Cases Of Large Cell Lymphoma Research Articles

Characterization of CD3+/CD20+ canine large-cell lymphoma.

Immunophenotyping of canine large-cell lymphoma (LCL) for B-cell and T-cell surface antigens is commonly performed to better predict the clinical outcome. Expression of surface antigen CD3 is associated with T-cell malignancies; surface antigen CD20 is expressed on B cells. However, a small subset of canine LCLs expresses both CD3 and CD20 (CD3+/CD20+); this form of lymphoma remains poorly defined at the molecular level. In a retrospective study, we aimed to better characterize immunophenotypic properties and antigen receptor clonality of CD3+/CD20+ LCL. We selected formalin-fixed, paraffin-embedded tissues from 10 cases of CD3+/CD20+ LCL and breed-matched controls of peripheral large T-cell lymphoma (PTCL) and diffuse large B-cell lymphoma (DLBCL). Using PCR for antigen receptor rearrangement (PARR), we identified monoclonal T-cell receptor gamma (TCRγ) rearrangements in all CD3+/CD20+ cases. Three of 10 cases had monoclonal rearrangements in the immunoglobulin heavy chain (IgH), supportive of cross-lineage rearrangement. There was no significant difference in the frequency of antigen receptor rearrangement between CD3+/CD20+ and PTCL cases. In comparison with DLBCL, CD3+/CD20+ LCL had TCRγ rearrangement more frequently and IgH rearrangement less frequently, respectively. Immunolabeling of the B-cell marker PAX5 occurred less frequently in all CD3+/CD20+ LCL cases compared to the DLBCL controls. Immunolabeling for BCL-2 was robust, regardless of immunophenotype. Nuclear Ki67 positivity was variable in CD3+/CD20+ cases, indicating a heterogeneity in proliferation. Overall, cases of canine CD3+/CD20+ LCL had properties similar to PTCL, suggesting a similar histogenesis of these 2 subsets.

MiR-497 suppresses cycle progression through an axis involving CDK6 in ALK-positive cells.

Anaplastic large-cell lymphoma, a T-cell neoplasm, is primarily a pediatric disease. Seventy-five percent of pediatric anaplastic large-cell lymphoma cases harbor the chromosomal translocation t(2;5)(p23;q35) leading to the ectopic expression of NPM-ALK, a chimeric tyrosine kinase. NPM-ALK consists of an N-terminal nucleophosmin (NPM) domain fused to an anaplastic lymphoma kinase (ALK) cytoplasmic domain. Pediatric NPM-ALK+ anaplastic large-cell lymphoma is often a disseminated disease and young patients are prone to chemoresistance or relapse shortly after chemotherapeutic treatment. Furthermore, there is no gold standard protocol for the treatment of relapses. To the best of our knowledge, this is the first study on the potential role of the microRNA, miR-497, in NPM-ALK+ anaplastic large-cell lymphoma tumorigenesis. Our results show that miR-497 expression is repressed in NPM-ALK+ cell lines and patient samples through the hypermethylation of its promoter and the activity of NPM-ALK is responsible for this epigenetic repression. We demonstrate that overexpression of miR-497 in human NPM-ALK+ anaplastic large-cell lymphoma cells inhibits cellular growth and causes cell cycle arrest by targeting CDK6, E2F3 and CCNE1, the three regulators of the G1 phase of the cell cycle. Interestingly, we show that a scoring system based on CDK6, E2F3 and CCNE1 expression could help to identify relapsing pediatric patients. In addition, we demonstrate the sensitivity of NPM-ALK+ cells to CDK4/6 inhibition using for the first time a selective inhibitor, palbociclib. Together, our findings suggest that CDK6 could be a therapeutic target for the development of future treatments for NPM-ALK+ anaplastic large-cell lymphoma.

