Diaphragmatic endometriosis associated with pelvic endometriosis: a case report

Endometriosis is defined as the presence of endometrial- like glands and stroma outside the uterine cavity. The peak prevalence of this condition is found in women aged 25–35 years [ 1], affecting approximately 5–10% of repro - ductive age population [ 2]. In adolescents (12–20 years old), the prevalence is around 13% using transvaginal and transrectal ultrasound [ 3, 4], but can be as high as BMC Women's Health *Correspondence: Rosana Maria dos Reis [email protected] 1Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil

Background Thoracic endometriosis is characterized by the presence of endometrial tissue in or around lungs and on the diaphragm and is frequently associated with pelvic endometriosis. Case presentation In this case report, a 22-year-old Caucasian patient reported right hypochondrium pain without other associated symptoms and was diagnosed with cholelithiasis. She underwent laparoscopic cholecystectomy, and an abdominal cavity examination revealed a diaphragmatic endometriotic nodule and endometriosis foci in the right diaphragm, pelvic ligaments, and left adnexal area. During the procedure, excision of the diaphragmatic endometriotic nodule and cauterization of the larger endometriosis foci in the diaphragm were also performed. After surgery, hormone therapy was administered as complementary treatment, which included a depot gonadotrophin- releasing hormone (GnRH) agonist for 5 months, followed by drospirenone 4 mg/day for 3 months. At the follow-up visit, the patient reported an improvement in right hypochondrium pain after surgery and complete remission after clinical treatment. Magnetic resonance imaging (MRI) performed before and after 6 months following the initiation of hormone therapy revealed a regression of diaphragmatic and pelvic endometriosis foci.

In our case, the combination of surgical treatment and hormone therapy was effective for managing pelvic and diaphragmatic endometriosis.

