UTERINE LESIONS ASSOCIATED WITH FIBROMYOMA*

UTERINE LESIONS ASSOCIATED WITH FIBROMYOMA* F. W. LIGHT, JR. From the Department of Pathology, St. John's Hospital, Springfield, Illinois Fibromyoma of the uterus is recognized as one of the commonest lesions of the female genital organs. Statistics based upon large numbers of cases all agree that this lesion is encountered most often during the latter part of the reproductive period. It is possible, of course, that some of the tumors arise much earlier and reach such a size as to be noted clinically only after years of slow, symptomless growth, but it seems more likely that most of them arise during the period of life just referred to, and become large enough to permit recognition clinically in a relatively few years. The age distribution, based upon the age at the time of hysterectomy, for the one hundred cases comprising this report, is shown in Figure 1. The average here is 41.7 years. That these tumors may be found in different relationships to the mucosa and serosa of the uterus, and that their size and number vary widely from case to case, is well known. Their microscopic structure is relatively simple and constant, and has been exhaustively studied. Necrosis, hemorrhage, calcification and sarcomatous change are not particularly common, considering the frequency of fibromyomas, and, with the exception of sarcomatous change, are usually of no great clinical importance. The frequency with which sarcoma arises in fibromyomas seems often to be overestimated. In large reported series, it has occurred in somewhat less than one per cent of the cases. The detection of only one such sarcoma in the present one hundred cases is in keeping with that figure. Adenocarcinoma primary in the endometrium of the body of the uterus is no more frequent in fibromyoma cases than in uteri from patients of the same age group who do not have fibromyomas. It was found in only one of the present one hundred cases. *Received for publication, May 7,1938. 483

484 F. W. LIGHT, JR. The etiology of uterine fibromyoma is of considerable interest, and seems to be somewhat more amenable to investigation than u 8 i-i s VD Age Groups 3 R $ \H a 1 I 30-10 ftufber of Caws 10' of Cans OH 10 Htuabei? of Gates 10 itatiber of Cases Bancs zmoueirul JOLW (sit cans) S3 iissoiffosis or COEPQSUHKBX (28 cases) FIG. 1. AGE INCIDENCE (AT TIME OF HYSTERECTOMY) OF FIBROMYOMA AND OF OTHER LESIONS OBSERVED DURING SAME PERIOD OF TIME Cross-hatched areas in three lower diagrams represent cases also having fibromyoma. Only cases in which entire body of uterus could be examined in laboratory are included. that of most other neoplasms. Witherspoon 1 - % 3-4 has studied this aspect of the problem recently, and feels that these tumors

UTERINE LESIONS IN FIBROMYOMA 485 arise as a result of the presence of excessive amounts of estrin, as hyperplasia of the endometrium is thought to do. The present series of cases is presented partly as a commentary upon Witherspoon's work. It is hoped that these data will also serve to emphasize the frequency with which other lesions of the uterus are associated with fibromyoma. Such lesions, which will be discussed below, usually cause symptoms when occurring alone. It appears likely that, in many cases in which they are present along with fibromyoma, they, rather than the fibromyoma, are the true sources of the patients' symptoms. The data here presented have been secured from one hundred consecutive cases studied in this laboratory, all but a few of which were operated upon in St. John's Hospital. Only three of the patients were of the colored race. In every case there was available for pathological examination the entire, intact body of the uterus. The cervix and adnexae were usually not removed, and lesions of these structures are, consequently, not included in the discussion. Every case showing one or more grossly detectable tumors, proven microscopically to be fibromyomas, is included. In a few of the cases, the only tumors present were so small (diameters as little as 2 mm) as to have been quite imperceptible on clinical examination. The largest single fibromyoma had a diameter of 15 cm. Of the one hundred cases, it was found that forty-two showed, besides fibromyoma, one or more of the lesions mentioned below. These lesions, the only ones observed with sufficient frequency to be of significance in a series of this size, are hyperplasia of the endometrium, benign endometrial polyp and adenomyosis (endometriosis) of the body of the uterus. The frequency of each is shown in table 1. The discrepancy between the sum of the figures in the table and that given above results from the fact that in some instances more than one additional lesion was observed. No case showed all three of these conditions in addition to fibromyoma. During the same period (seventeen months) in which the one hundred fibromyoma cases accumulated, there were seen, of course, cases of the other conditions under discussion, not associated with fibromyomas. In table 2 these are fisted, there