SATB1 Defines a Subtype of Cutaneous CD30+ Lymphoproliferative Disorders Associated with a T-Helper 17 Cytokine Profile

Cutaneous CD30+ lymphoproliferative disorders (LPDs), including lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large-cell lymphoma, comprise the second most common group of cutaneous T-cell lymphomas. Previously, we reported that special SATB1, a thymocyte-specific chromatin organizer, was overexpressed and promoted malignant T-cell proliferation in a portion of CD30+ LPDs. Here, we investigated the expression pattern of SATB1 in CD30+ LPDs with a large cohort of patient samples, and examined the potential of SATB1 as a molecular marker to classify CD30+ LPDs with differential clinicopathological behaviors. SATB1 expression was identified in the CD30+ anaplastic T cells in 11 of 12 (91.7%) lymphomatoid papulosis and 16 of 42 (38.1%) primary cutaneous anaplastic large-cell lymphoma cases. SATB1+ cases showed T-helper 17 polarization, together with more prominent epidermal hyperplasia and granulocytic infiltration. SATB1+ lesions responded better to combined treatment of methotrexate and interferon. SATB1 activated the expression of T-helper 17 cytokines while repressing T-helper 1-related genes. The heterogeneity in SATB1 expression across CD30+ LPDs was associated with the extent of promoter DNA methylation. Hence, SATB1 expression defines a subtype of CD30+ LPDs with characteristic pathobiology and prognosis. These data provide valuable insights into the heterogeneity of cutaneous T-cell malignancies, which may lead to individualized therapy in the future.

Efficacy and prognosis of antiviral therapy on hepatitis C following treatment of lymphoma in HCV-positive diffuse large-cell lymphoma

The purpose of this study is to study the usefulness of post-remission antiviral therapy in cases of HCV-RNA-positive diffuse large-cell lymphoma. Antiviral therapy against HCV was performed after remission using CHOP or CHOP-like chemotherapy in combination with rituximab in five successive cases of HCV-RNA-positive diffuse large-cell lymphoma. The control groups consisted of a group of HCV-RNA-positive diffuse large-cell lymphoma cases prior to this trial (control 1), and a group of cases that tested negative for HIV, HCV, and HBV (control 2). All the cases were in remission at the time of initial treatment. There were no significant differences between the three groups in terms of age, sex, treatment, stage, or International Prognosis Index (IPI). When HCV antiviral therapy was performed after treatment for diffuse large-cell lymphoma, we observed no recurrence or deaths, and the 2-year overall survival and progression-free survival rates were significantly greater than those in the control 1 group (P = 0.0246). It is possible that a better prognosis can be achieved by performing HCV antiviral therapy after achieving remission in cases of HCV-RNA-positive diffuse large-cell lymphoma through the use of R-CHOP or similar treatments.

Differential NFATc1 Expression in Primary Cutaneous CD4+ Small/Medium-Sized Pleomorphic T-Cell Lymphoma and Other Forms of Cutaneous T-Cell Lymphoma and Pseudolymphoma.