Diaphragmatic endometriosis, Endometrial tissue, Laparoscopy, Extrapelvic endometriosis Diaphragmatic endometriosis associated with pelvic endometriosis: a case report Rafael Tito Marques de Matos1, Maria Célia Mendes1, Maíra Cristina Ribeiro Andrade1, Carolina Gennari Verruma1, Rui Alberto Ferriani1 and Rosana Maria dos Reis1* Page 2 of 7 Matos de et al. BMC Women's Health (2025) 25:295 almost exclusively in the right hemithorax (80% of cases) [12, 13]. Since it was first described in 1912, its incidence has been very low, making high-quality studies very dif - ficult [14]. Video-assisted thoracoscopic surgery (VATS) evaluations showed that thoracic endometriosis also affects the diaphragm, which is the most common mani - festation, followed by involvement of the chest wall and lung parenchyma [8]. The main challenge in diagnosing diaphragmatic endo- metriosis is its potential rarity, in addition to its asymp - tomatic nature, which can reach almost 70% of cases [ 15, 16]. When symptomatic, it presents as arm, shoulder or right upper quadrant pain [ 15], and it is often diagnosed accidentally during complementary tests or surgical pro - cedures for other conditions. In this paper, we report a patient with upper abdominal pain, not accompanied by any pulmonary symptoms. The discovery of gallstones led to a diagnosis of cholelithiasis, without initially rais - ing clinical suspicion for diaphragmatic endometriosis, which was ultimately diagnosed during surgery. This case report was approved by the Research Eth - ics Committee (CAAE: 70087422.0.0000.5440) of the Ribeirão Preto Medical School, University of São Paulo (FMRP-USP). The patient signed a written informed con- sent for publication of this case report and any accompa - nying images. Case presentation A summary of patient medical history is detailed in Fig.  1. At the age of 2, Caucasian patient undergone a right salpingo-oophorectomy due to torsion of the right ovary, with histological confirmation of a hemorrhagic cyst and necrosis. Menarche occurred at the age of 12, and from the third menstrual cycle onwards, she began continuous use of combined oral contraceptives, drospi - renone 3  mg + ethinylestradiol (EE) 0.03  mg; and then desogestrel 150 mc + EE 0.02 mg, presenting amenorrhea during use. At 22years old, 74  kg, 170  cm, BMI 25.67  kg/m 2, she sought medical attention for nonspecific pain in the right hypochondrium without any other symptoms. The right hypochondriac pain was associated with ultrasound- diagnosed cholelithiasis, leading to a recommendation of a cholecystectomy by video-laparoscopy. During the abdominal cavity investigation, performed by a gastro - intestinal team, a diaphragmatic nodule and multiple endometriosis lesions were observed in the right dia - phragmatic region (Fig.  2), pelvic ligaments, and left adnexal area (Fig.  3). A bipolar electrosurgery was used to cauterize the endometriosis sites on the right dia - phragmatic region, and a diaphragmatic nodule of a 2.5 × 1.5  cm was excised and send to histopathological analysis, who confirmed to be endometriosis without Fig. 2 Patient diaphragm. (A) Disruption in the right diaphragm, lateral region. (B) Right diaphragm, medial region Fig. 1 Patient medical history Page 3 of 7 Matos de et al. BMC Women's Health (2025) 25:295 atypical features. During surgery, the uterosacral liga - ments were retracted from their points of attachment. The right ligament was mobilized by 2.3  cm, maintain - ing its normal thickness. Examination of the left ligament was more challenging due to its extension towards the posterior aspect of the broad ligament and its proximity to the ovary, suggesting potential adhesions to the adja - cent tissue. The sigmoid colon was potentially sticking to the pelvic floor on the left side and to the visceral nerve on the right side. After surgery, the patient reported mild pain in the right hypochondrium and underwent magnetic reso - nance imaging (MRI) of the abdomen and pelvis, with bowel preparation. Multiple plaques of various sizes with high T1 signal intensity were identified in the diaphrag - matic region, which is consistent with haemorrhagic foci. These plaques are adjacent to liver segments VII and VIII, ranging from 0.3 to 1.8 cm, with the largest being close to the pericardium, near the right ventricle (Fig.  4A and C) and two bleeding plaques above liver segment II, insepa - rable from the pericardium, both measuring 0.5  cm. A small amount of fluid was observed around the spleen, with slight thickening of the parietocolic gutter on the same side and behind the hepatic flexure. A 1.0 cm cyst Fig. 4 Patient MRI. Diaphragmatic disruption in relation to hepatic segments VII and VIII ( A) right after surgery and ( B) after six months of hormone treatment. Bleeding plaques close to hepatic segment VII and VIII ( C) right after surgery and ( D) after six months of hormone treatment. *White arrows highlighting the endometriosis sites Fig. 3 Injury in the left adnexial region Page 4 of 7 Matos de et al. BMC Women's Health (2025) 25:295 of the canal of Nuck, without bleeding, was observed on the abdominal wall. The uterus was slightly shifted to the left, had an endometrial thickness of 0.2 cm, and no other changes such as tubal dilation or endometrioma were observed on the left. Due to residual findings of endometriosis, the patient was referred to a specialized endometriosis center and a new surgical procedure to remove the remaining lesions was recommended. However, the patient opted for a sec - ond opinion and clinical treatment was offered as she was asymptomatic at the time. Thus, a monthly dose of 3.75  mg leuprorelin acetate was recommended for the mild symptoms. Two months after the initial evaluation, the patient reported no symptoms of hot flashes, insom - nia, or vaginal dryness. The treatment was then extended for an additional three months, with leuprorelin acetate 11.25 mg administered quarterly, followed by continuous oral progestogen (drospirenone 4 mg/day). A follow-up MRI, conducted 6 months after starting pituitary suppression medications, showed a regression of diaphragmatic endometriosis foci on the right (with the largest lesion shrinking from 1.1  cm to 0.7  cm and no visible bleeding plaques above the hepatic segments) (Fig. 4B and D), a bilateral reduction in uterosacral liga - ment endometriosis lesions, and a less prominent cyst of the canal of Nuck. On clinical reassessment, the patient reported complete absence of pain in the right hypo - chondrium, good tolerance to the medication, no vaso - motor symptoms, and only an increase in skin oiliness. Considering this, the decision was made to maintain the continuous oral progestogen therapy.

