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PubMed2003

14-day variant of the bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone regimen in advanced-stage Hodgkin's lymphoma: results of a pilot study of the German Hodgkin's Lymphoma Study Group.

PURPOSE: This multicenter pilot study assessed the feasibility and efficacy of a time-intensified bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) regimen given in 14-day intervals (BEACOPP-14) with granulocyte colony-stimulating factor (G-CSF) support in advanced Hodgkin's lymphoma. PATIENTS AND METHODS: From July 1997 until March 2000, 94 patients with Hodgkin's lymphoma stage IIB, III, and IV were scheduled to receive eight cycles of BEACOPP-14. Consolidation radiotherapy was administered to regions with initial bulky disease or residual tumor after chemotherapy. RESULTS: All patients were assessable for toxicity and treatment outcome. Eighty-six patients received the planned eight cycles of BEACOPP-14. Consolidation radiotherapy was given in 66 patients. Chemotherapy could generally be administered on schedule. Dose reductions varied among drugs but were generally low. Acute toxicity was moderate, with World Health Organization grade 3/4 leukopenia in 75%, thrombocytopenia in 23%, anemia in 65%, and infection in 12% of patients. A total of 88 patients (94%) achieved a complete remission. Four patients had progressive disease. At a median observation time of 34 months, five patients have relapsed, one patient developed a secondary non-Hodgkin's lymphoma, and three deaths were documented. The overall survival and freedom from treatment failure rates at 34 months were 97% (95% confidence interval [CI], 93% to 100%) and 90% (95% CI, 84% to 97%), respectively. CONCLUSION: Acceleration of the BEACOPP baseline regimen by shortening cycle duration with G-CSF support is feasible and effective with moderate acute toxicity. On the basis of these results, the German Hodgkin's Lymphoma Study Group will compare the BEACOPP-14 regimen with BEACOPP-21 escalated in a prospective multicenter randomized trial.

Adolescent↗

PubMed2005

Clinicopathologic and genetic profile of intracranial marginal zone lymphoma: a primary low-grade CNS lymphoma that mimics meningioma.

PURPOSE: Although rare overall, marginal zone B-cell lymphoma (MZBCL) is the most common primary low-grade CNS lymphoma reported in the literature. The aim of this study is to elucidate the biology and genetic features of this unusual tumor. PATIENTS AND METHODS: Fifteen CNS MZBCLs were studied clinically, pathologically, and genetically, including fluorescent in situ hybridization analyses with commercially available MALT1 and IgH break-apart and centromere 3, 7, 12, and 18 probes. RESULTS: CNS MZBCLs preferentially affect middle-aged women (female-to-male ratio, 4:1), with 93% presenting as dural-based masses mimicking meningioma. Ten patients with 1 to 7.6 years of follow-up after diagnosis showed no evidence of disease after radiation and/or chemotherapy. Like MZBCLs outside of the CNS, they consisted of CD20+, CD3- small B lymphocytes with varying degrees of plasmacytic differentiation and predominantly kappa light-chain restriction (78%). Lymphoid follicles with follicular colonization were seen in three patients and deposition of amyloid was noted in samples from two patients, one of which was tumefactive. Neither Bcl-6 protein nor Epstein-Barr virus-encoded RNA was expressed. Trisomy 3 was detected in six of 12 patients, with no rearrangements of MALT1 or IgH and no trisomies of 7, 12, or 18 detected. CONCLUSION: Our data suggest that intracranial MZBCL is an indolent primary CNS lymphoma that typically presents as a meningioma-like dural-based mass. Trisomy 3, but not MALT1 or IgH translocation, is a common genetic abnormality that may contribute to the pathogenesis of this CNS lymphoma.

Adult↗

PubMed2000

CD5+ follicle center lymphoma. Immunophenotyping detects a unique subset of "floral" follicular lymphoma.

