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PubMed1996

Gastric lymphoepithelioma-like carcinoma and jejunal B-cell MALT lymphoma with large cell transformation. Demonstration of EBV with identical LMP gene deletions in the carcinoma and large cell lymphoma.

The authors describe a patient with gastric lymphoepithelioma-like carcinoma (LELC) and jejunal low grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) with histologic transformation to large cell lymphoma. In situ hybridization studies for Epstein-Barr virus (EBV) demonstrated abundant EBV RNA (EBER) within the neoplastic cells of the gastric LELC and the jejunal large cell lymphoma. The low grade MALT lymphoma was EBER negative. Polymerase chain reaction (PCR) studies confirmed the in situ hybridization results, and demonstrated a 30 base pair deletion in the 3' end of the latent membrane protein gene in both the gastric LELC and the jejunal large cell lymphoma. These results suggest that the same viral strain infected both the stomach and jejunal tumors. In addition, the finding of EBV in the large cell lymphoma, but not the low grade component suggests that EBV may have played a role in large cell transformation.

Aged↗
PubMed1976

Malignant lymphoma with a high content of epitheloid histiocytes (Lennert's lymphoma).

Fifteen patients with a rare malignant lymphoma characterized by a high content of epithelioid histiocytes are reported. This lymphoma, referred to as "Lennert's lymphoma," was originally thought to be a variant of Hodgkin's disease, but has both histologic and clinical differences. Although the infiltrate is polymorphous, diagnostic Reed-Sternberg cells are difficult to find and involvement of tonsils relatively common. Lennert's lymphoma bears some resemblance to immunoblastic lymphadenopathy in that some patients have a history of allergies, polyclonal hyperglobulinemia, and all lymph nodes demonstrate variable proliferation of immunoblasts. However, both vascular proliferation and the amorphous eosinophilic interstitial material characteristic of immunoblastic lymphadenopathy are lacking. The clinical course in this series was unpredictable with rapid death in six cases, chiefly from sepsis, 1--18 months following diagnosis despite therapy as for Hodgkin's disease. The remaining eight patients for whom follow-up data are available are in apparent clinical remission. Further cases and investigations are needed to determine the precise behavior of Lennert's lymphoma and to learn its exact status in relation to other malignant lymphomas or immunoblastic proliferations.

Adult↗
PubMed1990

Low-grade B-cell lymphoma of mucosa-associated lymphoid tissue arising in the thymus. A thymic lymphoma mimicking myoepithelial sialadenitis.

We describe two cases of primary low-grade B-cell lymphoma of the thymus that showed histological features of low-grade B-cell lymphoma arising in mucosa-associated lymphoid tissue (MALT). The appearances most closely resembled MALT lymphoma arising in myoepithelial sialadenitis (MESA). In both cases, the tumor was excised. In one case, there has been no recurrence in 4 years of follow-up without further treatment; in the second case, the tumor has involved an axillary lymph node. Immunohistochemistry showed light-chain restriction in both cases, and the B-cell phenotype was similar to that previously described in MALT lymphomas. The occurrence of MALT lymphoma in the thymus is consistent with the presence of mucosal structures (Hassall's corpuscles) and with recent descriptions of a native B-cell population in this organ. The relationship of this previously undescribed thymic low-grade B-cell MALT lymphoma arising in the thymus has not yet been clarified.

B-Lymphocytes↗
PubMed2000

Hepatosplenic alphabeta T-cell lymphoma: an unusual case with clinical, histologic, and cytogenetic features of gammadelta hepatosplenic T-cell lymphoma.

Hepatosplenic gammadelta T-cell lymphoma is a recently identified entity in which lymphoma cells bearing the gammadelta T-cell receptor (TCR) infiltrate the sinusoids of the liver and the sinuses of the splenic red pulp and bone marrow, without lymph node involvement. It is also characterized by a recurrent cytogenetic finding, isochromosome 7q (i7q10). The authors report a case of hepatosplenic lymphoma of alphabeta T-cell phenotype that shares the same clinical, histologic, and cytogenetic characteristics of the previously described hepatosplenic gammadelta T-cell lymphoma. Fluorescent in situ hybridization performed with chromosome 7 probes showed the typical pattern of isochromosome 7q. Genomic analysis of the TCR gamma locus failed to detect a clonal rearrangement. This unique case of hepatosplenic lymphoma of alphabeta T-cell phenotype supports the possibility that lymphoid populations of different alphabeta or gammadelta phenotype that share similar homing and presumably functional properties could give rise to lymphomas displaying similar clinical and pathologic findings.

