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PubMed1977

Stem cell (immunoblastic) lymphoma. A variant of B lymphocytic lymphoma.

From a histologic review of cases coded as Hodgkin's disease and reticulum cell sarcoma, 12 cases were selected as examples of stem cell lymphoma in which the preponderant cell has characteristics of the B immunoblast. Clinically, these lesions affect the elderly (average age 57.3 years), disseminate early, and, with a few exceptions, progress rapidly to a fatal termination. Morphologically, the neoplastic stem cells, which have pyroninophilic cytoplasm, form diffuse infiltrates with an admixture of acidophilic cells. As a regional variation, the pattern in these lesions overlaps histologically with that seen in angioimmunoblastic lymphadenopathy. The overlap in patterns is presumptive evidence that the angioimmunoblastic pattern at times may be a precursory expression of the stem cell lymphoma. On the basis of morphologic features, these tumors are interpreted as a variant of B cell lymphomas.

Adult↗

PubMed2003

Primary central nervous system lymphoma in Korea: comparison of B- and T-cell lymphomas.

The great majority of primary central nervous system lymphoma (PCNSL) is known to be of B-lineage, with T-cell PCNSL (T-PCNSL) accounting for <5%. We report an unusually high incidence of T-cell lymphoma among the PCNSLs originated in a large general-care hospital in the metropolitan Seoul area. PCNSLs (n = 42) accrued from April 1995 through June 2001 were reviewed for histologic and clinical features, and immunohistochemical staining was done for CD3, CD20, CD4, CD8, Bcl-6, and CD10. Clonal rearrangements of the TCR-gamma and IgH genes were studied with semi-nested PCR in all seven cases of T-PCNSL and seven of 35 B-cell PCNSL (B-PCNSL). Formalin-fixed, paraffin-embedded specimens were used in all these studies. By immunohistochemical staining and molecular studies, seven cases (16.7%) were diagnosed as T-PCNSL, each displaying clonal rearrangement of the TCR-gamma gene, and 35 (83.3%) as B-PCNSL. Radiologically, T-PCNSL was significantly correlated with the superficial and subcortical lobar location (p <0.001), solitary mass formation (p = 0.001), presence of rim enhancement (p <0.001), and peritumoral edema (p = 0.029). Involvement of cerebrospinal fluid was observed only in B-PCNSL (n = 17) but not in T-PCNSL (p = 0.010). Histologically, T-PCNSL was characterized by a population of mixed predominantly small- and occasionally medium-sized cells (p <0.001), which were loosely scattered without forming a solid mass (p = 0.024), and perivascular infiltration was frequent (p = 0.007), in contrast to predominantly large cells of B-PCNSL, i.e., diffuse large B-cell lymphoma (DLBCL), in which the cells tended to aggregate to form monomorphous sheets (p = 0.024). In T-PCNSL, staining for CD8 was positive in five, including one with coexpression of CD4, and two were negative for CD4 and CD8. Of 24 DLBCLs tested, the pattern of Bcl-6+ tumor cells was diffusely dense, similar to that of the germinal center in nine cases (37.5%), with coexpression of CD10 in three of the nine cases. T-PCNSL accounted for 16.7% of the PCNSLs; thus, in Korea it may not be as rare as previously known. The T-PCNSL presented with certain clinical and pathologic features that were distinct from B-PCNSL and displayed preponderance of CD8 expression. DLBCL of the germinal center B-cell derivation defined by bcl-6 expression comprised 37.5% of DLBCL of the brain.

Adolescent↗

PubMed2002

The distinction between Burkitt lymphoma and diffuse large B-Cell lymphoma with c-myc rearrangement.