486 F. W. LIGHT, JR. being included there only instances in which the whole body of the uterus could be examined in the laboratory. There were, as would be expected, many other cases of hyperplasia of the endometrium and of polyp, represented only by curettings. They are not included in table 2, since the presence or absence of fibromyoma could not be determined. The diagnosis of the lesions just mentioned was made on what was considered a conservative basis. That of endometrial polyps can be open to least dispute, since they are readily noted with the naked eye. A diagnosis of hyperplasia of the endometrium TABLE 1 LESIONS OF BODY OF UTERUS ASSOCIATED WITH FIBROMYOMA Total cases of fibromyoma Cases also showing hyperplasia of endometrium... Cases also showing benign endometrial polyp Cases also showing adenomyosis of body of uterus 100 17 16 14 TABLE 2 CASES OF ASSOCIATED LESIONS OBSERVED DURING SAME PERIOD AS 100 FIBROMYOMA CASES* LESION TOTAL CASES CASES ALSO SHOWING FIBROMYOMA Hyperplasia of endometrium... Benign endometrial polyp Adenomyosis of body of uterus * Entire body of uterus available for examination in each case. was made only when there were found, in a thick endometrium, round or oval glands exhibiting considerable variation in size, distributed through an abundant, compact stroma. Adenomyosis was diagnosed only in cases showing patches of endometrial tissue embedded to a depth of at least several millimeters in the myometrium, and appearing, in single sections, to be quite isolated from the endometrium. Under this heading are included both more or less diffuse changes of this sort and distinct, grossly evident tumor nodules. The lesion here referred to is adenomyosis uteri interna; serosal deposits of endometrioid tissue are excluded. A good many other fibromyoma cases showed what 25 24 28 17 16 14

UTERINE LESIONS IN FIBROMYOMA 487 might be termed tendencies toward hyperplasia of the endometrium or adenomyosis, but they are not listed as such in this report. An examination of the average age incidence in these various conditions indicates that all of them have the same general incidence as fibromyoma. Table 3 is constructed from the already mentioned. Average ages at the time of hysterectomy, here and elsewhere, are given to the nearest year. When fibromyoma was associated with one or more of the other lesions, the age incidence tended, in general, to be a trifle higher than for any one alone. The difference is so slight, however, and the number of such cases so small, that this observation, while of interest, cannot be stressed. TABLE 3 AVERAGE AGE INCIDENCE (AT TIME OP HYSTERECTOMY) OP FIBROMYOMA AND OTHER LESIONS LESION Hyperplasia of endometrium Benign endometrial polyp Adenomyosis of body of uterus NUMBEK OF CASES 100 25 24 28 AVERAGE AGE 42 42 44 43 The data just presented are shown graphically in figure 1, which is so drawn as to have corresponding age groups in the same vertical line. DISCUSSION The frequency with which the various conditions mentioned above are combined with fibromyoma, in the present series, is not so high as in some other reports. Witherspoon finds hyperplasia of the endometrium in practically all of his fibromyoma cases. Kanter, Klawans and Bauer 6 report hyperplasia of the endometrium in 53 per cent, and adenomyosis in 52 per cent of their fibromyoma cases. The differences are probably to be explained on the basis of personal differences in the interpretation of the microscopic pictures observed. It may be pointed out that Reis, in discussing Kanter's paper, states that in his material

