Thoracic endometriosis syndrome: a literature review of catamenial pneumothorax and other uncommon clinical manifestations

Introduction

The thoracic endometriosis syndrome (TES) is an uncommon, yet significant gynecological disorder defined by the abnormal presence of ectopic endometrial tissue in the thoracic cavity, areas such as the parietal or visceral pleura, lung parenchyma, airways, or diaphragm (1). Despite its infrequency, it stands as the most common form of extra-abdominopelvic endometriosis (2,3).

While endometriosis is a disorder accounting for almost 10% of women in reproductive age (4), the prevalence of TES has traditionally been underestimated and undefined, and the disease could present with a variety of clinical manifestations, making diagnosis challenging. Recent studies, though, have highlighted an increasing awareness and recognition of this diagnostic entity (5,6).

This narrative review aims to provide a clinically relevant synthesis of available evidence of common and atypical presentations of TES, with particular emphasis on thoracic endometriosis-related pneumothorax (TERP) as the pathological hallmark of the disease, and on its varied clinical presentations, both catamenial and non-catamenial. We present this article in accordance with the Narrative Review reporting checklist (available at https://asj.amegroups.com/article/view/10.21037/asj-25-44/rc).

Methods

This narrative review was conducted to summarize the current understanding of TES, including its pathophysiology, clinical presentation, diagnostic approaches, and treatment strategies. A structured literature search was performed using PubMed database for articles published between January 2000 and March 2024, limited to publications in English. was employed for this review to guarantee a thorough synthesis of relevant data (Table 1).

The search used a combination of MeSH terms and free text including “Thoracic Endometriosis Syndrome”, “Catamenial Pneumothorax”, “Catamenial Hemothorax”, “Catamenial Hemoptysis”, “Endometriosis-related”, “Lung Disease”, and “Diaphragmatic Endometriosis”.

Relevant data extracted from selected articles, including original research studies, systematic reviews, meta-analyses, and case reports that provided significant clinical or pathological insights, were analyzed qualitatively to provide a comprehensive overview of the various presentation of TES.

As this is a narrative review, potential biases may arise from the non-systematic selection of articles. Additionally, the heterogeneity of included studies, variations in diagnostic criteria, and the limited number of large-scale studies on TES may affect the generalizability of the findings. Despite these limitations, this review aims to provide a clinically relevant synthesis of available evidence on TES.

Discussion

The main clinical manifestations of thoracic endometriosis are catamenial pneumothorax (CP), non-catamenial pneumothorax (non-CP), and non-pneumothorax related thoracic endometriosis (6).

The determination of whether endometriosis was proven relied on pathologic analysis. The pathologic diagnostic criteria for thoracic endometriosis included either the presence of both endometrial stroma and glands, or the observation of endometrial stroma combined with positive staining for CD10 and estrogen/progesterone receptors (7).

Etiology, pathogenesis & pathology

Endometrial implants may be found in the lung parenchyma, visceral and parietal pleura, diaphragm, and more rarely in the tracheobronchial tree (3). The clinical manifestations thus depend on the affected structures.

While the underlying mechanisms of TES remain not completely understood, various hypotheses attempt to explain the presence of endometrial tissue in the chest. Nevertheless, none of these theories can independently explain the full spectrum of clinical and pathological presentations seen in CP and non-CP manifestations, suggesting a multifactorial etiology for the disease (1,8).

Among the most widely accepted hypotheses are:

• Retrograde menstruation and transdiaphragmatic migration: retrograde menstruation is a key mechanism proposed for the development of thoracic endometriosis. Endometrial cells travel through the fallopian tubes into the peritoneal cavity and are transported by peritoneal fluid along the right paracolic gutter toward the subdiaphragmatic region. The hepatic ligaments (falciform medially and triangular posteriorly) are thought to act as barriers, potentially explaining the more frequent right-sided localization of diaphragmatic endometriosis and its subsequent spread into the chest (9,10). From there, these cells may reach the thoracic cavity through pre-existing congenital fenestrations or microdefects in the diaphragm. Therefore, transdiaphragmatic migration should not be viewed as an independent mechanism but rather as a direct consequence of retrograde menstruation. Endometrial implants may also cause diaphragmatic damage leading to acquired perforations, and ruptures, a theory supported by the finding of endometrial nodules and perforations on the diaphragm (11).
• Retrograde menstruation: it is hypothesized that endometrial cells in the peritoneal cavity can follow the peritoneal fluid circulation, moving from the pelvis, along the right paracolic gutter, towards the right subdiaphragmatic region. The hepatic ligaments (falciform medially and triangular posteriorly) are thought to act as barriers, potentially explaining the more frequent right-sided localization of diaphragmatic endometriosis and its subsequent spread into the chest (9,10).
• Coelomic metaplasia: given that the endometrium, pleural mesothelium, and peritoneum originate from the same embryonic tissue, it is possible that certain precursor cells in the pleura or peritoneum could transform into endometrial cells in response to pathological signals (1,5).
• Lymphatic or vascular embolization: the dissemination of endometrial cells through the lymphatic or vascular systems is also considered a possible mechanism (8).