To compare immunophenotypic and molecular features between Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) with c-myc rearrangements (c-mycR DLBCL), we analyzed 18 cases of B-cell non-Hodgkin's lymphoma with c-mycR that were confirmed by chromosomal and/or Southern blotting analyses. The cases were histologically classified into 10 BLs and five DLBCLs. The remaining three cases could not be classified because of suboptimal quality of the surgical materials. BLs were from five adults and five children, whereas all DLBCLs were from adults. BLs were positive for CD20 (10/10 cases examined), CD10 (9/10), Bcl-2 (1/9), and Bcl-6 (10/10), whereas they were negative for CD3 (0/10) and EBV (0/8), by Epstein-Barr virus (EBV) EBER-1 RNA in situ hybridization. c-MycR DLBCLs were positive for CD20 (5/5), CD10 (2/5), Bcl-2 (3/4), and Bcl-6 (4/4), whereas none of them were positive for CD3 and EBV. A mean of MIB-1 index (MIB-1+ cells/neoplastic cells, %) of BLs (98.1%) was higher than that of c-mycR DLBCLs (66.3%; P <.0001). Somatic mutation of immunoglobulin heavy-chain gene variable region (VH gene) in BLs (four cases) ranged from 0.7 to 4.9% with an average value of 2.3%, whereas those in DLBCLs (three cases) from 8.2 to 32.0% with an average value of 17.0%. It is, therefore, concluded that a growth fraction of nearly 100%, as well as a monotonous proliferation of medium-sized cells and c-myc(R), should be of value in the diagnosis of BL, which is probably different from c-myc(R) DLBCL. In addition, CD10+, Bcl-2-, and low frequency of mutation of the VH gene could be helpful for the histologic distinction of BL from (c-mycR) DLBCL.

Adult↗

PubMed2005

Isolated conjunctival lymphoma metastasis from previous low grade non-Hodgkin's lymphoma.

Ocular involvement of systemic non-Hodgkin's lymphoma is rare. This report describes the unusual occurrence of a biopsy confirmed low grade lymphoma recurring in the conjunctiva, three years after initial diagnosis of systemic disease. The tumour was surgically resected and the patient remains disease free four years later. After the diagnosis of lymphoma, long term follow up is advised as recurrences in unusual sites can occur.

Conjunctival Neoplasms↗

PubMed2005

Prognostic significance of BACH2 expression in diffuse large B-cell lymphoma: a study of the Osaka Lymphoma Study Group.

PURPOSE: BACH2, a B-cell-specific transcription repressor, is abundantly expressed in lymphocytes of B-cell lineage as well as B-cell lymphoma cell lines. BACH2 possesses an inhibitory effect on proliferation of Raji cell lines derived from Burkitt's lymphoma. In this study, the prognostic significance of BACH2 expression was examined in diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: BACH2 expression was immunohistochemically examined on the paraffin-embedded sections obtained by biopsy from 108 patients (62 males and 46 females; age range, 23 to 85 years) with DLBCL. Staining intensity in the cytoplasm of the tumor cells was categorized as equal to or stronger (level 1) or weaker (level 2) than that in the endothelial cells in the same specimens. RESULTS: Level 1 and 2 expression of BACH2 was found in 32.4% and 67.6% of patients, respectively. Patients with level 1 expression showed significantly better disease-free and overall survival rate than those with level 2 expression (both P < .05). Multivariate analysis revealed BACH2 expression level together with performance status, elevated serum level of lactate dehydrogenase, and treatment response to be independent factors for prognosis of the patients. CONCLUSION: BACH2 expression level is a useful marker to predict disease-free and overall survival of patients with DLBCL.

Adult↗

PubMed2005

AIDS-related Burkitt's lymphoma versus diffuse large-cell lymphoma in the pre-highly active antiretroviral therapy (HAART) and HAART eras: significant differences in survival with standard chemotherapy.

