Version May 2024
INTRODUCTION — Endometriosis most commonly involves the pelvis, particularly the ovaries, cul-de-sac, broad ligaments, and uterosacral ligaments. However, endometrial tissue can be found outside the pelvis in the abdomen, thorax, brain, and skin [1]. Thoracic involvement is the most frequent extra-pelvic location of endometriosis [2].
The management of patients with this problem frequently involves multiple disciplines including pulmonologists, thoracic surgeons, and gynecologists. Because of the multiple different services involved, good communication among clinicians is critical for successful outcomes.
The clinical presentation, diagnosis, and treatment of thoracic endometriosis will be reviewed here. The pathogenesis, epidemiology, and pathology of thoracic endometriosis and the clinical features and treatment of endometriosis are discussed separately. (See "Thoracic endometriosis: Pathogenesis, epidemiology, and pathology" and "Endometriosis in adults: Pathogenesis, epidemiology, and clinical impact" and "Endometriosis: Treatment of pelvic pain".)
TERMINOLOGY — Endometriosis is defined as the presence of ectopic endometrial tissue (glands and stroma) outside the confines of the uterine cavity and musculature. Thoracic endometriosis involves components of the thoracic cavity (eg, pleura, parenchyma, diaphragm, bronchus). The following terms apply:
●The term "thoracic" endometriosis is used when endometrial tissue is identified on histological specimens (hormone receptor-positive endometrial stroma and glands) obtained from chest tube aspirate, thoracotomy, or bronchoscopy.
●The term "probable" thoracic endometriosis refers to the identification of tissue within the thorax that is suggestive but not definitively diagnostic of endometrium (eg, stroma only or hormone negative tissue) [3].
●The term "thoracic endometriosis syndrome" is used when one or more clinical manifestations of thoracic involvement is present (eg, pneumothorax, hemothorax, hemoptysis, chest pain) in association with menstruation but without histological confirmation.
●The term "catamenial" refers to a temporal relationship with menses.
PNEUMOTHORAX — Thoracic endometriosis should always be suspected in young women during their reproductive age with catamenial pneumothorax or hemothorax, especially in those who have a history of prior uterine surgical procedures or proven pelvic endometriosis (present in 56 to 84 percent) [4-10]. In such patients, the diagnostic and therapeutic approach is often performed simultaneously (eg, thorascopic biopsy, blebectomy, and pleurodesis).
Clinical features
●Signs and symptoms – The most common presentation (70 to 73 percent) of thoracic endometriosis is catamenial pneumothorax [3,4,11-14]. A smaller proportion (approximately 15 percent), has catamenial pneumothorax due to probable thoracic involvement, and 10 percent or less have pneumothorax that has no temporal relationship with menses (non-catamenial pneumothorax) [5,14]. Patients with endometriosis-related non-catamenial pneumothorax are typically identified during surgery for recurrent pneumothorax. Thus, it is important to recognize that endometriosis-related pneumothoraces can be catamenial and non-catamenial and conversely, non-catamenial pneumothoraces can be endometriosis- or non-endometriosis-related.
Symptoms usually begin just before or within 72 hours after the onset of menstruation (rarely 96 hours). Chest or scapular pain is the most common symptom, noted by 90 percent of patients, while dyspnea develops in approximately one-third [11]. Examination findings may reveal reduced breath sounds and/or tracheal deviation. Symptoms and signs are usually right-sided. Importantly, clinicians should not expect that pneumothoraces or symptoms appear on a regular monthly basis but rather can be intermittent (months to years) and simply bear a close relationship with menses. (See "Clinical presentation and diagnosis of pneumothorax".)
Pneumothoraces are typically right-sided (88 to 100 percent) (figure 1), small to moderate in size, and rarely life threatening [3,5]. Case reports of left-sided or bilateral pneumothoraces have been reported [15-17].
Due to a delay in diagnosis, which is typical of patients with thoracic endometriosis, pneumothorax is frequently recurrent (figure 2). Thus, in patients who present with primary spontaneous pneumothorax, eliciting a history of prior episodes and of timing with the menstrual cycle for each episode is helpful for diagnosis.
In our experience, women do not present during or following pregnancy.
●Imaging features
•Chest radiography – Pneumothoraces on chest radiography can be of any size and are typically right-sided (88 to 100 percent), but can also be left-sided or bilateral [3,5,11,15-17]. Occasionally, pneumomediastinum or pneumoperitoneum is evident. Chest radiographs may additionally reveal other associated features of thoracic endometriosis including an effusion due to hemothorax with or without mediastinal shift depending upon the size, parenchymal nodules and cavities, and a nodular appearance of the diaphragm due to abdominal viscus protrusion through diaphragmatic perforations [18,19].
•Chest computed tomography (CT) – Chest CT scans are most likely to show abnormalities when patients are symptomatic (eg, perimenstrual) (image 1) [20-23]. Due to the higher resolution of CT, abnormalities not visualized on chest radiography may be better appreciated using this modality. These include pneumothorax, pneumomediastinum or pneumoperitoneum, bullae, pleural nodules, parenchymal nodules, small cavities, scarring, ground glass infiltrates, and/or pleural effusions.
