Cellular DNA of human neoplastic B-cells measured by flow cytometry

Flow cytometric analysis of DNA of tumor cells rapidly provides information on cell kinetics and tumor ploidy. Human B-cell lymphomas, however, often contain high numbers of nonneoplastic cells, mainly T-lymphocytes, which may hamper the accurate measurement of cell cycle phases and ploidy level of these tumors. The neoplastic cells in each B-cell lymphoma express a single immunoglobulin light chain. Therefore, we labeled surface immunoglobulin light chains to discriminate between predominantly neoplastic B-cells and nonneoplastic cells in the same tissues. Using this label as well as antibodies against nonneoplastic T-cells, we performed multiparameter correlated flow cytometric analysis of 52 human B-cell lymphomas measuring cellular DNA in neoplastic and nonneoplastic populations from the same tissues without physical separation of cells. Comparison of cellular DNA of immunoglobulin light chain-bearing neoplastic cells with that of nonneoplastic cells from the same tumor enabled us to detect DNA changes (aneuploidy) in almost 80% of the lymphomas, an incidence higher than observed previously by conventional DNA analysis of unseparated cells. These ploidy changes were confirmed by comparing in the same tumor the DNA of normal T-cells with that of predominantly neoplastic cells. The proportion of neoplastic cells in the synthetic phase of the cell cycle (S-fraction) varied widely from tumor to tumor. Lymphomas with high neoplastic S-fractions (higher than 10%) were mostly hyperdiploid tumors and histologically corresponded to intermediate- and high-grade unfavorable lymphomas. Tumors with low neoplastic S-fractions (less than 5%) were predominantly diploid and near diploid, histologically low-grade lymphomas. Six lymphomas showed two discrete cell populations bearing the same immunoglobulin light chain but containing different amounts of DNA suggesting the presence of two neoplastic clones in the same tumor (biploidy). In two patients in whom the lymphoma relapsed at 17 and 34 months, respectively, after the initial biopsies, repeat tumor samples were obtained. Despite an increase in the neoplastic S-fraction, no change in ploidy level was observed in either case. Light scatter analysis suggested a relationship between cell size and genomic size; large cells in these tumors were mostly presynthetic aneuploid cells. The ability to measure DNA, antigens, and cell size in individual cells in a rapid, correlated manner is a unique attribute of flow cytometry.(ABSTRACT TRUNCATED AT 400 WORDS)     

Immunologic markers in non-Hodgkin's lymphoma

The majority of non-Hodgkin's lymphomas (NHLs) are of B-cell lineage, with less than 20% of cases being of T-cell lineage. The B-cell NHLs phenotypically correspond to normal cells in the mid stages of normal differentiation. More specifically, by their expression of B-cell activation antigens, these tumors are the neoplastic counterparts of normal activated B cells. The follicular lymphomas--including the small cleaved, mixed small and large cell, and large cell types, as well as the small noncleaved cell (Burkitt's) lymphomas--represent malignant expansions of normal germinal center B cells by their expression of pan-B cell antigens, B-cell activation antigens, and CD10 (CALLA). The diffuse lymphomas also correspond to normal activated B cells. The small lymphocytic lymphomas express the low-affinity IL-2 receptor and CD5, both of which are induced on normal B cells following mitogen stimulation. The other diffuse B-cell NHLs similarly express activation antigens and resemble "transformed" B cells. The T-cell NHLs generally correspond to normal activated CD4+ T cells. These tumors--which include most peripheral T-cell lymphomas, cutaneous T-cell lymphomas, and HTLV-I-associated adult T-cell leukemias/lymphomas--express antigens induced on activated T cells, including IL-2 and transferrin receptors (CD25 and CD71, respectively), as well as HLA-DR. The lymphoblastic lymphomas, which are generally of T-cell lineage, phenotypically correspond to stages of intrathymic differentiation, often by their coexpression of CD4 and CD8, as well as expression of CD1. It remains controversial whether the immunophenotype of lymphoblastic lymphoma differs significantly from T-cell acute lymphoblastic leukemia. Since immunologic heterogeneity of NHL was first observed, attempts have been made to employ the data as a prognostic variable. Early studies suggested that lineage derivation or expression of markers of proliferating cells affected outcome in NHL. However, these reports were often retrospective, included various histologies, and did not treat patients uniformly. More recent prospective studies with relatively uniformly treated patients, predominantly involving DLCL, suggest that certain immunologically defined subgroups may have significantly different clinical outcomes. However, additional clinical studies will be necessary before treatment options are based upon immunologic markers.     

