Pathological Criteria for the Diagnosis of Endometriosis

Douglas R. Shanklin, M.D.
Professor of Obstetrics and Gynecology and of Pathology, University of Chicago

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

The histopathology of extrauterine endometriosis requires definition. Endometriosis is endometrial-like tissue found at some remove from the expected sites, such as the mullerian mucosa of the uterus itself. Normally this has an interface with the myometrium, which shows evaginations which normally penetrate as much as one-third of the thickness of the uterus. Because the endometrium is a compound tissue, it is possible to have ectopic elements from stroma or from glandular components.

The two other major components of the endometrium, the vasculature and the lymphoreticular apparatus, are not unique to the endometrium. It is not possible, accordingly, to speak of endometriosis of lymphoreticular tissue at an ovarian site. Theoretically this could be possible, but the problems of distinguishing such an entity from other forms of lymphoreticular involvement of the ovary make it an impractical exercise.

The endometrium is hormone-responsive, offering the possibility that ectopic endometrial tissue might also show some or all of the reactions to hormonal stimulation seen in the ordinary location. Since the normal menstrual cycle includes a breakdown with hemorrhage, this possibility also exists in the ectopic sites. In fact, the cyclical hemorrhage into ectopic endometrium has been generally considered to be the basis for the physical discomfort so many of these patients suffer.

A series of 15,000 consecutive specimens was examined for complete hysterectomy and bilateral adnexectomy to obtain a complete view of the relation between ectopic endometrium (endometriosis), other functional ovarian structures, and the normal responsiveness to those structures of the endometrium in proper situs. The actual number of cases examined closely was 106. Several of these contained only one ovary for reasons outside the control of the laboratory, and were dismissed from further consideration for inability to perceive the full range of ovarian structure. This reduced to 100 those available for analysis.

A full range of functional response was found in ectopic endometrial tissue, but this was characterized by a low order of secretory or luteal response. The analysis was further reduced to those cases in which a postovulatory response was possible due to the coordination of normal ovarian findings and endometrial reaction in normal situs.

Even from this consideration, the frequency of secretory response was greatly diminished, averaging less than 20% for a reasonably well-developed response and a total of less than 50% for any kind of secretory responsiveness at all. Very importantly, there was no instance in which the response was in phase with both the corpus luteum and the uterine mucosa. This negative correlation also followed in several cases of ectopic pregnancy. In those instances, the endometriosis showed no decidual conversion despite the greater levels of luteal hormone from the corpus luteum of early pregnancy. A further observation was made that even when the endometriotic tissue was in the same ovary as the corpus luteum, it showed no consistent pattern or degree of response.

Further analysis in those cases in which a quantitative estimate of responsiveness was possible showed that the tissue lagged behind the normal uterine mucosa, sometimes by as much as 7 to 10 days in apparent activity.

These observations suggest that attention should be placed elsewhere with respect to the source of the cyclical discomfort which tends to coincide with actual menstruation. The reason for a delay in responsiveness, when responsiveness occurs at all, may be based upon a differential level of hormone. This may be due to the abnormal vascular circuit required to reach the ectopic tissue, or may represent a different form of control because of the abnormal vascularity and location. The role of the visceral nervous system in regulating endometriotic lesions is unexplored.

A further problem was noted in the analysis, namely the differential diagnosis of a variety of lesions which can be confused under the microscope with endometriosis and which may also, on occasion, confuse the surgeon. Since the principal evidence for endometriosis is the interrelation of glands and stroma, the finding of isolated glands or isolated stroma poses the first problem. Here the age profile of endometriosis is sometimes helpful. Isolated subsurface gland units not always attached to the germinal epithelium are quite common in the menopausal and postmenopausal woman. While these might be related to earlier endometriosis, they are best considered as germinal inclusions and probably have no functional or etiologic relationship to endometriosis.

The finding of isolated stroma is perhaps more common in nonovarian sites, but poses a considerable interpretive problem. In the outer portion of the uterus, less difficulty is encountered because of the tendency for this stromal aggregation to follow the plane of major vascular arcades.

A variety of functional structures within the ovary in particular pose a problem in differential diagnosis. Although details will not be given here, these consist primarily of hemorrhagic follicles, corpora lutea with unusual amounts of residual iron pigment, and certain scars related to follicular atresia. Here the hallmark of scarring and iron-pigment deposit with focal chronic inflammation sometimes resembling endometrial stroma points up the specifics of the diagnostic difficulty.

Finally, despite literature statements that adenomyosis does not appear to be related to external endometriosis, our analysis found a coincidence of these lesions far above that expected on a chance basis. Such observations may be properly taken as evidence for an embryological "rest" hypothesis, in that one focus of differentiation of mullerian components towards endometrium outside of the central tube may indicate an additional focus.

Careful pathogenetical study and histological analysis of cases of endometriosis when the uterus and ovaries are both available for study should contribute to our understanding of the symptomatology as well as the development of these important and often debilitating lesions. In the present study, responsiveness to luteal stimuli of an ordinary kind was far less than that shown by the uterine mucosa itself. Furthermore, the endometriotic lesions respond out of phase, with a consistent delay in response of as much as 7 to 10 days behind the mucosal cycle. Since cyclical pain in patients with endometriosis is usually related more precisely to the actual menstrual flow, other mechanisms which produce the discomfort should be sought. It is not enough to say that the discomfort is related simply to the internal bleeding of endometriotic lesions.

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