•Magnetic resonance imaging (MRI) – May detect similar findings seen on CT. In addition, MRI can detect diaphragmatic nodules with better resolution compared to chest CT. (See 'Pulmonary nodules' below.)
●Laboratory tests – Serum carbohydrate antigen (CA) 125 and CA 19-9 concentrations may be elevated in patients with thoracic endometriosis but are poorly sensitive and nonspecific diagnostically [24-26].
Although endometrial cells have been found in the blood of women with endometriosis or catamenial pneumothorax, it is not routine and remains investigational at this point. One study described an association between circulating endometrial cells and presence of pelvic endometriosis in 90 percent of patients with histology proven pelvic endometriosis [27]. Similarly, another study identified circulating endometrial cells in the blood of women with spontaneous pneumothorax who were suspected as having catamenial pneumothorax [28].
Differential diagnosis — The features that distinguish thoracic endometriosis from other diseases that present similarly include the temporal relationship with menses (ie, catamenial), right-sided predominance of symptoms, female preponderance, young age, and presence of recurrent disease.
The major competing diagnosis for recurrent pneumothorax in young females of reproductive age is lymphangioleiomyomatosis (LAM). However, LAM usually presents with characteristic cysts and angiomyolipomas on CT. Cysts are also usually evident in lung diseases associated with pneumothorax including Birt-Hogg-Dubé syndrome (which is more common in young males), pulmonary Langerhans cell histiocytosis (older smokers), lymphocytic interstitial pneumonia (eg, Sjögren's disease), and premature emphysema. (See "Treatment of secondary spontaneous pneumothorax in adults" and "Sporadic lymphangioleiomyomatosis: Epidemiology and pathogenesis" and "Hereditary kidney cancer syndromes" and "Birt-Hogg-Dubé syndrome".)
Diagnostic approach — In many cases, the diagnosis is discovered incidentally during the thoracoscopic evaluation of patients with pneumothorax. However, when thoracic endometriosis is suspected clinically, patients should undergo contrast-enhanced CT imaging of the chest, preferably when symptoms are present (ie, usually during menses). CT is also frequently performed to rule out the presence of other etiologies of the presenting complaint and may also "map" lesions prior to surgery. Video assisted thoracoscopy (VAT) is the definitive diagnostic procedure helpful in the diagnosis of thoracic endometriosis with or without video laparoscopy.
For young women who present with their first episode of pneumothorax and a negative CT, most experts wait for a second event to establish a temporal relationship with menses before proceeding with thoracoscopy. Some experts send pleural fluid for the evaluation of endometrial cells during the initial placement of a thoracostomy tube, although the diagnostic yield is probably low. For patients in whom the CT or pleural fluid cytology is suggestive of the diagnosis (eg, pleurodiaphragmatic nodules or endometrial stromal cells), tube thoracostomy has failed, or those who have a second/recurrent event, most clinicians proceed with thoracoscopy. The purpose of thoracoscopy is to perform the following:
●Gross inspection of the pleura and diaphragm – Thoracoscopy allows direct visualization of endometrial implants (pleural and diaphragmatic) and diaphragmatic perforations characteristic of thoracic endometriosis. We and others additionally inspect the diaphragm in the reverse Trendelenburg position in order to expose hidden endometrial implants located posteriorly [29]. Thoracoscopy should be performed during menstruation for optimal visualization of pleurodiaphragmatic implants [13]. Details regarding the gross pathology of thoracic endometriosis are discussed separately. (See "Thoracic endometriosis: Pathogenesis, epidemiology, and pathology", section on 'Gross'.)
●Biopsy of suspicions lesions – All lesions suspicious for endometriosis should be biopsied. Details regarding microscopic features of thoracic endometriosis are discussed separately. (See "Thoracic endometriosis: Pathogenesis, epidemiology, and pathology", section on 'Microscopic'.)
●Therapeutic pleurodesis is usually performed subsequent to visual inspection and biopsy of suspicious lesions, the details of which are discussed separately. (See "Treatment of secondary spontaneous pneumothorax in adults".)
Treatment — Pneumothorax due to thoracic endometriosis is primarily treated by definitively managing the presenting feature (eg, chest tube drainage of pneumothorax) followed by secondary prevention of recurrence (eg, blebectomy and pleurodesis and hormonal suppression).
Drainage of pleural air — Most patients with a first pneumothorax require a thoracostomy tube or needle aspiration of air followed by a thoracostomy tube should aspiration fail. Similar to that described, for patients with primary spontaneous pneumothorax (PSP), should tube thoracostomy fail or the pneumothorax recur then blebectomy and pleurodesis is indicated. (See "Thoracostomy tubes and catheters: Indications and tube selection in adults and children" and "Treatment of secondary spontaneous pneumothorax in adults".)