Practical utility of the revised European-American classification of lymphoid neoplasms for Japanese non-Hodgkin's lymphomas.

A clinicopathological study of 515 non-Hodgkin's lymphoma (NHL) cases was performed using the revised European-American classification of lymphoid neoplasms (REAL classification) in an HTLV1-nonendemic area of Japan. The following characteristics were revealed: 1) frequency of extranodal lymphomas was high (59%) with 79% B-cell lymphomas in this series, while the overall ratio of B:T/NK lineage was 3.7:1; 2) the most common type was the diffuse large B-cell lymphoma (46%), follicle center lymphomas occurred at an incidence lower (15%) than that in European and American populations, and marginal zone B-cell lymphomas accounted for as much as 12%; 3) peripheral T-cell lymphomas were common (19%), with the unspecified type predominant (11%), while adult T-cell lymphomas were present at a level equivalent to that among European and American patients (1%). Clear segregation of survival curves was rated according to cell lineage and B-cell lymphomas had a better prognosis than T / NK-cell lymphomas. Furthermore, new subtypes in the REAL classification, such as marginal zone B-cell and mantle cell lymphomas, exhibited distinct curves. Taken altogether, the REAL classification demonstrated advantages for assessment of Japanese NHL cases.     

Histologic, immunophenotypic and genotypic analyses of bone marrow trephines from patients with non-Hodgkin's lymphoma

Marrow involvement in 20 patients with non-Hodgkin's lymphoma (NHL) were studied by histology, immunophenotypic and genotypic methods. Eighteen of these trephines were histologically involved with recognizable lymphomatous infiltrates and five of these were the primary disease site. In the remaining two cases (with histologically involved lymph nodes) the trephines were uninvolved with tumour. Three B-cell cases expressing surface immunoglobulin (sIg) and/or CD37 and one case not analysed phenotypically showed Ig gene rearrangements. The two remaining cases with B NHL showed no gene rearrangements, however, in one of these the trephine was histologically uninvolved with tumour. Twelve out of 14 T-cell cases were characterized by variable or absent expression of one or more T-cell antigens from the tumour population, one case was negative for all T-cell antigens and the remaining case was not histologically involved with tumour. All three lymphoblastic lymphomas and only 4/11 peripheral T-cell lymphomas (PTCL) cases revealed T-cell receptor (TcR) gene rearrangements. One of the latter cases also exhibited Ig J_H gene rearrangements. This study demonstrates the usefulness of bone marrow trephines (BMT) in histologic, phenotypic and genotypic analyses. However, although genotypic data confirm clonality in B NHL and the lymphoblastic lymphomas there was genotypic heterogeneity within the PTCL group.     

Characterization of malignant and non-neoplastic cell phenotypes in highly malignant non-Hodgkin lymphomas

Malignant and non-neoplastic cells in 38 cases of highly malignant non-Hodgkin lymphomas: 3 centrocytic anaplastic, 18 centroblastic, 13 immunoblastic and 4 lymphoblastic (according to the Kiel classification) were immunophenotyped in cryosections and cell suspensions by means of monoclonal antibodies. Additionally, cell cycle analysis on cell suspensions was performed by DNA flow cytofluorometry. In 33 (87%) lymphomas the malignant cells expressed monoclonal surface immunoglobulin (Ig), which indicated B-cell origin of tumors. In 7 of the 19 B-cell lymphomas tested by the peroxidase-antiperoxidase method, cytoplasmic Ig was found. Four lymphomas were of T-cell and one of non-B/non-T-cell origin. In II B-cell and 2 lymphoblastic non-B-cell tumors, common acute lymphoblastic leukemia antigen (CALLA) was found. In 25 of 30 studied NHL the malignant cells expressed receptor for transferrin and in 19 of 28 cases a high percentage of cells in S-phase (greater than 10.85%) was found. Number and distribution as well as type of non-B-cells infiltrating B-cell-derived lymphomas varied considerably from case to case. Among these cells Leu 3+ (T helper/inducer) cells predominated. Leu 2+ (T suppressor/cytotoxic) and Leu 7+ (natural killer and killer) cells constituted less numerous groups. Correlation of cytodiagnostic analyses with clinical observations indicates that high content of infiltrating T cells may be a favorable prognostic feature in highly malignant B-cell lymphomas.     