Adult↗
PubMed2005

CD20-negative T-cell-rich B-cell lymphoma as a progression of a nodular lymphocyte-predominant Hodgkin's lymphoma treated with rituximab: a molecular analysis using laser capture microdissection.

Rituximab is a chimeric anti-CD20 monoclonal antibody. It has shown efficacy in patients with B-cell non-Hodgkin lymphoma and also in CD20-positive Hodgkin lymphoma. Recently, CD20-negative tumors have been described after Rituximab therapy. We report a 34-year-old man with a history of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), treated with different chemotherapy regimens, including anthracyclines and Rituximab. After 4 years in complete remission, he developed a CD20-negative T-cell-rich B-cell lymphoma (TCRBCL) presenting as multiple lung lesions. This case shows the difficulties in the diagnosis of CD20-negative lymphomas when the number of tumor cells is low and when they are found in a predominant T-cell context. Using anti-CD79a as a B-cell marker is mandatory to overcome the difficulties in identifying these tumors. Moreover, this case illustrates the usefulness of laser capture microdissection to obtain purified cell populations for molecular studies in lymphomas with relative paucity of tumor cells, as well as the need to analyze different IgH gene regions to decrease the rate of false-negative results in PCR clonality studies.

Adult↗
PubMed1983

Delineation of subsets in human B-cell lymphomas by a set of monoclonal antibodies raised against B lymphoma cells.

Murine hybridoma antibodies to a human B-cell lymphoma were developed. After screening against normal T cells, monocytes, and granulocytes 11 antibodies that reacted with cells from other B-cell lymphomas remained, of which 10 showed individually distinct staining patterns, as tested by indirect fluorescence. When tested against lymphomas or cell lines, none of these antibodies revealed staining patterns suggesting reactivity with conventional B-cell surface markers, such as immunoglobulin, complement factor 3 receptors, or HLA-DR antigens. Only one of the antibodies (GB1) reacted with human serum, as determined by a blocking assay. The antibodies were found to belong to different immunoglobulin isotypes. Two antibodies (GB13 and GB14) reacted with greater than 5% of normal peripheral blood mononuclear cells. These reactions were mainly due to reactivity with B cells. The antibodies reacted only in a few cases with acute leukaemias, B-cell lines, and follicular lymphomas. On the other hand, distinct patterns of reactivity in different histological groups of diffuse lymphomas were obtained, suggesting that the antibodies may be useful in delineating phenotypic subsets among human B-cell lymphomas.

Animals↗
PubMed1996

Analysis of lectin binding properties on human Burkitt's lymphoma cell lines that show high spontaneous metastasis to distant organs in SCID mice: the binding sites for soybean agglutinin lectin masked by sialylation are closely associated with metastatic lymphoma cells.

Alterations in cell surface carbohydrates on human lymphoma cell lines with different spontaneous metastatic potential in the severe combined immunodeficiency (SCID) mouse model were analyzed. A difference in cell surface carbohydrates between high- (HBL-2, HBL-7 and HBL-8) and no- or low-(HBL-4, HBL-6, Daudi and Raji) spontaneous metastatic human lymphoma cell lines were analyzed on a FACScan using fluorescein-isothiocyanate (FITC)-conjugated lectins. The most consistent difference in lectin binding properties was found with soybean agglutinin (SBA) lectin. High-metastatic lymphoma cells (HBL-7 and HBL-8 cells) in vitro were found to bind the SBA lectin, but the cells in vivo (in primary tumors and metastatic tumors of SCID mice) showed considerably reduced SBA lectin binding. In addition, HBL-2 cells that almost did not bind SBA lectin in vitro and in vivo showed high spontaneous metastasis. Neuraminidase treatment revealed that SBA lectin binding sites were masked by sialic acid. On the other hand, no- or low-metastatic lymphoma cells in vitro and in vivo were found to bind SBA lectin. HBL-8 cell clones without SBA lectin binding showed high spontaneous metastasis to distant organs in SCID mice but HBL-8 cell clones with SBA lectin binding showed very low spontaneous metastasis. Sophora Japonica agglutinin (SJA) lectin is able to recognize the carbohydrates in common with SBA lectin, but it does not appear to be associated with metastatic capacity. These results suggest that the sialylation of particular carbohydrate residues on human lymphoma cells that are recognized by SBA lectin may be associated with the spontaneously metastatic capacity of human lymphoma cell lines in our SCID mouse model.