PURPOSE: To compare outcomes of patients with HIV-Burkitt's lymphoma (HIV-BL) and HIV-diffuse large-cell lymphoma (HIV-DLCL) after treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or M-BACOD (methotrexate, bleomycin, cyclophosphamide, etoposide) in pre-highly active antiretroviral therapy (HAART) versus HAART eras. PATIENTS AND METHODS: Three hundred sixty-three patients with AIDS-related lymphoma diagnosed from 1982 to 2003 were reviewed retrospectively, including 262 in the pre-HAART (HIV-BL, 117; HIV-DLCL, 145) and 101 in the HAART era (HIV-BL, 18; HIV-DLCL, 83). Pre-HAART included those who did not receive HAART, and HAART era included those diagnosed after January 1997 who received HAART. RESULTS: There were no significant differences between groups in terms of age, sex, history of injection drug use, prior AIDS, lactate dehydrogenase level, and disease stage at diagnosis. Compared with HIV-BL, HIV-DLCL was associated with significantly lower CD4 counts in the pre-HAART but not the HAART era. Although the overall median survival was similar for both groups in the pre-HAART era (HIV-BL, 6.4 months v HIV-DLCL, 8.3 months; P = .43), survival was significantly worse in patients with HIV-BL in the HAART era (HIV-BL, 5.7 months v HIV-DLCL, 43.2 months; P = .0003). Failure to attain complete remission and CD4 count less than 100 cells/mm(3) independently predicted for poor survival in the pre-HAART era. In comparison, histology of HIV-BL and no attainment of complete remission were independent poor prognostic factors in the HAART era. CONCLUSION: Survival of patients with HIV-DLCL has improved in the HAART era, along with CD4 count, whereas survival of similarly treated patients with HIV-BL remained poor. The current practice of using the same regimen for both groups of patients should be re-evaluated.

Adult↗

PubMed2004

Comparative immunohistochemical analysis of pediatric Burkitt lymphoma and diffuse large B-cell lymphoma.

Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) account for nearly all pediatric nonlymphoblastic B-cell lymphomas. Because clinical behavior, prognosis, and response to therapy might differ, diagnostic accuracy is important. Morphologic examination often is sufficient, but occasionally, diagnostic ancillary studies are required. In adults, immunophenotyping is useful; however, pediatric data are limited. We characterized the immunohistochemical expression of 6 proteins (c-myc, CD10, bcl-6, bcl-2, CD138, and MIB-1) in pediatric BL (33 cases) and DLBCL (20 cases) with classic morphologic features. Significant differences in c-myc (BL, 30/33 [91%] vs DLBCL, 5/20 [25%]; P < .0001), bcl-2 (BL, 1/25 [4%] vs DLBCL, 7/19 [37%]; P < .02), and mean MIB-1 (BL, 99% vs DLBCL, 56%; P < .0001) expression were observed. There were no significant differences for CD10 (100% expression in BL and DLBCL), bcl-6 (BL, 23/33 [70%] vs DLBCL, 15/20 [75%]), or CD138 (no expression). Thus, pediatric BL and DLBCL have distinctive immunohistochemical profiles, and staining for c-myc, MIB-1, and bcl-2 might be useful in morphologically difficult cases.

Adolescent↗

PubMed1996

Peripheral T-cell lymphomas respond well to vincristine, adriamycin, cyclophosphamide, prednisone and etoposide (VACPE) and have a similar outcome as high-grade B-cell lymphomas.

Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of T-cell malignancies including subentities with favourable (large cell anaplastic) or unfavourable (pleomorphic) prognosis. The clinical outcome of PTCL has been controversially discussed, but a worse prognosis than high-grade B-cell Non-Hodgkin's lymphomas (NHL) has been postulated by most authors. In this report we summarize the results of a prospective comparative study investigating the therapy outcome of 27 patients (pts) with PTCL and 55 pts. with high grade B-cell NHL and give an overview of therapy studies in PTCL. The histological subtypes were 14 pleomorphic, 8 large-cell anaplastic (Ki-1+), 2 angioimmunoblastic (AILD) and 3 other PTCL. In three patients the PTCL was associated with non-tropical sprue (11%). Nineteen patients presented with an advanced stage of disease (stage III and IV, 70%), 17 (63%) pts. had B-symptoms. The patients were treated with vincristine 2 mg d1, adriamycin 25 mg/m2 d1-3, cyclophosphamide 800 mg/m2 d1, prednisone 60 mg/m2 d1-7 and etoposide 120 mg/m2 d1-3 (VACPE). In 77% of pts. with PTCL and 84% of patients with high-grade B-cell NHL a complete remission (CR) was achieved. 75% of the complete responders with PTCL and 70% with B-NHL are still in ongoing CR. The subgroup of large-cell anaplastic attained a CR in 88%. The median observation time is 44 months (1(+)-77+). The probability of 1-, 3- and 5-year overall and disease-free survival for the T-cell group were 76%, 54%, 48% and 76%, 62%, 62%, respectively according to Kaplan-Meier. There was no significant difference regarding the remission rate, the overall-, event-free or disease-free survival compared to high-grade B-cell lymphomas. In conclusion, the VACPE regimen is an effective and feasible regimen in the management of PTCL achieving complete remissions in a large proportion of patients.