Primary cutaneous CD4 small/medium-sized pleomorphic T-cell lymphoma (PCSTCL) has recently emerged as a distinct clinicopathological entity. Because of a considerable degree of overlap with pseudolymphoma, the diagnosis is often challenging. Preliminary studies suggest that nuclear upregulation of calcineurin/nuclear factor of activated T cells (NFAT) may play a role in lymphomagenesis. 137 cases (70 males and 67 female, mean age = 55) of various forms of cutaneous T-cell and B-cell infiltration were evaluated for NFATc1 expression. The study comprised 18 cases of PCSTCL, 45 cases of mycosis fungoides (MF), 5 cases of lymphomatoid papulosis (LyP), 5 cases of anaplastic large-cell lymphoma (ALCL), 8 cases of other forms of peripheral T-cell lymphoma, not otherwise specified, 12 precursor lesions of MF (ie, cutaneous T-cell dyscrasias), 35 cases of pseudolymphomas, 8 primary cutaneous B-cell lymphoma, and 1 chronic lymphocytic leukemia. The number of cells exhibiting a nuclear stain was counted per 10 high-power field and 2-tailed statistical analysis was used for comparison of nuclear NFATc1 expression between primary PCSTCL and all other groups. A P-value <0.05 was considered to indicate statistical significance. All cases of PCSTCL showed nuclear staining for NFATc1 (mean = 296 ± 236) with no cases in which an exclusive cytoplasmic stain was observed. The cells exhibiting this staining pattern were oftentimes larger manifesting other features of a follicular helper T-cell phenotype, such as variable positivity for PD1, ICOS, CXCL13, and BCL6. In comparison, an exclusively cytoplasmic stain was observed in 29 cases of MF; in few cases, rare nuclear staining cells were observed averaging less than 10 per high-power field (P = 0.0001). These positive staining cases were not only limited to tumor-stage MF but also encompassed patch- and plaque-stage lesions and follicular variants of MF. The same pattern was observed in cases of T-cell dyscrasia (mean = 3 ± 3, P = 0.0001) and pseudolymphoma (mean = 2 ± 3, P = 0.0001), both revealing a dominant cytoplasmic staining pattern. In pseudolymphomatous folliculitis, a greater extent of nuclear staining for NFATc1 was observed compared with other forms of pseudolymphoma. No significant difference was seen between MF and T-cell dyscrasia or pesudolymphomas excluding pseudolymphotous folliculitis. Anaplastic large-cell lymphoma cases showed an almost exclusive cytoplasmic staining pattern with rare nuclear staining (mean = 55 ± 102, P = 0.0001); similar results were observed in LyP (mean = 17 ± 15, P = 0.004). Cutaneous B-cell lymphomas showed a similar extent of staining as that noted for PCSTCL. The greatest extent of staining was observed in chronic lymphocytic leukemia. A significant difference was noted between the extent of nuclear staining in PCSTCL and other forms of primary cutaneous T-cell lymphoma, type unspecified (mean = 22 ± 43, P = 0.0002), although not between PCSTCL and B-cell lymphoma. NFAT signaling plays a critical role in peripheral T-cell activation after T cell receptor engagement. When assessing T-cell-rich infiltrates where the differential diagnosis is largely between a PCSTCL and pseudolymphoma, a significant degree of nuclear staining of lymphocytes would be more in keeping with a diagnosis of PCSTCL. Upregulation of the NFAT pathway is not a feature of tumor progression in the setting of MF.

Role of computed tomography on large B-cell non-Hodgkin’s lymphoma follow-up and the risk of radiation-induced neoplasm: A retrospective cohort study

IntroductionTo evaluate the role of surveillance computed tomography (CT) in detection of tumor relapse after complete remission for large-cell lymphoma and to estimate the cancer risk related to those examinations. Materials and methodsWe retrospectively identified the cases of large-cell lymphoma diagnosed at our institution during a fifteen years period. We extracted from charts the information needed. Agreement between clinical and radiological evaluation for relapse detection was determined with index kappa and McNemar tests. We analysed the surveillance CT examinations performed to the patients in complete remission with no recurrence during the follow-up period and we estimated the life attributable risk (LAR) of radiation-induced cancer above base line using the approach of the Biological Effects of Ionizing Radiation (BEIR) VII. Results184 patients with biopsy confirmed large-cell lymphoma were included. Complete remission was attained in 125 patients. After a median follow-up of 93.73 months, 97 of them remain in remission. Relapse was confirmed in 28 patients; only 3 of them were asymptomatic. Kappa and McNemar analyses revealed good agreement for diagnosis of recurrence and significant difference for exclusion of relapse. Patients in remission received a median of 6 surveillance CT examinations. Fifty-seven patients had total cumulative doses greater than 100mSv. The mean increase in estimated radiation-induced cancer risk was 0.5%. ConclusionOur results suggest that periodic CT examinations have a limited role in detecting relapse in large-cell lymphoma as the clinical surveillance dictates the patient management.

