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PubMed1978

Malignant lymphoma, small lymphocytic type: a clinicopathologic study of 84 cases with suggested criteria for intermediate lymphocytic lymphoma.

Clinical and histopathologic findings were reviewed in 84 cases of malignant lymphoma of the small (well differentiated) lymphocytic type. The slides were studied without clinical information, and the following morphologic features were evaluated: pattern of growth, number of large lymphocytes, mitotic rate, degree of capsular involvement, presence of plasma cells and/or plasmacytoid lymphocytes, and presence of residual germinal centers. Subsequently, clinical information was obtained. The minimum follow-up period on living patients was 5 years. The patients were divided into 3 clinical categories: 1) monoclonal gammopathy (MG)-11 cases, 2) chronic lymphocytic leukemia (CLL) without MG-56 cases, and 3) those without MG or CLL at the time of lymph node biopsy-17 cases. The criterion for CLL was an initial absolute lymphocyte count less than 4000/mm3. Four of the patients with MG also had CLL, and 6 of those in the third group later developed CLL, from 1 to 61 months after lymph node biopsy. Generalized lymphadenopathy was the usual presentation in all 3 groups, and bone marrow examination was positive in all but 1 of the 49 cases, representing all 3 groups, in which it was performed. Median survival for the 84 patients was 51 months. The only clinical parameters which showed a significant association with poorer survival were age above 60 and anemia (Hb. conc. less than 11.0). There was no significant relationship between morphologic characteristics and clinical categories other than the association of plasmacytoid cells with MG in 6 cases. A mitotic rate of 30 or more mitoses per 20 high power fields (HPF), found in 5 cases with at least 1 in each clinical category, showed a highly significant association with decreased survival (p = .01). Variations in mitotic rate between 0 and 29 mitoses per 20 HPF and other morphologic parameters did not show a significant relationship with prognosis. It was concluded that malignant lymphoma of the small lymphocytic type is a definite clinicopathologic entity which may or may not exhibit MG or CLL, and it is proposed that the term "intermediate lymphocytic lymphoma" be applied only to those cases showing histopathologic characteristics of small lymphocytic lymphoma and a mitotic rate of 30 or more mitoses per 20 HPF.

Adolescent↗
PubMed1978

Biology of the human malignant lymphomas. IV. Functional characterization of ten diffuse histiocytic lymphoma cell lines.

Ten consecutive diffuse histiocytic lymphoma (DHL) cell lines established in our laboratory were studied for the presence of Epstein-Barr virus (EBV) genomes, lysozyme, nonspecific esterase and other cytochemical reactions, phagocytic activity, cytoplasmic immunoglobulin light and heavy chains, and surface receptors to sheep erythrocytes, complement, and the Fc fragment of immunoglobulin. In agreement with previous studies performed on biopsy specimens, our results indicate that the diffuse histiocytic lymphomas, as a histopathologic entity, represent a heterogeneous group of neoplasms, the majority of which are B-lymphocyte in origin. The cell lines appear to fall into three categories based on the following criteria: 1) presence of monoclonal cytoplasmic immunoglobulins (B-lymphocytic type, 6/10 cell lines); 2) presence of non-specific esterase, phagocytic activity, and/or lysozyme (histiocytic type, 2/10 cell lines); and 3) absence of all lymphoid and histiocytic cell characteristics (null cell type, 2/10 cell lines). Despite the fact that many of the lymphoma patients had positive serologies to EBV antigens, all of the DHL cell lines were negative for the presence of EBV genomes. Both of the two B-lymphocytic type and one of the two histiocytic type lines tested were susceptible to infection with EBV, as indicated by synthesis of early antigen and also, in a small proportion of the infected cells, of viral capsid antigen. These prototypic DHL cell lines may permit the development of new criteria for the differential diagnosis and treatment of this highly malignant and diverse group of lymphomas.

Animals↗
PubMed1982

Characteristics of a brain lymphoma cell line derived from primary intracranial lymphoma.

A brain lymphoma cell line, designated TK, was established from biopsy material of a patient with primary intracranial lymphoma. The TK cell line grew in suspension with clumps of cells and consisted of primitive lymphoid cells. TK cells and original lymphoma cells from which the cell line was derived bore surface immunoglobulin and lacked Epstein-Barr virus-determined nuclear antigen. Transplantation of the TK cells into immunosuppressed newborn hamsters gave rise to invasive growth of tumors with metastasis to the brain and eyes. These findings provide definitive evidence for a B-cell origin of the brain lymphoma in this case.