Animals↗
PubMed1998

Long survivors with Ki-1 lymphoma having t(2;5) (p23;q35). Does the presence or absence of t(2;5) influence the prognosis of patients with Ki-1 lymphoma?

We experienced three patients with CD30+ diffuse large cell lymphoma having chromosomal abnormalities. The first patient was an 8-year-old girl with bilateral cervical lymphadenopathy. A biopsy of a cervical lymph node revealed diffuse large cell lymphoma (stage III), positive for CD30 and a chromosomal abnormality, t(2;5). She attained a remission and is now in complete remission 108 months after diagnosis, despite frequent relapses. The second patient was a 13-year-old boy with right axillar and supraclavicular lymph-node adenopathy. A biopsy of a cervical lymph node revealed diffuse large cell lymphoma (stage III), positive for CD30 and a chromosomal abnormality, t(2;5). He attained remission and was in continuous first remission 112 months after diagnosis. The third patient was an 11-year-old boy with fever and bilateral cervical lymph node revealed diffuse large cell lymphoma (stage III), positive for CD30 and chromosomal abnormality without t(2;5). He showed a very aggressive clinical course. Only the patients with Ki-1 lymphoma having t(2;5) survived over 100 months from the diagnosis, despite the advanced stage of the disease. These findings and a review of the literature showed that the presence or absence of t(2;5) may influence the outcome of Ki-1 lymphoma.

Adolescent↗
PubMed1998

Nucleophosmin-anaplastic lymphoma kinase of large-cell anaplastic lymphoma is a constitutively active tyrosine kinase that utilizes phospholipase C-gamma to mediate its mitogenicity.

Large-cell anaplastic lymphoma is a subtype of non-Hodgkin's lymphoma characterized by the expression of CD30. More than half of these lymphomas have a chromosomal translocation, t(2;5), that leads to the expression of a hybrid protein comprised of the nucleolar phosphoprotein nucleophosmin (NPM) and the anaplastic lymphoma kinase (ALK). Here we show that transfection of the constitutively active tyrosine kinase NPM-ALK into Ba/F3 and Rat-1 cells leads to a transformed phenotype. Oncogenic tyrosine kinases transform cells by activating the mitogenic signal transduction pathways, e.g., by binding and activating SH2-containing signaling molecules. We found that NPM-ALK binds most specifically to the SH2 domains of phospholipase C-gamma (PLC-gamma) in vitro. Furthermore, we showed complex formation of NPM-ALK and PLC-gamma in vivo by coimmunoprecipitation experiments in large-cell anaplastic lymphoma cells. This complex formation leads to the tyrosine phosphorylation and activation of PLC-gamma, which can be corroborated by enhanced production of inositol phosphates (IPs) in NPM-ALK-expressing cells. By phosphopeptide competition experiments, we were able to identify the tyrosine residue on NPM-ALK responsible for interaction with PLC-gamma as Y664. Using site-directed mutagenesis, we constructed a comprehensive panel of tyrosine-to-phenylalanine NPM-ALK mutants, including NPM-ALK(Y664F). NPM-ALK(Y664F), when transfected into Ba/F3 cells, no longer forms complexes with PLC-gamma or leads to PLC-gamma phosphorylation and activation, as confirmed by low IP levels in these cells. Most interestingly, Ba/F3 and Rat-1 cells expressing NPM-ALK(Y664F) also show a biological phenotype in that they are not stably transformed. Overexpression of PLC-gamma can partially rescue the proliferative response of Ba/F3 cells to the NPM-ALK(Y664F) mutant. Thus, PLC-gamma is an important downstream target of NPM-ALK that contributes to its mitogenic activity and is likely to be important in the molecular pathogenesis of large-cell anaplastic lymphomas.