Prevention of recurrence — Recurrent pneumothorax is prevented using surgical blebectomy, pleurodesis, and diaphragmatic repair. Once the diagnosis is confirmed, adjunctive hormonal suppressive therapy is usually administered postoperatively, for 6 to 12 months. (See 'Hormonal suppression' below.)
Blebectomy and surgical pleurodesis — Because the diagnosis of thoracic endometriosis may not be readily suspected after the first event, most clinicians do not proceed with video-assisted thoracoscopic surgery (VATS) unless there is a high suspicion for the diagnosis (eg, young woman with suspicious findings on CT), tube thoracostomy has failed to reinflate the lung, pneumothorax recurs, or another indication for surgery is present (eg, cavitating nodule). When indicated, VATS is usually performed for both diagnostic and therapeutic purposes. Typically, a decision is made to perform blebectomy and pleurodesis to prevent recurrence even if the diagnosis is not histologically confirmed but is clinically suspected.
There is no consensus on the optimal number of blebs that should be resected or on the optimal type of pleurodesis. Among the choices, we prefer complete resection of visible blebs and chemical pleurodesis with talc poudrage [3,11,12,30]. Because the rates of recurrence in this population are high, our preference for talc is based upon the marginally higher rates of success compared with more limited approaches. However, other experts suggest pleural abrasion or partial pleurectomy in an attempt to avoid talc pleurodesis in young persons who may require a future thoracotomy (eg, lung transplantation) for unrelated reasons. (See "Treatment of secondary spontaneous pneumothorax in adults", section on 'Preventing recurrence and follow-up'.)
Resection of endometrial implants and closure of diaphragmatic defects — Most clinicians suggest concurrently ligating all diaphragmatic perforations and resecting all visible endometrial implant lesions, although it is unknown whether or not this reduces recurrence [3,12,30-34]. When perforation is extensive, diaphragmatic resection may be necessary; use of a polyglactin, polypropylene, or polytetrafluoroethylene (PTFE) mesh or bovine pericardial patch has also been reported, although the success rates with use of these materials are unknown [13,30,35-37].
Hormonal suppression — Most patients with endometriosis-associated pneumothorax should be treated with hormonal suppressive therapy for 6 to 12 months. If results following hormonal therapy are encouraging without serious side effects, continuation of hormonal therapy is an option with the hope that longer suppression of ovulation may result in regression of thoracic endometriosis (TES). However, if recurrence occurs during hormonal therapy or side effects are intolerable, then surgical intervention is appropriate. Details regarding agent selection and length of therapy are discussed below (see 'Hormonal suppression' below). Dienogest, a progestogenic drug with moderate estrogen suppression, anti-inflammatory, antiproliferative, and antiangiogenic properties, has been used in the treatment of pelvic endometriosis [38]. A study from Japan has demonstrated Dienogest to be effective in preventing recurrence of pneumothorax and hemoptysis. Considering the safety profile based on long-term studies and effectiveness in controlling symptoms, Dienogest may be an option in the management of TES [39].
Efficacy and adverse outcomes — Outcomes associated with the approach described above include the following:
●Recurrent pneumothorax – Pneumothorax recurs in 8 to 40 percent of patients despite the combined approach of surgery and hormonal suppression [3,11,13,35,36,40,41]. In general, these rates are higher than those of surgically treated patients with primary spontaneous pneumothorax (<5 percent). As examples (see "Pneumothorax in adults: Epidemiology and etiology"):
•In one retrospective case series of 114 women followed for three years who had surgery for recurrent pneumothorax, the highest recurrence rates were observed in those with endometriosis-related catamenial and non-catamenial pneumothorax, when compared with non-endometriosis–related pneumothorax (32 and 27 percent versus 5 percent) [3]. Patients with endometriosis-related pneumothorax in this analysis were also treated for at least six months with GnRH analogs.
•Another retrospective case series of 12 patients who underwent aggressive surgical therapy (thoracoscopic abrasion or pleurectomy, diaphragmatic repair, PTFE mesh) followed by postoperative hormonal suppressive therapy reported low rates of recurrence (1 percent) [30].
•A long-term retrospective follow-up study of 18 patients on catamenial pneumothorax showed a recurrence rate of 14 percent with surgery alone and a 5 percent recurrence rate when surgery was combined with hormonal therapy [39].
●Recurrent chest pain – Some patients may continue to experience monthly chest pain despite therapy [11,42,43]. Persistent symptoms in this setting presumably are due to cyclical proliferation of pleuropulmonary endometrial implants due to ovarian hormone stimulation, although post-thoracotomy pain may also contribute. Residual symptoms may be relieved by hormonal manipulation as described above.
●Routine complications of surgery and/or hormonal therapy – Patients may experience the routine complications of surgical pleurodesis and hormonal suppressive therapy, the details of which are discussed separately. (See "Chemical pleurodesis for the prevention of recurrent pleural effusion", section on 'Complications' and "Overview of minimally invasive thoracic surgery" and "Endometriosis: Long-term treatment with gonadotropin-releasing hormone agonists" and "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use".)