and conclusion In this case report, we describe a diaphragmatic endome - triosis incidentally diagnosed during video-laparoscopy for cholecystectomy. The diaphragmatic endometriosis is a rare and usually asymptomatic disease [ 17]. When symptomatic, the primary symptoms include thorax, shoulders, periscapular, or radiating to the neck pain [ 11, 12, 18, 19]. The origin of extra-pelvic endometriosis remains unclear, and several theories, such as retrograde men - struation, hematogenous spread, lymphatic dissemina - tion, and coelomic metaplasia have been proposed as a possible cause [ 11]. The common origin of pleura, peri - toneum and endometrium supports the theory that tho - racic endometriosis may be the result of a metaplastic transformation. However, the theory of retrograde men - struation is the one that better explains the presence of endometriosis foci on the diaphragm, since endometrial cells found in the peritoneal fluid reach the right side of the diaphragm via the right paracolic gutters [ 11, 16, 20, 21]. In our case, the patient presented with endometrio - sis sites in the right diaphragm, corroborating the data found by Piriyev and Römer [ 13]. In their review, the analysis of more than 200 cases showed a prevalence of diaphragmatic endometriosis on the right side. On the other hand, the left diaphragm is preserved, protected by the liver’s falciform ligament. These cells can adhere to the right diaphragm and/or infiltrate the chest through fenestrations that may be congenital or acquired [11]. Although rare, the diaphragmatic endometriosis is the most common manifestation of thoracic endometriosis [7]. Our patient reported pain in the right hypochon - drium and the primary investigation with abdominal ultrasound showed cholelithiasis. To investigate the cho - lelithiasis, a VATS was indicated. During surgery, sug - gestive lesions of endometriosis were identified in the diaphragm and pelvic region. The nodule was removed and sent for histopathologic analysis, which confirmed the suspicion of diaphragmatic endometriosis. Transvaginal Ultrasonography, Computed tomogra - phy (CT) and Magnetic Resonance Imaging (MRI) are often used in the evaluation of diaphragm endometriosis prior to invasive procedures (Box 1). Although CT is the first-line diagnostic test for thoracic endometriosis due to its easy availability and lower cost [ 11], it has limited specificity in diagnosing thoracic endometriosis, though it allows to rule out other diseases [ 11]. MRI is superior to CT in detecting lesions in the thoracic cavity [ 22]. It is capable of diagnosing pleural and hemorrhagic lesions and has an 83% sensitivity for detecting diaphragmatic lesions [ 11, 12]. These tests, ideally performed during the symptomatic or catamenial period, enhance the like - lihood of diagnosing the lesions [ 23]. However, in some cases of thoracic endometriosis such as ours, the diag - nosis is made only through invasive procedures such as Box 1 … Page 5 of 7 Matos de et al. BMC Women's Health (2025) 25:295 video-assisted thoracoscopy (VAT) and VATS (Box 1) [11, 24]. Despite having no symptoms of pelvic endometriosis, our patient was diagnosed with diaphragmatic and pelvic endometriosis at the age of 22 and the absence of symp - toms may be related to the use of oral contraceptives for 10 years. Diaphragmatic endometriosis is a type of endo - metriosis and appears to be associated with deep infiltra - tion and severe pelvic inflammation [ 13]. In our case, the first abdomen and pelvis MRI performed after surgery, corroborated the findings observed during the surgical procedure, both in the diaphragm and pelvis. Further - more, the histopathological analysis of the diaphragmatic nodule, resected via VAT S, confirmed the diagnosis of endometriosis without atypical features. The first-line treatment for thoracic endometriosis remains uncertain due to the lack of extensive studies and varies based on the clinical presentation of the con - dition, its primary symptoms, and the occurrence of con - current pelvic endometriosis. In a recent study, Naem et al. [ 25] described the diagnosis, surgery, and follow-up of 23 women with diaphragmatic endometriosis. They reported that most patients did not accept postopera - tive hormone treatment and linked this to the desire to become pregnant immediately after surgery. One concern was that our patient had diaphragmatic lesions on MRI after incomplete surgery to remove the lesions. A retrospective study that evaluated more than 100 patients diagnosed thoracic endometriosis syndrome showed that pneumothorax was the most common pre - sentation, occurring in 73% [ 26]. Our patient had a chest MRI that did not show intrathoracic endometriosis. Therefore, we cannot predict the risk of pneumothorax or other complications related to intrathoracic endome - triosis. Moreover, to our knowledge, there is no data in the literature related to residual endometriosis diaphrag - matic lesions in asymptomatic women. In our case, the patient preferred the hormonal treat - ment instead another surgical procedure. Hormone therapy can generally be recommended irrespective of whether surgical intervention is required (Box 1), which