Animals↗
PubMed1999

Multicenter phase II study of fludarabine phosphate for patients with newly diagnosed lymphoplasmacytoid lymphoma, Waldenström's macroglobulinemia, and mantle-cell lymphoma.

PURPOSE: Fludarabine phosphate (F-AMP) has significant activity in follicular lymphoma and in B-cell chronic lymphatic leukemia, where it has demonstrated high complete response (CR) rates. Lymphoplasmacytoid (LPC) lymphoma, Waldenstrom's macroglobulinemia (WM), and mantle-cell lymphoma (MCL) also present with advanced-stage disease and are incurable with standard alkylator-based chemotherapy. A phase II trial was undertaken to determine the activity of F-AMP in patients newly diagnosed with these diseases. PATIENTS AND METHODS: Between 1992 and 1996, 78 patients (aged 18 to 75 years) received intravenous F-AMP (25 mg/m2/d for 5 days, every 4 weeks) until maximum response, plus two further cycles as consolidation. The primary end point was response rate; secondary end points included time to progression (TTP), duration of response, and overall survival (OS). RESULTS: Forty-four (62%) of 71 assessable patients had a response to F-AMP (LPC lymphoma, 63%; WM, 79%; MCL, 41%); the CR rate was 15%. At a median follow-up of 1.5 years, 19 of 44 responding patients have had progression of lymphoma; the median duration of response was 2.5 years. The median survival has not yet been reached. There was no significant difference in the duration of response or OS between patients with different histologies; TTP was shorter in patients with MCL (P = .015). Myelosuppression was relatively common, and the treatment-related mortality (TRM) was 5%, mostly associated with pancytopenia and infection. CONCLUSION: Single-agent fludarabine phosphate is active in previously untreated LPC lymphoma and WM, with only moderate activity in MCL. However, the CR rate is low, and the TRM is relatively high. Its role in combination chemotherapy remains to be demonstrated.

Adult↗
PubMed2005

Small follicular lymphoma arising near the ampulla of vater: a distinct subtype of duodenal lymphoma?

A 49-yr-old Japanese woman underwent upper gastrointestinal endoscopy because of nonspecific dyspepsia. Endoscopy revealed a flat elevated lesion about 15 mm in diameter adjacent to the duodenal papilla, the surface of which was uneven and covered with whitish granules. Based on the results of histological examination with immunohistochemistry (positive for CD10, CD20, CD79a, and bcl-2 protein, negative for CD5 and cyclin D1), a diagnosis of grade 1/3 follicular lymphoma was established. Systemic staging examinations suggested the lymphoma was restricted to the mucosa and superficial portion of the submucosa in the duodenal wall. The patient was treated with a combination of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisolone) and monoclonal anti-CD20 antibody (rituximab), in addition to radiotherapy. After six courses of this combination chemotherapy, complete regression of the lymphoma was observed. Although reports of small duodenal lymphoma (<20 mm or localized to the mucosa or submucosa) are extremely rare, the features of this case are characteristic of small duodenal lymphoma in terms of evolution around the ampulla of Vater, low-grade follicular type, occurrence in a women, occurrence in the fourth decade of life, and favorable outcome, and this type of tumor may need to be distinguished by pathogenesis and clinical behavior from various other gastrointestinal lymphomas.

Ampulla of Vater↗
PubMed1990

Phase III trial of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) versus cisplatin, etoposide, bleomycin and prednisone (CisEBP) for the treatment of advanced non-Hodgkin's lymphoma of high grade malignancy. The Danish Lymphoma Study Group.