HEMOTHORAX
Clinical features — Hemorrhage into the pleural space occurs in less than 15 percent (12 to 14 percent) of patients with thoracic endometriosis [4,11]. Most cases are catamenial. Compared with endometriosis-associated pneumothorax, endometriosis-associated hemothorax is typically associated with extensive pleural endometrial implants [4].
Bleeding is typically minor, right-sided, and self-limiting (as endometrial tissue undergoes decidualization), but rarely, endometriosis-associated hemothorax can be life-threatening [4,6,44]. Presenting symptoms that increase the suspicion for endometriosis-associated hemothorax include dyspnea and/or cough in a young woman with infertility and diminished breath sounds and/or stony dullness on the affected side. Rarely, concomitant massive ascites has been reported [45].
Chest radiographs may additionally reveal other associated features of thoracic endometriosis including an effusion due to hemothorax with or without mediastinal shift depending upon the size. Loculations of air and/or fluid due to prior disease or surgical interventions may also be seen.
Imaging should confirm the presence of a pleural effusion with or without other associated imaging abnormalities including pneumothorax or nodules. (See "Imaging of pleural effusions in adults".)
Differential diagnosis — Blunt or penetrating trauma to the chest, which is the most common cause of hemothorax, may be elicited on history, examination, and imaging (eg, rib fractures). Other causes include coagulopathies usually evident on laboratory testing, pleuritis (eg, systemic lupus erythematosus) which is usually associated with pleuritic pain, malignancy which may be evident on imaging or thoracoscopy, and pulmonary embolus which is usually acute in onset and associated with dyspnea, hypoxemia, and pleuritic chest pain. (See "Initial evaluation and management of blunt thoracic trauma in adults", section on 'Hemothorax' and "Pleural fluid analysis in adults with a pleural effusion" and "Clinical presentation, evaluation, and diagnosis of the nonpregnant adult with suspected acute pulmonary embolism", section on 'Clinical presentation' and "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults", section on 'Clinical manifestations'.)
Diagnostic approach — The identification of blood in the pleural space (ie, ratio of pleural fluid to blood hematocrit >0.5 or pleural fluid hematocrit >15) on thoracentesis should prompt chest tube drainage. A sample should be sent for cytology for the identification of endometrial epithelial cells [46]. Immunohistochemistry using estrogen receptor (ER), progesterone receptor (PgR) CD10, and smooth muscle actin (SMA) has been shown to be useful in confirming the presence of endometrial tissue [47,48]. Diagnostic thoracoscopy is usually subsequently performed for inspection for the pleural space and biopsy of suspicious lesions to either confirm the diagnosis or to rule out other etiologies for hemothorax, especially malignancy. If thoracoscopy is performed, it should be done during or within 48 hours of menstruation to improve histological yield (because endometrial tissue is likely to be autolyzed after 48 hours which potentially reduces histological yield). (See "Pleural fluid analysis in adults with a pleural effusion" and "Initial evaluation and management of blunt thoracic trauma in adults", section on 'Hemothorax'.)
Treatment — Hemothorax due to thoracic endometriosis is primarily treated by definitively managing the presenting feature (eg, chest tube drainage) followed by secondary prevention of recurrence (eg, thoracoscopy and hormonal suppression).
●Chest tube drainage – Similar to patients with traumatic hemothorax, blood should be promptly drained from the pleural space using a large bore (minimum 28 to 36 French) chest tube. Although significant hemorrhage is rare in patients with endometriosis, immediate bloody drainage of ≥20 mL/kg (approximately 1500 mL), hemorrhagic shock, and persistent substantial bleeding (generally >3 mL/kg/hour) are indications for surgical thoracotomy and wedge resection of visible endometrial pleural implants. (See "Thoracostomy tubes and catheters: Indications and tube selection in adults and children" and "Initial evaluation and management of blunt thoracic trauma in adults", section on 'Hemothorax'.)
●Thoracoscopy – Most experts advise VATS with diagnostic and therapeutic wedge resection of visible lesions and closure of diaphragmatic defects, particularly if the diagnosis of thoracic endometriosis is suspected or known. Some, but not all experts will also perform concurrent gauze pleurodesis, while others wait for a recurring event to justify this procedure [7]. Organized loculations from old blood may also require decortication. (See "Diagnosis and management of pleural causes of nonexpandable lung", section on 'Management of trapped lung'.)
●Hormonal suppression – Following drainage and/or thoracoscopic wedge resection, hormonal manipulation is generally suggested for 6 to 12 months. The rationale for hormone suppression is similar to that for pneumothorax. (See 'Hormonal suppression' below and "Endometriosis: Treatment of pelvic pain".)
Similar to patients with endometriosis-associated pneumothorax, endometriosis-associated hemothorax can recur at a similar rate despite therapy. If not already performed, pleurectomy and pleurodesis to avoid the reaccumulation of blood in the pleural space is appropriate in this population.