488 F. W. LIGHT, JE. only 18 per cent of fibromyoma cases showed hyperplasia of the endometrium, a figure almost identical with that reported here. The frequent association of the lesions under consideration, which is striking even in the present one hundred cases, as well as the similarity in their age incidences even when not associated with one another, points toward the existence of some common etiological factor. They possess certain similarities from a pathogenetic point of view, too, since all of them represent a benign hyperplastic process occurring in some component of the body of the uterus. Endometrial polyps may be looked upon loosely as localized endometrial hyperplasia, and adenomyosis as "ingrowing" polyps. This characterization is supported by the fact that often the polyp or adenomyoma presents the microscopic picture of endometrial hyperplasia, even when the endometrium itself does not. This group of uterine lesions might be thought of together as the premenopausal complex. Witherspoon 3 is of the opinion that the etiological factor in fibromyoma, hyperplasia of the endometrium, and adenomyosis is the estrogenic hormone. This is based largely upon the fact that hyperplasia of the endometrium is generally believed to result from an excess of that hormone, or from its unrestrained action on the endometrium, when not opposed by adequate amounts of corpus luteum hormone. These ideas are derived from the claim that hyperplasia of the endometrium is accompanied by multiple follicular cysts of the ovaries, with the absence of recent corpora lutea. Strong support for this conception of the etiology of endometrial hyperplasia is furnished by animal experiments and by the constant presence of marked endometrial hyperplasia in cases of granulosa cell tumor of the human ovary. The ovarian changes just mentioned are not found with regularity by all observers, however (Kanter et al 6 ). In the cases here presented, too few ovaries were available for study to permit any definite statement in this connection, but even those few did not all display the changes mentioned. It is suggested by Witherspoon 4 that hyperestrinism first produces hyperplasia of the endometrium and later, if allowed to act over a period of time, causes the development of fibromyoma.

UTERINE LESIONS IN FIBROMYOMA 489 If this were strictly true, every fibromyoma should be accompanied by endometrial hyperplasia. Such a state of affairs is approached only in Witherspoon's own data. It does not seem likely that the type of lesion appearing in a given case is determined by the duration of action of some single etiological agent, since any one of the lesions can occur alone or in any sort of combination with the others. It might be proposed, more generally, that some single etiological agent would produce a greater variety of lesions the longer it was permitted to act. In opposition to such a hypothesis, it may be pointed out that additional lesions were twice as common in association with fibromyomas less than 5 cm in diameter (37 cases out of 62) as in association with those more than 5 cm in diameter (11 out of 38). The cases with the larger tumors, which had, presumably, been present for the longer periods of time, were, in other words, less likely to show additional lesions. The data at hand may be best interpreted by supposing that fibromyoma, hyperplasia of the endometrium, benign endometrial polyp and adenomyosis of the body of the uterus all possess a common etiological factor, probably hyperestrinism, but that each requires for its development some other, independent factor, the nature of which is, at present, obscure. SUMMARY There are presented one hundred cases of fibromyoma of the body of the uterus. In almost half of them, other lesions of the body of the uterus were also present. It is concluded that fibromyoma and these other lesions probably have a common etiological factor, but that other factors must participate in the production of each of them. REFERENCES (1) WITHERSFOON, J. T.: The interrelationship between ovarian follicle cysts, hyperplasia of the endometrium and fibromyomata. Surg., Gynec. & Obst., 56: 1026-1035, (June) 1933. (2) WITHEESPOON, J. T., AND V. W. BUTLEB: The etiology of uterine fibroids. Surg., Gynec. & Obst., 68: 57-61, (Jan.) 1934. (3) WITHEESPOON, J. T.: The estrogenic principle, the common etiological

490 P. W. LIGHT, JR. factor of endometrial hyperplasia, uterine fibroids and endometriosis. Surg., Gynec. &. Obst., 61: 743-750, (Dec.) 1935. (4) WITHERSPOON, J. T.: The estrogenic, carcinogenic and anterior pituitary growth principles, and their clinical relation to benign and malignant tumors. Am. J. Obst. & Gynec, 31: 173-177, (Jan.) 1936. (5) KANTER, A. E., KLAWANS, A. H., AND BAUER, C. P.: A study of fibromyomas of the uterus with respect to the endometrium, myometrium, symptoms and associated pathology. Am. J. Obst. & Gynec, 32: 183-193, (Aug.) 1936.