Atypical Epithelial Proliferation Research Articles

Atypical epithelial proliferation in the course of experimental production of ulcer-carcinoma of the stomach.

In our preliminary attempt at experimental carcinogenesis on the basis of gastric ulcer, we succeeded in producing a chronic penetrating ulcer associated with gelatinous adenocarcinoma in rats. The present study was performed to elucidate the correlation between the induced ulcer and its epithelial proliferation which appeared in that experiment. The method of the present experiment was essentially the same as that of the previous study. Rats were divided into four groups according to the type of pellet inserted into the pouch of the stomach. Namely, (1) group B with beeswax pellet, (2) group BH with pellet of beeswax and histamine phosphate, (3) group BC with pellet of beeswax and 4-nitroquinoline-1-oxide (carcinogen) and (4) group BHC with beeswax pellet containing both histamine phosphate and 4-nitroquinoline-l-oxide. Animals were sacrificed on 5, 7, 14, 30, 61) and 120 days following insertion of pellet and the mode of ulcer development and process of epithelial proliferation in four groups were compared. Necrosis and resultant ulceration of the gastric wall were found at the site of pellet application in all animals of the four groups 14 days after the operation. Most of the once formed ulcers healed with scar tissue in groups B and BH, whereas those in groups BC and BHC where carcinogen was used underwent a change into chronic penetrating ulcers. In such chronic ulcers, epithelial proliferation deep into the scar tissue beneath the ulcer was noted, being especially marked in groups BC and BHC with carcinogenic pellet. A few cases revealed cellular atypism in such deeply penetrating epithelia. It was concluded from these facts that in our experimental procedure to produce ulcer-carcinoma in rats, an acute ulcer occurred first which took the chronic process and gradually was followed by epithelial proliferation of various grade originating at the margin and extending deep into the floor of the ulcer.

RELATIONSHIP OF INTERSTITIAL PNEUMONIA HONEYCOMBING AND ATYPICAL EPITHELIAL PROLIFERATION TO CANCER OF THE LUNG.

RELATIONSHIP OF INTERSTITIAL PNEUMONIA HONEYCOMBING AND ATYPICAL EPITHELIAL PROLIFERATION TO CANCER OF THE LUNG.

Bowen's disease and its relationship to systemic cancer.

Introduction In this paper we shall report a previously unrecognized association of Bowen's disease of the skin with primary internal cancer. Bowen, 1 in 1912, described two patients with atypical epithelial proliferation of the skin. Each patient had a chronic solitary lesion composed of lenticular papules resembling a noduloulcerative syphiloderm. Darier, 2 in 1914, Bowen, 3 in 1915, and, more recently, Fraser 4 described multiple, nonelevated, scaly or crusted plaques as a variety of Bowen's disease. Histologically, these lesions were indistinguishable from those reported originally by Bowen. Since Bowen's original description, many similar lesions have been recorded. Furthermore, the concept has been broadened by some investigators to include sites other than the skin, such as the oral cavity, anus, eye, genital organs, and genitourinary tract. We shall record our experience and observations of a large group of patients with Bowen's disease of the skin which meet the criteria

A New Chromosome Stain and Its Relationship to Atypical Cell Proliferation

A new chromosome stain is described which is based upon the affinity of nucleoproteids for certain quinone derivatives. The relationship between this stain and the production of atypical epithelial proliferations and cancer produced by aromatic amines is discussed.

Consultant and Specialist Services

<h3>Introduction/Background</h3> Borderline ovarian tumors (BOT) are defined as atypical epithelial proliferation without histopathological stromal invasion. Tumors with low malignancy potential, tend to be limited to ovary and CA 125 is not elevated in majority of patients. In this study, we aim to investigate CA 125 levels in patients with BOT. <h3>Methodology</h3> 56 patients, final pathologies were reported as BOT were included. Age, menapausal status, histological type and stage of the tumor were evaluated and compared with CA 125 levels, retrospectively. <h3>Results</h3> The mean age of the patients was 42.9 (19–84) and 66.1% of the patients were premenapausal. Serous histology was detected in 67.9% of the patients, the remaining histology was musinous, brenner or mix type. 83.9% of the patients disease was limited to the ovary. 57.1% of the patients Ca 125 levels were above normal range. Mean level of CA 125 was 227.2 U/ml, ranged between 3–5668 U/ml (table 1). There was positive corelation between CA 125 levels and premenapausal status, serous histology and extraovarian spread (table 2). <h3>Conclusion</h3> CA 125 is especially used in monitoring the response to treatment in invasive epithelial ovarian cancer. In early stage disease and in premenopausal women its benefits are limited. It is reported that there isn’t a significant increase in CA 125 in BOT. However, in our study, elevation in CA 125 level was found in a significant number of patients and it was related to stage and serous histology, and higher levels were detected in the majority of premenopausal patients. This suggests that detection of CA 125 levels in BOT may have prognostic significance in addition to assisting the diagnosis. <h3>Disclosure</h3> Nothing to disclose.