The "floral" variant of follicle center lymphoma (FCL) may be confused with progressive transformation of germinal centers or lymphocyte predominance Hodgkin lymphoma. Immunohistochemistry and gene rearrangement studies are usually sufficient to differentiate among these entities. We present 11 cases of floral FCL that were evaluated at our institution by flow cytometry, immunohistochemistry, or both and by polymerase chain reaction-based molecular analysis. In 4 cases, the neoplastic B cells coexpressed CD5 antigens; 3 of these 4 cases also were CD10+, and all demonstrated rearrangement within the bcl-2 locus. These findings demonstrate that a subset of floral FCL is CD5+. Recognition of this immunophenotype is important to avoid misdiagnosis of nodular variants of small lymphocytic lymphoma and mantle cell lymphoma. Studies suggest that expression of CD5 by neoplastic germinal center cells might result from alterations of the follicular microenvironment and/or inappropriate B-cell responses to cytokine networks.

Adult↗

PubMed1994

[A case of primary thyroid T-cell lymphoma with infiltration of lymphoma cells in peripheral blood: diagnosed by DNA analysis].

A 57-year-old woman came to our hospital with complaints of neck swelling and headache in 1991. She was diagnosed as having chronic thyroiditis in euthyroidism because she had a diffuse goiter with both antithyroglobulin antibody (TGHA) and antimicrosomal antibody (MCHA). In 1992, she complained of the rapid growth of her thyroid gland and a swallowing disturbance. Atypical lymphocytes were observed in 16.5% of leukocytes in peripheral blood and similar atypical cells were found in bone marrow. Although an ultrasound scan of the thyroid gland revealed a symmetrical enlargement without a pseudocystic appearance, cytological study with fine needle aspiration biopsy of the thyroid gland demonstrated an abundance of atypical lymphoid cells. A whole body scintigram with 67gallium citrate showed no significant accumulation except in the thyroid gland. With a diagnosis of suspected primary thyroid lymphoma, total thyroidectomy was performed. However the diagnosis of malignant lymphoma was not confirmed histologically. A study of lymphocytes subset with two-color flow cytometry, which was performed for both lymphocytes in peripheral blood and infiltrating lymphocytes in the resected thyroid gland, revealed abnormal increased CD4 positive T cells and decreased HLA-DR expression. Additionally, southern blot DNA analysis for abnormal lymphocytes using restriction enzymes, EcoRI and BamHI, demonstrated rearrangement of the T-cell antigen receptor, which indicates a monoclonal proliferation of lymphocytes. After total thyroidectomy, atypical lymphocytes in peripheral blood decreased, and circulating autoantibodies including TGHA and MCHA disappeared. From these data, this patient was finally diagnosed as having a primary T-cell lymphoma of the thyroid gland, which is a very rare type of thyroid lymphoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

PubMed1993

High Epstein-Barr virus (EBV) susceptibility of both lymphoblastoid and lymphoma cell lines derived from a Japanese patient with EBV genome-positive Burkitt's lymphoma.

A Lymphoma cell line from the tumor tissue was established spontaneously from a Japanese patient with Epstein-Barr virus (EBV) genome-positive Burkitt's lymphoma (BL). Additionally lymphoblastoid cell lines from peripheral blood of this patient were established either spontaneously or by in vitro infection with B95-8 EBV. Lymphoma cells showed monoclonal surface immunoglobulins (kappa and gamma) with specific chromosomal translocations, t (8; 14). In contrast, lymphoblastoid cells expressed polyclonal surface immunoglobulins without specific chromosomal abnormalities. Lymphoma cells made colonies in soft agarose approximately 10 times more than those of the lymphoblastoid cells. When each cell line was cultured at lower temperature of 33 degrees C, treated with 12-O-tetradecanoyl- phorbol-13-acetate (TPA), and superinfected with P3HR-1 EBV, all cell lines expressed 5 to 10 times higher levels of EBV early antigens (EA) and viral capsid antigen (VCA) than lymphoblastoid cell lines from healthy controls. Furthermore, lymphoblastoid cell lines obtained from peripheral blood of this patient during the period of remission also exhibited high EA and VCA inducibility and superinfectibility. These findings suggested that the lymphoid cells in this patient were genetically highly susceptible to EBV infection, and this evidence possibly linked to the lymphomagenesis of EBV genome-positive BL.