Multicentre phase II study of the CyclOBEAP regimen for patients with peripheral T-cell lymphoma with analysis of biomarkers

Peripheral T-cell lymphoma (PTCL) has a poorer prognosis than diffuse large B-cell lymphoma (DLBCL). We administered the CyclOBEAP regimen (cyclophosphamide, vincristine, bleomycin, etoposide, doxorubicin, prednisolone) to patients with DLBCL, and reported its safety and efficacy. Here, we report the results of a multicentre phase II study of the CyclOBEAP regimen in patients with PTCL. In addition, NME1 remained a prognostic factor for survival, as shown in patients who were treated with CyclOBEAP. There were 84 eligible patients and the median age was 54 years. The 5-year overall survival (OS) rate was 72% and progression-free survival (PFS) rate was 61%. The 5-year OS was 93% among the anaplastic large-cell lymphoma cases, 74% among the angioimmunoblastic T-cell lymphoma cases, and 63% among the cases of PTCL-not otherwise specified. When the patients were divided according to the International Prognostic Index or Prognostic Index for PTCL, the 5-year OS and PFS rates did not significantly differ among the risk groups. Positivity for NME1 was found to be a significant independent prognostic factor. Grade 4 neutropenia was observed in 80 patients and thrombocytopenia in nine patients. Our results suggest that the CyclOBEAP therapy is safe and effective for PTCLs. Furthermore, the NME1 protein may be an important prognostic factor in PTCL.

Gastrointestinal B-cell lymphoma: a morphologic and immunohistochemical study of 194 cases

To study the morphologic and immunohistochemical features of gastrointestinal B-cell lymphomas. One hundred and ninety-four cases of gastrointestinal B-cell lymphoma were retrieved from the archival file. The clinical features and pathologic findings were reviewed. Immunohistochemical study for B-cell markers, T-cell markers, bcl-6, CD10, bcl-10, cyclin D1, TdT, MUM1 and Ki-67 was carried out. The male-to-female ratio was 1.4:1. The age of patients ranged from 8 to 85 years. Amongst the 194 cases studied, 128 (66.0%) were diagnosed as diffuse large B-cell lymphoma, including 16 cases of large cell lymphoma associated with mucosa-associated lymphoid tissue (MALT) lymphoma component. There were also 40 cases (20.6%) of MALT lymphoma, 8 cases (4.1%) of follicular lymphoma, 5 cases of (2.6%) of lymphoplasmacytic lymphoma, 3 cases (1.6%) of mantle cell lymphoma, 1 case of (0.5%) of B-lymphoblastic lymphoma and 9 cases (4.6%) of indefinite type (including 5 biopsy cases). The site of involvement included stomach (100 cases, 51.5%), small intestine (43 cases, 22.2%), ileocecal junction (26 cases, 13.4%), appendix (1 case, 0.5%), colon (21 cases, 10.8%) and rectum (3 cases, 1.6%). Amongst the 163 cases which had undergone surgical resection, 20 cases (12.3%) cases had invasion down to the mucosa, 20 cases (12.3%) down to the superficial muscular layer, 19 cases (11.6%) down to the deep muscular layer and 104 cases (63.8%) with full-thickness involvement. Histologic examination showed lymphoepithelial lesions in 52 cases, residual lymphoid follicles in 29 cases, coagulative necrosis in 66 cases and nodular growth pattern in 30 cases. The lymphoma cells in all cases were immunoreactive for B-cell marker CD20. There was also various degrees of positivity for bcl-6, CD10, bcl-10, cyclin D1, TdT, MUM1 and Ki-67. Gastrointestinal B-cell lymphomas can be subdivided into two main groups: large B-cell lymphomas and small B-cell lymphomas. The latter group often poses diagnostic pitfalls. Accurate pathologic typing requires correlation with histologic and immunohistochemical findings.