Cholecystographic Diagnosis of Double Gallbladder with Pathologic Verification

As far as we can determine, the following is the first complete report in the medical literature of a double gallbladder diagnosed by cholecystography and subsequently proved at operation and by pathologic examination. History: A 57-year-old white man was admitted to the Niagara Falls Memorial Hospital, service of Dr. Fred Leighton, on May 12, 1940, with a complaint of distress induced by numerous foods. The past history included appendectomy, tonsillectomy, removal of a pharyngeal polyp with atypical epithelial proliferation, undulant fever, passage of renal gravel, and pollinosis. For several years the patient had been disturbed by cardiac arrhythmia. Electrocardiograms by Dr. Grant Guillemont previous to admission to the hospital had shown this to be due to frequent premature contractions. There was no evidence of myocardial impairment, either clinically or electrocardiographically. Cholecystographic Reports: April 12, 1938. On a “scout” film no calculi were noted in the gallbladder area. A series of f...

Observations on Animals Painted with Tobacco Tar

The importance, in the etiology of cancer, of various agents, such as roentgen rays (1, 2), radioactive substances (3, 4), ultraviolet light (5), certain animal parasites (6, 7), coal tar (8), and some hydrocarbons (9, 10, 11) which produce prolonged or chronic irritation is now generally recognized. Such studies have not been limited to experimental animals, and a number of writers have suggested a relationship between these agents and certain forms of occupational cancer. The high incidence of cancer of the lip, tongue, and throat in men as compared to the infrequency of such cancer in women has frequently been attributed to persistent irritation of the epithelial surfaces by tobacco tar, to which men have been exposed to a much greater degree. Stimulated by these observations, several investigators have studied the action of tobacco tar and smoke in different species of animals. In 1911, Wacker and Schmincke (12) succeeded in producing an atypical proliferation in rabbits9 ears after application of tobacco tar, obtained from pipes, mixed with crude paraffin oil. Helwig (13) found that the ethereal extracts of tobacco tar obtained from the bowls of briar pipes and combustion products of tobacco distilled over at temperatures between 400 and 500° C. did not contain any carcinogenic substance capable of producing unlimited growth of epithelium in mice. Tobacco tar when mixed with olive oil and injected into the ears of rabbits caused atypical epithelial proliferation, but in no instance did it produce actual malignant transformation. Chikamatsu (14) painted the skin of mice and the ears of rabbits with tobacco tar and found it to be inactive on mice though it caused the development of a cancroid on a rabbit9s ear 225 days after the beginning of treatment.

Studies in Carcinogenesis: IV. Development of Liver Tumors in Pure Strain Mice following the Injection of 2-Amino-5-Azotoluene

The preceding studies on carcinogenesis (Shear, 1936, a, b ) dealt with the production of tumors by hydrocarbons related to 1:2-benzanthracene. The finding of Kennaway 1 and his colleagues that hydrocarbons are carcinogenic was the culmination of a search for the active agent in coal tar which began when Yamagiwa and Ichikawa (1915) announced the experimental production of skin tumors with coal tar. The success of these Japanese investigators was, in turn, the outgrowth of numerous attempts on the part of many previous investigators to induce malignancy in experimental animals by the administration of a wide variety of substances. Among the substances used by Yamagiwa and Ichikawa (1915, 1918) in attempting to produce malignant growths was scarlet red; this was used alone and in combination with tar. Hyperplasia was produced by scarlet red but, for various reasons, its use was discontinued and coal tar was used alone. Scarlet red was also injected into the wall of hens9 oviducts by Yamagiwa and Ohno (1918) in an attempt to produce glandular cancer; carcinoma was obtained in 3 of the 41 hens, and hypertrophy in many others. One tumor contained scarlet red in the center of the neoplasm. This use of scarlet red originated with B. Fischer (1906). After testing many substances in earlier attempts to produce malignant growths, he injected a solution of scarlet red into the ears of rabbits. The atypical epithelial proliferation which resulted was difficult to distinguish, histologically, from cancer, but the growths always receded. Fischer stated that this was the first instance in which tumor-like proliferation had been produced by a chemical compound, and suggested that this finding threw a new light on the genesis of malignant growths, especially on the genesis of paraffin cancer, chimney sweeps9 cancer, and similar occupational cancers.

