Journal of Okayama Medical Association
Published by Okayama Medical Association

Full-text articles are available 3 years after publication.

2-Methylcholanthreneによるハツカネズミリンパ性腫瘍の研究 第2編 リンパ球性白血病の成立過程に関する研究

岡田 耕一 岡山大学医学部平木内科教室
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After inducing lymphocytic leukemia by painting the skin of the mice of dba strain and other group of uncertain origin with 20-methylcholanthrene, the author carried out tissuc cultures of bone marrow, lymph nodes, and spleen of these test animals and also cytological and histological examinations for purpose of clarifying the origin and development of lymphocytic leukemia. On the basis of the peripheral blood pictures, the author classified the development of lymphocytic leukemia into the following three stages, i.e., (1) preleukemic stage (with leucopenia but no lymphoblasts in the peripheral blood), (2) initial stage of leukemia (with slight leucocytosis and a few lymphoblasts in the peripheral blood), and (3) advanced stage of leukemia (with marked leucocytosis and many lymphoblasts in the peripheral blood). The following are the results and conclusions of the present experiment. (1) The changes in the peripheral blood pictures observed during the preleukemic stage as described in Part I, that is, leucopenia and lymphopenia, are caused by the arrest of maturation in lymph follicles of the spleen and by hypoplasia of lymph nodes. Eosinophilia can be observed in bone marrow of every single case and the stimulation of the reticuloendothelial system is believed to be one of its causes. Lymphoblasts of the peripheral blood during the initial stage of leukemia are mainly derived from the spleen. The distribution curve of the greatest diameters of lymphocytes in the peripheral blood gradually shifts to the right as lymphocytic leukemia develops. This phenomenon coincides with the increase in large lymphocytes during the preleukemic stage and with the appearance of lymphoblasts during the initial stage of leukemia. (2) In tissue cultures, the bone marrow, spleen, thymus, and lymph nodes of leukemic mice show the growth patterns specific to acute lymphocytic leukemia, though these ars not so typical in mice as in men. Namely, the margin of growth zone is sharply defined, the density of cells is very high, and the growth zone is consisted mainly of lymphoblasts with some mature lymphocytes. In the preleukemic stage, the spleen shows relatively leukemic growth pattern, but the lymph nodes show hypoplasia or slight hyperplasia, In the initial stage of leukemia, the spleen shows the leukemic growth pattern, but the lymph nodes and thymus show hyperplasia or leukemic growth pattern. In the advanced stage of leukemia, the spleen, lymph nodes, thymus, and the bone marrow begin to show the leukemic growth pattern. (3) Cytomorphologically, leukemic cells appear first of all in the lymph follicles of the spleen, and they increase in the lymph nodes and bone marrow along with progress of leukemia. The lymphoblats in the lymph nodes during the preleukemic and initial stages of leukemia are little atypical, but they show prominent nucleoli and lobulation of the nucleus in the advanced stage and also mitochondria increase in number. The distribution curve of the greatest diameters of lymphocytes in the lymph nodes shifts gradually to the right through the development of lymphocytic leukemia as in the case of peripheral blood. (4) In autopsy findings, there can be observed a slight enlargement of spleen in the preleukemic stage, moderately enlarged spleen and slightly enlarged lymph nodes in the initial stage, and marked enlargement of spleen, lymph nodes, and liver in the advanced stage. (5) Histologically, the lymph follicles of spleen are enlarged due to the proliferation of reticulum cells and lymphoblasts in the preleukemic stage. Lymph nodes show hypoplasia or slight hyperplasia. Namely, lymphocytic leukemia can be understood to be circumscribed to the spleen in this stage. In the initial stage, lymphoblasts infiltrate diffusely through the whole spleen and lymph nodes show hyperplasia or gradual enlargement of germinal centers due to the proliferation of lymphoblasts with the formation of lymph follicles. In the bone marrow, diffuse infiltration of leukemic cells can be observed. In the advanced stage, spleen, lymph nodes, and thymus become totally leukemic, and leukemic cells metastasize to various other organs including bone marrow, liver, and kidneys through the hematogenous and lymphogenous channels. (6) Leukemia sets in about the time when papilloma appears on the skin, and by the time when papilloma begins to be transformed into skin cancer most of the mice with lymphocytic leukemia die. The mice with skin carcinoma show myelogenous leukemoid reaction, and some of them reveal the complication of reticulosis or reticulosarcomatosis.