Morphometric analysis of follicular center cell lymphomas

The Lukes/Collins classification of non-Hodgkin's lymphomas subdivides follicular center cell (FCC) lymphomas into four categories based on nuclear size, shape, and state of transformation. Because of the well-recognized difficulty in making these subdivisions in routine histologic sections, a morphometric analysis of typical small cleaved (SC), large cleaved (LC), small noncleaved (SNC), and large noncleaved (LNC) FCCs was performed to describe and compare these four categories using objective parameters. The following features, which had been previously tested on normal follicles, were measured and calculated: nuclear area (NA), nuclear contour index of ellipticity (NCIe), nuclear contour index of nuclear irregularity (NCIni), and a relative chromatin dispersal index (CDI). The presence of nucleoli also was recorded. Mean values for the NA, NCIe, NCIni, and CDI were significantly different among all four FCC lymphoma subtypes, except that the CDI, which reflects transformation, was similar for the SC and LC cell groups. Comparison using the proportion of cells with nucleoli in each case revealed significant differences between all but the SNC and LNC groups. The LC group had the highest mean nuclear ellipticity and nuclear irregularity values. Mean nuclear area was smallest for the SC group followed by the LC, SNC, and LNC groups. Despite these many differences, all parameters showed a broad spectrum of values when either mean values for individual cases of each FCC subtype or distribution curves for all cells within a certain subtype were compared. This morphometric data demonstrates that the four histologically recognized types of FCC lymphomas are distinctive using a more analytic technique. This study also provides further insight into the differences among them. Evidence of nuclear transformation (nuclear size, chromatin dispersal, and frequent nucleoli) is a more important criterion than nuclear contours in distinguishing LNC from LC lymphomas. Although LC lymphomas have some features intermediate between SC and the noncleaved FCC lymphomas, they more closely resemble SC lymphomas. Finally morphometric analyses such as these provide an objective morphologic foundation for future prospective investigations of transformation-related phenomena; these studies may facilitate comparison of morphologic data with immunophenotype and genotype in non-Hodgkin's lymphomas and comparison of various other B-cell neoplasms with follicular center cell neoplasms.