Antibodies, Viral↗

PubMed1999

Primary multifocal lymphoma of bone presenting as hypercalcemic crisis: report of a rare manifestation of extranodal lymphoma.

Primary non-Hodgkin's lymphoma of bone is uncommon and usually manifests clinically as localized bone pain. Here we report a woman who presented with hypercalcemic crisis and extensive investigation revealed a primary multifocal lymphoma of bone. The course of the disease was very aggressive and despite intensive supportive care and urgent chemotherapy the patient died within 1 month. Since her blood PTH and calcitriol levels were suppressed and her parathyroid-hormone-related peptide (PTHrp) was mildly elevated, we believe that release of cytokines combined with PTHrp, as well as extensive osteolytic lesions, were the causes of the hypercalcemia. This is an unusual presenting symptom of lymphomas and to the best of our knowledge severe symptomatic hypercalcemia and crisis has never been reported in primary lymphoma of bone before.

Aged↗

PubMed1992

[Elderly non-Hodgkin's lymphoma presenting with pulmonary squamous cell carcinoma as a complication of chemotherapy for malignant lymphoma].

The authors report a case of pulmonary squamous cell carcinoma which occurred after chemotherapy of non-Hodgkin's lymphoma (NHL). A 76-year-old man, who was admitted to our department because of swelling of cervical lymph nodes, was diagnosed as having NHL (follicular mixed cell lymphoma). He was treated with 11 courses of CHOP therapy. Thereafter, chemotherapy including ifosfamide was carried out for approximately three years. In June, 1991, he was readmitted to our department because of swelling and pain in his left thigh and an abnormal shadow on chest X-ray. Chest CT demonstrated a cavitated shadow (about 5 cm in diameter) with an irregular margin in right S1, which was suggested to be lung cancer or pulmonary infiltration of malignant lymphoma. Bronchoscopy, which was carried out on July 12, showed bloody sputa from the right B1 ramus and markedly reddened mucosa at the orifice of the right upper bronchus. Sputum cytology revealed no malignancy. ACVP-16 chemotherapy including ara-C, CBDCA and VP-16 was initiated on July 14 because of enlarged superficial lymph nodes. On July 18, he fell out of bed and fractured his left femur. He also suffered from respiratory failure. He died of pulmonary haemorrhage on July 26. Autopsy revealed pulmonary squamous cell carcinoma. The occurrence of pulmonary squamous cell carcinoma is rare after the chemotherapy of malignant lymphoma.

Aged↗

PubMed2000

MUC1 is activated in a B-cell lymphoma by the t(1;14)(q21;q32) translocation and is rearranged and amplified in B-cell lymphoma subsets.

The band 1q21 is among the most common sites affected by chromosomal translocations in lymphoid, myeloid, epithelial, and sarcomatous lesions. In non-Hodgkin's lymphoma (NHL), translocations and duplications affecting this chromosomal site are frequently, but not exclusively, seen in association with primary abnormalities such as the t(14;18)(q32;q21) and t(8;14)(q24;q32) translocations, suggesting a role for 1q21 rearrangements in tumor progression. We report here the characterization and cloning of breakpoints in a case of extranodal ascitic B-cell lymphoma with a t(1;14)(q21;q32) translocation. The breakpoints on the der(1) and der(14) chromosomes were mapped by fluorescence in situ hybridization and Southern blot analysis and cloned using an IGHG (Cgamma) probe. The translocation linked the IGHG4 switch (Sgamma4) sequences of the productively rearranged allele to chromosome 1 sequences downstream of MUC1, leaving the MUC1 transcriptional unit intact. MUC1 was markedly overexpressed in the tumor at the mRNA and protein levels relative to lymphoma cell lines lacking a 1q21 rearrangement. Presumably, MUC1 transcription is aberrantly regulated by the IGHA (Calpha) 3' enhancer element retained on the same chromosome. Screening of a panel of B-cell lymphomas by Southern blot analysis identified a subset with a 3' MUC1 breakpoint and another with low-level amplification of MUC1. MUC-1 mucin has previously been shown to be frequently overexpressed in human epithelial cancers and to be associated with tumor progression and poor clinical outcome. Thus, MUC1 activation by chromosomal translocation, rearrangement, and amplification, identified here for the first time in NHL, is consistent with its suggested role in tumorigenesis. (Blood. 2000;95:2666-2671)

B-Lymphocyte Subsets↗

PubMed2000

Primary splenic B-cell lymphoma (marginal zone lymphoma). Clinicopathological evaluation of 10 cases.