Adult↗
PubMed1982

Mantle-zone lymphoma: a follicular variant of intermediate lymphocytic lymphoma.

A clinicopathologic analysis of 12 cases of a morphologically distinctive non-Hodgkin's malignant lymphoma which appeared to arise from the mantle zones of secondary lymphoid follicles is presented. In lymph node and spleen sections, atypical small lymphoid cells with slightly irregular and indented nuclear contours proliferated as wide mantles around non-neoplastic-appearing germinal centers. Surface marker analysis performed on lymph nodes revealed a monoclonal B-cell proliferation in two cases. Clinically, the patients usually had advanced disease (Stage III or IV) associated with splenomegaly. This lymphoma appears to be relatively low-grade, since nine of 12 patients are alive with a median follow-up period of 28.5 months. We believe that thie "mantle-zone lymphoma" represents a nodular or follicular variant of intermediate lymphocytic lymphoma.

Adult↗
PubMed1983

Malignant lymphoma of follicular center cell origin in humans. IV. Small transformed (noncleaved) cell lymphoma of the non-Burkitt's type.

Small transformed cell lymphoma (STC) is the least common follicular center cell neoplasm in the Lukes-Collins classification system. If the cells are homogenous in size and shape, Burkitt's lymphoma (STC-BL) is diagnosed; otherwise STC lymphoma of the non-Burkitt's type (STC-nBL) is present. The authors have reviewed their experience with 17 cases of STC-nBL. This neoplasm affects all ages, both sexes equally, and most commonly is Stage IV based either on a visceral abdominal mass or bone marrow involvement. Surface immunoglobulin analysis revealed IgM in all cases tested. In spite of aggressive treatment protocols, there were only 5 of 17 (29%) clinical complete responses. Four of these five have continuous remission from 8 to 23 months after diagnosis; all four of these patients were treated with regimens containing high-dose cyclophosphamide. Future analyses including viral studies, chromosomal analyses, and uniform treatment protocols will help determine whether STC-nBL and Burkitt's lymphoma are truly distinct entities.

Adolescent↗
PubMed1985

Hypercalcemia, unusual bone lesions, and human T-cell leukemia-lymphoma virus in adult T-cell lymphoma.

Extensive generalized and subperiosteal bone resorption was demonstrated in a patient with adult T-cell lymphoma and marked hypercalcemia of unclear pathogenesis. Antibody to the human T-cell leukemia-lymphoma virus (HTLV) was present in the serum of the patient, consistent with the recently reported association of adult T-cell lymphoma, hypercalcemia, and HTLV. The unique feature of this case was the presence of bone radiographic and pathologic findings consistent with hyperparathyroidism, in the absence of elevated parathormone levels. These findings contrast with the few previously reported cases of adult T-cell lymphoma with hypercalcemia, which showed lytic, sclerotic, or osteoporotic bone lesions. The authors suggest that the patient's malignant T-lymphocytes may have produced an osteoclast-activating-factor-like substance or a parathormone-like substance, which caused the striking bone changes. The exact role of HTLV in the pathogenesis of such cases remains to be determined.

Adult↗
PubMedDate not supplied

Lymphoma type adult T-cell leukemia--a clinicopathologic study of HTLV related T-cell type malignant lymphoma.

The clinical and pathological features of T-cell type malignant lymphoma related to human T-cell leukemia virus (HTLV) were investigated in eight patients presenting lymphadenopathy. Biopsy of lymph nodes showed an histology of diffuse non-Hodgkin's lymphoma. All patients were positive for anti-ATLA antibody and HTLV proviral DNA in the lymph node cells. Most patients showed pronounced hypercalcemia and high serum levels of lactic dehydrogenase. All patients died between 3 and 17 months (mean 8 months) after the onset of disease. HTLV-related malignant lymphoma should be added to the spectrum of ATL, being classified as a lymphoma type ATL.

Adult↗
PubMed2006

In vitro Epstein-Barr virus-immortalized lymphoma cell line carrying t(9;14)(p13;q32) chromosome abnormality, derived from splenic lymphoma with villous lymphocytes.