HEMOPTYSIS
Clinical features — Hemoptysis occurs in less than 14 percent (7 to 14 percent) of patients and is typically due to parenchymal or endobronchial endometriosis [4,9,11,49]. The mean age of patients presenting with hemoptysis (26 to 29 years) appears to be lower than patients with other manifestations of thoracic endometriosis (34 years) [4,39]. Bleeding is usually catamenial, minor, and right-sided. Massive hemoptysis is rare.
Chest radiography or CT may be normal or may show nonspecific findings including a focal area of ground glass opacification, alveolar filling defect mimicking consolidation, or atelectasis due to an endobronchial clot [3,5,11,15-17]. Bronchial artery angiography, performed as a diagnostic tool in patients with hemoptysis, may show an arterial “blush” suggestive of hemorrhage [50].
Differential diagnosis — No other causes of hemoptysis are catamenial but a few are self-resolving including benign diseases of the airway (eg, bronchiectasis) and parenchymal disease (eg, lymphangioleiomyomatosis [LAM]) which are usually evident by history or by imaging. Malignancy should be distinguished from endometriosis pathologically on tissue biopsy. (See "Evaluation of nonlife-threatening hemoptysis in adults".)
Diagnostic approach — Bronchoscopy should be performed to inspect the airway which may reveal hyperemia and a bronchial surface that is friable and bleeds easily. Endometrial implants, with a similar appearance to those seen on thoracoscopy, may be also be visualized and should be biopsied [50-52]. Although bronchial lavage or brushing is rarely diagnostic, samples should be obtained for cytology that may occasionally reveal endometrial cells or stroma suggestive of endometriosis [53]. No reports of life-threatening hemorrhage have been reported due to biopsy of endobronchial endometrial implant lesions; however, it is prudent to adopt the typical precautions to avoid and/or treat iatrogenic-induced bleeding. (See "Evaluation of nonlife-threatening hemoptysis in adults" and "Thoracic endometriosis: Pathogenesis, epidemiology, and pathology", section on 'Gross'.)
Treatment — The initial approach to treating endometriosis-related hemoptysis is a similar to that in the general population. Hormonal suppression is typically administered to prevent recurrence.
●Locate and control the source of bleeding – The initial treatment of patients with presumed or known endometriosis-related hemoptysis (catamenial or non-catamenial) is similar to that in patients with other etiologies and varies according to the source of bleeding. (See "Evaluation of nonlife-threatening hemoptysis in adults".)
As examples:
•For patients with hemoptysis due to distal endobronchial lesions or pulmonary parenchymal nodules, wedge or subsegmental resection can be performed for simultaneous diagnostic and therapeutic purposes, depending upon the exact location of the lesion [11,49,54,55]. However, in patients with minor endometriosis-associated hemoptysis due to an unclear source (eg, ill-defined ground glass infiltrate on CT), hormonal suppression alone may be appropriate.
•For patients with hemoptysis due to airway lesion(s), local therapy with endoscopic Neodymium-yttrium-aluminum-garnet (Nd:YAG) laser treatment has been used to successfully treat tracheobronchial endometriosis [56]. (See "Bronchoscopic argon plasma coagulation in the management of airway disease in adults".)
•For patients with massive hemoptysis, which is rare, airway protection and lobar resection may be warranted. Bronchial artery embolization may be appropriate in those not candidates for surgery. (See "Evaluation and management of life-threatening hemoptysis".)
●Hormonal suppression – Although the data to support its use are less robust than those for the prevention of pneumothorax, 6 to 12 months of hormone suppressive therapy may be administered to those with hemoptysis on a case-by-case basis [22,53,57]. As an example, therapy may be administered to those who recur despite definitive therapy (eg, nodule resection). In contrast, some patients with infrequent episodes of minor hemoptysis may prefer to avoid it. Details of hormonal therapy are discussed separately. (See 'Hormonal suppression' below and "Endometriosis: Treatment of pelvic pain".)
PULMONARY NODULES
Clinical features — Thoracic endometriosis can occasionally present as solitary or multiple pulmonary nodules (2 to 6 percent of all patients with TES). Nodules can be incidental or symptomatic (eg, hemoptysis or chest pain), vary in size (0.5 to 3 cm) and are typically right-sided [4,11,58,59].
Nodules are best imaged using CT:
●Pulmonary nodules are variable in appearance and may have well defined or ill-defined borders, may be solid or have a ground glass appearance, or be cavitating [58,60-62]. They may be single or multiple and are often peripheral. Poorly defined infiltrates surrounding a nodule may suggest hemorrhage. Nodules may vary in morphology during the menstrual cycle and may even disappear between menstruations [20].
●Diaphragmatic nodules from viscus protrusion (ie, intrathoracic liver herniation) through diaphragmatic defects may appear as hypo-attenuating lesions that are often right-sided and posterior [18,19,36,63,64].
●Endometrial implants can appear as contrast-enhancing lesions attached to the diaphragm and/or pleural membrane.