SMZL has been included in the REAL classification of lymphoid neoplasms (1994) as an entity. It affects middle aged adults presenting with splenomegaly, mild lymphocytosis and in 40% of cases with the presence of monoclonal paraprotein. Our material includes 10 patients (6 women + 4 men). In all patients bone marrow biopsy was the initial material for histopathological examination. With characteristic intertrabecular nodular interstitial infiltrates of CD20+ small lymphocytes and corresponding clinical data (splenomegaly, lymphocytosis in peripheral blood and sporadic elevation of IgM levels) it was very suggestive of SMZL diagnosis. Splenectomy was the treatment of choice. The spleen showed micronodular white foci in all cases. Morphologically the pattern of white pulp involvement was observed with lymphoma infiltrates as well as small foci in the red pulp. The white pulp showed follicles surrounded by a wide marginal zone, resembling reactive splenic follicles. A corona-like rim consisted of medium size cells with abundant clear cytoplasm, resembling monocytoid B cells, often with plasmacytoid differentiation, or centrocyte-like cells. Smaller aggregates of these cells were present in the red pulp. Lymphoma cells were CD20+, bcl-2 and IgM+. In all cases monoclonal kappa light chains were found. Although SMZL is a disseminated lymphoma at diagnosis, its course is indolent and splenectomy is the treatment of choice. Clinical and histopathological differential diagnoses include hairy cell leukemia and secondary involvement of the spleen by infiltrates of nodal B-cell lymphomas.

Aged↗

PubMed2001

Evaluation of treatment response in patients with lymphoma using [18F]FDG-PET: differences between non-Hodgkin's lymphoma and Hodgkin's disease.

Fluorine-18fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) has become a very useful technique for the therapy monitoring of patients with lymphoma. It provides unique information about the metabolic behavior of the disease independent of morphological criteria. In recent years, [18F]FDG-PET has proven to be a technique with high sensitivity for the detection of residual tumor. Therefore, [18F]FDG-PET seems to be the ideal tool for the evaluation of treatment response. However, most recent published studies included both HD and NHL, although [18F]FDG-PET scan results in Hodgkin's disease (HD) has a different impact than in Non Hodgkin's Lymphoma (NHL). In this paper, we summarize our findings on the role of [18F]FDG-PET in the therapy evaluation of lymphoma patients in a large group of patients and highlight the differences between the interpretations of the results of HD and NHL patients. Finally, a strategy for the implementation of [18F]FDG-PET in the management of lymphoma patients is proposed.

Fluorine↗

PubMed1992

[Borderline between Hodgkin and non-Hodgkin lymphomas with unfavorable clinical course: a clinical, histological and immunohistochemical analysis of 33 cases within the German Hodgkin Lymphoma Study].

Reevaluation of diagnostic biopsies from 502 patients who entered the German Hodgkin Therapy trial was performed by a panel of four pathologists. Classification revealed 90% of unambiguous Hodgkin-lymphomas (HL), 1.6% of Non-Hodgkin-lymphomas (NHL) and 8.4% of cases difficult to evaluate, reflecting to the well-known problem of the border between these 2 groups of lymphoma. As these cases had the worst prognosis, a second attempt of reclassification, including immunohistochemical studies, was made, resulting in final classifying of 25% of these cases as NHL, 50% as HL, and 25% as further unclassifiable. The most common differential diagnostic problem was separating pleomorphic nodular sclerosing HL from large cell NHL's and HL with rather few Hodgkin- or Reed-Sternberg-cells from Lennerts lymphoma or angioimmunoblastic lymphadenopathy. Immunohistochemistry was helpful for the differential diagnostic decisions in these individual cases. A very high percentage of these problem cases had initially entered the trial as lymphocyte depleted HL, and the large majority of deaths came from the large cell NHL group.

