Diagnostic Benefit of the Detection of Mitotic Figures in Endometriotic Lesions

Abstract

Objectives Endometriosis is a chronic disease which is diagnosed by surgical intervention combined with a histological work-up. Current international and national recommendations do not require the histological determination of the proliferation rate. The diagnostic and clinical importance of the mitotic rate in endometriotic lesions still remains to be elucidated.

Methods In this retrospective study, the mitotic rates and clinical data of 542 patients with histologically diagnosed endometriosis were analyzed. The mean patient age was 33.5 ± 8.0 (17 – 72) years, and the mean reproductive lifespan was 21.2 ± 7.8 (4 – 41) years. Patients were divided into two groups and patientsʼ reproductive history and clinical endometriosis characteristics were compared between groups. The study group consisted of women with confirmed mitotic figures (n = 140, 25.83%) and the control group comprised women without proliferative activity according to their mitotic rates (n = 402, 74.27%).

Results Women with endometriotic lesions and histologically confirmed mitotic figures were significantly more likely to have a higher endometriosis stage (p = 0.001), deep infiltrating endometriosis (p < 0.001), ovarian endometrioma (p = 0.012), and infertility (p = 0.049). A mitotic rate > 0 was seen significantly less often in cases with incidental findings of endometriosis (p = 0.031). The presence of symptoms and basic characteristics such as age, age at onset of menarche, reproductive lifespan and parity did not differ between the group with and the group without mitotic figures.

Conclusion This study shows that a simple histological assessment of the mitotic rate offers additional diagnostic value for the detection of advanced stages of endometriosis. The possible role as a predictive marker for the recurrence of endometriosis or the development of endometriosis-associated cancer will require future study.

Zusammenfassung

Ziele Endometriose ist eine chronische Erkrankung, die durch einen chirurgischen Eingriff und einen histologischen Nachweis diagnostiziert wird. Laut den aktuellen internationalen und nationalen Empfehlungen ist der histologische Nachweis der Proliferationsrate nicht nötig. Die diagnostische und klinische Bedeutung der Mitoserate in endometriotischen Läsionen ist immer noch ungeklärt.

Methoden In dieser retrospektiven Studie wurden die Mitoseraten und die klinischen Daten von 542 Patientinnen mit histologisch nachgewiesener Endometriose analysiert. Das durchschnittliche Alter der Patientinnen betrug 33,5 ± 8,0 (17 – 72) Jahre, und ihre durchschnittliche Reproduktionsspanne lag bei 21,2 ± 7,8 (4 – 41) Jahren. Die Reproduktionsgeschichte und klinischen Endometriosemerkmale wurden verglichen. Die Studiengruppe bestand aus Frauen, bei denen Mitosefiguren nachgewiesen wurden (n = 140, 25,83%), und die Kontrollgruppe bestand aus Frauen ohne Proliferationsaktivität (n = 402, 74,27%).

Ergebnisse Frauen mit endometriotischen Läsionen und einem histologischen Nachweis von Mitosefiguren hatten signifikant häufiger ein klinisch höheres Endometriosestadium (p = 0,001), tief infiltrierende Endometriose (p < 0,001), ovarielle Endometriome (p = 0,012) oder Infertilität (p = 0,049). Frauen, bei denen eine Endometriose als Zufallsbefund entdeckt wurde, hatten signifikant weniger oft eine Mitoserate von > 0 (p = 0,031). Es gab keine Unterschiede in den Symptomen und Charakteristika wie Alter, Menarche, Reproduktionsspanne und Parität zwischen der Gruppe mit und der Gruppe ohne Mitosefiguren.

Schlussfolgerung Diese Studie zeigt, dass eine einfache histologische Evaluierung der Mitoserate für die Erkennung einer Endometriose im fortgeschrittenen Stadium einen diagnostischen Mehrwert bietet. Um die Bedeutung der Mitoserate als prädiktiven Marker für das Wiederauftreten einer Endometriose bzw. für die Entwicklung von endometrioseassoziiertem Krebs zu evaluieren, werden weitere Untersuchungen benötigt.

