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PubMed2000

Hodgkin's disease and peripheral T-cell lymphoma: composite lymphoma with evidence of Epstein-Barr virus infection.

This paper reports the case of a patient with a composite lymphoma consisting of nodular sclerosing Hodgkin's disease and peripheral T-cell lymphoma. The Hodgkin and Reed-Sternberg (HRS) cells harboured the Epstein-Barr virus (EBV) and displayed a type II EBV latency (LMP1(+)/EBNA2(-)), whereas the neoplastic T-cells were EBV-negative. Four years later, the patient presented with a relapse of the peripheral T-cell lymphoma. In situ hybridization revealed numerous EBV-carrying lymphocytes, which were shown to be polyclonal B-cells with a latency III pattern of EBV gene expression (LMP1(+)/EBNA2(+)). This observation suggests that impairment of EBV-specific immunity in the micro-environment of T-cell lymphomas may facilitate the outgrowth of EBV-carrying B-lymphocytes and emphasizes the importance of determining the phenotype of EBV-infected cells, particularly when studying T-cell lymphomas. The results further suggest that the HRS cells and neoplastic T-cells were of different clonal origins. The detection of EBV-carrying cell populations admixed with the neoplastic T-cells at primary presentation and at relapse raises the possibility that the growth of the T-cell lymphoma was dependent on the presence of such cells.

Aged↗
PubMed1983

Malignant lymphoma of mucosa-associated lymphoid tissue. A distinctive type of B-cell lymphoma.

As illustrated in the two cases described in this paper close morphologic and immunohistochemical similarities exist between Mediterranean lymphoma (MTL) and primary gastrointestinal lymphoma of follicle center cell (FCC) origin as it occurs in Western countries. Similarities between the two conditions include a dense noninvasive monotypic lamina propria plasma cell infiltrate, present in all cases of MTL and in some cases of Western gastrointestinal FCC lymphoma, and an invasive infiltrate of FCCs morphologically distinct from the plasma cells. A distinctive lesion produced by individual gland invasion characterizes both types of lymphoma. A clonal relationship between the lamina propria plasma cells and the invasive FCCs, long suspected but never proved in MTL, can be demonstrated in Western cases. Many of the histologic and clinical features common to these lymphomas can be explained in the context of the normal maturation sequences of gut associated lymphoid tissue. It is suggested that MTL and Western cases of primary FCC gastrointestinal lymphoma share a common histogenesis from mucosa associated lymphoid tissue.

Adult↗
PubMed1985

Lymphomas of the mucosa-associated lymphoid tissue. Signet ring cell lymphomas presenting in mucosal lymphoid organs.

Four cases of lymphoma are reported which were postulate to have developed from neoplastic transformation of the lymphoid cells of the mucosa-associated lymphoid tissue (MALT). This contention is primarily based on two observations: the peculiar "homing" tendency of these lymphomas and the immunoglobulin isotype. Both properties are characteristic of the lymphoid cells of the MALT. These lymphomas can also be identified by their histologic structure (signet ring cell lymphomas) and their presentation in an MALT organ. These lymphomas are probably separable from other lymphomas proposed to arise from lymphocytes of the gut-associated lymphoid system (GALT).

Aged↗
PubMed1986

Cell proliferation and DNA content in non-Hodgkin's lymphoma. Flow cytometry in relation to lymphoma classification.

Flow cytofluorometric (FCF) DNA analysis was performed on specimens from 154 patients with non-Hodgkin's lymphoma (NHL) and correlated to histopathology according to the Rappaport classification and the Working Formulation of NHL for clinical usage (WF). NHL associated with unfavorable prognosis (UP) had significantly higher proportions of cells in S-phase as compared to the favorable prognosis (FP) group. The proportion of S-phase cells also differed significantly between the low-, intermediate-, and high-grade malignancy groups of the WF. Aneuploidy was significantly more frequent in the UP (41%) than in the FP (15%) group. By stepwise discriminant analysis, the S-phase frequency was a stronger discriminator between prognostic groups than DNA content. Classification by discriminant analysis showed that over 90% of the low grade/FP lymphomas were allocated to the good prognosis group by their S-phase and DNA values. Due to the variation in the proportion of S-phase cells in the intermediate grade and high grade, as well as the UP lymphomas, only approximately 50% of the UP and 60% of the high-grade lymphomas were identified as such by this discriminant model, while almost one half of the intermediate-grade lymphomas were allocated to the low-grade group. The results suggest that S-phase analysis can be of value in distinguishing intermediate- and high-grade lymphomas with high and low proportions of proliferating cells, which may be prognostic importance.

