma tissues were collected, and the lymphomas were reclassified using the World Health Organization classification. In situ hybridization was used to detect EBV. RESULTS: Tissues from 35 patients were reviewed. Non-Hodgkin's lymphoma (NHL) was found in 33 patients and Hodgkin's lymphoma in 2 patients. There was an increased frequency of diffuse large B cell lymphoma (DLBCL) (22 of 33 NHL patients, 67%) compared with that in the general population (30-40%). EBV was detected in 5 of 30 examined lymphomas from patients (17%). Twenty of the 22 DLBCL patients had RA with medium or high inflammatory activity, and 6 had been treated with a disease-modifying antirheumatic drug for >or=1 year. CONCLUSION: The findings of this study suggest an increased incidence of one specific lymphoma subtype, DLBCL, in RA patients, as well as a possible association with RA disease activity.

Adult↗
PubMed2003

The relationship between primary gastric B-cell lymphoma and immunoglobulin heavy chain (IgH) gene rearrangement--a histopathological study of primary gastric lymphomas.

The aim of this study was to review our primary gastric lymphoma cases according to the new WHO classifications and to investigate the histopathological features of B-cell lymphomas. In addition, B-cell monoclonality was analyzed for immunoglobulin heavy chain (IgH) gene rearrangement using the polymerase chain reaction at the site of the lymphoma lesion, transitional lesion, and the non-lymphoma lesion. Specimens resected from 31 primary gastric lymphomas were examined. There were 28 cases (90.3%) of B-cell lymphoma and three cases (9.7%) of T-cell lymphoma. The B-cell lymphomas were classified as low-grade mucosa-associated lymphoid tissue (MALT) lymphoma (LGML) (9%), high-grade MALT lymphoma (HGML) (42%), and diffuse large B-cell lymphoma (DLBCL) (29%). Histopathologically, lymphoepithelial lesions (LEL) were higher in LGML (100%) than in DLBCL (22%), with statistical significance (p < 0.05). A monoclonal pattern of IgH rearrangement was detected in LGML (50.0%), HGML (60.0%), and DLBCL (80.6%), with a statistically significant difference between LGML and DLBCL (p < 0.01). The IgH monoclonal pattern may reflect the gross appearance of lymphoma or the lymphoma infiltration depth. Superficial spreading and shallow growth in LGML may correspond to an oligoclonal pattern, and mass-forming and deep invasive growth in DLBCL may correspond to a more monoclonal pattern.

Adult↗
PubMed1995

Clinicopathologic study of primary gastric lymphoma of B cell phenotype with special reference to low-grade B cell lymphoma of mucosa-associated lymphoid tissue among the Japanese.

Resection specimens from 83 patients with primary gastric lymphoma (PGL) of B cell phenotype at stage IE and at stage IIE according to the Ann Arbor classification were investigated. Histologically, these lymphomas could be divided into four types: Type I lesions (n = 24) were entirely made up of MALT lymphoma; Type II lesions (n = 13) were predominantly MALT lymphoma containing one to a few foci of high-grade B cell lymphoma; Type III lesions (n = 22) consisted largely of high-grade lymphoma with small areas of low-grade MALT lymphoma; and Type IV lesions (n = 24) were pure high-grade B cell lymphoma, mostly of the large cell type. All patients had undergone primary gastric resection, and 14 received additional chemotherapy (n = 12), or both chemotherapy and radiotherapy (n = 2). The survival probability was significantly higher for Types I and II lymphomas than for Types III and IV tumors (P < 0.05 by the generalized Wilcoxon test). According to The General Rules for the Gastric Cancer Study by the Japanese Research Society for Gastric Cancer, the stage of disease showed a clear distinction between each of them (P < 0.01 by the generalized Wilcoxon test). This staging method seemed to serve well as a prognostic indicator. The histological typing of the PGL of the present series also seemed to correlate with the gross appearance, pathologic stage and prognosis. Furthermore, the expression of cyclin D1, bcl-2 and p53 protein, and PCNA was immunohistochemically investigated in 42 cases of the present series. Most of the low-grade PGL (Types I and II) had less than 60% PCNA-positive cells, whereas the high-grade PGL (Types III and IV) had more than 60% positive cells. In a study for cyclin D1 protein, no cases showed the nuclear staining pattern characteristic for mantle cell lymphoma, and the cytoplasmic staining frequently observed in the node-based large B cell lymphoma was seldom identified in the PGL. This discrepancy might suggest a lineage difference among the morphologically similar, but site-different, lymphomas. On the other hand, bcl-2 protein overexpression was almost equal in frequency between the gastric and node-based high-grade B cell lymphomas. This is in contrast to the reports from Western countries, in which the majority of high-grade gastric tumors were bcl-2 negative.