Magnetic resonance imaging (MRI) of nodules may reveal similar findings to CT. However, the improved spatial resolution of MRI may allow imaging of small pleural or diaphragmatic endometriomas characterized by the presence of small cystic hyperintense lesions on T1-weighted images of the visceral or parietal pleura [20,65-67].
Differential diagnosis — Some endometriosis-associated nodules may wax and wane with the menstrual cycle; however, the vast majority may have a similar appearance to some other benign nodules (eg, leiomyoma). Cavitating and thick-walled endometriosis-associated lesions may be indistinguishable from malignant nodules or an abscess. Clinical and CT findings that distinguish benign nodules (eg, <0.8 mm, smooth, fully calcified) from malignant nodules (>0.8 mm, spiculated, partially calcified) are described separately. (See "Diagnostic evaluation of the incidental pulmonary nodule", section on 'Initial evaluation'.)
Diagnostic approach — Similar to that for patients who present with a solitary pulmonary nodule (SPN), tissue biopsy is indicated in symptomatic growing nodules well as in nodules that are cavitating. The choice of biopsy (eg, surgical excision, bronchoscopic biopsy, or needle aspiration) is dependent upon the size and location of the nodule. For asymptomatic nodules, the approach also should be similar to that of patients with a SPN. The management of SPNs is discussed separately. (See "Diagnostic evaluation of the incidental pulmonary nodule".)
Treatment — Similar to patients with symptomatic SPNs due to other etiologies, endometriosis-related SPNs (eg, presenting with a cavity or hemoptysis) are generally surgically excised [58,59]. Such an approach is often both diagnostic and therapeutic. Successful excision depends upon the size and location of the SPN. (See "Diagnostic evaluation of the incidental pulmonary nodule" and "Preoperative physiologic pulmonary evaluation for lung resection".)
Patients with small or multiple nodules may be more difficult to manage and successful excision may again depend upon the number of nodules, their size and location, and their associated symptoms. For example, for a patient with three nodules in one lobe, a lobectomy may be suitable if the patient is symptomatic from disease in that lobe and is a candidate for surgery. (See "Preoperative physiologic pulmonary evaluation for lung resection".)
The value of hormone suppression in this population is less certain and should be administered on a case-by case basis. As an example, following excision and provided no other visible nodules are evident, we prefer to observe patients and avoid hormonal suppression during observation. However, should nodules or symptoms recur, then hormonal therapy is appropriate. In addition, hormonal suppression may also be appropriate in those for whom resection is not suitable. (See 'Hormonal suppression' below.)
OTHER CLINICAL MANIFESTATIONS — Endometriosis confined to the diaphragm (picture 1) can be associated with pain in the ipsilateral chest, shoulder, arm, and neck and rarely can lead to diaphragmatic rupture and pneumoperitoneum [9,36,63,68,69]. Recurrent catamenial chest pain from diaphragmatic lesions is often intermittent and located in the right shoulder. It does not have the typical features of pain due to ischemic heart disease or reflux. (See "Outpatient evaluation of the adult with chest pain".)
For patients with pelvic endometriosis who have recurrent or catamenial shoulder or chest pain and in whom diaphragmatic lesions are suspected, laparoscopy for pelvic disease may identify lesions on the diaphragm suitable for biopsy [68]. (See "Endometriosis: Clinical features, evaluation, and diagnosis", section on 'Clinical features'.)
The optimal therapy in patients with recurrent chest pain from endometriosis-associated diaphragmatic lesions is unknown and depends upon the severity of pain. While medical therapy with hormonal suppression is preferred by most experts, resection of the lesions and repair of the diaphragm has been reported to reduce symptoms in one small case series [68]. The decision to perform extensive excision and repair procedures of the diaphragm should weigh the benefits of symptom reduction against the risk of complications including lack of proven efficacy, recurrence, and herniation. Following excision, most clinicians treat with hormonal suppression for 6 to 12 months, although the validity of this approach is uncertain. (See 'Hormonal suppression' below.)
For patients who present with diaphragmatic rupture, suspicious lesions, which are often located at the site of perforation, should be biopsied at the time of surgical repair, during which mesh may be used. (See "Recognition and management of diaphragmatic injury in adults".)
DIAGNOSIS — Thoracic endometriosis is typically a diagnosis that is made clinically and, although histopathologic confirmation is preferred, it is not necessary. Thoracic endometriosis should be suspected in women of reproductive age who present with pneumothorax, hemothorax, or hemoptysis especially when they present perimenstrually (usually 24 hours before, and up to 72 hours after menses) or have a history of pelvic surgery. It should also be suspected in those with right-sided, self-resolving, and/or recurrent symptoms. (See 'Pneumothorax' above and 'Hemothorax' above and 'Hemoptysis' above and 'Pulmonary nodules' above and 'Other clinical manifestations' above.)
