Nuclear morphologic and morphometric analyses of large noncleaved cell and immunoblastic non-Hodgkin's lymphomas

Both morphologically and immunologically, non-Hodgkin's lymphoma (NHL) of the large cell type has been shown to be a heterogeneous category. However, the homogeneity of the nuclear parameters, particularly size and condensed chromatin organization, used to classify this subtype of NHL has not been investigated. In fact, objective morphologic techniques have not been systematically applied to verify the segregation of NHL on the basis of nuclear parameters, a concept common to all current classification systems. In this study morphometric image analysis was used to compare the nuclei in 20 specimens from NHLs of the large cell type with those in mantle zone and germinal center lymphocytes from lymph nodes with reactive hyperplasia. Results of the assessment of mean nuclear area in large cell lymphomas revealed that this class is also heterogeneous, with some of the specimens having a nuclear size in the upper range of that for normal small lymphocytes. In addition, in only a few of these specimens was the mean nuclear area within the range of that for fully transformed germinal center lymphocytes. The majority of large cell lymphomas have a nuclear size more characteristic of partially transformed lymphocytes in germinal centers. In addition to indicating inconsistencies in the current diagnostic criteria used in NHL classifications, the results indicate reasons for interobserver variations in clinicopathologic trials; the validity of nuclear size as a prognostic indicator and the biologic basis for classifying NHL as a reflection of normal lymphocyte transformation are also questioned. In terms of patient management, the classifications of NHL currently used require objective reappraisal.