鼻腔鼻窦非霍奇金淋巴瘤免疫表型及其与EB病毒感染的关系

背景与目的:鼻腔鼻窦非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL)的患病率和免疫表型组成具有地域性差异.本研究探讨中国广州地区57例鼻腔鼻窦NHL免疫表型及其与EB病毒(Epstein-Barr virus,EBV)感染的关系.方法:收集2000年4月1日至2006年10月31日中山大学肿瘤防治中心病理科57例鼻腔鼻窦NHL标本.免疫组化染色确定免疫表型,EBER原位杂交及PCR检测EBV感染情况.结果:在同期诊断的1 412例NHL中,71例(5.03%)发生于鼻腔鼻窦,其中仅有57例适用于本研究.57例鼻腔鼻窦NHL患者中,男性38例,女性19例,年龄3～75岁,中位年龄50岁;44例(77.19%)为鼻型NK/T细胞淋巴瘤,其中37例(84.09%)为EBV /CD56 NK细胞肿瘤,7例(15.91%)为EBV /CD56-细胞毒性T细胞表型;11例(19.30%)为B细胞淋巴瘤,其中6例为弥漫大B表型,2例为Burkitt(Burkitt样)淋巴瘤(EBV ),1例为髓外浆细胞瘤(EBV ),1例为MALT淋巴瘤(EBV-),1例为小淋巴细胞性淋巴瘤(EBV-);2例(3.51%)为外周T细胞淋巴瘤(EBV-).37例适用DNA检测的病例中,25例(67.57%)感染缺失型LMP1(del-LMP1)EBV株,12例(32.43%)感染野生型LMP1(wt-LMP1)EBV株.结论:鼻腔鼻窦NHL最常见的类型为鼻型NK/T细胞淋巴瘤,可进一步分为EBV /CD56 NK细胞及EBV /CD56-细胞毒性T细胞表型.NK/T细胞淋巴瘤均感染了EBV,EBV株主要为del-LMP1型.     

Flow cytometric analysis of DNA ploidy in large cleaved cell lymphomas

The results of nuclear DNA content analysis of a series of 28 patients with large cleaved follicular centre cell non-Hodgkin's lymphomas (NHL) are reported. DNA aneuploidy was found in 11 (39 per cent) cases. The DNA indices of the DNA-aneuploid peaks ranged from 1.14 to 2.28. Seven (25 per cent) cases were tetraploid. DNA ploidy was not associated with prognosis. The percentage of S phase cells (SPF) ranged from 2.0 to 30.5 per cent (median 5.1 per cent). Lymphoma patients with SPF higher than 9.7 per cent had a worse survival rate than patients with lymphoma with less than 9.7 per cent S phase cells but the difference did not reach statistical significance. The results of the DNA ploidy and SPF were comparable to those of intermediate and high grade malignancy NHLs.     

Expression of the leucocyte integrin LFA-1 (CD11a/CD18) and its ligand ICAM-1 (CD54) in lymphoid malignancies is related to lineage derivation and stage of differentiation but not to tumor grade.

The leucocyte adhesion molecule LFA-1 (CD11a/CD18) and its counter structure ICAM-1 (CD54) play a pivotal role in cell-cell interactions in the immune system and hence their expression on malignant cells might play an important role in determining the biological behavior of lymphoid malignancies. This study examined the LFA-1 (CD11a/CD18) and ICAM-1 (CD54) expression profiles of a large series of non-Hodgkin's lymphomas (NHL, n = 220) and lymphoid leukemias (LL, n = 48), which, by their differentiation-antigen phenotype represented essentially all stages of lymphoid development from stem cell to mature activated T- and B-lymphocyte. It was found that NHL and LL differentially express LFA-1 and ICAM-1 molecules according to their lineage derivation, stage of differentiation, and growth pattern. Specifically: (a) T-cell neoplasms nearly always express LFA-1 whereas B-cell tumors are often LFA-1 low/negative; (b) ICAM-1 expression is largely confined to tumors with a mature or activated T- or B-cell phenotype; (c) neoplasms with a leukemic dissemination pattern are either ICAM-1 low or negative. Importantly, neither LFA-1 nor ICAM-1 expression was related to tumor grade.     