Diagnosis, Differential↗

PubMed1991

[Chemotherapy of malignant lymphoma, with special regard to non-Hodgkin's lymphomas].

Non-Hodgkin's lymphomas was considered an incurable disease 20 years ago, but it is now possible to administered intensive combination chemotherapy thanks to the development of new anticancer agents and the sophistication of their administration, making it possible to increase both the complete response rate and the 2-year survival rate to more than 80%. The outcome is that more than 50% of cases are now curable. One significant feature of non-Hodgkin's lymphoma in Japan is the fact that the prevalence of T-cell lymphomas, which is unfavorable, is higher than in Western nations. A check of the survival time of non-Hodgkin's lymphomas between the five years ending in 1970 and those beginning in 1971 indicates that it was significantly extended. In cases to which BACOP, HOP and other agents were concurrently administered during the initial course of treatment, the complete response rate increased over 70%, and the median survival time at 45 months, making it possible to hopes on the future development of chemotherapy.

Drug Administration Schedule↗

PubMed1990

[Tomodensitometric aspects of brain lymphomas: apropos of 19 cases. Brain lymphoma].

The authors present the results of CT studies for 19 patients with cerebral lymphoma (including 12 primary tumors). CT appearances varied considerably, because 5 of the 12 primary lymphomas presented as multifocal lesions, and lesion sites included the corpus callosum (3 cases), the central caudate nucleus (4 cases), the posterior fossa (3 cases), and the cerebral hemispheres (6 cases). These findings are in agreement with literature data. Although a solitary, hyperdense and homogeneous lesion in the corpus callosum or the central caudate nucleus is indicative of cerebral lymphoma, numerous other aspects are possible and owing to the increasing frequency of this pathology should suggest this diagnosis. There is no specific appearance for secondary lymphomas, but diagnosis is often facilitated by concomitant systemic involvement.

Adult↗

PubMed1987

T-immunoblastic lymphoma mimicking B-immunoblastic lymphoma.

A T-cell immunoblastic lymphoma having plasmacytoid features that mimic B-cell immunoblastic lymphoma, is described. The lesion was composed of sheets of pleomorphic plasmacytoid cells that displayed a helper T-cell immunophenotype (Leu-1+, Leu-3+, Leu-4+, Leu-5+, Leu-9-, Leu-2-). Ultrastructural features were consistent with a T-cell lymphoma. Flow cytometric analysis revealed that the cells were DNA triploid and had a high proliferative activity. Although the histology of immunoblastic lymphomas alone may suggest either a T- or B-cell phenotype, immunophenotyping is essential in making this distinction.

Aged↗

PubMed1985

Human T-cell leukemia-lymphoma virus type 1 and adult T-cell leukemia-lymphoma in Okinawa.

A serological survey for the presence of antibodies against the human T-cell leukemia virus, type 1 (HTLV-1) in patients seen at the Chubu Hospital in Okinawa was undertaken. All patients with the clinicopathological diagnosis of adult T-cell leukemia-lymphoma were positive. These cases had the characteristic features of adult T-cell leukemia-lymphoma: diffuse histology, often mixed cell or pleomorphic, and a high frequency of hypercalcemia, leukemic phase, diffuse visceral involvement, and opportunistic infections. The median survival of these patients was short, being only 18 weeks. Of the other patients with cancers screened, two of five other non-Hodgkin's lymphoma patients were positive and three of eight patients with other hematological cancers were positive. In addition, three of the four immediate family members of one adult T-cell leukemia-lymphoma case had antibodies. Of the other persons (both in- and outpatients) without hematological cancers, those under the age of 50 had a much lower antibody prevalence (4%) than those over 50 (30%). There was no significant difference in antibody prevalence between the two sexes in either the younger or older age group. These findings further document that Okinawa is an endemic area for HTLV-1. None of the 157 individuals screened for antibodies to HTLV-3 were positive, consistent with the fact that no cases of the acquired immune deficiency syndrome have been reported from Okinawa.