Adult↗
PubMed1988

Monocytoid B-cell lymphoma. Clinicopathologic study of 21 cases of a unique type of low-grade lymphoma.

The morphologic and immunologic features of three cases of an unusual and distinct B-cell lymphoma were recently described and termed monocytoid B-cell lymphoma (MBCL) because of the striking resemblance of the neoplastic cells to reactive monocytoid B-lymphocytes. The morphologic spectrum and the clinical behavior of MBCL were investigated in a series of 21 patients. This study indicates that patients with MBCL usually present with lymphadenopathy and Stage I or II disease. MBCL also occurs at extranodal sites including the salivary gland. Because four of the patients with MBCL had Sjögren's syndrome with characteristic laboratory profiles, these results raise the possibility that there may be a relationship between MBCL and Sjögren's syndrome. Eight patients were male and 13 female (M:F = 1:1.6), and MBCL primarily involved the elderly (median age, 66 years). The most striking clinical findings were high percentages of complete remissions and long survival times indicating that MBCL is a low-grade lymphoma. Of 21 patients investigated, 18 were in complete remission at the time of completion of this study. Two patients died with the disease and one was lost to follow-up. Patients with localized MBCL may have a better survival rate than those with generalized disease. Like other low-grade lymphomas, MBCL can progress to a higher grade lymphoma of large cell type. Unlike other low-grade lymphomas, in MBCL splenomegaly, bone marrow involvement, and leukemic conversion are uncommon.

Adult↗
PubMed2006

Dissemination of a Sjögren's syndrome-associated extranodal marginal-zone B cell lymphoma: circulating lymphoma cells and invariant mutation pattern of nodal Ig heavy- and light-chain variable-region gene rearrangements.

OBJECTIVE: Both the genesis and outgrowth of extranodal marginal-zone B cell lymphomas (MZLs) of the mucosa-associated lymphoid tissue (MALT) type are generally thought to represent antigen-driven processes. We undertook this study to analyze lymphoma progression and dissemination outside of the MALT-type lesions. METHODS: Histopathologic and Ig heavy- and light-chain variable-region gene (V(H/L)) analyses were performed in sequential tissue samples from a patient with primary Sjögren's syndrome (SS) with glandular (parotid) manifestations and subsequent nodal dissemination of a low-grade MZL. RESULTS: This MZL expressed a CD20+,CD27+,sIgM/kappa+,IgD-,CD5-,CD10-,Bcl-6-,CD23-,p53-,p21-,MDM2- phenotype and mutated V(H)1-69/D2-21/J(H)4alpha-V(kappa)A27/J(kappa)2 Ig rearrangements. Notably, circulating lymphoma cells from the parotid glands occurred transiently in the patient's blood, as detected by single-cell polymerase chain reaction. In addition, 2 minor B cell clones (clones 2 and 3, with V(H)3-07/D3-22/J(H)3b-V(lambda)3L/J(lambda)2/3 and V(H)3-64/D3-03/J(H)2-V(kappa)A19/J(kappa)2 rearrangements, respectively) were also detected in the parotid glands and blood, and 1 of these (clone 2) was also detected in the lymph nodes. Ig V(H/L) analyses revealed ongoing (antigen-driven) mutations of the glandular lymphoma rearrangements, but an invariant mutation pattern of their nodal counterparts. CONCLUSION: These data indicate coexpansion and transient (re)circulation of the lymphoma clone and 2 additional glandular B cell clones in a primary SS-associated extranodal MZL. Combined histologic and molecular features of the nodal lymphoma subclone reflect a process of "follicular colonization" that eventually froze the mutation machinery after accumulation of additional (antigen-driven) Ig V(H/L) mutations.

Female↗
PubMed1979

Sister chromatid exchange in cell lines from malignant lymphomas (lymphoma lines).

