Comment to: “Diagnostic Benefit of the Detection of Mitotic Figures in Endometriotic Lesions”

In: Geburtshilfe und Frauenheilkunde · 2022 · vol. 82(01) , pp. 93–94 · doi:10.1055/a-1580-0787 · PMID:35027864 · PMC8747901 · W4206322456
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This comment addresses the diagnostic benefit of detecting mitotic figures in endometriotic lesions, referencing a previously published article.

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This clinical comment discusses a study of 544 endometriosis patients in which macroscopic and microscopic morphological criteria were used to classify lesions as active versus inactive, including markers such as mitoses, endometrial-like differentiation, and stromal features like vascularization and inflammation, with inactivity characterized by lack of mitoses and endocrine modulation plus atrophy. The comment reports that in pain patients with active endometriosis, recurrence was lower and the recurrence-free interval longer after three-phase therapy compared with laparoscopic surgery alone, whereas no differences were seen for inactive disease. It further emphasizes that detailed lesion description and biopsy assessment should incorporate atypia and dysplasia, noting a reported ~8% prevalence of cellular atypia in endometriosis and an increased risk of certain ovarian cancers and a morphological continuum from normal epithelium to atypia to invasive carcinoma. Relevance to endometriosis: the paper is centrally about endometriosis lesion pathology and how activity/inactivity and atypia criteria relate to recurrence and cancer risk assessment.

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Abstract

Comment on: Diagnostic Benefit of the Detection of Mitotic Figures in Endometriotic LesionsGeburtshilfe Frauenheilkd 2022; 82(01): 85-92DOI: 10.1055/a-1580-0601
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In a clinical study 1 with 544 endometriosis patients, macroscopic and microscopic criteria were used to classify endometriosis into active and inactive. Criteria for the activity of the glandular epithelium were high, endometrial-like differentiation, mitoses, eutrophy and signs of hormonal influence, similar to the changes in the eutopic endometrium during the menstrual cycle. Signs of inactivity were cubic, flattened epithelium, lack of mitoses and lack of endocrine modulation, as well as atrophy. In assessing the stroma, good vascularization, edema, bleeding and signs of inflammation were criteria for activity and fibrosis, siderophages and lack of vascularization signs for inactivity. It was found that in the group of pain patients with active endometriosis, the recurrence rate was significantly lower and the recurrence-free interval significantly longer after three-phase therapy compared to laparoscopic surgery alone. In the case of inactive manifestations of endometriosis, no differences could be observed, so that this group of patients had no advantage from the six-month medical treatment and re-laparoscopy. But also the surgeon is required to describe the endometriosis lesions in more detail. Even the macroscopic aspects, color and type of the lesion are significant in terms of the endometriotic activity. In the above-mentioned study, vesicles-shaped or polypoid peritoneal implants that were colored red with perifocal bleeding and vascularization were judged to be active; brown, black or flattened foci and cicatricial thickenings of the peritoneum, on the other hand, as inactive form of endometriosis. The importance of these criteria, which are additive to the rASRM classification, has also been pointed out by other investigators 2 . Furthermore, a sufficient morphological assessment of endometriosis biopsies also requires the consideration of atypia and dysplasia. In a review of a large series of studies, approximately 8% of endometrioses contain endometriosis with cellular atypia 3 . Studies have shown that the risk of developing endometroid or clear cell ovarian cancer is increased by a factor of 2 – 3 in women with endometriosis and therefore it is necessary to search specifically for precursors 4 . Morphological examinations showed that there exists a continuous process of successive stages from normal epithelium in an endometrioma to cell atypia and subsequently to a possible invasive carcinoma 5 . As many of our patients suffer from endometriosis-related infertility we have to remember that – as we know from data of reproductive medicine –, after IVF therapy has been performed, the risk of malignancy is higher in endometriosis and in nulliparous patients 6 ,  7 . This means two things for the clinician: cooperation with the pathologist and motivation that he comments on additive criteria such as activity, inflammation and atypia in the endometriosis biopsies and the resulting individual treatment plan, which not only takes into account the severity and extent as well as localization of the disease, but also, depending on the morphological findings, a medical follow-up treatment, including a relapse prophylaxis, or merely a regular gynecological aftercare, similar to oncology.

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