leads to a reduction in lesions and prevents recurrence [16, 27]. Although the optimal duration of treatment has not yet been established [28], hormone therapy alone has shown a recurrence rate of over 50% within 6 months after treatment cessation [ 29]. Among hormonal treat - ments, current recommendations include the use of com- bined hormonal contraceptives, progestogens, and GnRH agonists and antagonists [ 27]. GnRH agonists have been widely used in thoracic endometriosis [ 30]. However, GnRH agonists and antagonists are currently considered second-line medications to treat endometriosis [27]. In cases where hormonal therapy is ineffective, a sur - gical approach should be considered [ 17]. For superficial endometrial lesions, techniques such as cauterization using bipolar cautery, CO2 laser, Nd-YAG laser, or plasma energy can be employed. Extensive resections, ranging from wedge resections to lobectomies, may be required for lesions with greater pulmonary parenchymal involve - ment [ 16, 31, 32]. In asymptomatic cases, patients may not need surgery to remove diaphragmatic endometriosis sites and could live normally [13]. For diaphragmatic lesions, specific techniques or posi - tions such as the reverse Trendelenburg can be used, which allows a better visualization of posterior lesions that may be hidden by the diaphragmatic dome [8, 25]. In cases of diaphragmatic perforations, suturing can be used for minor lesions, while larger lesions may require cor - rection using synthetic mesh, due to their higher recur - rence rates [8, 16]. Although it was an incomplete surgery since not all the endometriosis sites were removed, the patient under - went treatment with a GnRH analogue for five months, followed by progestogen therapy (4 mg of drospirenone). Six months after starting hormonal treatment, the sec - ond MRI revealed a reduction in the endometriosis foci in both the diaphragm and uterosacral ligaments, along with complete alleviation of pain in the right hypochondrium. The cauterization of endometriotic lesions and exci - sion of the endometriotic nodule may have contributed to improved right hypochondrium pain, although we cannot rule out the possibility that this was due to the cholecystectomy itself. However, there was an objective improvement in lesions visualized using MRI after sur - gical/clinical treatment. Given the slight persistence of pain in the right hypochondrium, what may be related to the incomplete resections of endometriosis sites, we opted for hormonal treatment and clinical-radiological follow-up. Surgical indication was not considered due to the absence of severe symptoms and the patient also expressed that she did not wish to undergo any further surgical procedures. Whenever possible, a multidisci - plinary team is recommended to minimize the risks of incomplete surgery and to provide the appropriate thera - peutic approach [25]. A limitation of this case report was that the surgical procedure was performed by a gastrointestinal surgical team and not in a multidisciplinary center with endo - metriosis specialists, as should be the case. This resulted in incomplete access to the diaphragmatic lesions, cau - terization of lesions that could have been resected, and incomplete mobilization of the liver for better identifica - tion and treatment of the lesions. In conclusion, diaphragmatic endometriosis is a very rare disease that presents with a variety of clinical mani - festations, which can make the diagnosis difficult (Box 1) or even accidental, as in our case. The combination Page 6 of 7 Matos de et al. BMC Women's Health (2025) 25:295 of surgical treatment followed by hormone therapy was effective for managing pelvic and diaphragmatic endo - metriosis. This study can contribute to the knowledge and for further investigation related to this rare disease. Abbreviations CA125 Cancer antigen 125 CT Computed tomography CO2 Carbon dioxide CXR Chest X-ray DNA Desoxiribonucleic acid EuSC Eutopic human endometrial stromal cells EcSC Ectopic endometriotic stromal cells EE Ethinylestradiol GnRH Gonadotrophin-releasing hormone MRI Magnetic resonance imaging Nd-YAG Neodymium-doped yttrium aluminium garnet VAT Video-assisted thoracoscopy VATS Video-assisted thoracoscopic surgery

The authors are grateful to the patient for participating in this study. Author contributions RTM, MCM, MCRA, RAF and RMR assisted in the patient care, case discussion and treatment, patient follow-up. RTM, MCM, MCRA, CGV, RAF and RMR assisted in the literature review, paper write and revision. All authors have approved the final version and submission of this manuscript. Funding This paper was supported by Fundação de Apoio ao Ensino, Pesquisa e Assistência (FAEPA). Data availability No datasets were generated or analysed during the current study. Declarations Ethical approval This case report was approved by the Ethics Committee of the Ribeirão Preto Medical School under the protocol no 6.580.212 (CAAE: 70087422.0.0000.5440). Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests The authors declare no competing interests. Received: 28 February 2024 / Accepted: 3 June 2025

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