Adolescent↗

PubMed2006

CARMA1 and chromosomal translocations in extranodal marginal zone B-cell lymphomas of MALT type or diffuse large B-cell lymphomas.

We analyzed the configuration of the CARMA1 gene, encoding a protein that closely interacts with BCL10 and MALT1, in a series of 120 extranodal marginal zone B-cell lymphomas of MALT-type and 35 diffuse large B-cell lymphomas. Our study suggests that CARMA1 is not targeted by chromosomal translocations in these lymphoma entities.

Apoptosis Regulatory Proteins↗

PubMed1996

Amplification of genomic DNA demonstrates the presence of the t(2;5) (p23;q35) in anaplastic large cell lymphoma, but not in other non-Hodgkin's lymphomas, Hodgkin's disease, or lymphomatoid papulosis.

Anaplastic large cell lymphoma (ALCL) is a distinct clinicopathologic variant of intermediate grade non-Hodgkin's lymphomas (NHL) composed of large pleomorphic cells that usually express the CD30 antigen and interleukin (IL)-2 receptors, and is characterized by frequent cutaneous and extranodal involvement. With variable frequency ALCL bear the t(2;5)(p23;q35) chromosomal translocation that fuses the nucleophosmin (NPM) gene on chromosome 5q35 to a novel protein kinase gene, Anaplastic Lymphoma Kinase (ALK), on chromosome 2p23. We determined the frequency of this translocation with a novel DNA polymerase chain reaction (PCR) technique using 0.5 microgram of genomic DNA, 5'-primers derived from the NPM gene and 3'-primers derived from the ALK gene and hybridization with internal probes. The presence of amplifiable DNA in the samples was tested with the inclusion in the PCR reaction of oligonucleotide primers designed to amplify a 3016-bp fragment from the beta-globin locus. NMP-ALK fusion amplicons were detected using DNA isolated either from all three ALCL cell lines tested, or from all four primary ALCL tumors known to contain the t(2;5)(p23;q35) translocation. Nested amplicons were detected by hybridization in 100% of specimens diluted 10(4)-fold and in 20% of those diluted 10(5)-fold. We subsequently examined archival genomic DNA from 20 patients with ALCL, 39 with diffuse large cell, 2 with mantle cell, 20 with peripheral T cell, 13 with low-grade NHL, 31 with Hodgkin's disease (HD), and 6 with lymphomatoid papulosis. Fusion of the NPM and ALK genes was detected in three of 18 patients with ALCL who had amplifiable DNA (17%, 95% confidence intervals 4% to 41%), but not in any patients with other NHL, HD, or lymphomatoid papulosis. The amplicon sizes were different in all cell lines and patients reflecting unique genomic DNA breakpoints. We conclude that with genomic DNA-PCR the rearrangement of the NPM and ALK loci is restricted to patients with ALCL. Further studies are needed to determine the prognostic significance of the NPM-ALK rearrangement, to determine whether its detection can aid in the differential diagnosis between ALCL. Hodgkin's disease, and lymphomatoid papulosis, and to establish the usefulness of the genomic DNA PCR in the monitoring of minimal residual disease in those patients whose tumors bear the t(2;5).

Adolescent↗

PubMed1989

Intermediate lymphocytic lymphoma encompassing diffuse and mantle zone pattern variants. A distinct entity among low-grade lymphomas?