Adult↗
PubMed2001

Long term outcome of ocular adnexal lymphoma subtyped according to the REAL classification. Revised European and American Lymphoma.

AIM: To classify ocular adnexal lymphomas according to the Revised European and American Lymphoma (REAL) classification and to determine any correlation between clinical features or histomorphological variables with the patients' outcome. METHODS: Conventional and immunohistology were performed on representative sections of 53 specimens of 46 patients with ocular adnexal lymphoma. The antibodies used were CD20, BCL-2, CD21, CD23, CD43, CD3, CD5, p53, cyclin D1, pan-cytokeratin, kappa, lambda, IgD, and IgM. The growth fraction of the tumours was determined using the MIB-1 antibody directed against the Ki-67 antigen. Clinical follow up data regarding the outcome were obtained from the treating physicians and/or hospital files. The Student's t test and log rank test were used for statistical analysis. RESULTS: The patient collective consisted of 29 females and 17 males with an age range of 32-89.7 years (average 63 years). Almost all specimens represented B cell non-Hodgkin's lymphomas: extranodal marginal zone lymphoma (EMZL) (n=38), diffuse large cell B cell lymphoma (n=8), lymphoplasmocytic lymphoma/immunocytoma (n=2), mantle cell lymphoma (n=2), follicle centre lymphoma (n=1), and plasmacytoma (n=1). One case of a secondary anaplastic large cell lymphoma of T cell type (T-ALCL) was diagnosed. The majority of the patients had stage I disease. A variety of therapeutic regimens was administered, the main form of treatment being radiotherapy. The average follow up time was 85 months. Complete remission was achieved in 24 patients (10 after excision alone, eight after radiotherapy alone, three after combined excision and radiotherapy, one after chemotherapy alone, and two after combined radiotherapy and chemotherapy). 12 patients died of causes related to lymphoma; in one patient the cause of death was unknown. Six patients had persistent tumour at final follow up and two patients were lost to follow up. The stage at presentation, as well as the lymphoma malignancy category, had a significant correlation with the final course of the disease (p=0.0001 and p=0.03, respectively). A significant correlation was also noted between the final outcome (p<0.05) and tumour cell expression for Ki-67 antigen and p53 protein. CONCLUSION: 67% of patients with ocular adnexal lymphoma had EMZL. The stage at presentation had a significant influence on the final outcome. MIB-1 and p53 expression by the tumour cells proved to be important immunohistochemical markers concerning the prognosis. It is suggested that, following thorough staging investigations, primary EMZL (stage I) (if accessible) should be treated with excisional biopsy and subsequent low dose radiotherapy. Primary diffuse large cell B cell lymphoma of the ocular adnexa requires at least similar therapeutic measures and regular intensive follow up.

Adult↗
PubMed1993

Noncutaneous T-cell lymphomas. Recognition of a lymphoma type (large cell anaplastic) with a relatively favorable prognosis.

BACKGROUND: The clinical relevance of the updated Kiel classification for T-cell lymphomas is discussed. Large series with long-term follow-up are needed to investigate the clinical relevance of a separation into high- and low-grade T-cell lymphomas, based on the Kiel classification. METHODS: The clinicopathologic data of 97 consecutive noncutaneous T-cell lymphomas, diagnosed in the Comprehensive Cancer Center Amsterdam, between July 1, 1985, and December 1, 1990, were reviewed and analyzed for their prognostic significance. RESULTS: Immunohistochemistry contributed substantially in the diagnosis of T-cell lymphoma. Using the updated Kiel classification, many difficulties occurred in classifying these lymphomas. Only large cell anaplastic lymphoma (LCAL) and lymphoblastic lymphoma (LBL) were classified with a high degree of confidence. Variables associated with prolonged survival were classified as LCAL and low stage of disease (Stage I and II) at clinical presentation. Multivariate survival analysis revealed that subtype (grouped as LCAL versus non-LCAL) was selected as the most significant variable, closely followed by stage of disease at clinical presentation (grouped as Stage I/II versus Stage III/IV). LCAL was associated with a significantly better survival than were all other types of high-grade T-cell lymphoma (P = 0.018) and tended to be associated with a better survival than low-grade T-cell lymphoma (P = 0.067). No significant differences in survival were found between the other types of T-cell lymphoma or between high- and low-grade T-cell lymphomas as classified according to the updated Kiel classification. Other variables, such as sex and age (younger than 60 years versus older than 60 years) had no significant influence on survival time. CONCLUSIONS: This study indicates that the clinical relevance of classifying primary noncutaneous T-cell lymphomas according to the updated Kiel classification is limited because only a diagnosis of LCAL has prognostic relevance in predicting survival.

