Tumor

TUMOR. - From tumor = swelling, better called "neoplasm" (from the Greek = new formation), it is an atypical proliferation of elements of the body's tissues, with autonomous, incessantly progressive development. The essential characteristic of these formations is the tendency to develop at the expense of the host organism, so that they can be considered true parasites.

This tendency, however, is not of the same intensity for all tumors; indeed, according to the greater or lesser tendency to this parasitism, they are distinguished into benign, with limited growth, with absence of dissemination to other sites (metastases) and of recurrence after removal, and malignant tumors or "cancers," endowed with particular aggressiveness toward the host organism and characterized by a profound cellular atypia, so as to be biologically akin only to monstrosities. The atypia in malignant tumors is at the same time morphological (with regard to the structure of the individual cells among themselves) and biological-functional (the cells being endowed with a particular metabolism and a functionality always different from the norm). Tumors must therefore be well differentiated from the phenomena of hypertrophy (increase in the volume of cells without a simultaneous increase in their number) and of hyperplasia (increase in the number of cells and not in volume), inasmuch as such phenomena do not always bear a decidedly pathological character, but can be an expression of the organism's defense or compensation, while in their structure they always reproduce the morphological and functional characteristics of the adult cells of the organ or tissue involved. The tumor must not be considered even a purely dysplastic fact (that is, of abnormal transformation of the elements of the tissue), being a neoformation rather than a dysplasia; nevertheless it must be observed that the boundaries between these two phenomena are not absolutely clear and precise, especially with regard to benign tumors.

Despite the numerous studies carried out, even recently, to clarify the etiopathogenetic problem of tumors, it can be said that nothing precise is yet known either about the causes or about the mechanism of action of the causes themselves; hence, alongside a group of scientists who consider the tumor as a disease of a single organ or tissue involving the whole organism only secondarily, there are others who consider the tumoral phenomenon as a primary disease of the whole organism, manifesting itself in this or that organ through the direct action of particular factors still unknown. Numerous theories have therefore been put forward to explain the genesis of tumors, and among these one must recall: Virchow's irritation theory, the viral theory, that is, from ultravirus (which in recent times has gathered many supporters), Fichera's theory of oncogenic imbalance, the theory of embryonic residues of Cohnheim-Durante, Hansemann's theory of anaplasia, that of hyperkalemia, that of vital induction. The discovery of the possibility of obtaining experimental cancers by bringing the organism into contact with certain substances (dibenzopyrene) and the observation of the existence of occupational cancers (e.g., lung cancer of miners) or voluntary ones (cancer of the lips or tongue of smokers), had raised the hope of having identified in this or that substance the element capable of determining the onset of tumors. Further studies, however, moderated the initial enthusiasms, especially because of the impossibility of clarifying the problem through the exclusive intervention of exogenous factors, and prompted the various authors to consider tumors as a disease due to particular predisposing genetic factors (the familial nature of cancer is well known), upon which the tumor would become implanted at a given moment of life, through the action of particular exogenous factors not yet identified (chemical, physical, parasitic, viral, dietary). Thus arises the problem of the heredity of cancer. Only some forms of tumor (e.g., glioma of the retina) appear frequently in the same family and prove to possess a notable heredity. In general it is held that even for the other tumors, although a similar repetition of the disease does not occur in members of the same family, a predisposing "quid" is nonetheless inherited; some authors thus speak outright of a "neoplastic diathesis," basing themselves mainly on certain statistical considerations of undoubted importance: cancer of the stomach would favor the Alpine and Nordic constitution (according to Nicoforo and Pittard), while others (Benecke and Benedetti) would have observed a certain predilection of tumors for paracentral individuals (normolinear, slightly macro-or microsplanchnic), a certain antagonism appearing between tuberculosis and tumors. A special humoral terrain proper to this diathesis is also indicated: the preneoplastic state or precancerous terrain, characterized by an increase of cholesterol in the blood and tissues, by a relative alkalosis, and by the inversion of the albumin-globulin ratio. N. Pende holds that there are certain temperaments (v.) particularly predisposed to tumors (hypertrophic parasympathicotonic, hyperpituitary in women).

It must then be recalled that the hypothesis of a certain heredity of cancer has found further confirmation in the numerous investigations conducted especially on the cancers of mice. The most probable hypothesis is therefore that there exists some familial nature of cancer, of a degree varying according to the family, sex, and organ affected.

From the epidemiological point of view, it must be observed that no certain fact argues for the contagiousness of cancer under ordinary conditions of life. At one time people spoke of "cancer houses," but these are today excluded by almost everyone.

As regards its diffusion, cancer must today be considered a ubiquitous disease that affects every race and age of life, although it has a certain predilection for senile age (55-56 years). The W.H.O. (World Health Organization) has recently declared that in recent years there has been an increase in mortality, especially from lung cancer. In Italy, recent statistics report that in 1944 37,495 individuals died of cancer, while in 1950 the deaths rose to 49,607. Statistics compiled in recent years in the Anglo-Saxon countries have shown that tumors are not rare even in childhood. In England from 1945 to 1947 there were 2,260 cases of death from cancer among children under 15 years of age, cancer thus constituting the second cause of death, after tuberculosis (with 6,075 deaths). In New York from 1942 to 1948 the mortality from tumors in children was higher than from any other cause.

