A retrospective clinicopathologic study of lymphoblastic lymphoma was based on 95 patients from the files of the Repository Center for Lymphoma Clinical Studies. All patients were treated according to different protocols of Cooperative Oncology groups sponsored by the National Cancer Institute. The patients ranged in age from 4 to 84 years, with a median of 30 years. Sixty-eight patients were male and 27 female, with respective median ages of 27 and 50 years. The male-to-female ratio was 2.5:1. Forty patients had mediastinal masses; 30 (75%) of whom were male. The median survival of all patients was 17 months (range 1-100 months). To ascertain the influence of various clinical and morphologic parameters of survival, univariate and multivariate statistical analyses were performed. Patients older than 30 years of age had significantly lower incidences of mediastinal involvement (P = 0.01), number of mitotic figures (P = 0.04), and development of leukemia (P = 0.02) than patients younger than 30. Whereas lymphoblastic lymphoma is generally considered to be a disease of children and young adults, this study indicates that lymphoblastic lymphoma occurs in all age groups. These findings further suggest that lymphoblastic lymphoma may have a different biologic behavior in older patients.
Numerous prospective (fresh tissue) and retrospective (archival tissue) studies of DNA flow cytometry have been undertaken to ascertain the biologic behavior of hematopoietic malignancies. We have critically examined most of the studies that relate DNA ploidy and proliferative activity to clinical outcome in nonHodgkin's lymphomas, acute leukemias, and multiple myeloma. Selected studies relating DNA flow cytometry to histologic grade, but not clinical outcome, of nonHodgkin's lymphomas were also considered. The goal was to reach a consensus, based on a review of the literature and on our collective experience, on the value of DNA flow cytometry in the characterization of hematopoietic malignancies.The following review of the literature covers lymphomas, multiple myelomas, and acute leukemias. LYMPHOMAS Hodgkin's DiseaseThere have been a few studies demonstrating subtle DNA ploidy abnormalities in Hodgkin's disease (l), but there does not appear to be a rationale for performing routine flow cytometric DNA ploidy and cell cycle studies in this entity. However, if obvious DNA aneuploidy is encountered in tissues presumed to be Hodgkin's disease, a non-Hodgkin's lymphoma must be considered. Non-Hodgkin's LymphomasTwenty studies that correlated flow cytometric analysis of DNA ploidy and cell cycle with clinical outcome in patients with non-Hodgkin's lymphomas were reviewed (2-21). These studies are summarized in Table 1. Selection was based on the availability of histologic grade and clinical data, including adequate survival information and/or clinical outcome. In seven of the studies (742 patients), the analyses were performed on freshly prepared cell suspensions. In the remaining 13 (1,471 patients), nuclei were extracted from archival specimens embedded in paraffin blocks. There was great variability with respect to numbers of cells analyzed, staining procedures, instrumentation, amount of debris, frequency of DNA-aneuploidy, and coefficient of variation (CV). The CVs were higher in the archival specimens (mean 5.4%; range L3.8-7.0%1) than in the fresh specimens (mean 3.2%; range [2.5-4.4%1). The data analysis of cell cycle kinetics varied from study to study. There were differences in the mathematical strategies for cell cycle phase calculations. Additionally, numerous laboratories excluded cases that had overlapping DNA-diploid and DNA-aneuploid histograms. Some laboratories reported proliferative indices (S + G,M), whereas others reported S-phase fractions.General conclusions are limited by nonuniformity of therapeutic regimens and variability and flaws in the analysis of survival data.Several publications that correlated DNA-ploidy and cell cycle kinetics to histopathologic grade were reviewed (22)(23)(24). These were considered to be informative and of high quality. Although a direct correlation with survival and/or clinical outcome was not provided, it is generally accepted that most histopathologic classifications of non-Hodgkin's lymphomas correlate well with survival. Clinical Utility of DNA Index inNon...
DNA content and light scatter were measured by flow cytometry (FCM) in 103 patients including 43 patients with non‐Hodgkin's lymphoma (NHL), eight patients with Hodgkin's disease (HD), 17 patients with acute lymphoblastic leukemia (ALL), ten patients with acute nonlymphocytic leukemia (ANLL), and 25 patients with chronic lymphoid leukemias. Controls consisted of 42 nonneoplastic specimens obtained from lymph nodes, spleen, bone marrow, and peripheral blood. Each specimen was analyzed after staining with a hypotonic solution of propidium iodide using nuclei isolated from chicken erythrocytes as an internal standard. The DNA content and light scatter of the human populations was expressed as a ratio between the DNA content (or light scatter) of the human G0‐G1 cells and that of the chicken erythrocyte nuclei. The mean DNA ratio for the 42 nonneoplastic samples was 2.58 ± 0.045 (SD). In these samples the DNA coefficient of variation of the human G0‐G1 peak ranged from 1.48–3.28% (mean, 2.33 ± 0.54%). The FCM data in the NHL was compared to morphologic diagnoses made according to the “working formulation of NHL for clinical usage” recently proposed by a panel of international experts. Eight of 17 (47%) low grade NHL, one of two (50%) mycosis fungoides, ten of 14 (71%) intermediate grade NHL, nine of ten (90%) high grade NHL, nine of 17 (53%) ALL, three of ten (30%) ANLL, and seven of 25 (28%) chronic lymphoid leukemias had abnormal DNA ratios indicative of aneuploidy. In addition, several cases had normal DNA ratios but G0−G1 coefficients of variation outside of the normal range. All cases of HD had normal DNA values except one case with a small percentage of near tetraploid cells. The mean percentage of cells with S‐phase DNA content for the low grade NHL (2.2 ± 0.8%) was significantly lower than that of the intermediate grade NHL (12.1 ± 4.9%; P < 0.0001). The mean S‐phase value for the intermediate grade NHL was significantly lower than that of the high grade NHL (22.6 ± 11.1%; P < 0.001). The three prognostic categories of NHL designated by the new formulation were clearly distinguishable by the FCM data. Light scatter was not particularly useful for distinguishing nonneoplastic from neoplastic populations. The mean light scatter coefficient of variation of the ALL (15.2%) was significantly lower than that of ANLL (20.5%), however (P < 0.04).
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