In this setting, most clinicians use a combination of imaging features (eg, diaphragmatic nodules seen on CT or magnetic resonance imaging [MRI]), as well as gross (eg, pleural nodules and diaphragmatic fenestrations seen via pleuroscopy or video-assisted thoracoscopic surgery [VATS]) and/or microscopic findings (endometrial tissue) to support the diagnosis. However, in many cases, thoracic endometriosis is discovered incidentally while investigating patients for their presenting complaint.
We agree with other experts regarding the following diagnostic terms:
●Proven thoracic endometriosis – This term is used when hormone receptor-positive endometrial glandular and stromal tissue is identified on histopathology (eg, from lung, bronchus, pleura, diaphragm, and/or pericardium) [3,14,47]. Although diagnostically definitive, obtaining tissue in the luteal phase where endometrial gland and stroma architecture is preserved can be challenging and thus biopsy results are often inconclusive. (See "Thoracic endometriosis: Pathogenesis, epidemiology, and pathology", section on 'Pathology'.)
●Probable thoracic endometriosis – This term is used when tissue is insufficient or not available or histopathology is inconclusive in a patient with a convincing history and supportive imaging.
Although not necessary, histopathologic confirmation is preferred because it provides a definitive diagnosis, which is useful for predicting the risk of recurrence and for discussing the benefits and risks of prolonged hormonal suppressive therapy that may be required to treat select patients. (See 'Hormonal suppression' above.)
Because the association of symptoms with menses is not typically appreciated, the diagnosis is often delayed until there have been several episodes. In the older literature, the average duration of symptoms prior to diagnosis was 8 to 19 months; however, in subsequent reports, the diagnosis has been established earlier due to increased awareness [11,14].
HORMONAL SUPPRESSION — Because eradication of endometrial implants in the thoracic cavity is challenging, hormonal suppressive therapy is often administered to reduce the risk of recurrence. The rationale for hormonal suppression is that it treats the underlying cause of the disease, similar to the rationale in patients with pelvic disease. In patients who have undergone pleurodesis, reducing recurrence may also allow sufficient time for effective pleural adhesion. An additional advantage of hormone suppression is that it functions as a primary therapy for symptomatic pelvic disease, the details of which are discussed separately. (See "Endometriosis: Treatment of pelvic pain".)
Despite the lack of randomized studies, we and other experts believe that most patients with thoracic endometriosis should be treated with hormone suppressive therapy. Experience and data from observational studies support a reduction in the rate of recurrent pneumothorax and hemothorax with these agents. Dienogest, a prostogenic drug with moderate estrogen suppression, anti-inflammatory, antiproliferative, and antiangiogenic properties, is a new treatment available for initial management of thoracic endometriosis [38,39]. (See 'Efficacy and adverse outcomes' above.)
Agents should be started two to three weeks following surgical intervention (eg, pleurodesis for endometrial-associated pneumothorax). Patients are typically treated for 6 to 12 months but longer periods may be necessary for those with recurrent or recalcitrant disease (eg, pneumothorax or hemothorax despite pleurodesis).
Typically, gonadotropin-releasing hormone (GnRH) analogs are the first-line agents because they are highly effective at suppressing ovarian hormone production and inhibiting the growth of endometrial tissue [3,11,12,30,35,36,40,70-73]. However, prolonged therapy with GnRH analogs is often complicated by intolerance from the acute symptoms of menopause and the risk of osteoporosis. Consequently, the decision to use GnRH analogs is dependent upon weighing the benefits of reduced recurrence against the adverse effects in the context of patient preferences regarding the temporary induction of menopause and inability to become pregnant.
For those not willing to become menopausal or who have a contraindication to GnRH analogs, oral contraceptives or progestins, and less commonly, danazol or aromatase inhibitors, are alternatives. The advantage of oral contraceptive agents is that endometrial implant stimulation is low grade and withdrawal bleeding can be avoided, if necessary, by the administration of continuous therapy.
All hormonal agents should be stopped in those who cannot tolerate the side effects and in those who have a desire to become pregnant.
REFRACTORY DISEASE — Recurrence rates are high particularly when hormonal suppressive therapy is not administered. However, some patients develop recurrence despite hormonal therapy. The optimal therapy for patients with refractory disease is unknown. Options include:
●Switching to an alternate hormonal agent (eg, trial of Dienogest, switching from oral contraceptives to danazol)
●Pleurectomy and repeat pleurodesis for recalcitrant pneumothorax or hemothorax
●Hysterectomy with bilateral salpingo-oophorectomy (BSO) [11]
However, the efficacy of hysterectomy and BSO is uncertain because case reports suggest recurrence despite this approach [42,74,75].
The role of anti-angiogenesis therapy for endometriosis is investigational. One case report suggested regression of endometriosis with vascular endothelial growth factor receptor inhibitors sunitinib and regorafenib [76].
Importantly, the adverse effects of prolonged hormonal suppression can be substantial. In those cases, clinicians will advocate adding back low dose estrogen and/or progesterone therapy, similar to that performed in patients with pelvic disease. (See "Endometriosis: Long-term treatment with gonadotropin-releasing hormone agonists".)
