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 of the pelvis in the abdomen, thorax, brain, and skin [1]. Thoracic involvement is the most frequent extra-pelvic location of endometriosis [2].
The pathogenesis, epidemiology, and pathology of thoracic endometriosis will be reviewed here. Details regarding the clinical presentation, diagnosis, and treatment of thoracic and pelvic endometriosis are discussed separately. (See "Clinical features, diagnostic approach, and treatment of adults with thoracic endometriosis" 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:
Thoracic endometriosis — 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.
Probable thoracic endometriosis — 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 receptor-negative tissue) [3].
Thoracic endometriosis syndrome — The term "thoracic endometriosis syndrome" has been 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 [4].
Catamenial — The term "catamenial" refers to the occurrence of symptoms or signs that bear a temporal relationship with menses (eg catamenial pneumothorax). (See "Pneumothorax in adults: Epidemiology and etiology", section on 'Catamenial pneumothorax'.)
PATHOGENESIS
Pathogenetic theories — Several hypotheses have been proposed to explain the pathogenesis of thoracic endometriosis, some of which are shared with pelvic disease (see "Endometriosis in adults: Pathogenesis, epidemiology, and clinical impact", section on 'Pathogenesis'). Sampson's theory of autotransplantation of endometrium via retrograde menstruation is the most popular theory. Microembolization and coelomic metaplasia are alternate theories:
●Autotransplantation via retrograde menstruation – Sampson's theory provides an explanation for the presence of endometrial tissue in the thoracic cavity by retrograde movement of menstrual endometrium through the fallopian tube leading to auto-transplantation of endometrial tissue/cells into the peritoneal and thoracic cavities [5]. It has been proposed that ectopic endometrium may migrate directly through diaphragmatic defects that are observed in patients with thoracic endometriosis (picture 1) [6-12]. However, a number of observations suggest that this theory does not completely explain how endometrial tissue is located in the thoracic cavity:
•Diaphragm defects are uncommon.
•Thoracic endometriosis is predominantly right-sided; if defects were truly portals of entry for endometrial tissue, the disease would be expected to be bilateral in distribution. However, defects may be more apparent on the right for unclear reasons.
•Pneumothorax can recur after diaphragmatic repair and/or hysterectomy [6,11,13-17].
•The proximity of diaphragmatic endometrial implant tissue to diaphragmatic defects on pathologic specimens suggests that the defects may represent areas of involuted endometrial implants. (See "Clinical features, diagnostic approach, and treatment of adults with thoracic endometriosis".)
•Ectopic endometrial tissue differs significantly from eutopic endometrium in clonality, enzymatic activity, protein expression, and histologic properties [18,19].
●Micro-embolization/metastasis – Metastatic spread of endometrial tissue through the venous or the lymphatic system to the lungs is another proposed mechanism [4,15,20-24]. Endometrial foci in tissue remote from the pelvis and thorax (eg, brain, knee, and eye) support the “metastatic” theory. The presence of circulating endometrial cells has been found in 90 percent of patients with histology proven pelvic endometriosis [25]. Furthermore, in a proof-of-concept study, circulating endometrial cells were identified in the blood of women with spontaneous pneumothorax who were suspected as having catamenial pneumothorax [26]. These findings strengthen the evidence for microembolization as a mechanism for thoracic endometriosis. However, in opposition to this theory, microembolization would be expected to affect both hemithoraces approximately equally, whereas thoracic endometriosis is found overwhelmingly in the right hemithorax (>80 percent of patients) [22].
●Coelomic metaplasia – Transformation of pluripotent cells to differentiated endometrium (ie, coelomic metaplasia) has also been proposed. In support of this theory, pluripotent cells have been identified in uterine endometrium and a case of endometriosis has been reported in a 20-year-old woman with congenital agenesis of uterus, cervix, vagina, and fallopian tubes (ie, Mayer-Rokitansky-Küster-Hauser syndrome) [27,28].
Mechanism of symptoms — Similar to eutopic endometrium, ectopic endometrial implants undergo the proliferative luteal phase of growth upon stimulation by ovarian hormones followed by decidualization withdrawal of hormones. Thus, foci of endometrial tissue on the visceral and/or parietal pleura are thought to cause hemothorax and pneumothorax as they undergo decidualization in response to hormone withdrawal during menses. Parenchymal foci, undergoing the same process, result in hemoptysis [4,15,22-24].
The "physiologic" theory of catamenial pneumothorax has also been used to explain both endometriosis- as well as non-endometriosis-related catamenial pneumothorax. This theory suggests that vasoconstriction and bronchospasm caused by high levels of circulating prostaglandin F2 during menses may induce alveolar rupture, particularly in pre-existing bullae [11,15,23,24].