Adolescent↗
PubMed2003

Cytotoxic/natural killer cell cutaneous lymphomas. Report of EORTC Cutaneous Lymphoma Task Force Workshop.

BACKGROUND: Cutaneous lymphomas expressing a cytotoxic or natural killer (NK) cell phenotype represent a group of lymphoproliferative disorders for which there is currently much confusion and little consensus regarding the best nomenclature and classification. METHODS: This study analyzes 48 cases of primary cutaneous lymphoma expressing cytotoxic proteins and/or the NK cell marker, CD56. These cases were collected for a workshop of the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Task Force, to better clarify the clinical, morphologic, and phenotypic features of these uncommon tumors. RESULTS: Several categories with different clinical and pathologic features were delineated: 1) aggressive, CD8+, epidermotropic, cytotoxic T-cell lymphoma; 2) mycosis fungoides, cytotoxic immunophenotype variant; 3) subcutaneous panniculitis-like T-cell lymphoma; 4) NK/T-cell lymphoma, nasal type; 5) CD4+, NK cell lymphoma; 6) blastoid NK cell lymphoma; (7) intravascular NK-like lymphoma; and 8) cytotoxic, peripheral T-cell lymphoma. CONCLUSIONS: Our data show that primary cutaneous cytotoxic/NK cell lymphomas include distinct groups of diseases, clinically, histologically, and biologically. Because the finding of a cytotoxic phenotype often has prognostic significance, the routine use of cytotoxic markers in the diagnosis and classification of cutaneous lymphomas should be expanded.

CD4-Positive T-Lymphocytes↗
PubMed2003

T(11;18)(q21;q21) in gastric MALT lymphoma and diffuse large B-cell lymphoma of Chinese patients.

T(11;18)(q21;q21) occurs at variable frequencies in mucosa-associated lymphoid tissue (MALT) lymphomas of different sites. In gastric MALT lymphoma, it occurs in 30% cases and the translocation positive tumours are frequently at advanced stages and do not respond to Helicobacter pylori eradication. Intriguingly, t(11;18)(q21;q21) has been observed only rarely in mucosal diffuse large B-cell lymphomas (DLBCL), despite that at least a proportion of these tumours are believed to be the result of transformation of an MALT lymphoma. We previously examined t(11;18)(q21;q21) in gastric MALT lymphoma of Chinese in Taiwan and found the translocation in one of the three transformed MALT lymphomas studied. To extend this observation, we have examined t(11;18)(q21;q21) in a large cohort of gastric lymphomas of Chinese in China including 39 MALT lymphomas (12 with high-grade components) and 53 DLBCL by reverse transcription and PCR. Of these cases, RNA samples extracted from 36 MALT lymphomas including 10 cases with high-grade component and 46 DLBCL were adequate for detection of the translocation as judged by control RT-PCR of a house-keeping gene. T(11;18)(q21;q21) was found in 8/36 (22%) MALT lymphomas and 1/46 (2%) DLBCL. None of the MALT lymphoma with high-grade component showed t(11;18)(q21;q21). Our results suggest that t(11;18)(q21;q21) occurs only occasionally in transformed MALT lymphoma.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Extranodal head and neck lymphomas in Guatemala: high frequency of Epstein-Barr virus-associated sinonasal lymphomas.

Sinonasal lymphomas of T cell or natural killer cell (T/NK cell) phenotype represent a subset of extranodal head and neck lymphomas. T/NK cell sinonasal lymphomas have been described in diverse geographic settings, including China, Japan, Peru, Northern Europe, and North America. The frequency of these lymphomas is highly dependent on the geographic location in which they occur, their incidence being low in Europe and North America and relatively high in Asian countries and in Peru. Regardless of their geographic location, they are typically associated with the Epstein-Barr virus (EBV). Few studies have addressed the relative frequency of sinonasal lymphoma within the group of extranodal head and neck lymphomas. We investigated the anatomic distribution, immunophenotypical profile, and EBV status of 33 cases of extranodal head and neck lymphoma from patients in Guatemala. The anatomic distribution of these lymphomas is similar to that seen in Asian countries: 17 (52%) in the sinonasal area, five (15%) in the palate, and 11 (33%) in other locations. Fifteen (88%) of the 17 sinonasal lymphomas showed a T or null cell phenotype with a strong association with EBV by in situ hybridization. Most Guatemalan patients with these lymphomas were of Mayan descent. In Guatemala, the relative frequency of sinonasal lymphomas within the group of head and neck lymphomas is significantly higher than that reported for Western countries. In addition, the relative frequency of T/NK versus B cell sinonasal lymphomas is higher than that described in North America and similar to that observed in Asian countries and Peru.