Intermediate lymphocytic lymphoma has been operationally included among low-grade lymphomas, but few clinical data appeared to support definitely such an inclusion. The clinicopathologic features of 13 out of 14 cases of intermediate lymphocytic lymphoma either encompassing diffuse or mantle-zone pattern variants (ILL or MZL, respectively), diagnosed by conventional histology according to established criteria, are reported. Frozen section immunophenotypic analysis was also performed in 10 cases and enzyme studies were done in five. The 14 cases formed 6.9% of 203 non-Hodgkin's lymphomas (NHL) histologically diagnosed over a 2-year period. Among the 13 cases studied, there were nine males (five with ILL and four with MZL) and four females (one with ILL and three with MZL). Median age was 59 years. Splenomegaly (46%), high stage diseases (100%), involvement of bone marrow (92%) and peripheral blood (38%), and diffusion to and/or involvement of extranodal sites (38%), all were common findings at presentation. The 34 low-grade NHL of the total series classified according to the Working Formulation did not significantly differ from the ILL/MZL group in terms of frequency of involvement of bone marrow (69%) and peripheral blood (56%) as well as diffusion to and/or involvement of extranodal sites (26%). In ILL/MZL, therapy modalities were not uniform and the short follow-up time precluded firm conclusions on prognosis. Immunohistology demonstrated that ILL/MZL diagnosed by adequate morphologic criteria is a fairly homogeneous entity, also sharing most of its consistent immunological features with low-grade NHL. Thus, ILL/MZL is a relatively frequent and consistently recognizable clinical and pathological entity that may deserve a distinct place among NHL according to the Working Formulation. Proper clinical studies are needed to establish on a firmer basis the prognosis and optimal treatment of ILL/MZL.

Adenosine Triphosphatases↗

PubMed2004

Association between Epstein-Barr virus and classic Hodgkin lymphoma in Jordan: a comparative study with Epstein-Barr virus-associated Hodgkin lymphoma in North America.

An association between Epstein-Barr virus and Hodgkin lymphoma has been shown in several parts of the world. The reported incidence of Epstein-Barr virus in Hodgkin lymphoma varies significantly from one country to another and ranges from <30% in Swedish patients to 100% in patients from Kenya. Using in situ hybridization for detection of Epstein-Barr virus-encoded RNA and immunohistochemistry for detection of Epstein-Barr virus latent membrane protein, we analyzed 28 cases of Hodgkin lymphoma from Jordan and 30 cases from the United States. Eight of 28 Jordanian cases and 9 of 30 North American cases were Epstein-Barr virus positive. Our studies show that the incidence of Epstein-Barr virus among Jordanian patients with Hodgkin lymphoma is similar to the rate in patients from the United States. This rate appears to be low to intermediate compared with rates in other parts of the world.

Adolescent↗

PubMed1988

Acute renal failure due to focal necrotizing glomerulonephritis in a patient with non-Hodgkin's lymphoma. Resolution with treatment of lymphoma.

Renal disease in association with lymphoma is more prevalent than generally recognized. Glomerulonephritis may occur as a paraneoplastic phenomenon. We report a patient who presented with acute renal failure due to focal necrotizing glomerulonephritis in association with non-Hodgkin's lymphoma in whom the acute renal failure and glomerulonephritis resolved on clinical, biochemical and histological grounds with treatment of the lymphoma. Focal necrotizing glomerulonephritis is extremely uncommon in association with lymphoma and, to our knowledge, this association with follow-up and histological resolution of glomerulonephritis has not previously been reported.

Acute Kidney Injury↗

PubMed2002

Rapidly alternating COPP/ABV/IMEP is not superior to conventional alternating COPP/ABVD in combination with extended-field radiotherapy in intermediate-stage Hodgkin's lymphoma: final results of the German Hodgkin's Lymphoma Study Group Trial HD5.

PURPOSE: To investigate whether treatment results in intermediate-stage Hodgkin's lymphoma can be improved by rapid application of non-cross-resistant drugs, the 10-drug regimen cyclophosphamide, vincristine, procarbazine, and prednisone (COPP), doxorubicin, bleomycin, and vinblastine (ABV), and ifosfamide, methotrexate, etoposide, and prednisone (IMEP), repeated every 6 weeks, was compared with conventional alternating COPP/doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) administered every 8 weeks. PATIENTS AND METHODS: From January 1988 to January 1993, 996 patients in stage I or II Hodgkin's lymphoma with at least one risk factor (massive mediastinal tumor, massive spleen involvement, extranodal disease, elevated ESR, or more than two lymph node areas involved) and all patients in stage IIIA Hodgkin's lymphoma were randomized to receive two cycles of COPP/ABVD or COPP/ABV/IMEP followed by extended-field radiotherapy. RESULTS: Both regimens produced similar rates for treatment responses (complete remission, 93% v 94%), freedom from treatment failure (80% v 79%), and overall survival (88% for both regimens) at a median follow-up time of 7 years. Most serious toxicities during chemotherapy were similar in both regimens. However, World Health Organization grade 3 and 4 leukocytopenia occurred significantly more frequently in the COPP/ABV/IMEP arm (53% v 44% of patients; P =.010). There were no differences in the number of serious infections and toxic deaths during therapy. The number of second malignancies was also the same in both arms (22 each). CONCLUSION: Alternating COPP/ABVD and rapid alternating COPP/ABV/IMEP in combination with extended-field radiotherapy are equally effective in intermediate-stage Hodgkin's lymphoma and produce excellent long-term treatment results.