The frequency of sister chromatid exchanges (SCEs) was studied in cells from three freshly established lymphoma lines, derived from two patients with Hodgkin's disease and one patient with non-Hodgkin lymphoma. These values were compared to SCE rates found in cells from two long-established lymphoma lines (Raji and BJAB) and to those recorded in control cell lines of normal human donors. The highest SCE levels were demonstrated in the freshly established lymphoma lines, the lowest SCE values separated the lymphoblastoid cell lines from healthy controls, and the older lymphoma lines Raji and BJAB presented rates in between. The influences of BUDR concentration and of the duration of BUDR treatment on the frequency of SCEs were tested. Furthermore, the dependence of the SCE rate on the time interval between establishment of the cell line and its SCE investigation was considered. The connection between elevated SCE rates and the neoplastic nature of lymphoma lines is discussed.

Animals↗
PubMed1981

Effect of gene dosage on cell-surface expression of Thy-1 antigen in somatic cell hybrids between Thy-1- Abelson-leukemia-virus induced lymphomas and Thy-1+ mouse lymphomas.

Hybrids between pseudodiploid Thy-1.1+ lymphomas and Thy 1.2- pseudodiploid Abelson-leukemia-virus-induced-(ALV-induced) lymphomas express Thy-1 glycoprotein on their cell surface. These Thy-1+ hybrids invariably express the Thy 1.1 allelic form of the glycoprotein and may be either Thy 1.2+ or Thy 1.2-. Sublines expressing both Thy 1.1 and Thy 1.2 can be isolated from Thy 1.1+, Thy 1.2- hybrids by cell sorting. In contrast to hybrids with pseudodiploid ALV-induced lymphomas, hybrids between Thy 1.1+ lymphomas and pseudotetraploid Thy 1.2- Abelson-leukemia-virus-induced lymphomas do not express Thy-1 glycoprotein on their cell surface and Thy-1 glycoprotein cannot be detected in detergent extracts of these cells. Thy-1+ revertants were isolated from one of the Thy-1- hybrids by cell sorting. - These results demonstrate a gene dosage effect for the expression of the Thy-1 glycoprotein in somatic cell hybrids. They are consistent with the idea that diffusable gene products regulate Thy-1-glycoprotein expression in these hybrids. They also suggest that there may be additional, apparently cis-active, regulatory mechanisms which determine the ability of the Thy-1 structural genes of the Abelson-leukemia-virus-induced lymphoma parent to be expressed in somatic cell hybrids.

Abelson murine leukemia virus↗
PubMed2000

IDEC-C2B8 (Rituximab) anti-CD20 antibody treatment in relapsed advanced-stage follicular lymphomas: results of a phase-II study of the German Low-Grade Lymphoma Study Group.

PURPOSE: The current study was initiated to assess the clinical efficacy and side effects of rituximab in patients with relapsed advanced stage follicular lymphoma. PATIENTS AND METHODS: The study was performed as an open-label non-randomized multicenter phase-II trial and included patients older than 18 years of age with relapsed advanced-stage follicular lymphomas (FL) grades I and II, according to the REAL classification, or with centroblastic/centrocytic (CB/CC lymphomas according to the Kiel classification. Four weekly doses of 375 mg/m2 rituximab were applied. RESULTS: 38 patients from eight centers were included between January 1997 and January 1998 and were evaluable for response and toxicity on an intention to treat basis. The median age was 55 years (range 26-75 years). Thirteen patients (35%) were in first relapse, 11 patients (30%) in second, and 13 patients (35%) in third relapse. The median time between primary diagnosis and study entry was 4.6 years (range 0.9-14.7 years). Twenty-three patients tolerated the application of rituximab without adverse events; in 13 cases the infusion rate had to be reduced because of side effects; in two patients the application was stopped because of pharyngeal edema and anaphylactoid reaction. The most frequent side effects were fever (13 patients) and rigor (13 patients); 65% of the side effects were observed after the first infusion. Twenty grade-III/IV side effects were considered to be related to treatment: lymphocytopenia (3), granalocytopenia (1), thrombocytopenia (2), fever (1), hyperglycermia (1), venous thrombosis (1), syncope (1), plasmatic coagulation disorder (1), shortness of breath (2), photosensitivity (1), cardiac failure (1), chills (1), sepsis (1), tumor lysis (1), anemia (1), and pharyngeal edema (1). Eight patients were not eligible for assessment of response because of non-follicular subtypes of low-grade lymphomas (n =6) or early termination of therapy at the first infusion because of severe side effects (n =2). From the 30 evaluable cases with follicular lymphomas, five patients achieved a complete remission (CR) (17%), nine patients a partial remission (PR) (30%), and two patients a minor response (MR) (7%). The overall response rate was 47%. The median time to treatment progression (TTP) was 201 days (range 64-293 days), with five patients experiencing long-lasting remissions of 214-293 days duration. In three patients, the rituximab-induced remission exceeded the preceding progression-free interval substantially. Bulky disease (P=0.058) and/or bone-mar row involvement (P=0.046) were associated with poor response. CONCLUSION: This study confirms the moderate treatment-related toxicity and the high antilymphoma activity of rituximab in patients with relapsed follicular lymphoma. Further studies are needed to determine the role of rituximab in the first-line treatment of these disorders and its combination with conventional chemotherapy.