Adolescent↗
PubMed1997

Three-color flow cytometry in the diagnosis of malignant lymphoma based on the comparative cell morphology of lymphoma cells and reactive lymphocytes.

This study examines the identification of unusual cell populations highly associated with lymphoma cells (UCP-L) in diagnostic biopsy specimens using three-color flow cytometry (3-FCM). Patterns of surface antigen expression were used to compare the morphology of distinct lymphoid cell populations present in biopsy specimens and determine the presence or absence of UCP-L. UCP-L were identified by their larger size as compared to admixed reactive lymphocytes, and the method is based on the concept that neoplastic lymphoma cells are larger than reactive lymphocytes. The comparison of relative cell sizes was determined by overlaying forward scatter histograms by multicolor gating using PAINT-A-GATE software. In order for separate gates to be set on UCP-L and reactive cell populations, UCP-L had to fulfill one or more immunophenotypic criteria. These included: (1) belonging to a subset of B cell antigen-positive cells showing restricted expression of kappa or lambda light chains; (2) belonging to a subset of CD4-positive cells having dim or absent expression of CD45RA; (3) showing alterations in antigen expression (loss, dimmer or brighter); or (4) expressing an immunophenotype that is present on only rare cell populations or is absent from reactive lymph nodes. The immunophenotypic profiles of the respective cell populations were demonstrated by cubic representations to assess more easily the co-expression of three antigens. The common morphology of UCP-L as defined by forward and side scatter grams was consistent with a 'lymphoid appearance' except in several cases of HTLV-I-positive T cell lymphoma and gammadelta T cell lymphoma. The immunophenotypic profiles of UCP-L were confirmed to correspond to the presumptive lymphoma cell population by use of a live gating procedure on the large cells, which eliminated interference by reactive cells or necrotic tissue fragments. Using this method, we identified UCP-L in 208 of 293 (71%) consecutive cases of non-Hodgkin's lymphomas, while no UCP-L were seen in 72 cases of non-specific hyperplasia of lymph nodes. Twenty-seven cases could not properly be examined about the existence of UCP-L because of massive necrosis, extensive fibrosis or strong non-specific staining reactions of unknown cause. When those cases were eliminated from the analysis, 80% of non-Hodgkin's lymphoma were found to contain UCP-L. In B cell lymphoma, the incidence of UCP-L in nodal lymphomas (80%) was much higher than in extranodal lymphomas (47%). Only one of 21 cases of Hodgkin's lymphoma was found to have UCP-L. The 3-FCM procedure was validated by the combined use of immunohistochemistry, morphologic examination, cytogenetic and antigen receptor gene rearrangement analysis by Southern blot hybridization. Our findings indicate that detection of UCP-L by 3-FCM is a reliable method to distinguish non-Hodgkin lymphomas from reactive hyperplasias in the majority of cases, even when the reactive cell population predominates over the malignant cell population.

Antigens, CD↗
PubMed1984

An effective therapy for both undifferentiated (including Burkitt's) lymphomas and lymphoblastic lymphomas in children and young adults.

