Incidence of Multiple Primary Tumors and the Problem of Acquired Cancer Immunity

Abstract

While multiple tumors of identical type are frequently encountered in the same person, as for instance in all cases of multicentric skin lesions and of metastasis, we are justified in speaking of multiple primary tumors only when we are reasonably sure that such tumors have developed independently and have no ascertainable direct or indirect connection with each other. This lack of connection is obvious in the case of combinations of tumor types entirely dissimilar morphologically and clinically, as for example tumors arising from embryologically different layers, as connective tissue and epithelium, and in the case of manifestly benign tumors and definitely malignant neoplasms. On the other hand, the differential diagnosis may become extremely difficult or even impossible if we are confronted with a combination of morphologically or clinically similar tumors. To exclude metastases, Billroth formulated the following postulates, which he believed should be fulfilled before a diagnosis of multiple primary tumors can be given: 1. That the tumors have a different anatomical structure. 2. That each tumor be histogenetically derived from the tissues of the organ in which it is primarily found. 3. That each malignant growth have its own metastases. These requirements appear too strict. It is impossible to insist on metastasis as a diagnostic sine qua non in every case of malignant neoplasm. In addition, it is well possible that, because of a variety of factors, a tumor may be modified in structure and character to such a degree as almost completely to lose its original type and identity. Etiologically, tumor multiplicity may be explained as the effect of multiple cell implantation, of multiple stimuli, or of multiple primordial cell nests (Geschwulst-Anlagen). Lubarsch interprets the occurrence of multiple tumors as evidence of a general tumor diathesis, while Walter thinks that in the majority of cases it signifies nothing more than a coincidence. Among 3,700 consecutive autopsies performed by the Department of Pathology of the University of Colorado Medical School from 1925 to 1940, 42 examples of multiple primary tumors were recorded. An analysis of these cases shows that in 38 instances two tumors were found in the same person, while in 4 cases the patient harbored three tumors. A combination of benign tumors only was seen but twice. The most frequent combination was that of a benign and a malignant tumor. This combination was seen in 27 patients. The combination of two benign tumors and one malignant tumor occurred in 3 cases. In 9 cases, two independent malignant tumors were observed simultaneously, while in still another case two primary malignant tumors were seen together with a benign tumor.