Practical Utility of the Revised European-American Classification of Lymphoid Neoplasms for Japanese Non-Hodgkin's Lymphomas

A clinicopathological study of 515 non-Hodgkin's lymphoma (NHL) cases was performed using the revised European-American classification of lymphoid neoplasms (REAL classification) in an HTLV1-nonendemic area of Japan. The following characteristics were revealed: 1) frequency of extranodal lymphomas was high (59%) with 79% B-cell lymphomas in this series, while the overall ratio of B:T/NK lineage was 3.7:1; 2) the most common type was the diffuse large B-cell lymphoma (46%), follicle center lymphomas occurred at an incidence lower (15%) than that in European and American populations, and marginal zone B-cell lymphomas accounted for as much as 12%; 3) peripheral T-cell lymphomas were common (19%), with the unspecified type predominant (11%), while adult T-cell lymphomas were present at a level equivalent to that among European and American patients (1%). Clear segregation of survival curves was rated according to cell lineage and B-cell lymphomas had a better prognosis than T/NK-cell lymphomas. Furthermore, new subtypes in the REAL classification, such as marginal zone B-cell and mantle cell lymphomas, exhibited distinct curves. Taken altogether, the REAL classification demonstrated advantages for assessment of Japanese NHL cases.     

Cutaneous lymphomas other than mycosis fungoides: follow-up study of 52 patients

Cutaneous lymphomas other than mycosis fungoides (MF) represent a rare and heterogeneous group of lymphomas. Their clinical behavior remains largely unknown. In this study, the clinical and immunohistologic characteristics and follow-up data of 52 well-documented cases of cutaneous lymphomas other than MF, presenting with initial cutaneous lesions, were reviewed. Twenty-seven patients presented with skin disease alone (stage IE), and 25 patients had concurrent cutaneous and extracutaneous disease (stage IV). The tumors were grouped into high-grade lymphomas (HGLs; 21%), intermediate-grade lymphomas (IGLs; 58%), and low-grade lymphomas (LGLs; 21%). A B-cell phenotype was most often expressed by cutaneous lymphomas (73%), particularly by stage IE lymphomas (85%). Among 13 cases of T-cell lymphomas, loss of one of the pan-T-cell antigens was detected in all cases but one. The clinical course of cutaneous lymphoma was closely dependent on stage and histologic subtype but not on T-cell or B-cell phenotype. Of 20 patients with stage IV HGL or IGL, 13 were treated by polychemotherapy with curative potential. Their median survival was 37 months. Fourteen patients with stage IE HGL or IGL were treated by radiotherapy alone. Nine patients (69%) relapsed within 2 years posttreatment. Seven of them relapsed in the skin outside the initial site involved, suggesting that radiotherapy alone is not an adequate treatment for these patients. Preliminary results concerning seven other patients with stage IE IGL or HGL treated by an initial third-generation polychemotherapy regimen are presented.     

Histomorphologic and immunophenotypic spectrum of primary gastro-intestinal B-cell lymphomas.

In order to compare primary gastro-intestinal (GI) B-cell lymphomas histomorphologically and immunophenotypically with orthologous steps of B-cell differentiation within the mucosa-associated lymphoid tissue (MALT) of the GI tract, a comprehensive panel of well characterized leucocyte differentiation antigens was composed. It comprised immunoglobulin constituents CD5, CD10, CD11c, CD20, CD23, CD24, CD30, CDw32, CD38, CD39, CDw75, CD76, and vimentin. These antigens yield characteristic immunoprofiles for the following B-cell compartments of the MALT, per se closely linked to cytologically distinct B-cell phenotypes: mantle zone (MZ), extrafollicular compartment (EF), follicle center (FC), and plasma-cell compartment (PC). An unselected series of 31 MALT B lymphomas (13 of low and 18 of high grade malignancy) was classified histologically in routine preparations and subsequently characterized immunohistochemically using fresh frozen tissue, monoclonal antibodies (MAbs) against the antigen panel listed above, and an indirect immunoperoxidase method. The final classification considered both morphology and immunoprofile of tumor cells. Ten tumors were "typical" in both respects: 2 closely corresponded to MZ, 5 to EF, 2 to FC and 1 to PC. The remaining 21 cases were characterized as "atypical" because of anaplastic cytology and/or abnormal co-expression and/or loss of antigens. A hybrid EF/FC phenotype was most frequently observed together with centrocyte-like or centrocytic anaplastic cytology of tumor cells. We conclude that MALT B-cell neoplasia comprises a broad spectrum of histo- and immunophenotypes ranging from well differentiated forms closely mimicking normal B-cell development to highly abnormal tumors which cannot be subclassified.     