Adult↗
PubMed1997

Generation of lymphoma-type variant hamster polyomavirus genomes in hamsters susceptible to lymphoma induction.

The hamster polyomavirus (HaPV) induces either hair follicle epitheliomas or lymphomas in either Z3 or HaP respectively. Syrian hamsters. In the lymphomas specifically deleted "lymphoma-type" (lt) HaPV genomes are accumulated. In the present study the temporal pattern of generation of HaPV (lt) DNA was investigated in context of the development of lymphomas in neonatally infected HaP hamsters. The generation of HaPV (lt) DNA was first detectable during the postnatal phase of high level replication of viral DNA in hemopoietic organs (at 7 days post infection), thus clearly preceding the development of overt lymphoma. A variety of HaPV (lt) DNA species is generated in lymphoid cells, but usually only one of them is accumulated to high amounts in lymphoma cells. Furthermore, the pattern of HaPV (lt) and wild-type (wt) DNA was studied in normal and tumor tissues of tumor-bearing hamsters as well as in tumor-free hamsters. In tumor-bearing hamsters predominantly HaPV (lt) DNA species were found in the infected tissues, while HaPV (wt) DNA was detected rarely and only in tumor-free tissues. In contrast, in tissues of tumor-free hamsters HaPV (wt) DNA prevailed over HaPV (lt) DNA species.

Animals↗
PubMed1993

Genetic resistance to lymphoma-leukemia: role of natural killer cells in the rejection of lymphoma grafts.

Lethally irradiated genetically resistant (C57 x AKR) mice, unlike non-resistant (C3H x AKR) mice, which display genetic resistance to transplantation of parental C57 bone marrow grafts (GR to BMT), also reject transplanted parental AKR lymphoma grafts (GR to lymphoma). Depletion of natural killer (NK) cell activity of resistant (C57 x AKR) mice by anti-asialo GM-1 serum abrogated the resistance, whereas stimulation of NK cell activity of non-resistant (C3H x AKR) mice by polyinosinic: polycytidillic acid (poly I:C) induced the resistance to parental AKR lymphoma grafts. This shows that NK cells contribute to GR of (C57 x AKR) hybrid mice to parental AKR lymphoma grafts. Further, these results indicate that NK cells which confer genetic resistance to bone marrow transplantation (GR to BMT) in lethally irradiated (C57 x AKR) hybrid mice, also mediate GR to lymphoma transplantation in these mice, thereby linking GR to BMT with GR to lymphoma-leukemia.

Animals↗
PubMed2005

Systemic non-Hodgkin's lymphoma simulating primary intraocular lymphoma.

PURPOSE: To describe a case of an unusual presentation of systemic non-Hodgkin's lymphoma with clinical and histopathologic findings closely resembling that of primary intraocular lymphoma. DESIGN: Observational case report. METHODS: A 58-year-old woman with a history of treated systemic non-Hodgkin's lymphoma presented 2 years later with a subretinal lesion and intraocular inflammation in her left eye. RESULTS: Diagnostic enucleation and histopathologic studies revealed findings consistent with primary intraocular lymphoma including intraretinal, subretinal, and subretinal pigment epithelial tumor cells without involvement of the choroid. CONCLUSIONS: We conclude that systemic non-Hodgkin's lymphoma can present remotely with findings resembling primary intraocular lymphoma and should be included in the differential diagnosis of intraocular inflammation and subretinal infiltrates.