Autologous Peripheral Blood Stem Cell Transplantation in Children with Refractory or Relapsed Lymphoma: Results of Children’s Oncology Group Study A5962

This prospective study was designed to determine the safety and efficacy of cyclophosphamide, BCNU, and etoposide (CBV) conditioning and autologous peripheral blood stem cell transplant (PBSCT) in children with relapsed or refractory Hodgkin and non-Hodgkin lymphoma (HL and NHL). Patients achieving complete remission (CR) or partial remission (PR) after 2 to 4 courses of reinduction underwent a granulocyte-colony stimulating factor (G-CSF) mobilized PBSC apheresis with a target collection dose of 5 × 10⁶ CD34(+)/kg. Those eligible to proceed received autologous PBSCT after CBV (7200 mg/m², 450-300 mg/m², 2400 mg/m²). Forty-three of 69 patients (30/39 HL, 13/30 NHL) achieved a CR/PR after reinduction. Thirty-eight patients (28 HL, 10 NHL) underwent PBSCT. All initial 6 patients who received BCNU at 450 mg/m² experienced grade III or IV pulmonary toxicity compared to none of the subsequent 32 receiving 300 mg/m² (P < .0001). The probability of overall survival (OS) at 3 years for all patients is 51% and for transplanted patients is 64%. The 3-year event-free survival (EFS) is 38% (45% for HL; 30% NHL). The 3-year EFS in transplanted patients is 66% (65% HL; 70% NHL). Initial duration of remission of ≥12 versus <12 months was associated with a significant increase in OS (3 years OS 70% versus 34%) (P = .003). BCNU at 300 mg/m(2) in a CBV regimen prior to PBSCT is well tolerated in relapsed or refractory pediatric lymphoma patients. A short duration (<12 months) of initial remission is associated with a poorer prognosis. Last, a high percentage of patients achieving a CR/PR after reinduction therapy can be salvaged with CBV and autologlous PBSCT.

Primary Cardiac Lymphoma: Clinical, Histologic, Immunophenotypic, and Genotypic Features of 5 Cases of a Rare Disorder

Primary lymphomas of the heart are rare and frequently are diagnosed at autopsy. Modern imaging technology now permits early diagnosis and treatment. This report describes the clinical, histologic, immunophenotypic, and molecular genetic findings for 5 patients with malignant lymphoma restricted to the cardiac muscle, with or without pericardial involvement. All patients were women, with ages ranging from 40 to 68 years (median 55 y). The right atrium was involved in all cases with the left atrium, right ventricle, and pericardium affected in 1 case each. Clinical presentation included pericardial effusions associated with precordial pain, dyspnea, and bradycardia. Electrocardiographic changes included junctional rhythm, incomplete right bundle branch block and ST and T waves abnormalities, and ST segment elevation and first-degree atrioventricular block with intermittent complete heart block. In all cases, biopsy or resection of the lesion or cytologic examination of the pericardial fluid established a diagnosis. All tumors were of B-cell phenotype and included 4 cases of large cell lymphoma and one unclassifiable small cell lymphoma. In 2 cases, a follicular center cell origin was supported by reactivity of the neoplastic cells for CD10 and bcl-6 and by bcl-2 gene rearrangement by molecular analysis. One patient died shortly after diagnosis due to cerebral infarction. Two patients are alive without disease after chemotherapy with CHOP after 120 and 192 months. One patient underwent chemotherapy with CHOP and rituximab, and shows persistent cardiac involvement by lymphoma but with a decrease in tumor burden at 7 months of follow-up. One patient was lost to follow-up. Clinical outcome is variable; however, early diagnosis in conjunction with effective treatment (surgery and/or chemotherapy) may result in an excellent prognosis. Primary cardiac lymphoma should be included in the differential diagnosis of a right atrial mass.

AIDS-related non-Hodgkin's lymphomas: From pathology and molecular pathogenesis to treatment

