What should be the morphologic criteria for the subdivision of follicular lymphomas?

The members of the Pathology Panel for Lymphoma Clinical Studies undertook a collaborative study with the hope of resolving some of the controversies regarding the criteria and methods for the subclassification of follicular lymphomas (FLs). A group of 105 patients with FL were subclassified by seven hematopathologists according to two methods. In the first method, cases were subclassified according to the Rappaport, Lukes and Collins, and Working Formulation systems. In each of these systems, FLs are subclassified by estimation of the different cell populations, without actual counting of cells. In the second method, precise counts of different cells were made according to the standard and modified Berard methods. With this counting method, diagnoses were independently derived, based on counts provided by the seven pathologists, for large cleaved (LC), small noncleaved (SNC), and large noncleaved (LNC) cells. To ascertain what method and which criteria are most useful in predicting survival, we made clinicopathologic correlations. When the subjective (first method) diagnoses were rendered, and when the consensus diagnoses of the seven pathologists were used, there were no significant differences in survival among patients with the different subtypes. On the other hand, when we used the counting method of Berard (second method) and the cut-off points for the cell counts suggested by him for the subclassification, we were able to divide the patient population into prognostic subgroups. Because the cut-off points proposed by Berard are not derived objectively, we made statistical comparisons of survival curves to determine cut-off points (and thus to establish objective criteria). We found that the patient population could be separated into at least two prognostic groups, for SNC and/or LNC and for SNC + LNC + LC cells. The cut-off points which we derived differed with cell type, however. Until the usefulness of these new cut-off points is established, we recommend that the cut-off points and the counting method of Berard be used for the subclassification of FL. Because the choice of treatment for the different subtypes of FL is totally dependent on the histologic diagnosis, and because of the variability among the diagnoses of pathologists, treatment planning is difficult.