Abstract
Most histologic studies of irradiation changes have been based on the effect of a single massive radium exposure producing overwhelming destructive changes in the tumor. Few histologic studies have been made of the effects of fractionated roentgen irradiation, although this method predominates in modem radiotherapeutic technics. The administration of roentgen rays in small daily fractions permits the normal epithelium to recover somewhat each day from the irradiation injury, while the less differentiated tumor cells, for the most part, show no evidence of recovery. Fractionation also increases the number of times each tumor cell is exposed to irradiation while in the premitotic or mitotic phase, which is believed by many to be the most radiosensitive phase. Melnick and Bachem (1) described the findings in transplantable tumors of rats following both the single massive dose method and fractionated, protracted irradiation. With the massive dose method, they noted radiation necrosis of tumor cells, associated with hyperemia, cellular infiltration, granulation tissue proliferation, fibrosis, and blood vessel changes. With the fractionated protracted technic they observed, in addition to necrosis of radiosensitive cells, a gradual transformation of all the refractory tumor cells into hyperchromatic giant cells. These cells did not degenerate by necrosis, but by calcification of the nucleus. This method of treatment had no apparent effect on the adjacent normal tissues. There was no fibrosis and no blood vessel damage. Halley and Melnick (2) described the changes observed in twenty-one breasts that were irradiated preoperatively. Their findings were similar to those observed in animal tumors. Glücksmann (3) studied the effects on human squamous-cell and basal-cell carcinoma of different technics of fractionated roentgen and gamma-ray irradiation with varying daily and total doses. He evaluated in each biopsy specimen the dividing, degenerating, resting, and differentiating cells. The dividing cells showed rapid and early reduction of the number of mitotic figures, which often reached zero in eighty minutes. Later there was partial resumption of mitotic activity, chiefly in the form of abnormal mitoses. Many of these “broke down,” contributing to the “degenerating cell” count, that increased until mitotic activity ceased. In successfully treated carcinoma, mitotic division ultimately ceased. Reduction of the number of resting cells in the growing areas of the tumor was due either to degeneration or differentiation. Increased differentiation of the cells in most cases was related to a fall in the resting cell count. Glücksmann (3) regarded many of the monster-sized cells as differentiating cells; this is contrary to our impression.