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The Pathology and Nomenclature of Hodgkin's Disease

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The Pathology and Nomenclature of Hodgkin's Disease ICANCER RESEARCH 26 Part 1, 1063-1081,June 1966] The Pathology and Nomenclature of Hodgkin's Disease ROBERT J. LUKES AND JAMES J. BUTLER Department of Pathology, University of Southern California, School of Medicine, Los Angeles, California (R. J. L.) and Department of Pathology, M. D. Anderson Hospital, Houston, Texas (J. J. B.) Summary relate the histologie features to survival and to depict the as yet The diverse morphologic expressions of Hodgkin's disease have unsettled nature of the basic process. Over SO terms for the disease were collected from the literature by Wallhauser (35) been reviewed and compared to the numerous histologie terms in from the 1st century after Thomas Hodgkin's description. This the literature and the author's recently proposed histologie profusion of names for the disease primarily reflects the different, types. The relationship of the histologie findings to the clinical concepts of the disease particularly in relationship to etiology. stages and survival has also been analyzed. The histologie ex pressions of the Hodgkin's disease process appear to be reparable The noncommittal eponymic designation has gained general acceptance in the United States at the present time, even though into the following 6 groups: (a) lymphocytic and/or histiocytic (L & H),1 nodular; (b) lymphocytic and/or histiocytic (L & H), the process is generally regarded as a neoplasm and included with the malignant lymphomas. In the past 4 decades numerous diffuse; (c) nodular sclerosis; (d) mixed; (e) diffuse fibrosis; and terms have been proposed for the histologie types of Hodgkin's. (/) reticular. The L & H types represent essentially a pre disease as a result of the attempts to relate the histologie changes dominant lymphocytic proliferation with histiocytes, while to the extremely variable rates of progression of the disease and diffuse fibrosis and reticular are associated with lymphocytic to provide a prognostic basis for the recognition of potential depletion. Nodular sclerosis has a remarkably high incidence of prolonged survivors. mediastinal involvement when initially observed, exceeding all Interest in the importance of the histologie findings in prog other types combined, and appears to represent a regional expression of Hodgkin's disease in the mediastinum. The mixed nosis was initiated by Rosenthal (31) when he demonstrated the relationship between lymphocytic proliferation and slowly type appears to reflect a changing disease state. These histologie progressive disease and stressed the importance of the frequency types, with the exception of nodular sclerosis, represent differ ences in the frequency of lymphocytes and Reed-Sternberg cells of lymphocytes in prognosis. Earlier E wing (7) proposed the term sarcoma for a pleomorphic neoplastic proliferation of Reed- and serve to emphasize their inverse relationship. The histologie Sternberg cells. The classical histologie types of Jackson and findings are regarded as reflections of differences in the state of Parker (11-15), namely paragranuloma, granuloma, and sar the host responsiveness and are believed to be related to the coma, are related to many of the findings of Ewing (7) and recently described immunologie defect. The demonstrated Rosenthal (31). Subsequently the prognostic importance of the relationship between these histologie types, and the clinical predominant lymphocytic lesions has been supported by the stages and survival, provides further support for the importance studies of Harrison (9), Lumb (22), Smetana and Cohen (33), of host factors and also presents an effective basis for prog Wright (37, 38), and Dawson and Harrison (6), although a nostication. In addition a new histologie type, nodular sclerosis, variety of terms have been suggested for the association of has emerged as the most important prognostic type when lymphocytic proliferation with prolonged survival. The dis observed in clinical Stage I. The majority of the terms proposed in the literature for the tinctive character of the predominant lymphocytic proliferation histologie types of Hodgkin's disease represent designations for and its contrast to the granuloma type of Jackson and Parker the lesion with a predominantly lymphocytic proliferation of stimulated Smetana and Cohen (33) to question its relationship to Hodgkin's disease. The term reticular lymphoma was proposed either nodular or diffuse type. This lesion is of prognostic signifi cance, but it includes only a small proportion of the prolonged by Lumb (22) for this group to emphasize the distinctive histo survivors. The classical histologie types of Jackson and Parker logie character, and in recognition of its neoplastic potentiality. are