Key words

endometriosis - mitotic rate - infertility - laparoscopy - endometriosis-associated ovarian cancer

Schlüsselwörter

Endometriose - Mitoserate - Infertilität - Laparoskopie - endometrioseassoziiertes Ovarialkarzinom

Publication History

Received: 22 April 2021

Accepted after revision: 05 August 2021

Article published online:
10 January 2022

• References

• 1 Giudice LC, Kao LC. Endometriosis. Lancet 2004; 364: 1789-1799 DOI: 10.1016/S0140-6736(04)17403-5.
• 2 Nicolaus K, Reckenbeil L, Bräuer D. et al. Cycle-related diarrhea and dysmenorrhea are independent predictors of peritoneal endometriosis, cycle-related dyschezia is an independent predictor of rectal involvement. Geburtshilfe Frauenheilkd 2020; 80: 307-315
• 3 Bjorkman S, Taylor HS. MicroRNAs in endometriosis: biological function and emerging biomarker candidates. Biol Reprod 2019; 100: 1135-1146 DOI: 10.1093/biolre/ioz014.
• 4 Moustafa S, Burn M, Mamillapalli R. et al. Accurate diagnosis of endometriosis using serum microRNAs. Am J Obstet Gynecol 2020; 22: 557.e1-557.e11 DOI: 10.1016/j.ajog.2020.02.050.
• 5 Dunselman GA, Vermeulen N, Becker C. et al. European Society of Human Reproduction and Embryology. ESHRE guideline: management of women with endometriosis. Hum Reprod 2014; 29: 400-412 DOI: 10.1093/humrep/det457.
• 6 Burghaus S, Schäfer SD, Beckmann MW. et al. Diagnosis and Treatment of Endometriosis. Guideline of the DGGG, SGGG and OEGGG (S2k Level, AWMF Registry Number 015/045, August 2020). Geburtshilfe Frauenheilkd 2021; 81: 422-446 DOI: 10.1055/a-1380-3693.
• 7 Zeppernick F, Zeppernick M, Janschek E. et al. for the QS Endo Working Group of the Endometriosis Research Foundation (SEF). QS ENDO Real – A Study by the German Endometriosis Research Foundation (SEF) on the Reality of Care for Patients with Endometriosis in Germany, Austria and Switzerland. Geburtshilfe Frauenheilkd 2020; 80: 179-189
• 8 Nisolle-Pochet M, Casanas-Roux F, Donnez J. Histologic study of ovarian endometriosis after hormonal therapy. Fertil Steril 1988; 49: 423-426 DOI: 10.1016/s0015-0282(16)59766-0.
• 9 Nisolle M, Casanas-Roux F, Anaf V. et al. Morphometric study of the stromal vascularization in peritoneal endometriosis. Fertil Steril 1993; 59: 681-684
• 10 Yadav KS, Gonuguntla S, Ealla KK. et al. Assessment of interobserver variability in mitotic figure counting in different histological grades of oral squamous cell carcinoma. J Contemp Dent Pract 2012; 13: 339-344 DOI: 10.5005/jp-journals-10024-1148.
• 11 Barry M, Sinha SK, Leader MB. et al. Poor agreement in recognition of abnormal mitoses: requirement for standardized and robust definitions. Histopathology 2001; 38: 68-72 DOI: 10.1046/j.1365-2559.2001.01034.x.
• 12 Kahyaoglu I, Kahyaoglu S, Moraloglu O. et al. Comparison of Ki-67 proliferative index between eutopic and ectopic endometrium: a case control study. Taiwan J Obstet Gynecol 2012; 51: 393-396 DOI: 10.1016/j.tjog.2012.07.013.
• 13 Fukunaga M, Nomura K, Ishikawa E. et al. Ovarian atypical endometriosis: its close association with malignant epithelial tumours. Histopathology 1997; 30: 249-255 DOI: 10.1046/j.1365-2559.1997.d01-592.x.