Diagnosis, Differential↗
PubMed1987

Circulating lymphoma cells in patients with B & T non-Hodgkin's lymphoma detected by immunoglobulin and T-cell receptor gene rearrangement.

We studied peripheral blood mononuclear cells from 50 patients with active B- and T-cell non-Hodgkin's lymphoma by DNA hybridisation. Nineteen patients (38%) had circulating clones of cells detected by immunoglobulin gene rearrangement (17 patients) or T-cell receptor gene rearrangement (2 patients) with JH and J beta 2 probes. Lymphoma tissue and peripheral blood were studied simultaneously in 22 patients, 9 of which had a circulating clone of cells in peripheral blood. In 7 patients the gene rearrangement in lymphoma tissue and peripheral blood mononuclear cells was identical. However, in 2 patients both heavy chain and light chain gene rearrangements were different in tissue and peripheral blood. The incidence of peripheral blood involvement was commonest in advanced CSIII & IV disease (54%) compared to CSI & II disease (18%) (P less than 0.05), and in low grade (45%) compared to intermediate and high grade lymphoma (31%) (difference not statistically significant). Only 4 patients had definite lymphoma cells seen on peripheral blood smear. The presence of circulating lymphoma cells correlated with conventional assessment of bone marrow involvement although circulating clones were detected in 30% (12/40) of patients with apparently normal bone marrow.

B-Lymphocytes↗
PubMed2003

Graft-versus-lymphoma effect of donor lymphocyte infusion in indolent lymphomas relapsed after allogeneic stem cell transplantation.

Donor lymphocyte infusions (DLI) are used to treat relapsed haematological diseases after allogeneic stem cell transplantation (SCT). We treated seven patients with DLI for indolent non-Hodgkin's lymphoma relapsed after SCT. In available blood and bone marrow samples, lymphoma cells were analysed by real-time quantitative polymerase chain reaction of t(14;18)-positive cells in follicular lymphoma, and by immunophenotyping in small lymphocytic lymphoma. Before DLI, three patients were treated with chemo- and/or radiotherapy, and one with rituximab. Evaluable responses to pre-DLI therapy were stable disease in one and partial remission (PR) in two patients. Six patients responded to DLI (complete remission (CR) in four and PR in two). After DLI, acute graft-versus-host disease (GVHD) occurred in 3/6 patients, classified as grade 2, whereas only limited chronic GVHD was seen (n=5). The four continuous CR are lasting for median 65+ (43-89) months. In the remaining patient, not responding to DLI, progressive disease was seen later on; chemotherapy followed by another DLI resulted in CR. In three cases, clinical responses to DLI could be substantiated by molecular or immunophenotypic analysis of lymphoma cells. We conclude that DLI is effective for treatment of indolent lymphoma relapsing after SCT.

Adult↗
PubMed1997

The clinical outcome of 65 cases of mantle cell lymphoma initially treated with non-intensive therapy by the British National Lymphoma Investigation Group.

Mantle cell lymphoma (MCL) was first described as a distinct biological entity on the basis of its association with the t(11;14)(q13;q32) resulting in over-expression of the cyclin D1 gene. Recognition of the morphological, immunophenotypic and clinical characteristics of MCL has enabled the accurate diagnosis of this entity and appreciation of its poor prognosis. Most published series of patients with MCL have used anthracycline-containing regimens. In contrast the British National Lymphoma Investigation (BNLI) group have treated 65 patients with MCL with non-intensive 'low-grade lymphoma' therapy. The median overall survival of 57 months and progression-free survival of 24 months compares favourably with the more intensively treated series. Although the disease was generally more aggressive than other low-grade lymphomas, some patients were asymptomatic and had indolent disease. When compared to 1853 patients with non-MCL low-grade lymphomas entered on the BNLI database, patients were found on average to be older (P=0.02), to have more extranodal disease (P<0.00001), and a higher proportion to have a raised ESR (P=0.02) and a low serum albumin (P=0.002). Multivariate analysis of significant prognostic markers in all BNLI low-grade lymphomas failed to identify MCL as an independent prognostic factor.

Adult↗
PubMed1999

A case of natural killer/T cell lymphoma of the subcutis resembling subcutaneous panniculitis-like T cell lymphoma.

