{"paper_id":"7c938766-a301-4360-8071-995303dc80a9","body_text":"Amsterdam UMC\nRecurring perineal endometriosis in a patient with von Willebrand disease\nde Kat, A.C.\nPublished in:\nGynecological and Reproductive Endocrinology & Metabolism\nDOI:\n10.53260/grem.2450107\nPublished: 01/01/2024\nDocument Version\nPublisher's PDF, also known as Version of record\nDocument license\nCC BY\nLink to publication\nCitation for pulished version (APA):\nde Kat, A. C. (2024). Recurring perineal endometriosis in a patient with von Willebrand disease. Gynecological\nand Reproductive Endocrinology & Metabolism, 38. Article 1. https://doi.org/10.53260/grem.2450107\nGeneral rights\nIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s),\nother than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons).\nDisclaimer/Complaints regulations\nIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Amsterdam UMC\nMedical Library know, stating your reasons. In case of a legitimate complaint, the Medical Library will make the material inaccessible and/or\nremove it from the website. Contact address: outputregistratie@amsterdamumc.nl\nDownload date: 14. Jul. 2026\n\n38\nLicense Gynecological and Reproductive Endocrinology and Metabolism 2024; 5(1):38-41\nIntroduction\nEndometriosis is a prevalent condition which occurs in an estimated \n1 out of 10 women during their reproductive lifespan [1]. Worldwide, \nthis translates to 190 million women with endometriosis. The most \ncommonly occurring symptom is dysmenorrhea, but clinical pre-\nsentation and disease severity vary widely [1].  Endometriosis usu-\nally involves the pelvic organs including the peritoneum, the genital \norgans, ligaments, bowels and/or urinary system. Less commonly, \nendometriosis may occur extra-abdominally in the thoracic cavity, \nabdominal wall, as well as in the perineum. In this case report we \npresent a patient with repeated perineal endometriosis recurrence \nin an episiotomy scar, with a potential pathophysiological role of \nvon Willebrand Disease (vWD).  \nCase report \nWe present a 34-year-old patient, with type 1 vWD, who visited \nthe outpatient clinic of her local hospital in 2021 with a painful \nswelling in her episiotomy scar. She was multiparous after two \nvaginal deliveries. Her first delivery occurred in 2013 with an \nepisiotomy, and was complicated by postpartum hemorrhage of \n3,500 mL based on uterine atony and episiotomy wound bleed-\ning, with vWD as predisposing factor. Desmopressin was admin-\nistered before her second delivery, which occurred in 2015 with-\nout complications. After her last delivery the patient did not use \nany form of hormonal contraception. The swelling was treated \nthrough incision and drainage, releasing a dark-brown fluid, \nwhich was not sent in for analysis. \n    Two months later, the painful swelling re-emerged. Because of \nher comorbid vWD, she was referred to our tertiary hospital. At \nphysical examination, a blue-colored swelling at the site of her \nepisiotomy scar was observed, with a diameter of 1-2 cm. Due to \nthe severity of her pain, she was directly admitted to the operating \ntheater for drainage of the swelling. Based on clinical suspicion of \nendometriosis, the lesion was excised with a margin of neighbor-\ning tissue under general anesthesia. Remaining tissue was elec-\ntrocoagulated and the defect was closed primarily.  Intravenous \ndesmopressin, a vasopressin analog, was administered pre- and \npostoperatively as a hemostatic agent, inducing the production of \nvon Willebrand factor. Endometriosis was diagnosed after histo-\npathological analysis (Figure 1), and hormonal treatment with a \ncombined oral contraceptive (COC) pill was started.  \n     Six months after initial presentation, while still using COC \ncontinuously, the patient returned with a recurrence of the pain-\nful swelling in her episiotomy scar. A MRI was performed, \nshowing a T2 non-well-demarcated soft tissue collection of 11 \nx 13 x 6 mm between vulva and anus. The T1 imaging revealed \nfoci of high intensity, indicative of blood, therefore confirming \nthe suspicion of a perineal endometriosis recurrence (Figure 2). \nABSTRACT\nA 34-year-old para 2 with type 1 von Willebrand Disease (vWD) presented with blue-tinted swelling in her episiotomy scar. \nEndometriosis was diagnosed histologically after excision of the lesion. Local recurrence was diagnosed six months after \nexcision, during the use of hormonal therapy. A re-excision was performed with a wider margin and plasma argon energy \ntreatment of the remaining tissue. A second recurrence, also while on hormonal treatment, was treated with a repeat \nre-excision and lotus petal flap perineal reconstruction. Endometriosis in an episiotomy scar is a known, but very uncom-\nmon, manifestation of endometriosis, with an estimated incidence of 0.01%. Disease presentation and severity may be \naffected by vWD. As such, the management of endometriosis in patients with vWD may present additional challenges. \nKEYWORDS\nEndometriosis, von Willebrandt disease, episiotomy.\nArticle history\nReceived 3 Dec 2023 - Accepted 8 Mar 2024\nContact\nVelja Mijatovic, MD PhD; mijatovic@amsterdamumc.nl\nAcademic Endometriosis Center\nDepartment of Obstetrics & Gynaecology\nAmsterdam UMC\nMeibergdreef 9\n1105AZ Amsterdam, The Netherlands\nDOI\n10.53260/grem.2450107\nRecurring perineal endometriosis in a patient  \nwith von Willebrand disease \nAnnelien C. de Kat1*, Marieke Lemmers1*, Laura van Loendersloot1, Sabrine Kol2,  \nWouter B. van der Sluis3, Maaike Bleeker4, Jan H. van Waesberghe2, Velja Mijatovic1\n* Joint first authors\n1Endometriosis Center, Amsterdam University Medical Centers, Amsterdam, The Netherlands\n2 Department of Nuclear Science and Radiology, Amsterdam University Medical Centers, Amsterdam, The Netherlands \n3 Department of Plastic, Reconstructive and Hand Surgery, Amsterdam University Medical Centers, Amsterdam, The Netherlands\n4 Department of Pathology, Amsterdam University Medical Centers, Amsterdam, The Netherlands\n\n39\nLicenseGynecological and Reproductive Endocrinology and Metabolism 2024; 5(1):38-41\nvon Willebrand disease and recurring endometriosis\nA second re-excision, containing a margin of 5-10 mm of sur -\nrounding tissue was performed. The tissue of the wound bed \nwas treated with plasma argon energy to further decrease the \nrisk of recurrence.  In addition to the desmopressin adminis -\ntered pre- and postoperatively, TachoSil fibrin sealant patches \nwere used for local hemostasis. Histological analysis supported \nagain the diagnosis of endometriosis. \n    Sixteen months after initial presentation, and 10 months after \nthe second excision, the patient presented with a renewed painful \nswelling at the site of her episiotomy scar, which had appeared \nat the end of a hormone-free week (which she took every several \nmonths to prevent prolonged spotting complaints while using \nCOCs). The resulting pain was such that the patient was unable to \nsit and had severe pain during defecation. Upon examination there \nwere two blue-colored lesions with a diameter of 4-5 mm, located \nrespectively right above the posterior commissure of the labia and \nventrally of the anal sphincter, which were extremely sensitive to \ntouch (Figure 3). A MRI was performed which revealed a peri-\nneal endometriosis lesion, adjacent to the sphincter complex but \nwithout signs of muscular infiltration. A second re-excision was \nperformed, during which approximately 5 cm3 of endometriosis \ntissue (Figure 4) with a margin of 10 mm was removed and the \nremaining field of tissue was treated with argon plasma energy. \nThe perineum was reconstructed using a pedicled, partly de-ep-\nithelialized, lotus petal flap, based on internal pudendal artery \nperforators from the left groin area. Prophylactic measures to \nprevent blood loss were undertaken again, for which reason the \npatient was admitted until 5 days post-surgery. The hormonal \ntreatment was switched to dienogest 2 mg continuously.  At six \nweeks follow-up post-surgery the surgical site was healing ade-\nquately and without complications (Figure 5). \nDiscussion\nAlthough the occurrence of endometriosis in an episiotomy scar \nhas been described previously [2-4], it rarely presents at this loca-\ntion, with an estimated prevalence of 0.01% [5]. The exact patho-\nphysiology of endometriosis in a perineal scar remains unknown, \nbut most consensus exists on the theory of transplantation and \nimplantation of endometrial cells towards the perineum during \nvaginal delivery [5].  \nFigure 1 Histopathology indicating endometriosis tissue in the surgical excision of the episiotomy scar lesion (A); with focal signs of bleeding, iron \ndeposits as a result of bleeding and multicellular endometrium-like stroma (B); and with progesterone receptor positivity (C). The re-excised lesion \nexhibits a similar image with focal endometrium gland ducts which stained PAX8 positive, consistent with a genital origin (D,E). \nFigure 2  MRI imaging (T1) showing perineal high-intensity foci, \nsuggestive of endometriosis\n\n40\nLicense Gynecological and Reproductive Endocrinology and Metabolism 2024; 5(1):38-41\nde Kat  A. C. et al. \n     The ‘classic diagnostic triad of perineal endometriosis’ has \nbeen described elsewhere [3] and additionally applies to our \npatient: 1. an episiotomy of past perineal tear during vaginal \ndelivery; 2. a tender mass or nodule at the perineal lesion; and 3. \nprogressive (cyclic) perineal pain. Physical examination should \ninclude the examination of the painful nodule, as well as the ano-\nrectal region and rectovaginal septum. Both ultrasound and MRI \ncan be used as diagnostic modalities, however MRI is the pre -\nferred imaging technique for precise measurement of the lesion \nsize as well as an assessment of the involvement of the rectum \nand the anal sphincter complex. Furthermore, with endometriosis \nin the differential diagnosis, examination should include the iden-\ntification of endometriosis in the broader pelvic and intra-abdom-\ninal regions. In a cohort of 14 women with perineal endometrio-\nsis, 3 women (21%) were found to have pelvic endometriosis [6].  \nIn this cohort there was a recurrence rate of 14%, with most pre-\nsentations within a year of initial treatment [6]. \n     The treatment of perineal scar endometriosis is primarily \nsurgical. A local excision of the nodule or lesions should be \nundertaken with up to 10 mm margin of healthy tissue, as an \nincomplete resection can lead to lesion recurrence. Subsequent \ntreatment with plasma argon energy is additionally preferred to \nminimize the risk of recurrence [2,7]. The excised tissue should be \nexamined histologically to confirm the diagnosis of endometri-\nosis as well as ruling out the possibility of malignancy, specifi-\ncally in recurrent disease, as malignant evolvement of perineal \nendometriosis has been described previously [8].  With larger per-\nineal resections, a collaboration with a reconstructive surgeon \nseems advisable, to maximize postoperative cosmetic and func-\ntional outcomes and to minimize wound healing complications. \n     vWD is the most common bleeding disorder, affecting up \nto 1% of the population based on abnormal laboratory param -\neters alone [9]. This inherited condition occurs equally in men \nand women as well as across all races and ethnicities. However, \nwomen may be more symptomatic due to heavy menstrual bleed-\ning periods. A combination of blood tests was used to diag -\nnose vWD, including vWF antigen, as well as a platelet bind -\ning assay to differentiate between qualitative and quantitative \ndefects. The three recurrences, despite adequate surgical mea -\nsures and continuous COC treatment, are striking in this case. In \na study conducted by the American Centers for Disease Control \n(CDC) among 102 women with vWD, 30% of the women were \nfound to have endometriosis, in comparison to 13% in the con-\ntrol group (p=0.005) [10]. Moreover, a recent case reported recur-\nrent ovarian endometriomas in a 17-year-old vWD patient using \ncontinuous hormonal medication [11], similar to our patient who \nalso had recurrences despite hormonal treatment. While the lit-\nerature is still scarce, the increased prevalence and seemingly \nmore severe or treatment-resistant presentation of endometriosis \nsuggest that the hematological hallmarks of vWD may directly \ninfluence the pathophysiology of endometriosis. It is possible \nthat the increased bleeding tendency in vWD increased the risk of \nendometrial cell implantation and may have exacerbated the acti-\nvation of existing endometriosis lesions. Interestingly, however, a \nrecent Mendelian randomization analysis demonstrated a causal \nrelationship between the coagulation factors ADAMTS13 and \nvWF and the risk of endometriosis, with higher vWF antigen lev-\nels predisposing