We herein describe splenic lymphoma with villous lymphocytes (SLVL) carrying t(9;14)(p13;q32). The t(9;14)(p13;q32) is a rare reciprocal chromosome translocation found in a subset of B-cell malignancies, mainly in low-grade non-Hodgkin's lymphomas. In t(9;14)(p13;q32), PAX-5 gene on 9p13 is involved with the immunoglobulin heavy-chain gene on 14q32. It has been thought that the deregulated expression of PAX-5 as a result of t(9;14)(p13;q32) may contribute to abnormal cell proliferation. Although continuous cell lines are invaluable tools for studying lymphomagenesis in the t(9;14)(p13;q32)-bearing lymphomas, establishment of such cell lines is extremely difficult since they are usually mature B-cell malignancies. In an attempt to transform the SLVL cells into a proliferating cell line, we examined the responses of the cells to infection by Epstein-Barr virus (EBV). SLVL cells were found to be susceptible to immortalization by EBV, resulting in a permanent cell line. The cell line, designated SL-15, possessed the t(9;14)(p13;q32). Genotype analysis and immunophenotype profiles confirmed that the cell line arose from the primary lymphoma cells. The cells had characteristic cytoplasmic villi. SL-15 cells has been growing over 2 years equivalent to 350-400 population doubling levels without proliferative crisis that is often observed in EBV-positive lymphoblastoid cell lines. Furthermore, SL-15 cells, when inoculated into nude mice, formed t(9;14)(p13;q32)-bearing tumors with cytoplasmic villi. The validated SLVL-derived cell line provide a useful model system to study molecular biology of t(9;14)(p13;q32)-bearing B-cell malignancies as well as lymphomagenesis of SLVL in vitro and in vivo.

Animals↗
PubMed1993

Insulin dependence of murine T-cell lymphoma. II. Insulin-deficient diabetic mice and mice fed low-energy diet develop resistance to lymphoma growth.

Physiological concentrations of insulin support the in vitro growth of LB T-cell lymphoma. We could not detect similar insulin dependence in other tumor cell lines. This study reports that insulin also enhances the growth of LB cells in vivo. Mice treated with Streptozotocin (SZ) developed partial resistance to LB lymphoma growth and they survived longer (p < 0.0025) than non-diabetic mice after LB-cell inoculation. A few diabetic mice developed complete tumor resistance, manifested by total regression of the lymphoma. SZ-treated diabetic mice reconstituted with external insulin died as fast as non-diabetic mice when both were inoculated with the same number of LB cells. The SZ-treated diabetic mice did not develop resistance to the growth of BCLI B-cell leukemia, which demonstrated only a marginal proliferative response to insulin in vitro. Mice fed a low-energy diet exhibited low insulin levels and also developed resistance to lymphoma growth (50% survival 21 days vs. 15 days; p < 0.0005), supporting the concept that insulin enhances LB T-cell tumor development in mice.

Animals↗
PubMed2003

Differential expression and function of A20 and TRAF1 in Hodgkin lymphoma and anaplastic large cell lymphoma and their induction by CD30 stimulation.

A20 and TRAF1 are two anti-apoptotic components of the intracellular signalling pathway of the tumour necrosis factor receptor (TNFR) family. Induction of apoptosis seems to be a main function of these receptors. It is astonishing that a member of this family, CD30, is overexpressed by highly proliferating tumours such as Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL). It is known that CD30 stimulation leads to the apoptosis of ALCL tumour cells but not of Hodgkin-Reed-Sternberg (HRS) cells. We have already established the overexpression of TRAF1 in HRS cells. In this study we demonstrate that A20 is highly expressed in the HRS cells in 20/22 of cases of classical HL, in 4/4 cases of nodular lymphocyte-predominant HL (NLPHL), and in 2/2 cases of the anaplastic variant of diffuse large B cell lymphoma. In contrast, all other non-Hodgkin lymphomas, including ALCL, revealed either no A20 reactivity, or reactivity in less than 1% of all tumour cells. CD30 stimulation induced A20 and TRAF1 expression. This effect was most prominent in HL and ALCL cell lines with low basal expression levels of these molecules. Immunohistological studies of reactive lymphoid blasts in tonsillar tissue demonstrated that co-expression of CD30, A20, and TRAF1 also occurs in vivo. Cell lines with high basal A20 and TRAF1 expression were resistant to CD30-mediated apoptosis. The sensitivity to CD30-induced apoptosis was increased by inhibition of protein synthesis. TRAF1 transfection decreased CD30-induced apoptosis. Our data suggest that A20 and TRAF1 contribute to apoptosis resistance and, therefore, play an important role in the pathogenesis of classical HL.

Apoptosis↗
PubMed2000

Gastric mucosa-associated lymphoid tissue lymphoma: implications of animal models on pathogenic and therapeutic considerations--mouse models of gastric lymphoma.

