Patterns of presentation of Hodgkin disease. Implications for etiology and pathogenesis.

BACKGROUND: The etiology of Hodgkin disease remains uncertain. Patterns of presentation of Hodgkin disease are analyzed by histologic subtype with implications for etiology and pathogenesis.
METHODS: The authors performed a detailed analysis of anatomic sites of involvement, histopathologic findings, and clinical features in 719 patients with Hodgkin disease who underwent staging laparotomy with splenectomy between April 1969 and December 1986. The presence of disease in each of 17 sites of potential nodal involvement was determined for each patient from a combination of clinical and surgical staging. Association among nodal sites was assessed in 2 x 2 tables by estimating the odds ratio and testing the significance with the chi-square test. A strict significance level (P = 0.01) was used. Log-linear models were used for assessing association in 2 x 2 tables while adjusting for other factors.
RESULTS: The mediastinum, left side of neck, and right side of neck were the most common sites involved for patients with nodular sclerosing (NS) or mixed cellularity (MC) histologic subtypes. Each of these sites was involved 60% of the time. These sites were four or more times as common as other nodal sites above or below the diaphragm. In contrast, the mediastinum was involved in only 8% of patients with lymphocyte predominance (LP) histologic subtype. Significant associations were found between mediastinal disease and low cervical/supraclavicular lymph node disease, mediastinal disease and NS histologic subtypes, peripheral nodal disease and LP histologic subtypes, and between splenic disease and mixed cellularity/lymphocyte depletion (MC/LD) Hodgkin disease. The age at onset and sex of patients with Hodgkin disease and the patterns of nodal distribution were somewhat different for NS and MC/LD histologic subtypes. Even greater differences were seen between LP and other histologic subtypes.
CONCLUSIONS: This study supports the conclusion that NS and MC Hodgkin disease spread by continguity, most often originating in the neck or mediastinum, and is consistent with evidence suggesting an infectious agent in the pathogenesis of these subtypes of Hodgkin disease. In contrast, LP Hodgkin disease is characterized by different sites of presentation and patterns of spread. This suggests that two or perhaps three clinicopathologic subtypes of Hodgkin disease exist. Implications for etiology and pathogenesis are discussed.