• 14 DeAngelo C, Tarasiewicz MB, Strother A. et al. Endometriosis: A malignant fingerprint. J Cancer Res Ther Oncol 2020; 8: 206 DOI: 10.17303/jcrto.2020.8.206.
• 15 Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril 1997; 67: 817-821 DOI: 10.1016/s0015-0282(97)81391-x.
• 16 Haas D, Chvatal R, Habelsberger A. et al. Preoperative planning of surgery for deeply infiltrating endometriosis using the ENZIAN classification. Eur J Obstet Gynecol Reprod Biol 2013; 166: 99-103 DOI: 10.1016/j.ejogrb.2012.10.012.
• 17 Nisolle M, Casanas-Roux F, Donnez J. Immunohistochemical analysis of proliferative activity and steroid receptor expression in peritoneal and ovarian endometriosis. Fertil Steril 1997; 68: 912-919 DOI: 10.1016/s0015-0282(97)00341-5.
• 18 Louis D, Ohgaki H, Wiestler O, Cavenee W. eds. WHO Classification of Tumours of the central nervous System. 4th ed. Lyon: WHO Press; 2016
• 19 Sinaii N, Plumb K, Cotton L. et al. Differences in characteristics among 1,000 women with endometriosis based on extent of disease. Fertil Steril 2008; 89: 538-545 DOI: 10.1016/j.fertnstert.2007.03.069.
• 20 Abbas S, Ihle P, Köster I. et al. Prevalence and incidence of diagnosed endometriosis and risk of endometriosis in patients with endometriosis-related symptoms: findings from a statutory health insurance-based cohort in Germany. Eur J Obstet Gynecol Reprod Biol 2012; 160: 79-83 DOI: 10.1016/j.ejogrb.2011.09.041.
• 21 Fauconnier A, Chapron C, Dubuisson J-B. et al. Relation between pain symptoms and the anatomic location of deep infiltrating endometriosis. Fertil Steril 2002; 78: 719-726 DOI: 10.1016/s0015-0282(02)03331-9.
• 22 Kho RM, Andres MP, Borrelli GM. et al. Surgical treatment of different types of endometriosis: Comparison of major society guidelines and preferred clinical algorithms. Best Pract Res Clin Obstet Gynaecol 2018; 51: 102-110 DOI: 10.1016/j.bpobgyn.2018.01.020.
• 23 Vercellini P, Fedele L, Aimi G. et al. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients. Hum Reprod 2007; 22: 266-271 DOI: 10.1093/humrep/del339.
• 24 Wimberger P, Grübling N, Riehn A. et al. Endometriosis – A Chameleon: Patientsʼ Perception of Clinical Symptoms, Treatment Strategies and Their Impact on Symptoms. Geburtshilfe Frauenheilkd 2014; 74: 940-946 DOI: 10.1055/s-0034-1383168.
• 25 Nepomnyashchikh LM, Lushnikova EL, Molodykh OP. et al. Immunocytochemical analysis of proliferative activity of endometrial and myometrial cell populations in focal and stromal adenomyosis. Bull Exp Biol Med 2013; 155: 512-517 DOI: 10.1007/s10517-013-2190-5.
• 26 Audebert A, Petousis S, Margioula-Siarkou C. et al. Anatomic distribution of endometriosis: A reappraisal based on series of 1101 patients. Eur J Obstet Gynecol Reprod Biol 2018; 230: 36-40 DOI: 10.1016/j.ejogrb.2018.09.001.
• 27 Findeklee S, Radosa JC, Hamza A. et al. Treatment algorithm for women with endometriosis in a certified Endometriosis Unit. Minerva Ginecol 2020; 72: 43-49 DOI: 10.23736/S0026-4784.20.04490-1.
• 28 Bulun SE, Wan Y, Matei D. Epithelial Mutations in Endometriosis: Link to Ovarian Cancer. Endocrinology 2019; 160: 626-638 DOI: 10.1210/en.2018-00794.