Diaphragmatic endometriosis associated with pelvic endometriosis: a case report

Abstract

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.

Conclusion

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

Background

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 reproductive 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 60–65% when associated with pelvic pain and 70% when associated with dysmenorrhea [5, 6].

Although endometriosis primarily affects the pelvic organs, particularly the ovaries and uterine ligaments, it can rarely involve extrapelvic sites, which makes it a complex condition difficult to diagnose and treat [7]. Extrapelvic endometriosis occurs in approximately 12% of cases [7, 8], and can affect the gastrointestinal and urinary tract, pulmonary system, extremities, skin, central nervous system [9], and abdominal wall [10], which is the most common site according to a previous study [10].

Thoracic endometriosis is an important type of extrapelvic endometriosis [11] characterized by the presence of endometrial tissue in or around the lungs and occurs 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 difficult [14]. Video-assisted thoracoscopic surgery (VATS) evaluations showed that thoracic endometriosis also affects the diaphragm, which is the most common manifestation, followed by involvement of the chest wall and lung parenchyma [8].

The main challenge in diagnosing diaphragmatic endometriosis is its potential rarity, in addition to its asymptomatic 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 procedures 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 raising clinical suspicion for diaphragmatic endometriosis, which was ultimately diagnosed during surgery.

This case report was approved by the Research Ethics Committee (CAAE: 70087422.0.0000.5440) of the Ribeirão Preto Medical School, University of São Paulo (FMRP-USP). The patient signed a written informed consent for publication of this case report and any accompanying 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, drospirenone 3 mg + ethinylestradiol (EE) 0.03 mg; and then desogestrel 150 mc + EE 0.02 mg, presenting amenorrhea during use.

Fig. 1.

Patient medical history

At 22years old, 74 kg, 170 cm, BMI 25.67 kg/m², 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 gastrointestinal team, a diaphragmatic nodule and multiple endometriosis lesions were observed in the right diaphragmatic region (Fig. 2), pelvic ligaments, and left adnexal area (Fig. 3). A bipolar electrosurgery was used to cauterize the endometriosis sites on the right diaphragmatic 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 atypical features. During surgery, the uterosacral ligaments were retracted from their points of attachment. The right ligament was mobilized by 2.3 cm, maintaining 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 adjacent tissue. The sigmoid colon was potentially sticking to the pelvic floor on the left side and to the visceral nerve on the right side.

Fig. 2.

Patient diaphragm. (A) Disruption in the right diaphragm, lateral region. (B) Right diaphragm, medial region

Fig. 3.

Injury in the left adnexial region

After surgery, the patient reported mild pain in the right hypochondrium and underwent magnetic resonance imaging (MRI) of the abdomen and pelvis, with bowel preparation. Multiple plaques of various sizes with high T1 signal intensity were identified in the diaphragmatic 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, inseparable 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 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.

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

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 second 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, insomnia, 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 ligament 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 hypochondrium, good tolerance to the medication, no vasomotor symptoms, and only an increase in skin oiliness. Considering this, the decision was made to maintain the continuous oral progestogen therapy.

Discussion and conclusion

In this case report, we describe a diaphragmatic endometriosis 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 menstruation, hematogenous spread, lymphatic dissemination, and coelomic metaplasia have been proposed as a possible cause [11]. The common origin of pleura, peritoneum and endometrium supports the theory that thoracic endometriosis may be the result of a metaplastic transformation. However, the theory of retrograde menstruation 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 endometriosis 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 hypochondrium and the primary investigation with abdominal ultrasound showed cholelithiasis. To investigate the cholelithiasis, a VATS was indicated. During surgery, suggestive 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 tomography (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 likelihood of diagnosing the lesions [23]. However, in some cases of thoracic endometriosis such as ours, the diagnosis is made only through invasive procedures such as video-assisted thoracoscopy (VAT) and VATS (Box 1) [11, 24].

Box 1.

…

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 symptoms may be related to the use of oral contraceptives for 10 years. Diaphragmatic endometriosis is a type of endometriosis and appears to be associated with deep infiltration 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. Furthermore, the histopathological analysis of the diaphragmatic nodule, resected via VATS, 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 condition, its primary symptoms, and the occurrence of concurrent 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 postoperative 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 presentation, 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 endometriosis. Moreover, to our knowledge, there is no data in the literature related to residual endometriosis diaphragmatic lesions in asymptomatic women.

In our case, the patient preferred the hormonal treatment 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 treatments, current recommendations include the use of combined 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 surgical 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 involvement [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 positions 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 correction using synthetic mesh, due to their higher recurrence rates [8, 16].

Although it was an incomplete surgery since not all the endometriosis sites were removed, the patient underwent treatment with a GnRH analogue for five months, followed by progestogen therapy (4 mg of drospirenone). Six months after starting hormonal treatment, the second 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 excision 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 surgical/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 multidisciplinary team is recommended to minimize the risks of incomplete surgery and to provide the appropriate therapeutic 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 endometriosis specialists, as should be the case. This resulted in incomplete access to the diaphragmatic lesions, cauterization of lesions that could have been resected, and incomplete mobilization of the liver for better identification and treatment of the lesions.

In conclusion, diaphragmatic endometriosis is a very rare disease that presents with a variety of clinical manifestations, which can make the diagnosis difficult (Box 1) or even accidental, as in our case. The combination of surgical treatment followed by hormone therapy was effective for managing pelvic and diaphragmatic endometriosis. 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

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 n^o 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.