The trial included 85 previously untreated patients (median age 61 years) with stage III or IV non-Hodgkin's lymphoma (NHL) of the subtypes centrocytic lymphoma, diffuse centroblastic lymphoma, immunocytoma, immunoblastic lymphoma, or unclassified lymphoma of high grade malignancy. The patients were randomized to 9 monthly treatment cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or CisEBP (cisplatin, bleomycin, etoposide, prednisone). Patients who had failed to achieve even a partial response (PR) after the completion of 2 cycles were switched to the alternative regimen. Complete response (CR) on primary treatment was obtained in 70% (55-83%) of CHOP-treated patients and in 25% (13-41%) of CisEBP-treated patients (p = 0.0004). Secondary CHOP treatment produced CR in 7 (30%) of 24 patients and secondary CisEBP treatment led to CR in 2 (15%) of 14 patients. The median survival was 3.4 years in the CHOP arm and 2.6 years in the CisEBP arm (p = 0.78). Hematologic toxicity was mainly leukocytopenia and anemia in both treatment arms. Non-hematological toxicity was slight, and late toxicity was insignificant. Three treatment-related deaths were noted. We conclude that CHOP induces more remissions than CisEBP in advanced lymphomas of high grade malignancy.

Adult↗
PubMed2002

Dural marginal zone lymphoma with massive amyloid deposition: rare low-grade primary central nervous system B-cell lymphoma. Case report.

The authors report the case of a 63-year-old woman who presented with a primary dural extranodal marginal zone lymphoma (MZL) associated with massive kappa light chain amyloidosis of the meninges. Extranodal MZL is a low-grade B-cell lymphoma that may show variable degrees of plasmacytic differentiation. Like solitary plasmacytoma of soft tissue, which can also be associated with amyloid, extranodal MZL generally responds well to local therapy and has a good prognosis. It is important to distinguish these entities from high-grade primary central nervous system (CNS) B-cell lymphomas and more aggressive and/or widespread, potentially amyloidogenic conditions such as multiple myeloma, lympho-plasmacytoid lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma. To the authors' knowledge this is the first reported case of dural MZL associated with massive meningeal amyloid deposition. Extranodal MZL is a rare low-grade primary CNS B-cell lymphoma that may be associated with amyloidosis. It should be considered in the differential diagnosis of CNS lymphoproliferative lesions and CNS amyloidosis.

Amyloidosis↗
PubMed2006

High-grade hepatic mucosa-associated lymphoid tissue (MALT) lymphoma probably transformed from the low-grade gastric MALT lymphoma.

The Mucosa-associated lymphoid tissue (MALT) lymphoma, which was first described in 1983, is known to be caused by chronic Helicobacter pylori (HP) infection, which triggers lymphoid infiltration and formation of organized lymphoid tissue. In approximately two thirds of cases of MALT, the lymphoma has been observed to regress after treatment of H. pylori infection; this provides strong evidence of a causative role of HP in the etiology of MALT. We report a case of a 67-year-old female patient with a high-grade MALT lymphoma of the liver; this occurred six years after complete remission of a low-grade gastric MALT lymphoma and after complete eradication of H. pylori. there was no recurrence of the previous low-grade gastric MALT lymphoma. Based on radiological and pathologic findings, the high-grade MALT was considered to result from transformation of the low-grade gastric MALT lymphoma.

Aged↗
PubMed2000

[Epidemiology and geo-pathology of malignant lymphomas with special emphasis on Japanese lymphomas].

The descriptive epidemiology and geo-pathology of malignant lymphomas have been hampered by the absence of a unified classification. Recent proposal of the REAL classification which will soon become the WHO classification is a significant step toward better understandings of the epidemiology of this interesting neoplasia. Worldwide epidemic of non-Hodgkin's lymphoma was discussed with possible relationships to herbicides. General characteristics of Japanese lymphomas as compared to Western lymphomas were described with special emphasis on the correlation between the low incidence rates of follicular lymphomas and Hodgkin's lymphomas.

Female↗
PubMed2001

Common germinal-center B-cell origin of the malignant cells in two composite lymphomas, involving classical Hodgkin's disease and either follicular lymphoma or B-CLL.

