Pathogenesis of human reactive-appearing "non-monomorphous" malignant lymphoproliferative disorders: a hypothesis

Human reactive-appearing "non-monomorphous" malignant disorders, such as Hodgkin's disease, T-cell-rich B-cell lymphomas and angioimmunoblastic lymphadenopathy display a peculiar and unifying characteristic, which biologically differentiates them from "monomorphous" non-Hodgkin's lymphomas. It consists in the coexistence within the pathologic tissue of a polyclonal, normal-appearing, presumed reactive cellular component, mainly composed of T-lymphocytes together with a clonal cell component constituting a minority of the pathologic mass. To explain the long-lasting coexistence of such polymorphic cell populations in the pathologic tissue of synchronous and metachronous localizations of the disease, it is hypothesized that they are interconnected by "biological interactions" which determine and sustain the pathologic process. Based on the biological characteristics of an experimental model (the follicular center cell "lymphoma" of the SJL murine strain), it is suggested that these human "non-monomorphous" malignant diseases should be regarded as a continuous spectrum of lymphoproliferative disorders sustained by a biological loop which interconnects different cell populations able to stimulate each other for growth.