The hallmark of thoracic endometriosis is the presence of structurally normal endometrial tissue inside the chest. No matter the location, endometriotic foci are made up of both stroma and glands in varying ratios, often featuring dilated glands typically lined by pseudostratified cuboidal to cylindrical epithelium (1).

Pleural involvement in thoracic endometriosis commonly manifests as nodular or nodulocystic lesions affecting either the parietal, visceral, or diaphragmatic pleura. These lesions are often associated with pleural thickening, adhesions, and varying degrees of hemorrhage, fibrosis, and inflammatory infiltration. Macroscopically, they may appear as dark red or blue-brown implants, often described as “chocolate spots” or “chocolate cysts”, and occasionally as either nodular or nodulocystic lesions, or multiple well-defined nodules or as thin-walled cavities or bullae, frequently associated with both old and recent bleeding in the surrounding lung tissue (12,13) (Figure 1). These pleural changes are critical in the development of catamenial and non-CP.

Figure 1 Parietal pleural implants of endometriosis.

Recent evidence has therefore suggested that the traditional hypothesis of transdiaphragmatic air passage may not fully account for all cases of pneumothorax. Was found that visceral pleural lesions, such as small blebs or endometriotic implants directly involving the lung surface, were more frequently identified at the site of air leakage than diaphragmatic fenestrations. These findings suggest that air leakage through fragile areas of the visceral pleura may represent an alternative or complementary mechanism in the pathophysiology of endometriosis-related pneumothorax (14). Incorporating this pleural-centered hypothesis is essential to better understand the variability of thoracic endometriosis presentations and to refine surgical strategies.

Clinical presentations of TES

CP is the most common clinical presentation of TES and is estimated to account for approximately 70–80% of cases (1).

A CP is traditionally defined as a spontaneous and recurrent pneumothorax occurring from 24 hours before to 72 hours after the onset of menstruation. This diagnosis is based exclusively on the temporal association between pneumothorax and menses, without requiring histologic confirmation (15-17). However, such definition presents important limitations. In particular, it may erroneously include cases of primary spontaneous pneumothorax (PSP) in women of reproductive age that coincidentally occur during menstruation (1).

To address this issue, Alifano et al. proposed the term “thoracic endometriosis-related pneumothorax (TERP)” to describe a catamenial or a non-CP in which histopathologic confirmation of endometrial tissue is obtained from thoracic specimens, either pleura, diaphragm, or lung (18). TERP thus represents a pathologically confirmed entity, while CP remains a clinical diagnosis based on symptom timing. Importantly, TERP can occur both within and outside the strict menstrual window, as endometriotic thoracic lesions may cause recurrent pneumothorax independently of hormonal cycling, a condition known as endometriosis-related non-CP (8).

The distinction between CP and TERP is crucial: the former may overestimate the prevalence of TES if used without pathological confirmation, whereas the latter, although more specific, is limited by the challenge of obtaining histological evidence. From a clinical perspective, CP should not be used interchangeably with TES or TERP, it raises suspicion of TES, prompting further evaluation, but only TERP confirms the diagnosis.

It is worth mention, then, that CP represented up to 25% of spontaneous pneumothorax among women who underwent surgery and among the patients with CP, pathologically proven thoracic endometriosis reached 65% of cases (16,17).

While typically unilateral and right-sided, rare instances of left-sided CP have been documented (8), and bilateral involvement, though possible, is exceptionally uncommon (19).

Patients with CP typically experience cough, chest pain, and shortness of breath; the chest pain can be indistinguishable from that of a spontaneous pneumothorax or manifest as periscapular or neck-referred pain, often described as “diaphragmatic pain”, and although symptoms are usually mild to moderate, severe cases can occur (20).