In the highly active antiretroviral therapy (HAART) era, AIDS-related non-Hodgkin's lymphomas (AIDS-NHL) and their treatment still represent an open issue, because HAART may not be sufficient to prevent the development of NHL. The present spectrum of AIDS-NHL includes systemic lymphomas, primary central nervous system lymphomas, and 2 rare entities, primary effusion lymphomas (PEL) and plasmablastic lymphomas of the oral cavity. The vast majority of systemic AIDS-NHL belongs to 3 high-grade B-cell lymphomas: Burkitt's lymphoma (BL), immunoblastic lymphoma (IBL), and large-cell lymphoma (LCL). The pathologic heterogeneity of AIDS-NHL is correlated with the heterogeneity of the molecular lesions associated with these lymphomas. The molecular lesions associated with AIDS-BL involve activation of c-MYC inactivation of p53, and infection by Epstein-Barr virus (EBV). EBV infection occurs in 40% of LCL cases and in 90% of IBL cases. Rearrangements of BCL-6 are detected in 20% of AIDS-LCL cases. In the presence of EBV infection, BCL-6 expressing AIDS-LCL fails to express the latent membrane protein 1 (LMP1) antigen. Conversely, AIDS-IBL are characterized by absent BCL-6 expression, absence of BCL-6 rearrangements, and frequent expression of LMP1. Consistently, the molecular pathways of viral infection and lesions of cancer-related genes associated with AIDS-NHL vary substantially in different clinicopathologic categories of the disease. The marked degree of biologic heterogeneity of AIDS-NHL is highlighted by their histogenetic differences, because AIDS-NHL are related to distinct B cell subsets (ie, germinal center [GC] or post-GC B cells). The phenotypic pattern of AIDS-BL and systemic AIDS-LCL closely reflects B cells residing in the GC, namely centroblasts and centrocytes. Conversely, the phenotype of AIDS-IBL, either systemic or localized primarily to the central nervous system, and AIDS-PEL reflects post-GC B cells in all cases. New information on the molecular and virologic pathogenesis of AIDS-NHL may serve as a point of attack for pathogenic-driven therapies. Moreover, a greater knowledge of other biologic features of these tumors may help investigators identify new potential targets for “intelligent” therapies. HUM PATHOL 33:392-404. Copyright 2002, Elsevier Science (USA). All rights reserved.

Primary Non-Hodgkin's lymphoma of the jaws: Immunohistochemical and genetic review of 10 cases

Purpose: Non-Hodgkin's lymphoma (NHL) comprises a group of malignant lymphoproliferative diseases characterized by clonal expansion of lymphocytes at various levels of ontogenetic development. The aim of this study was to review the immunohistochemical and cytogenetic features of 10 cases of NLH of the jaws to determine their respective derivation.Patients and Methods: Histopathologic and immunohistochemical review of 10 cases of large-cell lymphomas of the jaws, together with Southern blot analysis of 2 of the cases, was performed and results compared with the findings in the literature.Results: In the 10 cases studied, the average age of onset of the NHL was 51 years, with a male-to-female ratio of 3:2. Tumefaction was the first clinical sign of disease. Eight of 10 cases were high-grade, large-cell NHLs, centroblastic type. Two cases were high-grade, large-cell NHL, immunoblastic type.Conclusion: The immunohistochemical and Southern blot data remain the principal laboratory aids in the diagnosis and characterization of NHL, and they provide critical information for guiding clinicians to the appropriate treatment protocol for these malignancies.

Primary non-hodgkin's lymphoma of the jaws: Immunohistochemical and genetic review of 10 cases

<h2>Abstract</h2> <b>Purpose:</b> Non-Hodgkin's lymphoma (NHL) comprises a group of malignant lymphoproliferative diseases characterized by clonal expansion of lymphocytes at various levels of ontogenetic development. The aim of this study was to review the immunohistochemical and cytogenetic features of 10 cases of NLH of the jaws to determine their respective derivation. <b>Patients and Methods:</b> Histopathologic and immunohistochemical review of 10 cases of large-cell lymphomas of the jaws, together with Southern blot analysis of 2 of the cases, was performed and results compared with the findings in the literature. <b>Results:</b> In the 10 cases studied, the average age of onset of the NHL was 51 years, with a male-to-female ratio of 3:2. Tumefaction was the first clinical sign of disease. Eight of 10 cases were high-grade, large-cell NHLs, centroblastic type. Two cases were high-grade, large-cell NHL, immunoblastic type. <b>Conclusion:</b> The immunohistochemical and Southern blot data remain the principal laboratory aids in the diagnosis and characterization of NHL, and they provide critical information for guiding clinicians to the appropriate treatment protocol for these malignancies. © 2000 American Association of Oral and Maxillofacial Surgeons