of limited effectiveness in prognosis since the heterogeneous The nodular character of the lymphocytic proliferation was granuloma group includes 80-90% of reported series, contains initially recognized by Rappaport et al. (28), in their classical 79% of the survivors at 15 years in our study, and yet has a re-evaluation of follicular lymphoma. They included this nodular relatively short median survival in our comparison study. proliferation in follicular lymphoma as Type V (follicular lymphoma, Hodgkin's type), although it was acknowledged that Introduction this type more appropriately might be included with the para The unique diversity of the morphologic features in Hodgkin's granuloma group rather than with the general group of malignant disease and the variable rates of progression of the disease have lymphomas. Neither Croizat et al. (4) nor Winterhalter (36) evoked an almost unparalleled variety of terms in an attempt to found definite evidence of a relationship between the course of the disease and the histologie features. The importance of clinical staging in Hodgkin's disease as 1The groups designated lymphocytic and/or histiocytic will be referred to as "L & H" hereafter with the modification of the initially defined by Peters (26) and later refined by Peters and nodular or diffuse type. Middlemiss (27) emphasized the prognostic importance of JUNE 1966 1063 Downloaded from cancerres.aacrjournals.org on October 2, 2021. © 1966 American Association for Cancer Research. Robert J. Lukes and James J. Rutler localized manifestations in Hodgkin's disease and provided the neoplastic nature of the process. The critical point appears to basis for the recent proposal of the possibility of cure in Hodgkin's revolve about the debatable issue whether the Reed-Sternberg disease. The significance of the histologie features in untreated cell is a neoplastic cell or simply a modified reticulum cell that Hodgkin's disease in relationship to the clinical stages and at times may become pleomorphic—at which time it is definitely survival was re-evaluated in the authors' recent study (R. J. neoplastic. The common occurrence of numerous abnormal Lukes, J. J. Butler, and E. Hicks, in preparation; Refs. 18, 20), reticulum cells, without the distinctive features of classical Reed- of the World War II cases of Hodgkin's disease in a 15- to 18- Sternberg cells, that appear to represent intermediate or partially year follow-up study. The results of this study reemphasizecl the developed Reed-Sternberg cells provides support for the latter importance of the lymphocyte in Hodgkin's disease and its possibility. It has not been established whether the process, if inverse relationship to Reed-Sternberg cells, and demonstrated a neoplastic, involves all the cellular components and is a mixed definite relationship between the histologie features and the lymphoma as proposed by Lumb (22), Herman (2), and others, clinical stages existing at the time of biopsy. A new histologie or the Reed-Sternberg cell is the only neoplastic component—if type, nodular sclerosis, emerged as an important prognostic indeed it is a neoplastic cell—and the associated histologie com group and the regional expression of Hodgkin's disease in the ponents are inflammatory reactions. Definite evidence of neo anterior superior mediastinum. These observations on the plasia is observed in a small proportion of cases at biopsy with nodular sclerosing type have been supported by Hanson (8). In fulminating disease and a limited number of cases at autopsy the recent historic meeting on Hodgkin's disease in Paris (21), the where Reed-Sternberg cells predominate and are distinctly re-evaluation by Lukes, Nezelof and Gompel (in preparation) of pleomorphic. Biopsy specimens in the majority of cases exhibit the pretherapy biopsies from the prolonged survival cases from morphologic expressions of an inflammatory process associated many of the major radiotherapy groups provided evidence that with an increase in the frequency of the Reed-Sternberg cells the nodular sclerosing type was of major prognostic significance. and a decrease in lymphocytes and other cellular elements with The purpose of this presentation will be to consider in detail progressive disease. The change in character of the Reed-Stern the numerous histologie expressions of Hodgkin's disease grouped berg cells with the development of distinctive pleomorphic according to the histologie types reported by the authors (18-20) features provides a basis for suggesting that the evolution of the Hodgkin's disease process may represent the induction of and relate them to the variety of histologie types that appear in the literature. The possible relationship of the histologie findings malignant neoplasia. In this situation the cellular and connective to the clinical stages, survival, and
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