BACKGROUND: Classical Hodgkin's disease (HD) and B-cell non-Hodgkin lymphoma (NHL) occasionally occur in the same patient. Such composite lymphomas represent interesting models to study the pathogenesis of B-cell lymphomas and the relationship between HD and B-cell NHL. MATERIALS AND METHODS: We analyzed two composite lymphomas (a combination of classical HD with follicular lymphoma [FL] and a combination of classical HD with B-cell chronic lymphocytic leukemia [B-CLL]) by micromanipulation of single cells from tissue sections and amplification of immunoglobulin V region genes for the clonal relationship of the tumor cells. RESULTS: In both cases, clonally related variable (V) genes with both shared as well as distinct somatic mutations were obtained from the two lymphomas, showing that in each of the cases the distinct tumor cells were members of a common germinal center (GC) B-cell clone. FL cells from two different lymph nodes of patient 1 showed a similar mutation pattern, suggesting that infiltration of these lymph nodes by tumor cells was not restricted to a particular FL cell or subclone. In the FL, a single cell was identified with a mutation signature indicating that premalignant cells can persist in the tissue. CONCLUSIONS: The cases presented here further underline the close relationship between HD and B-cell NHL and the role of the GC in lymphomagenesis. Whereas the latter was already suggested for FL and HD, the present study indicates that also in the B-CLL subset characterized by mutated Ig genes, important steps in malignant transformation happen in the GC, and that HRS cells can derive from CD5-positive B cells.

Aged↗
PubMed2005

Localised non-Hodgkin lymphoma of the testis: the Sheffield Lymphoma Group experience.

We evaluated clinical features, management and survival of patients with localised (stage 1E or 2E) testicular non-Hodgkin lymphoma (NHL) presenting to the Sheffield Lymphoma Group between 1972 and 2002. Thirty consecutive eligible patients were identified from the lymphoma database and clinical records of all were reviewed. Survival data were statistically analysed. The median age of patients was 74 years (range 38-87). Sixty-three percent were >70 years of age. The median duration of follow-up was 15 months (range 2.1-211). All patients had orchidectomy. Eleven (37%) had orchidectomy alone. Twelve (40%) had orchidectomy and chemotherapy, 4 (13%) had orchidectomy and radiotherapy. Three (10%) had orchidectomy, chemotherapy and radio-therapy. Five (17%) had immediate disease progression following orchidectomy or whilst on treatment. A complete response was seen in the remaining 25 (84%) irrespective of treatment modality. Seven (23%) of patients remain alive, with a median follow-up of 73 months (range 9.9-211). Six (20%) died of causes not related to their lymphoma. Twelve (40%) relapsed following a complete response and median time to relapse was 9 months. Only 1 of these relapses was in the central nervous system; 1 in bone, 1 in skin, 2 in the contralateral testis. The majority of relapses (58%) occurred in the lymph nodes. Primary testicular lymphoma is an uncommon and poor prognosis disease usually affecting older men. The data and experience available to guide the treatment strategies for testicular lymphoma are limited. However, the evidence points to a combined modality approach being the most likely effective treatment, comprising surgery, anthracycline-containing combination chemotherapy with or without prophylactic contralateral testis and regional lymph node irradiation.

Adult↗
PubMed1989

Progression of transplanted SJL/J lymphomas attributed to a single aggressive H-2Ds-negative lymphoma.

Spontaneously arising, H-2Ds-positive SJL/J lymphomas have been reported to become irreversibly more aggressive and H-2Ds-negative upon successive transplantation in syngeneic mice. In an effort to determine whether this process was one of tumor progression, we sought to: (a) establish whether a clonal relationship exists between readily transplantable aggressive SJL/J lymphomas and their respective indolent predecessors; and (b) identify genetic events critical to the process of acquisition of increased malignancy. Examination of putatively distinct, aggressive, H-2Ds-negative lymphomas, including the long term transplantable line RCS5, revealed them to have the same heavy and light immunoglobulin chain gene rearrangement patterns, a characteristic karyotype marked by nine chromosomal abnormalities, and approximately ten newly acquired ecotropic murine leukemia proviruses at similar genomic sites. Independent, spontaneously arising H-2Ds-positive lymphomas, in early transplant, were found to be genetically distinct from the respective more malignant H-2Ds-negative tumors to which they gave rise during successive transplantation. The data are interpreted as indicating that the aggressive H-2Ds-negative tumors in this study originated from a common source, most likely the RCS5 tumor, rather than through progression of separate spontaneously arising SJL/J lymphomas. It cannot be concluded which of the multiple genetic abnormalities of the H-2Ds-negative tumors were critical to their highly malignant phenotype. However, chromosomal abnormalities and newly acquired murine leukemia proviruses are discussed as to the roles they might play in SJL/J lymphomas.

Animals↗