The mechanisms underlying CP and TERP are complex and multifactorial. A widely accepted hypothesis involves the transdiaphragmatic passage of air from the peritoneal to the pleural cavity, occurring through pre-existing congenital diaphragmatic fenestrations or acquired diaphragmatic defects secondary to endometrial implants, where their functional disruption is closely linked to retrograde menstruation (10).

In addition to CP and TERP, the TES can present with less common manifestations (1,5,21), including:

• Catamenial chest pain (CCP): chest pain that worsens during menstruation.
• Catamenial hemothorax (CHt): accumulation of blood in the pleural cavity occurring in conjunction with menstruation.
• Catamenial hemoptysis (CH): coughing up blood in relation to the menstrual cycle.
• Pulmonary nodules: nodular lesions in the lung parenchyma.
• Diaphragmatic hernia: protrusion of abdominal organs through the diaphragm.

It is important to note that diagnosing TES can be challenging and is often delayed due to its rarity and the variety of clinical presentations. Awareness of these less common manifestations, in addition to the classic CP, is essential for early diagnosis and appropriate treatment (22).

CCP

CCP was defined as thoracic discomfort recurring in the menstrual period. It is experienced as a deep, visceral pain localized in the lower hemithorax and hypochondrium, often radiating to the shoulder—an area corresponding to the dermatome of the phrenic nerve sensory pathway. It is typically right sided (6,23,24).

The only reported series specifically focusing on isolated CCP was published by Bobbio et al. in 2017 (21). This series detailed 20 patients who experienced recurrent catamenial thoracic pain without a history of pneumothorax. Of these patients, 11 underwent surgical exploration after conservative treatment failure, revealing macroscopic diaphragmatic endometriosis with noticeable patchy red-brown nodules in 8 patients. Notably, all 20 patients had pathologically confirmed pelvic endometriosis.

The authors concluded that chronic thoracic pain could be related to diaphragmatic thicknesses and nodules (21).

Surgery may be indicated in CCP when the thoracic pain is resistant to analgesics or hormonal therapy or if that is contraindicated or not accepted by the patient.

CHt

CHt is an uncommon manifestation of TES, characterized by hemorrhagic pleural effusion that occurs during the menstrual cycle. Studies indicate it affects up to 14% of individuals with TES (21). The right side is involved in nearly all reported cases, and it is usually accompanied by pneumothorax on the same side (25), though at least one case has described a right pneumothorax occurring with a left hemothorax (9).

Symptoms of hemothorax are nonspecific and include cough, pleuritic chest pain, and dyspnea. The volume of effusion can vary, with some cases presenting with hypovolemic shock (26). In some instances, signs can mimic those of pulmonary embolism (27,28).

Endometrial implants responsible for CHt are generally found on either the visceral or parietal pleura. The bleeding from these implants is thought to occur due to fluid shifts during menstruation, leading to capillary rupture within the lesions (1,29).

CH

CH, defined as menstruation-related coughing up of blood, can occur in up to 7% of cases of TES (21). The bleeding typically originates from an endometrial implant located in the large airways or within the lung tissue.

CH is typically observed in younger patients, and while the amount of bleeding can vary considerably, it is rarely life-threatening; neither massive bleeding episodes nor deaths have been reported. It can also initially be misdiagnosed as tuberculosis (6).

Despite its rarity, some authors have observed that the onset of symptoms in CH occurs significantly earlier than in CP, and the occurrence of CH was equivalent in terms of the laterality, thus suggesting a different pathogenic mechanism. While pleural endometriosis, which leads to CP, may result from the retrograde flow of endometrial tissue, intrapulmonary endometriosis, which causes CH, may develop from the microembolization of endometrial cells (30,31).

Pulmonary nodules

Endometriotic lung nodules are described in 2–6% of cases (16,21) and often associated with CH (1,32).

In comparison to other clinical and radiological signs of TES, lung nodules are more commonly seen in older women, likely due to lower hormonal activity, and are less frequently associated with catamenial symptoms (1,3); despite a slight tendency to occur on the right, lung nodules have been observed in both lungs, supporting the previously described mechanism for CH (5), and while bilateral lesions are rare, they have been documented in a patient who underwent sequential video-assisted thoracoscopic surgery for pneumothorax, during which multiple hemorrhagic areas of the lungs were resected (32).

Pulmonary endometrial implants are thought to arise from the lung’s filtration system, which traps endometrial cells (3). These implants can present as single or multiple merging nodules, or as thin-walled cavities or bullae, often located in the smaller peripheral bronchi or the lung parenchyma itself, leading to CH due to capillary rupture within the lesion during menstruation (13,33).

