Histopathologic effects of x-rays, radiophosphorus, nitrogen mustard, urethane, and steroids upon the spleen in leukemias and lymphomas.

Abstract

Practically all prior investigations of the effect of therapy upon the spleen of patients with leukemias and lymphomas have been limited to studies made at autopsy. It is the purpose of this paper to investigate the histopathologic effects of treatment of these diseases by comparing the morphology of biopsy specimens obtained following treatment with a control biopsy obtained immediately prior to therapy. Materials and Methods Technic: Biopsy of the spleen was performed with a Vim-Silverman needle by transthoracic or transabdominal route (1). A piece of tissue about half to two-thirds as thick as the lead in a pencil (1 mm.) and varying from 1 to 3 cm. in length (usually 2 to 3 cm.) was obtained. The larger spleens were biopsied transabdominally, since this is probably safer in the thrombopenic patient, a category into which most of the cases fell. There were no serious complications except for a temporary fall in blood pressure in a single instance. Splenic tissue was prepared by the Maximow technic: Immediate Zenkerformol fixation, sectioning at 6 micra in nitrocellulose, and staining by hematoxylin eosin azure II (2). Slides were also stained for iron (3), and for connective-tissue fibers by the Mallory-azan technic (4). A small piece of tissue was removed from each biopsy specimen for preparation of dry smears by the abklatch technic (5, 6), in which a piece of spleen is gently touched between two slides. These slides were colorized by Wright's stain. All specimens were examined as unknowns and an objective description was made of the microscopic findings. The latter served as a basis for the conclusions drawn in this study. Smears of splenic tissue were not only useless but often misleading, the most important reason being errors inherent in this technic. A multilayered mass of cells with twisted fibers was found wherever the spleen was touched (abklatch of Downey) or smeared on the slide or cover-slip. Because of distortion or opaqueness, the more immature cells, reticular and stem cells, in this mass could not be studied. As a result, only the more mature cells at the periphery of the splenic “touch” or abklatch were available for study. Mitotic cells and nuclear débris were never seen in the smears. A second reason was that it was impossible to determine which type of splenic tissue (normal white or red pulp, fibrous tissue, or tissue specifically involved in the malignant process) was studied. Consequently it was impossible to be certain whether changes seen in smears of repeat biopsies were due to differences in the type of tissue being sampled or to the effect of treatment. Comparability of Biopsies: A study such as this depends upon the comparability of the tissue obtained in sequential biopsies. In the leukemias the spleen has a sufficiently uniform appearance so that this is not a major problem. Serial biopsies from a lymphomatous spleen, however, may vary.