B-cell marker negative (CD7+, CD19-) Epstein-Barr virus-related pyothorax-associated lymphoma with rearrangement in the JH gene

Pyothorax-associated lymphoma (PAL) develops decades after receiving artificial pneumothorax for pulmonary tuberculosis. The lymphomas, develop in tissue affected by long-standing severe inflammatory process. Most cases demonstrate diffuse large B-cell lymphoma. We present a patient with T-cell phenotype-positive and B-cell phenotype-negative (CD7+, CD43+, CD19-, and CD20-) PAL. Southern blot hybridization using immunglobulin heavy chain J region (IgH) gene probe revealed a monoclonal rearrangement, and hybridization using T-cell receptor beta chain (TCR) gene probe revealed a germline configuration. This indicates that the tumor origin was of B-lymphocytes. Chromosomal abnormality of the lymphoma was complicated. It suggested that many transformations occurred. In the transformation process, probably B-cell antigens were lost, and T-cell antigens were aberrantly expressed.     

Primary non-Hodgkin's lymphoma of bone: a rare disorder with high frequency of T-cell phenotype in southern Taiwan

Primary non-Hodgkin's lymphoma of bone (PLB) is a rare disorder representing less than 1% of all non-Hodgkin's lymphomas and has rarely been reported in Taiwan. A retrospective clinicopathological study was performed according to the 2002 World Health Organization criteria and identified 14 cases during a 13-year period in 2 medical centers in southern Taiwan. There was male predominance (M:F = 6:1) with a median age of 42 and bone pain (6 patients, 43%) as the most common symptom. Half of the patients had monostotic and the other half polyostotic lesions. Axial skeletons (10 cases, 71%) were the most frequent sites of involvement. The staging results were stage I (9 patients, 64%), stage II (2, 14%) and stage IV (3, 21%). Eight cases (57%) were of B-cell phenotype and the remaining 6 (43%), T-cell. Histologically, 7 (50%) were diffuse large B-cell lymphomas (DLBCLs) and 5 (36%) anaplastic large cell lymphomas. Seven patients received chemotherapy and radiotherapy; 4 chemotherapy and 3 radiotherapy alone. Of the 11 patients with follow-up information, 6 (55%) died of disease within 1 year including 5 with T-cell lymphomas, while all the 5 patients surviving over 1 year were of B-cell phenotype. The overall 1-year survival rate was 45%. The survival of B-cell lymphomas was significantly better than T-cell tumors (p = 0.016, log-rank test). In summary, this study reported the largest series of PBL in Taiwan and confirmed that the majority was DLBCL and B-cell tumors had more favorable prognosis. As compared to the Western series, the cases showed a striking male predominance, higher percentage of axial skeleton involvement, higher relative frequency of T-lineage tumors and poorer prognosis.     

Low proliferative activity is associated with a favorable prognosis in peripheral T-cell lymphoma

Peripheral T-cell lymphoma (PTCL) consists of a diverse group of post-thymic tumors bearing a mature T-cell phenotype and, excluding mycosis fungoides, comprises approximately 10-20% of the non-Hodgkin's lymphomas in the United States. This category of non-Hodgkin's lymphomas exhibits considerable morphological, immunological, and clinical diversity and is generally considered to be a high-grade malignancy. In the present study, paraffin-embedded biopsy specimens of lymph nodes from 31 patients with PTCL who were treated with curative intent were evaluated by flow cytometry for DNA ploidy and proliferative activity (PA). DNA ploidy was not predictive of the clinical outcome. However, low PA, defined by less than or equal to 10% of cells in S + G2M phase of cell cycle, was associated with a favorable prognosis. Patients with tumors having low PA had a significantly higher complete remission rate (100%) as compared to those with high PA (55%; P less than 0.02), and the predicted actuarial 4-year survival of those with low PA was 85% versus only 50% for those with high PA (P less than 0.04). This is the first report of the effects of PA and DNA ploidy in patients with PTCL who were treated with curative intent. Additional studies of similar patients are needed to confirm these findings.     