Endometriosis-related diaphragmatic rupture and herniation

The diaphragm, and particularly the right dome, shows a particular affinity for endometrial cell implants, and diaphragmatic endometriosis has been described in association with CP (3,34).

Diaphragmatic endometriosis is frequently symptomatic. These symptoms can occur due to phrenic nerve irritation and referred pain to the periscapular region or to the neck, most often on the right side, or lower-lateral chest pain (6,21).

Endometrial diaphragmatic implants could be presented as nodule, “blueberry spot”, cystic lesions or small defects or perforation at surgical exploration (5,35).

Spontaneous diaphragmatic rupture is a rare event with few series described in literature and is supported by the invasiveness of endometriotic tissue causing diaphragm fragility, which finally lead to its complete rupture without traumatic event (36). More, cyclical necrosis of multiple endometrial implants may eventually coalesce into larger defects that can lead to intrathoracic herniation of abdominal viscera. The first reported case of a diaphragmatic hernia resulting from endometriosis was published by Bobbio et al. in 2007 (37).

Subsequently, the same authors reviewed all surgically treated cases of TES at their institution, finding that 8% of these patients presented a diaphragmatic hernia, and that this could be in association with CP or chest pain, or without precedent history of pneumothorax in 35% of cases (38). The high predominance of right-side disease supported the retrograde menstruation mechanism sharing some common pathways with CP (1).

Even if rare, the identification of a diaphragmatic hernia must be considered a formal indication for surgery (Figure 2).

Figure 2 Diaphragmatic endometriosis implants and liver herniation through diaphragmatic defect.

Management & treatments strategies

Effective management of TES relies on a multidisciplinary approach, involving thoracic surgeons, gynecologists, and radiologists to ensure comprehensive diagnosis and treatment. Surgical intervention remains a cornerstone of treatment, allowing for the resection of ectopic endometrial tissue, repair of diaphragmatic defects, and pleurodesis when indicated. However, recurrence is frequently observed when surgery is used alone. Therefore, postoperative hormonal therapy, typically involving gonadotropin-releasing hormone (GnRH) analogs or progestins, is considered essential to suppress residual endometrial activity and reduce the risk of recurrence.

The foundational study by Joseph and Sahn (3) had already observed high recurrence rates following surgery alone. More recently, a large-scale study by Tsuboshima et al. (39) demonstrated that patients who received postoperative hormonal therapy after surgical treatment experienced significantly lower recurrence rates compared to those who underwent surgery alone. These findings strongly support the multidisciplinary, combined approach, integrating surgery with long-term hormonal suppression to reduce recurrence risk and improve patient outcomes as the current gold standard for TES management.

Conclusions

In conclusion, while CP remains the most widely recognized manifestation of TES, numerous evidence reveals a broader clinical spectrum that includes atypical presentations such as TERP, CCP, hemothorax, hemoptysis, pulmonary endometriosis nodules, and even diaphragmatic hernia.

These less frequent manifestations not only reflect the complex and heterogeneous nature of thoracic endometriosis but also pose significant diagnostic challenges. Their often subtle and overlapping clinical features can be underestimated or mimic other thoracic conditions, leading to potential misdiagnosis or delayed identification of the underlying pathology. Consequently, patients may be subjected to a series of ineffective treatments or invasive procedures before a definitive diagnosis is established.

This mismanagement underscores the urgent need for heightened clinical vigilance and a multidisciplinary approach involving thoracic surgeons, radiologists, and gynecologists: radiologists should evaluate imaging for subtle signs of diaphragmatic or pleural endometriosis, thoracic surgeons ensure definitive diagnosis and provide surgical management, gynecologists coordinate hormonal therapy and manage concurrent pelvic endometriosis and long-term follow-up.

By recognizing the temporal relationship between these atypical symptoms and the menstrual cycle, clinicians can refine their diagnostic strategies, thereby reducing the risk of diagnostic errors.

Ultimately, a comprehensive understanding of both the common and uncommon presentations of thoracic endometriosis is crucial not only for improving diagnostic accuracy but also for guiding tailored therapeutic interventions that can significantly enhance patient outcomes.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://asj.amegroups.com/article/view/10.21037/asj-25-44/rc

Peer Review File: Available at https://asj.amegroups.com/article/view/10.21037/asj-25-44/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://asj.amegroups.com/article/view/10.21037/asj-25-44/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All clinical procedures described in this study were performed in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this article and accompanying images.

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