Histologic classification and staging of chronic lymphocytic leukemia. A retrospective and prospective study of 503 cases.

Bone marrow biopsies of 503 untreated patients with chronic lymphocytic leukemia (CLL) were processed for diagnostic evaluation. Histologic variables were correlated with the initial clinical features registered when the biopsies were taken, to determine factors of value in predicting prognosis. Four cellular characteristics (small round nuclei, notched nuclei, large round nuclei and presence of nucleoli) were used to classify CLL into the following three histologic types: (1) small round, (2) notched and (3) mixed. Patients classified according to these types had significantly different median survival times: 53, 26 and 28 months, respectively. CLL showed three growth patterns in the bone marrow: nodular, interstitial and packed, and these patterns had outstanding prognostic significance at all clinical stages (median survivals of 90, 46 and 28 months, respectively). The results are discussed in relation to the various growth patterns and their significance previously reported in the literature. In addition, the quantity of lymphoid cell burden in the bone marrow served as a useful criterion for histologic staging of CLL, thus supplementing any clinical staging system in use. All three histologic parameters--cell type, growth pattern and tumor cell burden--provide information on prognosis and thus provide a basis for decisions on treatment modalities in CLL.