The organs most affected are the lung and the stomach for the male sex and the uterus and the breast for the female sex, but it can be said that no organ or system is absolutely immune from this disease, apart from the spleen which, according to most authors, seems to possess oncolytic properties (that is, capable of destroying cancerous elements), so that it would not permit the implantation and development of the neoplasm.

Given the multiplicity of organs involved, the variety of macroscopic and microscopic appearance and of the clinical course that this disease, so little known in its intrinsic nature, can assume, it is natural that numerous classifications have been proposed, all of them, however, more or less incomplete. Besides the distinction between benign and malignant tumors, already mentioned above and based mainly on the clinical course, tumors are distinguished into vegetating, plaque-like and ulcerative based on macroscopic appearance, while depending on the tissue affected there may be epithelial, glandular, connective-tissue, endothelial, nervous, muscular, and osseous tumors. The most precise classification, however, and the one currently in use, is the one that resorts to the histological and embryogenetic criterion, basing itself on the derivation of the cells of the various tumors from one or another of the various embryonic germ layers. According to this classification, tumors are distinguished into: 1) ectodermal tumors, derived from the embryonic ectoderm properly so called; 2) mesodermal tumors, deriving from the epithelia of the kidney, adrenal cortex, ovary, uterus, prostate; from the endothelia of the serous membranes; from the striated muscle fibers; 3) ectodermal tumors, of the tegumentary and glandular epithelia of the respiratory and digestive apparatus, tumors of the thymus and thyroid, of the urinary bladder; 4) mesenchymal tumors, deriving from the supporting connective tissues, from the vascular-blood tissues, from smooth muscle tissue, from undifferentiated mesenchymal remnants; 5) tumors from complex embryonic remnants.

Currently, certain systemic diseases affecting the blood and the hematopoietic organs (leukemias, erythremias) are also included in the large group of tumors, interpreting them as tumors of the bone marrow. The diagnosis of the various tumor forms is exceedingly arduous, given the necessity that it be made at the first onset of the disease, when the therapeutic means today available to medicine can still be useful. The majority of malignant tumors, however, apart from those localized on the skin and on mucous membranes directly accessible to the human eye, gives no characteristic clinical sign until it has by then reached such a development and such a diffusion as to render every therapeutic aid useless. This fact today induces physicians and the specialists of the various bodies set up, under the care of the State, in all nations, for the fight against tumors, to discover and combat the so-called "precancerous states," that is, those chronic alterations with a hyperplastic and dysplastic character, but not yet neoplastic, which often constitute the basis on which the tumor in the strict sense comes to be implanted at a given moment. Included in this group are certain chronic suppurations, oral leukoplakia, gastric ulcers, warts and verrucae, and cutaneous nevi. At the present moment, however, the certain diagnosis of a more or less suspected tumor form can be made only by biopsy, that is, by the histological examination of a fragment of the suspected mass taken directly from the patient.

The problem of tumors absolutely cannot be said to be solved from the therapeutic point of view. An index published by the National Institute of Bethesda (U.S.A.) and due to Dyer reports that by the end of 1948 more than 5,000 substances had already been tested with more or less null results in the fight against tumors. Current therapy is based principally on: 1) physico-chemical means (röntgen or radium irradiation, iontophoresis, diathermy, electrophoresis, fulguration, electrocoagulation); 2) surgical means (early, radical, demolitive intervention, carried out before the tumor has already produced metastases); 3) medical treatment; in addition to the normal palliative and symptomatic treatments suited to mitigating the sufferings of the organism and sustaining the individual, various substances with cancerolytic and antimitotic action have recently been tested (nitrogen mustards, aminopterins, urethane, sodium cyanate, triplaflavine, atebrine) with modest and for the most part momentary results; even the attempts made with organ lysates or by stimulating the spleen, by means of X-rays, to produce antiblastic substances, have not led to better results.

At the present moment, therefore, the problem of cancer must still be considered unsolved, even though undoubted results have been able to be obtained from the practical point of view. A statistic by Smiles (U.S.A.) reports in fact that the average survival of cancer patients has passed from 60 years (in 1920) to 64 (in 1940). This fact has all the more value if one considers that cancer affects individuals above 65 years of age only in the percentage of 0.83 per thousand.

gener., Rome 1949; M. Bufano, Tratt. di patol. spec. med. e terapia, Milan 1949; C. H. Andrews, The bearing of recent works on the virus theory of cancer, in Brit. Med. Journ., 4645 (14 Jan. 1950), p. 81 ff.; G. Vernoni, s. v. in Enc. Ital., XXXIV, pp. 474-81 and in App., II, pp. 1030-34.

Alessandro Marolla