Acquired Immunodeficiency Syndrome↗

PubMed1988

Clonal ambiguity of human immunodeficiency virus-associated lymphomas. Similarity to posttransplant lymphomas.

Initial biopsy specimens from two patients with lymphadenopathy and human immunodeficiency virus antibody-positive serum presented considerable difficulty in making specific histologic and immunologic diagnoses, although subsequent biopsy specimens revealed clear progression to acquired immunodeficiency syndrome (AIDS)-associated lymphomas. The initial biopsy specimens revealed multifocal clusters of large blastic lymphoid cells, with some clusters showing a monoclonal lambda light chain predominance, whereas other clusters showed a kappa predominance, indicating considerable phenotypic ambiguity suggestive of polyclonality. This initial clonal ambiguity was followed within two to three months by overt histologic, phenotypic, and clinical malignant transformation to a diffuse high-grade monoclonal B-cell lymphoma. These data have significant implications for the clonality and pathogenesis of AIDS-associated lymphoproliferative disorders. AIDS-related lymphomas may evolve from an initial multiclonal B-cell expansion similar to that described in other severely immunosuppressed patients (eg, with posttransplantation lymphoma).

AIDS-Related Complex↗

PubMed1979

Classification of animal lymphomas: the implications of applying Rappaport's classification for human lymphomas to experimental tumors.

One hundred and seventy animal lymphomas (species ranging from molluses to monkeys) were reclassified histologically according to the modified Rappaport classification for human lymphomas. The results were correlated with the etiology of the lymphomas, their clinical course, and in selected cases with their immunological type. The study stresses the value of such a procedure for comparative reasons, allowing a more adequate selection of animal models for human lymphomas.

Animals↗

PubMed1984

Enzymatic and organizational difference in expression of a Burkitt lymphoma-associated antigen (globotriaosylceramide) in Burkitt lymphoma and lymphoblastoid cell lines.

In our previous study, a Burkitt lymphoma-associated antigen defined by a monoclonal antibody, designated 38.13, was characterized as globotriaosylceramide (Gb3, Gal alpha 1----4 Gal beta 1----4 Glc beta 1----1 Cer) (Nudelman, E., Kannagi, R., Hakomori, S., Parsons, M., Lipinski, M., Wiels, J., Fellous, M., and Tursz, T. (1983) Science (Wash. D.C.) 220, 509-511). Consequently, we have studied the enzymatic basis and organization of Gb3 expression in Burkitt as compared with non-Burkitt lymphoblastoid cell lines. Burkitt lymphoma cell lines (Ramos, Daudi, Put) were characterized by a high chemical quantity of Gb3, high enzyme activity for synthesis of Gb3 (UDP-Gal:LacCer alpha-galactosyltransferase), and a high degree of surface exposure of Gb3, as determined by galactose oxidase/NaB[3H]4 and by cytofluorometry with the monoclonal antibody to Gb3 (38.13). Non-Burkitt lymphoblastoid cell lines (Priess, Remb1, and ARH77) were characterized by the absence of Gb3 at the cell surface detected by cytofluorometry or cell-surface labeling. The cell lines Priess and Remb1 did not contain Gb3 and showed a low alpha-galactosyltransferase activity for Gb3 synthesis. However, the cell line ARH77, though it did not express Gb3 at the cell surface, was found to contain a large chemical quantity of Gb3 and a high level of alpha-galactosyltransferase activity for Gb3 synthesis. However, Gb3 of ARH77 cells was exposed by sialidase treatment, but not by protease treatment, although Gb3 itself was not sialylated. The crypticity of Gb3 in ARH77 cells could be associated with an adjacent sialosyl residue of a second glycoconjugate at the cell surface, in the same way as Gg3 in mouse lymphoma L5178 (Urdal, D. L., and Hakomori, S. (1983) J. Biol. Chem. 258, 6869-6874). Thus, the expression in Burkitt and non-Burkitt lymphoma is dependent on (i) Gb3 synthesis due to alpha-galactosyltransferase activity and (ii) membrane organization of Gb3, which may be controlled through interaction with the sialosyl residue of a second glycoconjugate.

Antigens, Neoplasm↗