Splenic involvement by aggressive malignant lymphomas of B-cell and T-cell types. A morphologic and immunophenotypic study.

To determine whether there are any consistent morphologic differences between B-cell and T-cell aggressive non-Hodgkin's lymphomas of the spleen, the authors analyzed 16 spleens involved by mixed cell (1 case) or large cell (15 cases) lymphomas. Immunologic data were derived from cell suspensions or frozen tissue in each case. Five cases had a T-cell phenotype, and 11 were B-cell. Morphologic features favoring a T-cell phenotype included epithelioid histiocytic reactions, confinement of the lymphomas to the splenic T-zones (periarteriolar lymphoid sheath and marginal zone), and clear cell or polymorphous cytologic features. Features favoring a B-cell phenotype included multiple discrete nodules in the white pulp, large coalescent tumor nodules in association with small lymphocytic lymphoma, and large non-cleaved or immunoblastic plasmacytoid cytologic characteristics. Four cases were unusual because most neoplastic large cells were distributed diffusely or formed only small aggregates in the red pulp without definite tumor masses or nodules involving the white pulp. Because of this distribution and the frequently encountered erythrophagocytosis by benign-appearing histiocytes, these cases resembled malignant histiocytosis. A T-cell phenotype was predicted for all four cases; however, only one case, a lymphoma with polymorphous cytologic characteristics, was of T-cell lineage. The other three cases were of B-cell lineage. The authors' results indicate that in most instances the B-cell or T-cell nature of aggressive splenic lymphomas is predictable from the distributional and cytologic features. As in lymph nodes, there are cases for which the morphologic characteristics of B-cell and T-cell lymphomas are indistinguishable.     

Precursor T-cell lymphoma associated with human immunodeficiency virus type 1 (HIV-1) infection. First reported case

The majority of lymphomas that develop in human immunodeficiency virus type 1 (HIV-1) positive patients have a B-cell phenotype, with few reported cases of T-cell lymphoma. Within the latter group, those that have been comprehensively phenotyped had a mature helper T-cell phenotype (CD4+). We report, for the first time, an HIV-1 positive patient with a precursor T-cell lymphoma (CD7+,CD1-,CD3-,CD4-, and CD8-). T-cell receptor beta and gamma genes were in the germline configuration and integration of HIV-1 DNA could not be detected in the lymphoma cell genome.     

Correlation between histology and immunophenotype in a series of 322 cases of non-Hodgkin's lymphoma

The non-Hodgkin's lymphomas (NHL) are a heterogeneous group of lymphoid neoplasms displaying a wide variation in cell morphology, histological patterns, immunological phenotype and prognosis. In this paper we compare the results of phenotypic investigation of 322 tissue biopsies with the histology based on the Kiel classification. Immunological analysis revealed that 81 per cent of these tumours were of B cell origin, 12 per cent of T cell origin and the remaining 7 per cent could not be characterized as representing either cell lineage. This last group included a number of cases which had received a histological diagnosis of true histiocytic lymphoma. The original morphological diagnosis, based on routine haematoxylin and eosion sections correlated with the immunologically determined phenotype in 86 and 93 per cent of the T- and B-cell cases respectively. The B cell tumours were phenotypically heterogenous with respect to immunoglobulin (Ig) heavy chain and B lymphocyte subset marker expression. IgG was most often found associated with NHL of cb/cc histology and a small subgroup of lymphocytic NHL. IgA expression was uncommon and occurred in combination with IgD and G in three cases and alone in two cases of NHL. The most common immunoglobulin isotype expressed was IgM this isotype occurred with IgD most often in lymphocytic and centrocytic NHL and less often in tumours of cb/cc histology. Whilst greater than 90 per cent of the lymphocytic NHLs expressed the CD5 antigen, between 20 and 75 per cent of B-cell tumours of other histologies also expressed this epitope. The CD10 antigen and the epitope recognized by the monoclonal reagent FMC7 were widely distributed on tumour cells from all histologies. TdT expression commonly regarded as a marker for immature cells was found in one case of follicle centre cell lymphoma. All cases of T cell NHL displayed marked heterogeneity for both pan T and T subset antigens which is significant in terms of the routine diagnosis of T NHL and with regard to the rational classification of node based T NHL. Unlike resting peripheral blood T cells, MHC class II, OKT 10 and CD25 epitopes were expressed reflecting activation of tumour populations.(ABSTRACT TRUNCATED AT 400 WORDS)     

