Is There Microscopic or Occult Endometriosis

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“Endometriosis can have very subtle visual appearances. All theories of origin imply some early and presumably tiny form of the disease which potentially cannot be detected by the unaided human eye. A review of the literature indicates that with increasing magnification at surgery, virtually all endometriosis can be visualized. Invisible microscopic endometriosis is an unproven entity which retards intellectual progress in the study of this disease.”

“In this issue of Human Reproduction, Khan et al. (2013) revive the debate on the existence and clinical relevance of invisible microscopic endometriosis (IME)—now renamed by them as occult microscopic endometriosis (OME). They report new evidence for immunoreactive microscopic endometriosis in visually normal peritoneum during laparoscopy, as well as an incidence of OME, which is higher than that reported in previous laparoscopic studies of visually normal peritoneum (Redwine, 1988a; Redwine and Yocom, 1990; Nezhat et al., 1991). It is important to outline the concepts central to any discussion on OME— namely, the definition of OME, the criteria and methodology employed to identify visually normal peritoneum, and the definition of endometriosis applied in judging the presence or absence of disease in the biopsied tissue. 

“In defining OME an important distinction must be drawn between failure to recognize visually detectable areas of disease and the presence of microscopic disease that truly cannot be visually detected by the laparoscope. Recognition of the complete morphological repertoire of endometriosis, in all its protean presentations, and the utilization of well-defined criteria and methodology to detect all areas of visually abnormal peritoneum are paramount. Doing so ensures that contributions to the IME/OME literature are internally valid, reproducible and can be critically evaluated within the context of the existing body of research. Moreover, consensus is needed as to the histological definition of endometriosis. If different authors apply ever-broader definitions of disease, there is a risk of defining endometriosis into existence from any histologic appearance. The concept of OME is of importance not only in predicting the outcomes and clinical utility of the complete surgical excision of endometriosis but also has far-reaching implications regarding disease phenomenology, pathogenesis and prognosis as indicated in the historical quote introduced in this editorial (Redwine, 1990). How confused has the endometriosis literature become by virtue of incomplete identification of disease? Murphy et al. (1986) introduced the concept of OME in, reporting microscopic disease in visually normal peritoneum in 25% of a series of 20 patients undergoing laparotomy for endometriosis. This prevalence of OME remains to this day the highest rate ever reported. No formal criteria for normal peritoneum were used in that study, however, and the peritoneal surfaces were viewed at arm’s length and with the limited illumination attendant to laparotomy. Subsequent studies conducted via laparoscopy found ever-smaller rates of OME (Nisolle et al., 1990; Balasch et al., 1996), which seemed to correlate directly with the distance between the tip of the laparoscope and the peritoneal surface being examined (Redwine, 2003). With sufficient magnification, OME virtually ceases to exist (Redwine, 1988a; Redwine and Yocom, 1990; Nezhat et al., 1991). Khan et al. (2013) dispute this thesis in their current publication. We will now turn to examine whether this challenge is valid. To support or reject the previously published findings, authors must use substantially the same methodology. The methodology of Khan et al. (2013) differs significantly from the methodology of Redwine (1988a) and Redwine and Yocom (1990) in four critical ways: (i). viewing distance, (ii) adherence to criteria of normal peritoneum, (iii) size and location of biopsies and (iv) histologic definition of endometriosis. The viewing distance of Khan et al. (2013) was stated to be 4 cm from the peritoneal surface, which differs markedly both from the nearcontact laparoscopy used by Redwine (1988a), and Redwine and Yocom (1990), in which the viewing distance was typically ,1 cm, and the viewing distance of Nezhat et al. (1991), which was ,2 cm. If Fig. 1 of Khan et al.’s article represents their viewing distance, it is clear that their methodology differs from the aforementioned studies, since a panoramic view of the pelvis is shown. The incidence of OME at the authors’ viewing distance is predictable from the graph in Fig. 1—their findings are not new. Khan et al.’s (2013) criteria of normal peritoneum roughly follow that of Redwine (1988a) and Redwine and Yocom (1990) but their surgical stills show a clear departure from these criteria as shown in our annotations of the same photos (Fig. 2). These subtle peritoneal changes are more obvious on the high-definition image, which was supplied with the authors’ submission. If the viewing distance was decreased, even more abnormalities might be obvious. The two surgical stills presented in Fig. 2 of this commentary undermine Khan et al.’s methodology and results….

“For readers of this journal, what can be learned from Khan et al.’s (2013) paper? Although their different methodologies do not support a valid rejection of Nezhat’s et al. (1991), Redwine’s (1988a) and Redwine and Yocom’s (1990) findings, the authors have nonetheless provided even more evidence of a very important point: most women with endometriosis do not have OME. Thus, patients and surgeons alike can be encouraged that proper identification of subtle forms of endometriosis combined with aggressive excision of disease will not leave behind a great burden of overlooked foci of OME of uncertain clinical significance.”