We have used a single intensive chemotherapy regimen in the treatment of young patients with diffuse, aggressive, malignant lymphomas. There were two major histologic types of lymphoma in our series: lymphoblastic lymphomas, which presented most often with mediastinal tumor (64%), and undifferentiated lymphomas (mostly Burkitt's lymphomas), which occurred predominantly in the abdomen (86%). Our objective was to examine the determinants of prognosis in a uniformly treated patient group that included 31 children (2-16 yr) and 34 young adults 17-35 yr). Patients with extensive bone marrow involvement (greater than 50% replacement by tumor cells) were included in the study. Treatment consisted essentially of a 4-drug combination (cytoxan, adriamycin, vincristine, and prednisone) alternating with a 42-hr methotrexate infusion, followed by leukovorin rescue, and included intrathecal prophylactic therapy against central nervous system (CNS) disease. Patients with localized or resected undifferentiated lymphoma received 6 therapy cycles; all other patients received 15 cycles. Radiation therapy was used only in exceptional circumstances. Fifty-eight of 65 patients (89%) achieved complete remission: 97% of children and 82% of adults. The estimated 3-yr survival was 60% (SE 6.4%) with a median follow-up of 3 yr. Analysis of factors associated with remission duration and survival indicated that bone marrow involvement at referral and extensive disease were poor prognostic variables. Patients with lymphoblastic lymphomas and patients with completely resected undifferentiated lymphomas had the best prognosis (81% +/- 12% and 94% +/- 6% estimated 3-yr survival, respectively). Patients with extensive intraabdominal undifferentiated lymphoma (stage D) had the worst prognosis (33% +/- 11% estimated 3 yr survival), but even in this subgroup, bone marrow involvement was an adverse factor (estimated survival in stage D patients with and without bone marrow involvement was 14% +/- 13% and 43% +/- 15%, respectively). Elevated uric acid and/or lactic dehydrogenase (LDH) were also of prognostic significance, but predominantly reflected state, i.e., extent of disease. Age did not significantly influence prognosis. In the undifferentiated lymphoma subgroup, histology (i.e., Burkitt's lymphoma versus non-Burkitt's lymphoma) was not of prognostic significance. Total white count was below 1,000/cu mm in 39% of cycles, and fever associated with granulocytopenia occurred in 17% of cycles. Stomatitis of moderate to severe extent occurred in 50% of cycles.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1998

CD10 expression in follicular lymphoma and large cell lymphoma is different from that of reactive lymph node follicles.

BACKGROUND AND OBJECTIVES: CD10 is a proteolytic enzyme expressed on the surface of germinal center cells and lymphomas derived from these cells. There is a well-known association between CD10 expression and lymphomas of follicular center cell origin. However, the reported frequency of CD10 positivity in follicular lymphomas is widely variable, and no studies have addressed the importance of assessing the intensity of CD10 expression in the diagnosis of these tumors. In this study, we utilized flow cytometry to determine differences in CD10 expression in lymphomas and follicular hyperplasias. METHODS: Cell suspensions from 61 follicular lymphomas, 43 diffuse large B-cell lymphomas, and 44 lymph nodes with follicular hyperplasia were analyzed simultaneously with phycoerythrin-labeled anti-CD20 and fluorescein isothiocyanate-labeled anti-CD10. RESULTS: CD10 expression was mainly observed on B cells and was detected in 89% of follicular lymphomas, 56% of diffuse large B-cell lymphomas, and 55% of lymph nodes showing follicular hyperplasia. In follicular hyperplasia, two subpopulations of B cells displaying dim and bright CD20 expression were recognized. CD10 expression was restricted to the bright CD20-positive cells, which accounted for an average of 16% of B cells. In CD10-positive follicular and diffuse large B-cell lymphoma cases, a significantly higher proportion of B cells (73%) coexpressed CD10. Furthermore, the intensity of CD10 expression in follicular lymphoma and diffuse large B-cell lymphoma was much higher than that of follicular hyperplasia. CONCLUSIONS: Quantitative flow cytometry can detect significant differences in CD10 expression between normal follicular cells and follicular or diffuse large B-cell lymphoma. The use of CD10 intensity of expression as well as the fraction of CD10-expressing B cells should help distinguish reactive from neoplastic B-cell processes.

B-Lymphocyte Subsets↗
PubMed1999

Frequency of CD43 expression in non-Hodgkin lymphoma. A survey of 742 cases and further characterization of rare CD43+ follicular lymphomas.

CD43 expression on B cells is an immunophenotypic feature suggestive of malignancy. In the light of its diagnostic importance, we performed a comprehensive survey of CD43 expression in various types of non-Hodgkin lymphoma (NHL) and determined the frequency of its expression in routinely fixed paraffin-embedded tissues. Tissue sections in 742 cases of NHL, pretreated by the heat-induced epitope retrieval technique, were immunostained using an anti-CD43 antibody. Three categories of CD43 positivity were found: (1) more than 90% of T-cell lymphoma, mantle cell lymphoma, B-cell small lymphocytic lymphoma, and Burkitt lymphoma cases were positive; (2) 20% to 40% of nodal and extranodal marginal zone lymphoma (MZL), diffuse large B-cell lymphoma, Burkitt-like B-cell lymphoma, and lymphoplasmacytoid lymphoma cases were positive; and (3) 0% to 6% of primary splenic MZL and various types of follicular lymphoma cases were positive. Most CD43+ follicular lymphomas were predominantly large cell type with focally diffuse areas; their follicular center cell origin in 4 of 8 cases was supported by the presence of CD10 immunoreactivity and/or t(14;18) fusion gene product. CD43 is frequently detectable in a subset of B-NHL, and, thus, it seems to be a highly sensitive marker for these tumors. CD43 also may be a useful marker for classifying B-cell NHLs by virtue of its differential expression in these tumors.