There are a number of Helicobacter species that will readily colonise the mouse stomach for the duration of the animal's life. They are Helicobacter felis, "Helicobacter heilmannii" and Helicobacter pylori. Early studies on long-term infection of BALB/c mice showed the presence of lesions resembling low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Because of the suggestion that H. pylori was the cause of these tumors in humans, this phenomenon was studied further as it was reasoned that the Helicobacter-infected mice would provide a valuable model of the human disease. Low-grade gastric MALT lymphomas have been shown to follow infection with all the Helicobacter species listed above. These lesions are indistinguishable from the human disease with the presence of centrocyte-like cells, characteristic lymphoepithelial lesions and glandular destruction. Treatment with antimicrobial therapy results in regression of the lymphomas. There is evidence of progression to high-grade in some animals. The Helicobacter mouse models of lymphoma are likely to provide important information relevant not just to H. pylori-induced lesions in the human, but to antigen-driven tumors in general.

Animals↗
PubMed1991

Ki-1 positive meningeal lymphoma in a patient with a history of Hodgkin lymphoma.

We describe the case of a woman in whom a Ki-1 lymphoma confined to the meninges developed nearly 4 years after complete remission of a Hodgkin lymphoma. The neurological symptoms appeared in two stages. The first, marked by multi-radicular impairment, cleared almost completely within a few months. The second, a year after the beginning of the first, manifested with a syndrome of meningeal irritation, which quickly led to death. We discuss the clinical course and the possible relationship between Hodgkin lymphoma and Ki-1 lymphoma.

Adult↗
PubMed2003

Primary periosteal lymphoma: an unusual presentation of non-Hodgkin's lymphoma with radiographic, MR imaging, and pathologic correlation.

This report describes a primary periosteal location of non-Hodgkin's lymphoma, without nodal disease, and without adjacent intramedullary disease at presentation. The clinical and imaging appearance of periosteal lymphoma simulates other neoplastic osseous surface tumors more than that of lymphoma in other locations. Consideration of this rare presentation of non-Hodgkin's lymphoma in the differential diagnosis of periosteal bone lesions can be helpful to ensure proper diagnosis and treatment.

Adult↗
PubMed1993

Non-Hodgkin's lymphoma of the thyroid gland: prognostic factors and treatment outcome. The Princess Margaret Hospital Lymphoma Group.

PURPOSE: Non-Hodgkin's lymphoma presenting in the thyroid gland is uncommon. A review of the Princess Margaret Hospital experience was performed to assess treatment outcome and prognostic factors in this rare extranodal presentation of localized lymphoma. METHODS AND MATERIALS: Fifty-two patients treated at the PMH between 1978 and 1986 were identified and their records reviewed retrospectively. Staging procedures revealed 16 patients with Stage I, 28 with Stage II, and eight with Stages III or IV disease. Five patients were treated on a protocol designed for anaplastic carcinoma of thyroid and they were excluded from detailed analysis. Of 39 patients with Stages I and II disease, 18 were treated with radiotherapy alone, three chemotherapy alone, and 18 combined modality therapy. Combined modality therapy was used mainly in patients with large tumor bulk. RESULTS: The overall 5-year actuarial survival and cause-specific survival were 56% and 64%, respectively. The overall relapse-free rate was 61% at 5 years. Among the 39 patients with Stages I and II disease, the 5-year actuarial survival, cause-specific survival, and relapse-free rate were 64%, 73%, and 66%, respectively. There were no significant differences in outcome between those treated with radiotherapy alone and those treated with combined modality therapy (cause-specific survival: p = 0.25, relapse: p = 0.06). A univariate analysis showed that the only variable to reach statistical significance was tumor bulk. Age was marginally significant while stage and histology were not statistically significant, possibly due to the fairly homogeneous distribution of patients in each of these variables. Patients with progression or relapse of lymphoma after initial treatment frequently died of disease. Isolated gastrointestinal relapses occurred in three cases, representing 27% of all relapses. CONCLUSION: Based on the above results, we recognize that the majority of patients with localized thyroid lymphoma require combined modality therapy and we recommend radiotherapy alone only for a small, select group of patients with Stage I disease and small tumor bulk.

Adult↗
PubMed2004

Localised extranodal lymphoma of the head and neck: the Sheffield Lymphoma Group experience (1971-2000).