Cytotoxic/natural killer cell cutaneous lymphomas. Report of EORTC Cutaneous Lymphoma Task Force Workshop

BACKGROUND: Cutaneous lymphomas expressing a cytotoxic or natural killer (NK) cell phenotype represent a group of lymphoproliferative disorders for which there is currently much confusion and little consensus regarding the best nomenclature and classification. METHODS: This study analyzes 48 cases of primary cutaneous lymphoma expressing cytotoxic proteins and/or the NK cell marker, CD56. These cases were collected for a workshop of the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Task Force, to better clarify the clinical, morphologic, and phenotypic features of these uncommon tumors. RESULTS: Several categories with different clinical and pathologic features were delineated: 1) aggressive, CD8+, epidermotropic, cytotoxic T-cell lymphoma; 2) mycosis fungoides, cytotoxic immunophenotype variant; 3) subcutaneous panniculitis-like T-cell lymphoma; 4) NK/T-cell lymphoma, nasal type; 5) CD4+, NK cell lymphoma; 6) blastoid NK cell lymphoma; (7) intravascular NK-like lymphoma; and 8) cytotoxic, peripheral T-cell lymphoma. CONCLUSIONS: Our data show that primary cutaneous cytotoxic/NK cell lymphomas include distinct groups of diseases, clinically, histologically, and biologically. Because the finding of a cytotoxic phenotype often has prognostic significance, the routine use of cytotoxic markers in the diagnosis and classification of cutaneous lymphomas should be expanded.     

Non-Hodgkin's lymphoma: correlation of cell surface marker phenotype with clinical features and prognosis

The correlation of surface marker phenotype with prognosis was analysed in 64 patients with non-Hodgkin's lymphoma who had been treated in Shikoku Cancer Center Hospital. B-cell lymphomas (21 cases) had significantly better prognosis than T-cell lymphomas (21 cases). The complete remission (CR) rate was 52%, and the 50% survival time was 13 months for T-cell lymphomas. All T-cell lymphoma patients died within 31 months. In B-cell lymphomas, on the other hand, the CR rate was 100%, 50% survival time was 30 months, and there were no cases of relapse in patients who had been in continuous CR for more than 2 years. About 40% of B-cell lymphomas appeared to have the potential for cure.     

Peripheral blood lymphocytes of nonleukemic lymphoma patients exhibit aberrant expression of T-cell activation markers after polyclonal stimulation in vitro

The authors evaluated suppressed in vitro functions of peripheral blood lymphocytes (PBL) as a possible tool in the early diagnosis of human lymphoma. In 13 of 22 patients with recent onset of various types of nonleukemic lymphomas (Mb. Hodgkin and non-Hodgkin's lymphomas of B-cell and T-cell origin) the mitogen response of PBL against phytohemagglutinin (PHA) and concanavalin A (Con A), as measured by 3H-thymidine (3HTdR) uptake, was found to be significantly suppressed, whereas the response to pokeweed mitogen (PWM) was normal in 18 cases. In parallel, cytofluorimetric analysis was done with PBL after 72 hours in culture with and without PHA, using antibodies against the differentiation antigens: CD3, CD8, CD4, CD19, and CDw14 and the activation antigens: interleukin-2 (IL-2) receptor (IL-2R, CD25), human leukocyte antigen DR (HLA-DR), and transferrin receptor (TR). Compared with healthy controls and patients with other diseases, a significant reduction of the total T-cell blast response, i.e., the percentage of large T-cells bearing activation markers, was found in all lymphoma cases including those with a normal 3HTdR uptake. Furthermore, a pronounced inhibition in the expression of the activation markers Il-2R and TR, but not of HLA-DR, was detected on CD3+ cells in PHA-stimulated PBL of all lymphoma cases. Thus, polyclonal activation combined with activation antigens seems to give more accurate information about the functional defect(s) of PBL in an early state of lymphoma; these parameters may therefore be valuable diagnostically. The abnormal pattern in the expression of T-cell activation antigens after polyclonal stimulation may help in the understanding the cellular immune defects associated with lymphoma.