A case of nasal type natural killer (NK)/T cell lymphoma of the subcutis showing clinical and morphological features that resemble subcutaneous panniculitis-like T cell lymphoma (SPTCL) is presented. A 73-year-old man presented with swelling of the left arm and was diagnosed with panniculitis by a dermatologist. It was concluded from a skin biopsy specimen that the patient had non-Hodgkin's lymphoma of the large cell, NK/T cell type because the neoplastic cells showed polyclonal CD3 immunoreactivity. Treatment with interferon-gamma was initiated, but the patient died of disseminated intravascular coagulation and multiple organ failure 2 months after the initial symptoms appeared. However, involvement of additional organs by the lymphoma was not apparent clinically. An autopsy was not performed. A routinely stained section of the biopsy skin specimen revealed massive necrosis of the subcutaneous fat, karyorrhexis admixed with reactive histiocytes, and large atypical lymphoid cells. Immunoreactivity for polyclonal CD3 was present in the perinuclear region, but absent in the neoplastic cell membranes. CD56, CD45RO (UCHL-1), CD43 (MT1), CD45 (leukocyte common antigen), and the cytotoxic molecules perforin, granzyme B and TIA-1 were positive, but CD20 (L26), CD4, CD8, and betaF1 were negative. Epstein-Barr virus (EBV) mRNA was detected in the nuclei of neoplastic cells by in situ hybridization. Subcutaneous panniculitis-like T cell lymphoma is reported to be an EBV-negative, clonal T cell neoplasm. Although this case showed clinical and morphological features that resembled SPTCL, perinuclear polyclonal CD3 staining and membranous CD56 reactivity seen in neoplastic cells were suggestive of NK cells. Furthermore, the neoplastic cells were positive for EBV. This case is considered to be a NK/T cell lymphoma of the subcutis resembling SPTCL. It is believed that it is important to recognize such a tumor because patients may undergo a fulminant clinical course, despite the tumor being localized in the subcutaneous adipose tissue.

Aged↗
PubMed2002

Human herpesvirus-8-associated lymphoma of the bowel in human immunodeficiency virus-positive patients without history of primary effusion lymphoma.

This report describes two cases of human herpesvirus-8 (HHV-8)-associated large cell lymphoma of the bowel in human immunodeficiency virus (HIV)-positive men. Immunohistochemistry provides evidence of HHV-8 infection of the lymphoma cells (LNA1+, vIL-6+). In both cases, lymphoma cells were coinfected by the Epstein-Barr virus. One case was of B-cell lineage, but the second one was of null phenotype with isolated expression of the CD3 molecule. However, in the latter case, assessment of B- or T-cell clonality remained elusive. The chief finding for these two cases was the lack of history of primary effusion lymphoma. There was an apparent restriction of the tumor to the large bowel in the first case. For the second case, the bowel tumor was preceded by lymph node and liver involvement. The cases suggest that the incidence of HHV-8 infection in large cell lymphoma arising in the setting of HIV infection (other than primary effusion lymphoma) may be underestimated and that the detection of the viral gene products would be appropriate for greater understanding of the pathogenesis of these tumors. HUM PATHOL 33:846-849.

AIDS-Related Opportunistic Infections↗
PubMed2004

Lymphoma-specific genetic aberrations in microvascular endothelial cells in B-cell lymphomas.

BACKGROUND: The growth of most tumors depends on the formation of new blood vessels. In contrast to genetically unstable tumor cells, the endothelial cells of tumor vessels are considered to be normal diploid cells that do not acquire mutations. METHODS: Using a combined immunohistochemical and fluorescence in situ hybridization assay, we examined the endothelial cells in 27 B-cell lymphomas for cytogenetic alterations that are known to be present in the lymphoma cells. RESULTS: We found that 15 to 85 percent (median, 37 percent) of the microvascular endothelial cells in the B-cell lymphomas harbored lymphoma-specific chromosomal translocations. In addition, numerical chromosomal aberrations were shared by the lymphoma cells and the endothelial cells. CONCLUSIONS: Our findings suggest that microvascular endothelial cells in B-cell lymphomas are in part tumor-related and therefore reflect a novel aspect of tumor angiogenesis.

Adult↗