Adult↗
PubMed1992

Immunohistochemistry of Hodgkin and non-Hodgkin lymphomas with emphasis on the diagnostic significance of the BNH9 antibody reactivity with anaplastic large cell (CD30 positive) lymphomas.

BACKGROUND: Morphologic and immunohistologic studies were performed on a series of 213 lymphoma cases, including CD30-positive anaplastic large cell (ALC) lymphomas (45 cases), other CD30-positive (18 cases) or CD30-negative (72 cases) non-Hodgkin lymphomas (NHL), cases of Hodgkin disease (HD) (73 cases), and an additional 5 cases exhibiting features of both CD30-positive ALC and Hodgkin lymphomas. METHODS: The aim was to assess differential expression by tumor cells of CD30/BerH2, epithelial membrane antigen (EMA), and other monoclonal antibodies, including BNH9, an epithelial and endothelial marker that has been found to be reactive with ALC lymphoma cells. RESULTS: A significantly greater proportion of cases of ALC lymphoma compared with HD exhibited positive results for CD45, EMA, CD45RO, and CD3 in CD30-positive atypical large cells, whereas Reed-Sternberg cells in HD most frequently coexpressed CD15 and CD30 antigens. ALC lymphoma cells reacted with BNH9 MoAb in 10 of the 42 (23.8%) assessable cases, whereas Reed-Sternberg cells reacted with this antibody in 5 of 73 (6.8%) HD cases. Only 3 of 90 (3.3%) NHL cases had positive results for BNH9; they were CD30-negative high-grade or low-grade lymphomas. It was noteworthy that 9 of 10 BNH9-positive ALC lymphomas also were EMA positive. Four of the five cases with morphologic features intermediate between those of HD and ALC lymphoma showed immunohistologic findings (positive results for CD30 and CD15, negative results for EMA, CD45, and BNH9) similar to those frequently observed in the HD cases; conversely, the remaining case showed a profile (positive results for CD30, CD45, and EMA, negative results for CD15) typically observed in ALC lymphomas. CONCLUSIONS: This study suggests that the differential expression of CD45, EMA, and CD15 could be used in the distinction of ALC lymphomas and HD, whereas it seems that BNH9 antibody reactivity may be of diagnostic use only in that it reinforces the diagnostic value of EMA expression in the differentiation of these entities.

Antibodies, Monoclonal↗
PubMed2005

[Minimal residual disease in follicular and mantle cell lymphoma. Detection using quantitative molecular monitoring of circulating lymphoma cells].

BACKGROUND AND OBJECTIVE: In patients with follicular lymphoma and mantle cell lymphoma circulating lymphoma cells can be detected by quantitative real-time PCR with a high sensitivity and reproducibility. With this study we wanted to ascertain whether a continuous molecular remission achieved in patients with mantle cell lymphoma and follicular lymphoma has an impact on survival of these patients. PATIENT AND METHODS: We conducted these investigations in 32 patients (24 with follicular lymphoma and 8 with mantle cell lymphoma) who were treated in a randomized trial with chemotherapy plus/minus rituximab (MCP, R-MCP). A further ten patients had follicular lymphoma (stage I and II) in long-term complete remission after radiation therapy. RESULTS: Up to 18 years after initial diagnoses of a stage I or II follicular lymphoma circulating t(14;18) positive cells could be detected in the peripheral blood. In advanced stage follicular lymphoma patients molecular remissions could only be achieved when they were treated with combined chemo-immunotherapy (MCP+R). A significantly higher relapse-free survival correlates with sustained molecular remission. In contrast, the frustrating clinical results obtained from the treatment of patients with mantle cell lymphoma corresponded to an achievement of only short molecular remissions in very few patients. CONCLUSIONS: The consequent application of quantitative real-time PCR will further improve current treatment strategies in lymphoma patients. Especially, individual treatment options can be developed for patients who do not respond to a standard chemotherapy or progression of disease is recognized, if results of molecular monitoring will be confirmed in large prospective studies.

Humans↗