AIMS: Over the 30-year period from 1971-2000, 3750 cases of lymphoma were referred to the Sheffield Lymphoma Group for investigation and treatment. Of these, 580 were extranodal presentations and, of these, 190 (33%) were localised to the head and neck region. The aim of this lymphoma database review was to evaluate the patient characteristics and survival rates for these patients. MATERIALS AND METHODS: The sample included 98 women and 92 men, with a median age at presentation of 65 years. RESULTS: The most common site affected was tonsil (34%), followed by salivary glands (16%). Other common sites were the thyroid, orbit and nasopharynx. The most frequent presenting feature was a swelling or mass, with pain, dysphagia and nasal obstruction also comprising large groups. All cases were non-Hodgkin's lymphoma. Fifty-five cases were histological grade 1; 132 were grade 2. Diffuse large B cell was the most common histological subtype. The overall 5- and 10-year survival rates were 55% (95% CI 47-62) and 44%, (95% CI 36-53), respectively, with a median survival of 92 months (95% CI 56-128). Stage and grade were both found to influence survival. CONCLUSION: This data concords with and extends information available from previous studies. More detail is now required on specific head and neck sites.

Adolescent↗
PubMed2004

Oral solid form of primary effusion lymphoma mimicking plasmablastic lymphoma.

Primary effusion lymphoma (PEL) is a rare large cell lymphoma subtype that usually is associated with human immunodeficiency virus infection. Features facilitating PEL identification are its clinical presentation, cytologic findings, immunophenotypic profile, and particularly, relation to human herpesvirus 8 (HHV8) infection. Uncommonly, PEL may present as a solid form that predominantly involves the distal digestive tract and poses major diagnostic problems, especially when unassociated with body cavity effusions. We herein report the case of an HIV-positive 42-year-old male with synchronous presentation of a pleural cavity PEL and a tongue-based lesion, both displaying plasmablastic features. Demonstration of HHV8 presence in the lingual lesion excluded a plasmablastic lymphoma and established the diagnosis of an oral solid form of PEL. This case illustrates the need for investigating HHV8 in any plasmablastic-looking lymphoma, especially in HIV-infected patients.

Adult↗
PubMed2002

The nucleophosmin-anaplastic lymphoma kinase fusion protein induces c-Myc expression in pediatric anaplastic large cell lymphomas.

The majority of pediatric anaplastic large cell lymphomas (ALCLs) carry the t(2;5)(p23;q35) chromosomal translocation that juxtaposes the dimerization domain of nucleophosmin with anaplastic lymphoma kinase (ALK). The nucleophosmin-ALK fusion induces constitutive, ligand-independent activation of the ALK tyrosine kinase leading to aberrant activation of cellular signaling pathways. To study the early consequences of ectopic ALK activation, a GyrB-ALK fusion was constructed that allowed regulated dimerization with the addition of coumermycin. Expression of the fusion protein caused a coumermycin-dependent increase in cellular tyrosine phosphorylation and c-Myc immunoreactivity, which was paralleled by a rise in c-myc RNA. To assess the clinical relevance of this observation, c-Myc expression was determined in pediatric ALK-positive and -negative lymphomas. Co-expression of c-Myc and ALK was seen in tumor cells in 15 of 15 (100%) ALK-positive ALCL samples, whereas no expression of either ALK or c-Myc was seen in six of six cases of ALK-negative T-cell lymphoma. C-Myc may be a downstream target of ALK signaling and its expression a defining characteristic of ALK-positive ALCLs.

Child↗
PubMed2003

Fatigue in long-term survivors of Hodgkin's lymphoma; a report from the German Hodgkin Lymphoma Study Group (GHSG).

Although treatment regimens for Hodgkin's lymphoma have become more sophisticated, little is known about the prevalence of fatigue in long-term survivors. Therefore, we investigated the fatigue status of long-term survivors of Hodgkin's lymphoma and a control group using a pre-validated questionnaire. In 1995/1996, we contacted 1981 patients, who were enrolled in the German Hodgkin Studies HD 1-6. All patients were treated according to the treatment protocols HD1-3 (1981-1988) and HD 4-6 (1988-1993). The patients with a current status of complete remission were asked to complete a quality-of-life (QoL) questionnaire (European Organisation for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ C-30)) and a fatigue questionnaire (Multidimensional Fatigue Inventory (MFI)). The results were compared with the data from 935 controls, matched for age, gender and living area. Eight-hundred and eighteen questionnaires from the patients were available for analysis. The median time between the end of treatment and completing the questionnaire is 5.2 years. Fatigue levels of patients with Hodgkin's lymphoma are high, even years after treatment. Fatigue dimensions are significantly influenced by several clinical and non-clinical factors. Fatigue levels of Hodgkin's lymphoma patients are significantly higher than those of the control group. Further investigations are warranted to explore the effectiveness of treatment strategies for fatigue.

Activities of Daily Living↗