Adolescent↗

PubMed1999

Diagnosis of anaplastic large-cell lymphoma, including multifocal osseous KI-1 lymphoma, by fine-needle aspiration biopsy.

We present the fine-needle aspiration (FNA) findings of 4 cases of anaplastic (Ki-1) large-cell lymphoma (ALCL). A primary diagnosis of ALCL was made on FNA material in 2 cases, of which one was a multifocal osseous Ki-1 lymphoma. In the other 2 patients who had a known history of ALCL, FNA was used to detect recurrent disease. In all cases, large discohesive pleomorphic cells in the absence of lymphoglandular bodies in the background raised the possibility of a nonhematopoietic neoplasm. Immunochemical staining for CD30 was positive in all cases. The cytomorphologic and immunochemical features are discussed, along with the differential diagnosis of Ki-1 lymphoma. Diagn. Cytopathol. 1999;21:174-179.

Adolescent↗

PubMed1982

National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas: summary and description of a working formulation for clinical usage. The Non-Hodgkin's Lymphoma Pathologic Classification Project.

An international multi-institutional clinicopathologic study of 1175 cases of non-Hodgkin's lymphoma sponsored by the National Institute has been completed. Histologic slides and clinical records were examined from previously untreated patients seen during the period between July 1971 and December 1975 at four institutions, three in the United States and one in Italy. The reproducibility and clinical relevance of the six major classifications of the non-Hodgkin's lymphomas was tested by six "expert" pathologists, each a proponent of a major classification, and six very experienced pathologists not identified with one of the major classifications. Immunologic methods were not employed in the study design. A summary of the methods employed and the conclusions of the study is described. The major conclusion was that all six classifications were valuable and comparable in reproducibility and clinical correlations. The clinical significance of a follicular architecture, independent of cell type was confirmed. A working formulation of non-Hodgkin's lymphomas is described which separates the disease into ten major types utilizing morphologic criteria only. Subtypes are also described which allow translation of all of the major classifications into comparable groups. Histologic criteria are presented for each major type and equivalent terms are given for each type in the six major classifications. The formulation is not proposed as a new classification but a means of translation among the various systems and to facilitate clinical comparisons of case reports and therapeutic trials. The report contains commentaries by five of the "expert" pathologists on the value and conclusions of this unique study.

Actuarial Analysis↗

PubMed1989

Progression of follicular large cell lymphoma to Burkitt's lymphoma.

Histologic progression of lymphoma into more aggressive cell types is well documented. We describe a patient who had the histologic and cytogenetic features of Burkitt's lymphoma after 15 years of therapy for follicular large cell lymphoma. To the best of our knowledge, this clinical progression with histologic and cytogenetic confirmation has not been reported.

Burkitt Lymphoma↗

PubMed1991

Late relapse with nodular lymphoma after treatment for diffuse non-Hodgkin's lymphoma.

Histologic conversion from a low-grade non-Hodgkin's lymphoma (NHL) into a more aggressive histologic pattern is a common, well-documented event in NHL. The converse phenomenon, appearance of a low-grade, follicular NHL after treatment for diffuse, intermediate, or high-grade NHL, has only recently been recognized. The clinical, morphologic, and immunologic features of a patient in whom relapse with an indolent nodular lymphoma was noticed after combination chemotherapy for diffuse lymphoma are presented. Immunologic markers at presentation and relapse were similar. Other previously reported cases are reviewed. Implications for diagnosis and therapy as well as the pathogenesis of this unique form of conversion are discussed.

Aged↗