to the endometriosis development [12]. Consistent \nwith these findings, ectopic endometrial cells in patients with \nadenomyosis generally appear to exhibit more angiogenic prop-\nerties and increased vWF antigen activity [13]. \n     Taken together, there is a clear link between both increased \nand impaired coagulation and endometriosis, further highlight-\ning the complexity of the disease and the impact of comorbidity \non its pathophysiology. Although there is no evidence to date \nFigure 3  Two blue-colored lesions (diameter of 4-5 mm), located \nrespectively right above the posterior commissure of the labia and \nventrally of the anal sphincter\n\n41\nLicenseGynecological and Reproductive Endocrinology and Metabolism 2024; 5(1):34-37\nHRT and Skin Aging\nto support the treatment of coagulation disorders as a means of \nimproving the symptoms of endometriosis, awareness of such \nproblems can be helpful in tailoring endometriosis treatment.\n      In conclusion, while unlikely, endometriosis can occur in \nthe perineum and can be included in the differential diagnosis \nof perineal swelling in women. Patients with vWD may present \nwith more severe symptoms and/or recurring disease, increas -\ning complexity and challenging clinicians to find an appropri -\nate choice of therapy which has to be tailored to the needs of \nthe patient. \nReferences\n1. Shafrir AL, Farland LV , Shah DK, et al. Risk for and consequences of \nendometriosis: A critical epidemiologic review. Best Pract Res Clin \nObstet Gynaecol. 2018;51:1-15.\n2. Hakim H, Halima SB, Zouari A, et al. Perineal endometriosis: A rare \ncase of a unique sizeable nodule. Pan Afr Med J. 2021;38:47.\n3. Bindra V , Reddy N, Reddy CA, Swetha P, Alapati KV , Nori M. \nRecurrent perineal scar endometriosis: A case report. Case Rep \nWomens Health. 2022;36:e00457.\n4. Botezatu R, Turcu-Duminica A, Ciobanu AM, Gica N, Peltecu G, \nPanaitescu AM. Episiotomy scar endometriosis. case presentation. \nMaedica (Bucur). 2021;16(4):713-716.\n5. Leite GK, Carvalho LF, Korkes H, Guazzelli TF, Kenj G, Viana \nAde T. Scar endometrioma following obstetric surgical incisions: \nRetrospective study on 33 cases and review of the literature. Sao Paulo \nMed J. 2009 Sep;127(5):270-277.\n6. Matalliotakis M, Matalliotaki C, Zervou MI, Krithinakis K, Goulielmos \nGN, Kalogiannidis I. Abdominal and perineal scar endometriosis: \nRetrospective study on 40 cases. Eur J Obstet Gynecol Reprod Biol. \n2020;252:225-227.\n7. Lockyer EK, Schreurs A, Lier M, Dekker J, Melgers I, Mijatovic V . \nTreatment of ovarian endometriomas using plasma energy in endome-\ntriosis surgery: Effect on pelvic pain, return to work, pregnancy and \ncyst recurrence. Facts Views Vis Obgyn. 2019;11(1):49-55.\n8. Kasahara K, Itatani Y , Kawada K, et al. Laparoscopic posterior pelvic \nexenteration for clear cell adenocarcinoma arising in an episiotomy \nscar. Asian J Endosc Surg. 2022;15(3):642-646.\n9. Weynand AC, Flood VH. V on Willebrand Disease: Current Status \nof Diagnosis and Management. Hematol Oncol Clin North Am. \n2021;35(6):1085-1101.\n10. James AH. Women and bleeding disorders. Haemophilia. 2010;16 \nSuppl 5:160-167.\n11. Rizzello F, Ralli E, Romanelli C, Coccia ME. Severe recurrent endo-\nmetriomas in a young woman with congenital von willebrand disease. \nGynecol Endocrinol. 2019;35(12):1040-1042.\n12. Li Y , Liu H, Ye S, et al. The effects of coagulation factors on the \nrisk of endometriosis: a Mendelian randomization study. BMC Med. \n2023;21(1):195.\n13. Harmsen M, Wong C, Mijatovic V , et al. Role of angiogenesis in ade-\nnomyosis-associated abnormal uterine bleeding and subfertility: a sys-\ntematic review. Hum Reprod Update. 2019;25(5):647-671.\nConflicts of interest\nThe authors declare having no conflicts of interest.\nData availability statement\nThe data presented in this paper are not publicly available as they pertain to \npersonal medical results. Any queries can be presented to the authors.\nEthics statement\nThe patient in question gave written informed consent for inclusion of her data \nin this case report.\nFigure 4 During the second re-excision 5 cm3 of endometriosis tissue \nwas removed.\nFigure 5 At six weeks post-surgery using reconstruction with a Lotus \nflap.","source_license":"CC0","license_restricted":false}