Differentiation of Benign and Malignant Pulmonary Nodules by Growth Rate

Solitary pulmonary nodules have been analyzed by many investigators (11, 13, 15, 16, 17, 31, 33, 38, 43) for signs indicative of their etiology, the main effort having been directed toward separation of benign and malignant lesions. Of all the signs mentioned, including size, shape, density, sharpness of margin, umbilication, satellite nodules, cavitation, densities extending into the hilus and/or pleura, growth, and calcification, only the last has been considered to be a reliable aid in differentiation. The presence of any calcification in a pulmonary lesion makes malignancy extremely unlikely, although it is recognized that minute central calcification can on rare occasions be found in malignant lesions. Ring-shaped, laminated, and large central "popcorn" calcifications are reliable signs of benignity (16, 31). In general, the appearance of a nodule in a lung which was previously normal or enlargement of a pulmonary nodule, with the reservation that there are some exceptions, is thought by most to indicate a malignant lesion. Because of the difficulty in differentiating benign from malignant nodules, the general attitude in the last few years, particularly since about 1945, has been to recommend the immediate removal of all solitary pulmonary nodules except those in which the presence of calcification indicates their benign nature. Few objections have been raised against this procedure. One of those who protests is Garland (13) who advised: "Don't be like Lady Macbeth. Don't say 'Out, damned spot!' and I think you will diagnose most of these nodules correctly. " The concept of exponential growth of cancer at a constant rate, advanced by Mottram in 1935 (29) and later by Collins et al. in 1956 (5), has received support in the work of several independent investigators (1, 2, 10, 21, 22, 25, 34, 41, 42). Collins collected a series of 177 cases of malignant pulmonary nodules with serial chest films showing the growth of neoplastic nodules. The nodules were measured and growth rate was expressed as "doubling time." Values ranged from 7 to 465 days (5–9). Enlargement of non-neoplastic. nodules also may occur, but the mechanisms are not the same as for neoplasms and would not be expected to result necessarily in exponential growth at a constant rate. Although granulomas, pneumonitis, abscesses, infarcts, hematomas, fluid collections, etc., may enlarge, they do not do so by cell division. Nevertheless, observation of change (or lack of change) in size may demonstrate that the pattern of growth is not that of a malignant tumor. This may therefore be a useful diagnostic test. If differences could be found to exist between the rate of tumor growth and the rate of enlargement of benign lesions, then a useful diagnostic tool would become available to add to the few radiographic and clinical signs for differential diagnosis.