Fibromata with Atypical Epithelial Proliferation

Fibromata with Atypical Epithelial Proliferation

BOWEN'S PRECANCEROUS DERMATOSIS AND MULTIPLE BENIGN SUPERFICIAL EPITHELIOMA

In 1912, Bowen 1 reported a study of two cases of chronic atypical epithelial proliferation to which he gave designation of precancerous dermatosis. Since then, this condition has been subject of investigation by many workers, including Darier, 2 Highman, 3 Fraser, 4 Wise 5 and others. A great deal has been written regarding its exact status in field of neoplastic growths, but most dermatopathologists are in accord with Fraser, who believes that the cellular changes constituting this lesion are, from beginning, those generally considered as characteristic of malignancy. He pointed out that pathologically the cells in Bowen lesion have already undergone changes of malignant neoplasia, and for this reason lesion should be classified as an intraepidermal carcinoma. As Wise 5 has pointed out, a definite diagnosis of Bowen's disease cannot be made on clinical evidence, but only on characteristic microscopic

A Critical Study of Vitamin a and Carcinogenesis

In recent years some interest has arisen concerning the influence of a dietary deficiency of vitamin A in the production of tumors in rats. Fuzimaki and his associates (1, 2, 3) reported that prolonged feeding of rats with a diet deficient in vitamin A was followed by the development of carcinoma in the fore-stomach of five rats out of 49 animals tested. One of the five animals developed metastases in the lungs. Their recent communication (4) indicated that the hyperkeratosis or atypical epithelial proliferation in the fore-stomach of albino rats was not marked unless the animals were fed with a diet deficient in fat, as well as in vitamin A. The investigations of Erdmann and Haagen (5) also lead to the conclusion that lack of vitamin A in the diet is an important factor in carcinogenesis. Following special feeding they found a number of rats with spontaneous tumors. Of the 83 specially fed rats, 6 developed tumors. Four tumors originated from the mammary gland of female animals. Three of the tumors were adenocarcinomas, and one was an angioma. Two other tumors were papillomas of the stomach. They stated that the great increase over the control animals (7 per cent against less than 1 per cent) could only be accounted for by the kind of diet eaten (6). In her last paper (7) Erdmann stated that after being subjected to a diet over-rich in vitamin B and D, eight rats in three series of experiments developed malignant growths. In the first series, consisting of 80 rats, 3 adenocarcinomas of the mammary gland developed (5). In the second series, consisting of 100 rats, one papilloma of the stomach appeared.

MULTIPLE SUPERFICIAL BENIGN EPITHELIOMA OF THE SKIN

Opinions are divided with respect to certain dermatoses associated with a form of atypical epithelial proliferation to which the name "dyskeratosis" was given by Darier in 1914. This dyskeratosis is observed in Bowen's, Paget's and Darier's diseases, in chronic roentgenray and radium dermatitis, in molluscum contagiosum, in senile keratoderma, in xeroderma pigmentosum and occasionally in various types of epithelioma of the skin. While Paget's disease of the nipple has long been regarded as a clinical and histologic entity, the identity of Bowen's precancerous dermatosis and of extramammary Paget's disease is often predicated on vague and indeterminate clinical and microscopic observations. <h3>DIAGNOSTIC ERRORS</h3> A number of cases appearing in the literature under such designations, as Bowen's disease, the Bowen type of epithelioma and extramammary Paget's disease, are in reality examples of peculiar forms of epithelioma, usually of the basal cell variety, but at times prickle cell and more rarely of the

THE GROWTH-PRODUCING EFFECTS OF EXTRACTS OF TOBACCO ON MICE

Experimental carcinoma has been produced through the medium of x-ray, coal tar, various paraffin oils, arsenic, soot, wood tar, and parasites. In the latter case it is seen that the parasitic tumors were obviously due to the chronic irritation set up by the parasite. I refer only to the two well established experiments: first, that of Fibiger, who produced carcinoma of the stomach in rats by the feeding of cockroaches infected with the nematode worm Spiroptera neoplastica and, second, sarcoma in the liver of rats produced by Bullock and Curtis through feeding them the Taenia crassicollis of cats. Atypical proliferation not progressing to malignancy has been produced by injections in the ears of rabbits of scharlach r, constituents of certain aniline dyes and the cleavage products of albumin, such as indole and skatole. Only one instance wherein the use of tobacco tar produced any atypical epithelial proliferation could be found