Immunogold Labelling of Large Cell Lymphoma with Monoclonal TIA-1 Antibody

Large cell (T - cell) lymphoma is a malignant neoplasm derived from activated lymphoid cells, involving lymph nodes, spleen, subcutaneous lesions. Ultrastructural examination facilitates the determination of this particular type of lymphoma, specifically by the presence of lytic granules in the cytoplasm containing proteins involved in the target cell destruction. One of these, expressed specifically is TIA-1, a cytotoxic granule-associated protein with RNA binding domains initially identified using a monoclonal antibody reactive with a 15KD protein present in the granules of cytotoxic lymphocytes.Tissue from seven cases of large cell lymphoma from the archives of our department were fixed for electron microscopy studies with a mixture of4% paraformaldehyde and 1% glutaraldehyde in 0.1M sodium cacodylate buffer and embedded either in Poly/Bed 812 with osmium tetroxide postfixation, or in LR White without osmication. For immunogold labelling, ultrathin sections placed on Nickel grids were incubated with a murine monoclonal TIA-1 antibody (1:50) (Coulter Co) overnight at 4°C.

Detection of the t(2; 5)(p23; q35) chromosomal translocation in large B-cell lymphomas other than anaplastic large cell lymphoma

In general, the large cell lymphomas are a cytogenetically heterogeneous group of diseases, and the cytogenetic findings do not correlate with morphological findings in this group of malignant lymphomas. The CD30-positive anaplastic large cell lymphomas, however, are thought to be an exception, with the t(2; 5) reported to correlate with the morphological changes of this disease entity. A subgroup of Hodgkin's disease cases have been reported by some investigators to have the t(2; 5) translocation, leading to speculation that these two diseases are related. In the current study, the authors used a sensitive reverse transcriptase polymerase chain reaction (RT-PCR) methodology to evaluate the frequency of t(2; 5) in 33 cases of large cell lymphoma, of B lineage, other than anaplastic large cell lymphoma. The authors detected evidence of t(2; 5) in four of the cases (12%), a frequency similar to that of the authors' previous study of cases of CD30 positive anaplastic large cell lymphoma. Three of the positive large B-cell lymphoma cases were CD30 negative and were morphologically indistinguishable from the cases without evidence of t(2; 5). The fourth case had a subpopulation of CD30 positive cells but also did not have morphological features of anaplastic large cell lymphoma. These results would suggest that t(2; 5) is not restricted to cases of malignant lymphomas with anaplastic morphology or to CD30 expression.

Relationship between DNA ploidy level, nuclear size, and survival in large cell lymphoma.

Intermediate and high grade subtypes of non-Hodgkin's large cell (LCL) and immunoblastic lymphomas exhibit considerable variability, and histologic morphology alone may not adequately characterize those features important for prognosis. The relationship between nuclear morphology and survival was assessed in a series of 50 cases of large cell lymphomas in which ploidy, proliferation, and nuclear area (NA) were measured. Ploidy was calculated by both DNA index (DI) and DNA histogram type (DHT). Proliferation was calculated from the proportion of S phase (SPF) cells present in the DHT. These four parameters were measured using image cytometry of Feulgen-stained nuclei from fine-needle aspirations. To characterize the relationship with survival, these parameters were associated with the clinical follow-up of the patients. The results show that of the 50 LCL cases, only 5 were clearly aneuploid, whereas the remaining 45 were either diploid (29 cases), tetraploid/hypotetraploid (13 cases), or weakly aneuploid (hyperdiploid, 3 cases). Of the 34 patients who died from their disease, both smaller NA and DI correlated with longer survival in an equivalent fashion; neither conferred greater sensitivity when combined with the other. The SPF did not correlate with survival. In LCL, aneuploidy seems to be a relatively uncommon event, but when present ploidy measurement appears useful to define prognosis.

