Historical Aspects of Endometriosis:
Histogenesis, Histopathology, Diagnosis

Robert B. Greenblatt, M.D.
Professor Emeritus, Department of Endocrinology, Medical College of Georgia. Augusta, Georgia

Endometriosis, Aspects and Proceedings of a Symposium
Saint John's Hospital and Health Center, Santa Monica, California
Editor: J.J. Marik

Histogenesis: Ectopic endometrial tissue received scant notice until Cullen in 1920 named at least 10 sites in which external adenomyoma (sic endometriosis) had been found. Although sporadic reports appeared in the European literature before the turn of the century, it was the definitive contributions of Sampson (1921-27) that brought this disease entity into prominence. Sampson's theory of transtubal regurgitation of endometrial tissue at the time of menstruation, with subsequent implantation and growth in the ovaries and cul-de-sac, seemed a most plausible explanation. His studies furrowed a field that had lain fallow. Since then, interest in this disease has mounted steadily.

Controversy soon arose as to the etiology of endometriosis. The viability of desquamative endometrial tissue was questioned. Geist (1933) collected menstrual discharge and with vital staining observed that cells were alive more than an hour after collection. Keettel and Stern (1951) demonstrated growth of cast-off endometrium in tissue culture. Te Linde and Scott's experiment, in which the monkey uterus shed its menstruum directly into the peritoneal cavity, with pelvic endometriosis resulting, lent supportt to Sampson's theory. Several gynecologists have observed retrograde menstruation at time of laparotomy, an observation confirmed by laparoscopy if performed during menstruation. Ridley and Edwards (1958) reported that centrifuged menstrual fluid injected into the subcutaneous fat of the moos veneris survives and grows.

Sampson's theory did fail to explain the occurrence of extrapelvic lesions-though he himself was the first to admit it and suggested a hematogenous route. Meyer believed thatt celomic metaplasia should be considered. Novak (1931) and Greenwald (1943) supported this theory, claiming that the celomic epithelium, being the mother tissue of the mullerian ducts, should be regarded as the most probable source of endometriosis. Celomic metaplasia may explain the presence of endometriosis in any site of the body, particularly when this occurs in such structures as the umbilicus. The very fact that six months elapsed before pelvic endometriosis developed in the Te Linde (1953) and Scott (1950) experiments in the macaque seems to indicate that menstrual detritus, inflammation and irritation probably are capable of inducing metaplastic change in celomic epithelium. The hormonal role in endometriosis remains unknown. The author has on several occasions examined histologic sections of appendices removed during pregnancy; the serosal surface showed a decidual reaction.

Other possible explanations are lymphogenous and hematogenous spread. Halban (1924) felt that all heterotopic areas of endometriosis were metastatic growths originating in the endometrium and reaching their destination via the lymphatic system. Hematogenous metastases may also explain the presence of endometrial tissue in lungs, pleurae, arms and thighs. This essayist studied in 1964 a patient with bloody pleural effusions which could be brought under complete control so long as she was given prolonged and continuous doses of norethindrone. When medication was discontinued, bloody pleural effusions returned, only to again respond to prolonged courses of this progestogen.

Endometriosis was thought to be a disease of women late in their reproductive years, usually between 30 and 45 years of age. It is uncommon in the Negro race and seems to be found more often among women of higher socioeconomic groups. Sampson stated that next to leiomyoma of the uterus, endometriosis probably furnishes the most frequent pelvic lesions found during operations in women between age 30 and menopause. During a one-year period, he reported 37 cases of endometriosis in 170 abdominal operations for pelvic disease in women in these age groups. Meigs (1941) made a diagnosis of endometriosis, based on observation at laparotomy, in 36 per cent of 400 consecutive female patients. Holmes (1942) reported 80 proven cases of endometriosis among 307 gynecologic laparotomies, an incidence of 26 per cent.

Holmes stated that endometriosis was a disease of middle menstrual life and Meigs believed that there was a latent period of 13-19 years before manifestations presented. However, in recent years, several reports of endometriosis in teenagers have appeared. Endometriosis, therefore, may no longer he considered a disease found only in the middle years of reproductive life, but one that may begin within a few years after onset of menses, even though its full manifestations may be delayed for several years.

Histopathology: A true diagnosis of endometriosis is entertained only when endometrial glands and typical stroma are found on histologic examination. The endometrial tissue may show cyclic changes and signs of cyclic hemorrhage, but not all aberrant endometrium undergoes such changes.

Wide variations in histologic appearance which permit the presumptive diagnosis of endometriosis have been observed. Sometimes glands and stroma are absent in chocolate cysts of the ovary or in the brownish pigmented implants on serosal surfaces. On microscopic examination, hemosiderin-laden macrophages and fibrous connective tissue containing inflammatory cells are in evidence.

Diagnosis: Every woman with idiopathic or first-day dysmenor-rhea and infertility should be suspected of having endometriosis, particularly those in whom dysmenorrhea has increased to two or more days' duration, or in those with acquired dysmenorrhea. The complaint of dyspareunia and/or infertility should heighten the suspicion.

Pelvic examination, pathognomonic of endometriosis, may show the presence of tender, thickened, rigid, often nodular, uterosacral ligaments. Fixed retroversion of the uterus or induration of the cul-de-sac, or both, are most significant, especially if irregularly enlarged ovaries are present. Menstrual pains referred to the rectum, the bladder, and the lower sacral or coccygeal regions are not uncommon.

Conclusions: Endometriosis is a far more common disease than is generally appreciated, and it occurs earlier than hitherto acknowledged. Every young woman with dysmenorrhea should be suspect and the dysmenorrhea should be actively treated. The sequelae of progressive ectopic endometrial proliferation lead to increasing infirmity (dysmenorrhea, dyspareunia, pelvic discomfort, etc.) and to infertility. It would be advantageous, whenever possible, to slow its progression while reproductive function is still intact and before endometriosis destroys the ovaries or extensive disease makes panhysterectomy obligatory. Conservative surgery (dilatation and curettage, uterine suspension, removal of endometriomas), androgens, estrogens and/or progestogens and a new, impeded androgen with moderate antigonadotropic properties and antiendometrial activity, known as danazol (Danocrinef", Winthrop), may be employed to lessen pain and to enhance fertility. Panhysterectomy is indicated when the disease is extensive and no longer responsive to simple therapeutic procedures.

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