STUDIES BASED ON A MALIGNANT TUMOR OF THE RABBIT

A malignant tumor which developed at the site of a primary syphilitic lesion in the scrotum of a rabbit, about 4 years after inoculation, and eventually led to the death of the animal, has formed the basis for an extensive series of investigations beginning with the study of the spontaneous tumor. The present report contains the clinical history of the animal from the time of inoculation to its death and the results of pathological examinations. The most important events recorded may be summarized as follows: 1. A mild but persistent syphilitic infection with an occasional relapse and the eventual development of chronic inflammatory lesions in the skin associated with atypical epithelial proliferations. 2. The occurrence, at about the same time, of extensive degenerative changes in the dermis accompanied by an atypical growth of hair follicles, with the production of diffuse and nodular areas of thickening and induration (scleroderma). 3. The development of a growth in the skin of the left scrotum which recurred after removal and spread diffusely over adjacent parts of the skin, and metastasized to the regional lymph nodes and to internal organs. 4. The transplantation of the growth to other rabbits by intratesticular inoculation and the successful propagation of the growth over a period of nearly 2 years (twenty generations). 5. The development of a cachexia and of pressure phenomena from metastases involving the cervical and lumbar regions of the spinal column which eventually led to the death of the animal. 6. The discovery, post mortem, of an extensive leucoplakia of the tongue and buccal mucosa, chronic inflammatory lesions in the esophagus with atypical epithelial proliferation, and a nodular growth in the left testicle differing in character from that in the scrotum. 7. The presence of extensive degenerative changes in the vascular system, degeneration of the parenchymatous organs, atrophy of the thymus and lymphoid system, with chronic lymphadenitis, atrophy, degeneration, and necrosis of the suprarenals, and atrophy and hyperplasia of the thyroid with chronic thyroiditis. The conclusion was reached that the growth in the scrotum represented a neoplasm of epithelial origin which was composed of cells allied to those found in the bulb and root sheath of the hair. No explanation was offered for the origin or unusual malignancy displayed by the tumor pending the introduction of experimental data. It was stated, however, that the evidence presented was sufficient to warrant the assumption that the factor of foremost importance in the development of the tumor was constitutional rather than local.

The reaction of the endocrine system of the rabbit to tumor inoculation and the relation of this reaction to malignancy

Within recent years, a great deal of evidence has been accumulated from both clinical and laboratory sources which has tended to show that some kind of connection exists between the occurrence and growth of tumors and the system of organs regulating animal economy. For the most part, the evidence bearing upon this problem has been circumstantial. In a few instances a definite relationship appears to have been established as in the case of the experiments reported by Loeb concerning the effects of castration on the incidence of mammary tumors in mice and those of Rohdenburg, Bullock, and Johnson on the effects of operative removal of various organs upon the growth of transplanted tumors and the immunity of tumor animals. There are also therapeutic observations on the use of thyroid and of thymic products alone or combined with castration which might be regarded as equally suggestive were it not for the fact that similar results have been obtained by the use of a variety of means. Two years ago, we reported the occurrence of a malignant tumor in the scrotum of a rabbit infected with Treponcma pallidum. Since that time, a careful study has been made of the conditions presented by this animal and a long series of investigations based upon the behavior of transplanted tumors derived from this stock has been carried out which have shown that there is an essential connection between the growth of transplanted tumors and certain members of the endocrine system on the one hand, and the mechanism of animal defense on the other. In the animal with the spontaneous tumor, there was a notable tendency to atypical epithelial proliferation in many parts of the body associated with a deficiency in the reaction of the surrounding connective tissues and a widespread tendency to degeneration. There were also very striking alterations in such organs as the thyroid the thymus, the suprarenals and the lymphoid tissues, which might have been regarded as part of a general organic deterioration attributable to one or both of the diseases present.

PRECANCEROUS DERMATOSES: THE FURTHER COURSE OF TWO CASES PREVIOUSLY REPORTED

The object of this communication is to record briefly the subsequent histories of two of the three cases which I reported inThe JournalofCutaneous Diseasesfor May, 1912, and December, 1915, under the respective headings: Precancerous Dermatoses: A Study of Two Cases of Chronic Atypical Epithelial Proliferation; and Precancerous Dermatoses: A Sixth Case of a Type Recently Described. The subject was greatly elaborated and clarified by J. Darier in an article in the Annales de dermatologie et de syphiligraphie for August-September, 1914, entitled: La dermatose precancereuse de Bowen, dyskeratose lenticulaire et en disques, in which is embodied the description of three typical examples of the same affection. Since that time several cases of a similar or allied nature have been referred to, particularly by American writers, which have varied somewhat in their clinical and histologic features, and in the opportunity of their reporters for a complete study. FURTHER