Clinicopathologic Features and Treatment Outcome of Children With Large-Cell Lymphoma and the t(2;5)(p23;q35)

The t(2;5)(p23;q35) was detected in 9 of the 18 cases of large-cell lymphoma with an abnormal karyotype among 115 children with large-cell lymphoma treated at St Jude Children's Research Hospital from 1975 to 1993. When the cases containing the t(2;5) were classified according to the National Cancer Institute Working Formulation, 7 were large-cell, immunoblastic and 2 were diffuse large cell; according to the Kiel classification system, 6 were anaplastic large cell, 2 immunoblastic, and 1 centroblastic. CD30 expression was documented in 6 of 8 cases tested. All patients had nodal disease and 6 had extranodal involvement (bone in 4 cases and skin in 3). Eight of nine had advanced disease at diagnosis (stage Ill in 7 and stage IV in 1). Complete remission (CR) was attained in all patients and 6 remain in first CR for 19+ to 97+ months. Three relapsed, but successfully obtained second remissions; 2 are 58+ and 80+ months after retrieval therapy for local recurrences, and 1 patient died of recurrent disease. The t(2;5)(p23;q35) is associated with, but not limited to, anaplastic histology, a CD30+ T-cell phenotype, advanced stage disease with nodal (+/- extranodal) involvement, and chemosensitivity at diagnosis and relapse.

Clinicopathologic features and treatment outcome of children with large- cell lymphoma and the t(2;5)(p23;q35)

The t(2;5)(p23;q35) was detected in 9 of the 18 cases of large-cell lymphoma with an abnormal karyotype among 115 children with large-cell lymphoma treated at St Jude Children's Research Hospital from 1975 to 1993. When the cases containing the t(2;5) were classified according to the National Cancer Institute Working Formulation, 7 were large-cell, immunoblastic and 2 were diffuse large cell; according to the Kiel classification system, 6 were anaplastic large cell, 2 immunoblastic, and 1 centroblastic. CD30 expression was documented in 6 of 8 cases tested. All patients had nodal disease and 6 had extranodal involvement (bone in 4 cases and skin in 3). Eight of nine had advanced disease at diagnosis (stage Ill in 7 and stage IV in 1). Complete remission (CR) was attained in all patients and 6 remain in first CR for 19+ to 97+ months. Three relapsed, but successfully obtained second remissions; 2 are 58+ and 80+ months after retrieval therapy for local recurrences, and 1 patient died of recurrent disease. The t(2;5)(p23;q35) is associated with, but not limited to, anaplastic histology, a CD30+ T- cell phenotype, advanced stage disease with nodal (+/- extranodal) involvement, and chemosensitivity at diagnosis and relapse.

Incidence of Epstein-Barr virus bcl-2 expression and chromosomal translocation t(14;18) in large cell lymphoma associated with paragranuloma (lymphocyte-predominant Hodgkin's disease)

Seven cases of large cell lymphoma (LCL) developing simultaneously or secondarily to lymphocyte-predominant Hodgkin's disease (nodular paragranuloma [NP]) were investigated for the presence of Epstein-Barr virus genomic material and the chromosomal translocation t(14;18) involving the major breakpoint region of the bcl-2 gene using the polymerase chain reaction on paraffin-embedded material. The translocation t(14;18) and Epstein-Barr virus could not be demonstrated in any case. The expression of the bcl-2 oncogene product was investigated using immunohistochemistry. Only in one case were the lymphocytic and histiocytic cells positively stained with the bcl-2 antibody, whereas the associated LCL demonstrated a completely negative immunoreaction. In another case the LCL had a positive immunoreaction with this antibody and the corresponding lymphocytic and histiocytic cells were completely negative. We conclude that Epstein-Barr virus infection is rare or absent in NP and in the LCLs associated with NP. The chromosomal translocation t(14;18) does not seem to be a factor in the transformation of NP into LCL.

Primary large cell lymphoma of the splenic sinuses: A variant of angiotropic B-cell lymphoma (neoplastic angioendotheliomatosis)?

A case of large cell lymphoma of B-cell lineage originating in the splenic sinuses is described. In addition to widening the spectrum of primary malignant lymphomas of the spleen, this case raises the possibility that variants of angiotropic large cell lymphomas may exist that do not involve blood vessels but do involve the spleen and lymph node sinuses.