A Functional Approach to the Classification of Malignant Lymphoma

Summary and Conclusions

• 1. The malignant lymphomas are neoplasms of the immune system. The traditional classifications lack a valid conceptual basis and bear no relationship to our understanding of modern immunology.

• 2. It now appears possible from our clinical and morphologic studies to propose a functional classification based on the T- and B-cell lymphocytic system in order that we might begin to study the lymphomas from an immunologic standpoint. The lymphomas of lymphocytes frequently appear to involve alterations in lymphocyte transformation, either as a block or a “switch-on” (derepression).

• 3. A number of functional studies capable of identifying membrane markers that appear relatively specific for T and B cells are presently available and already have indicated that certain malignancies can be classified according to T- and B-cell types.

• 4. Lymphomas of follicular center cells, either cleaved or noncleaved (transformed cells), are included in the B-cell group and represent the most common cytologic types of lymphoma. They occur in follicular, follicular and diffuse, and diffuse forms, with or without sclerosis, and appear to begin usually, if not always, in follicular centers. The follicular or nodular character of lymphomas relates directly to the nature of the follicular-center-cell proliferation and the basic association of these cells with follicle formation. The favorable prognosis with some lymphomas of follicular pattern reflects ’the less aggressive nature of cellular proliferation that is still capable of follicle formation.

• 5. The majority of lymphomas previously classified as reticulum-cell sarcoma or histiocytic lymphoma present features of transformed lymphocytes. Lymphomas of histiocytes as macrophages are rare. Lymphomas of immunoblasts have been included in the reticulum-cell-sarcoma group in the past and have been observed to develop in chronic abnormal immune disorders. It seems likely that a similar neoplasm develops in a variety of immune disorders, including immune deficiencies, alpha-chain disease, immunosuppression of patients for graft rejection, and Sjogren’s syndrome.

• 6. A functional immunologic classification of lymphomas is necessary for a proper understanding of the clinical manifestations of the lymphomas and eventually the development of more appropriate therapeutic approaches. It is believed that the study of malignant lymphomas from an immunologic standpoint, combining sophisticated morphologic and immunologic techniques with in-depth clinical investigation, will establish the classification of lymphomas on a sound conceptual basis in the near future.

The remarkable progress in our understanding of immunology in the past decade has demonstrated that the traditional classifications of malignant lymphomas, the neoplasms of the immune system, bear no relationship to our modern view of immunology. The lack of appreciation of the new lymphocytic systems of B-cell and T-cell types and the remarkable phenomenon of lymphocyte transformation readily accounts for the absence of a sound conceptual basis and the resultant confusion concerning lymphomas. The older classifications of malignant lymphoma were developed principally on the basis of suspected cellular derivation, the degree of apparent differentiation, and the proposed multipotential capability of the reticulum cell to produce a limitless variety of neoplastic lesions.

From our current morphologic studies it now appears possible to identify some of the lymphomas of the thymic-dependent (T-cell) and bursal-equivalent (B-cell) systems and to propose a new functional classification for the lymphomas [1, 13]. These studies suggest that lymphomas of the T- and B-cell systems develop from either a block or “switch-on” (derepression) in lymphocyte transformation rather than from alterations in degree of differentiation [13]. In addition, the lymphomas pre-viously regarded as histiocytic lymphoma or reticulum-cell sarcoma seem, with few exceptions, to be neoplasms of large transformed lymphocytes, most commonly of the B-cell type [13]. A number of functional immunologic techniques that identify membrane markers are being translated rapidly from animal models to the study of human leukemias and lymphomas [6, 19]. These techniques in correlation with morphologic features may in the near future permit the classification of lymphomas to be established on a modern functional immunologic basis.

In this presentation we will review briefly the problems of the traditional classifications, discuss the immunologic basis for our new functional classification of malignant lymphomas, and demonstrate some of the clinical and prognostic implications. This proposal of a functional classification of malignant lymphomas emphasizes the need for a new approach to these neoplasms, with fresh tissue being collected for a variety of functional studies designed to establish a sound conceptual basis for their understanding.