FOLLOW-UP — During follow-up, patients should be fully assessed by history and examination for recurrent catamenial or non-catamenial symptoms suggestive of residual disease as well as for the signs and symptoms of pelvic disease. Patients should also undergo repeat imaging to ensure resolution of the pneumothorax, effusion, or nodule.
Most patients are managed during follow-up by a multidisciplinary team of clinicians encompassing a pulmonologist and gynecologist as well as a thoracic surgeon or interventional pulmonologist, when needed.
Patients on hormonal suppression should be monitored for adverse effects including the symptoms of menopause and osteoporosis (gonadotrophin releasing hormone analogues), venous thromboembolism (oral contraceptives, danazol), and hepatitis and pseudotumor cerebri (danazol). (See "Endometriosis: Long-term treatment with gonadotropin-releasing hormone agonists", section on 'Side effects'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Endometriosis".)
SUMMARY AND RECOMMENDATIONS
●Definition – Endometriosis is defined as the presence of ectopic endometrial tissue (glands and stroma) outside the confines of the uterine cavity and musculature. Thoracic endometriosis is that which involves components of thoracic cavity (eg, pleura, parenchyma, diaphragm, bronchus). (See 'Terminology' above.)
●Clinical features – Thoracic endometriosis most commonly presents in young women as catamenial pneumothorax (70 to 73 percent) and catamenial hemothorax (12 to 14 percent). Less common presentations include catamenial hemoptysis, catamenial chest or scapular pain, noncatamenial pneumothorax or hemothorax, a parenchymal cavity or nodule, or diaphragmatic rupture (picture 1). A high index of suspicion should exist in women of reproductive age who present with any of these features, especially when the findings are right-sided, symptoms present perimenstrually (usually 24 hours before, and up to 72 hours after menses), or the patient has a history of pelvic surgery. (See 'Pneumothorax' above and 'Hemothorax' above and 'Hemoptysis' above and 'Pulmonary nodules' above.)
●Diagnostic and therapeutic approach – When suspected, patients should undergo contrast-enhanced CT of the chest (image 1), preferably when symptoms are present (ie, perimenstrual). Magnetic resonance imaging may be useful for those with diaphragmatic nodules suspected to be endometriosis. (See 'Pneumothorax' above and 'Hemothorax' above and 'Hemoptysis' above and 'Pulmonary nodules' above.)
•For those in whom the clinical suspicion is high and/or imaging is supportive of the diagnosis, we suggest that most patients undergo an interventional procedure (eg, thoracoscopy) which serves both to manage the primary presenting feature and diagnose the underlying thoracic endometriosis.
•For most patients with pneumothorax in whom endometriosis is suspected (eg, first pneumothorax with suspicious imaging findings, recurrent or catamenial pneumothorax, coexistent hemothorax), we suggest video-assisted thoracoscopic (VATS) pleural inspection, blebectomy, and pleurodesis. During VATS, we also perform endometrial implant resection and ligation of diaphragmatic perforations, if found.
•Following diagnosis, we suggest postoperative hormonal suppressive therapy for 6 to 12 months rather than no therapy, to reduce the risk of recurrence (Grade 2C). The agent of choice for hormonal suppression includes Dienogest, oral contraceptives, and gonadotropin-releasing hormone (GnRH) analogs. (See 'Pneumothorax' above and 'Hormonal suppression' above and "Treatment of secondary spontaneous pneumothorax in adults".)
•For all other patients in whom thoracic endometriosis is suspected, the diagnostic and therapeutic approach should be individualized and focus on definitively managing the presenting feature followed by secondary prevention of recurrence, most often by hormonal suppression for 6 to 12 months. (See 'Hemothorax' above and 'Hemoptysis' above and 'Pulmonary nodules' above and 'Other clinical manifestations' above and 'Hormonal suppression' above.)
•For patients with disease refractory to primary intervention and hormonal suppression, the optimal therapy is unknown. Options include switching to an alternate hormonal agent (eg, from oral contraceptives to danazol), pleurectomy and repeat pleurodesis for recalcitrant pneumothorax or hemothorax, and rarely, hysterectomy with bilateral salpingo-oophorectomy (BSO). (See 'Refractory disease' above.)
●Diagnosis – Thoracic endometriosis is typically a diagnosis that is made clinically and, although histopathologic confirmation is preferred, it is not necessary. In the correct clinical context, most clinicians use a combination of imaging features (eg, diaphragmatic nodules identified on CT or magnetic resonance imaging), as well as gross (eg, pleural nodules and diaphragmatic fenestrations seen via pleuroscopy or VATS) and/or microscopic findings (endometrial tissue) to support the diagnosis. (See 'Diagnosis' above.)
●Follow-up – During follow-up, patients should be fully assessed by history and examination for recurrent catamenial or non-catamenial symptoms suggestive of residual disease as well as for the signs and symptoms of pelvic disease. Patients should also undergo repeat imaging to ensure resolution of the pneumothorax, effusion, or nodule, and monitored for adverse effects from medical and surgical therapies. (See 'Follow-up' above.)
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