Another theory has been suggested that during menses, atmospheric air passes from the vagina to the uterus via the cervix (absent cervical mucus during menses), that then moves to the peritoneal cavity through the fallopian tubes, and finally to the pleural space through diaphragmatic defect(s) [11,15,23,24,29]. However, recurrences of pneumothorax after hysterectomy, fallopian tube ligation, and diaphragmatic resection suggest that this theory cannot explain all cases of catamenial pneumothorax [6,11,13-17].
EPIDEMIOLOGY — Thoracic endometriosis is a rare disease that primarily affects young women. The incidence in the general population is unknown. However, it has been reported in <1 percent of women undergoing pelvic surgery for suspected or known pelvic endometriosis [30,31]. Higher rates are reported in those with primary spontaneous pneumothorax (3 to 6 percent), and the highest rates are reported in those with recurrent pneumothorax or pneumothorax requiring surgery (6 to 20 percent) and catamenial pneumothorax (65 to 89 percent).
Thoracic endometriosis predominantly affects young females of reproductive age [3,4,11,22,23,32]. However, rare case reports have also described endometriosis in men receiving estrogen, in women on infertility agents (eg, clomiphene), and in older women on estrogen supplementation [33,34]. One retrospective analysis of 110 patients, reported that the mean age at presentation was 35 years but ranged from 15 to 54 years (ie, similar to that for pelvic endometriosis) [4]. Catamenial hemoptysis tends to occur at a younger age compared with other manifestations of TES [22,35]. However, the peak incidence for pelvic endometriosis lies between 24 and 29 years, five years earlier than the peak incidence for thoracic endometriosis (30 and 34 years).
Most patients (but not all patients) with thoracic endometriosis also have pelvic disease. Retrospective analyses have reported that 50 to 84 percent of patients presenting with thoracic endometriosis have pelvic disease with the remainder having thoracic cavity involvement only [4,11,23,29,36]. (See "Endometriosis in adults: Pathogenesis, epidemiology, and clinical impact", section on 'Epidemiology'.)
While thoracic endometriosis is an unusual cause of primary spontaneous pneumothorax (PSP; 3 to 6 percent), it appears to be more common than originally thought, particularly in those with recurrent pneumothorax or pneumothorax requiring surgery (6 to 20 percent) and catamenial pneumothorax (65 to 89 percent) [37]. As examples:
●Among 156 premenopausal women who were surgically treated for PSP, histologically documented thoracic endometriosis was found in 23 percent and one quarter of those had a prior pneumothorax (6 percent) [32]. In a separate case series of patients undergoing surgery for pneumothorax, a history of recurrent pneumothorax was reported in 20 percent [3].
●Among 229 women (mean age 33 years) who underwent surgery for PSP, 35 percent were catamenial and half of those were endometriosis-related [38].
●Among patients with a history of catamenial pneumothorax, retrospective analyses report that the incidence of thoracic endometriosis ranges from 65 to 89 percent [16,32].
●Among women who were surgically treated for PSP, thoracic endometriosis can be found in those without a history of catamenial symptoms (approximately 10 percent) [32,38].
RISK FACTORS — Although specific risk factors for the development of pelvic endometriosis have been described (eg, nulliparity, early menarche/late menopause, short menstrual cycles, prolonged menses, tall thin body habitus), it is unknown whether or not the same factors increase the risk for thoracic involvement.
One retrospective study of 49 women reported that infertility (odds ratio [OR] 4.21, 95% CI 1.28-13.88) and a history of pelvic surgery for a uterine procedure and/or uterine scraping (OR 2.85, 95% CI 1.12-7.26) were the strongest predictors of catamenial and/or endometriosis-related pneumothorax.
While a genetic predisposition for endometriosis has been described, no such association has been reported for the thoracic variant. (See "Endometriosis in adults: Pathogenesis, epidemiology, and clinical impact", section on 'Epidemiology'.)
PATHOLOGY
Gross — Characteristic macroscopic findings may occur in isolation, coexist, or be absent. They include the following:
●Endometrial implants may be found on the pleural, diaphragmatic (picture 2), and pericardial surfaces [3,39]. They can be single or multiple, vary in size (1 mm to a few centimeters), and are raised and red, but sometimes purple, grey, black, or white. During bronchoscopy, these implants may be seen in the tracheobronchial tree.
●Diaphragmatic perforations are circular or elliptical, single or multiple, and usually located at the central tendon. They are usually small, measuring 1 to 3 mm in size but can be larger in some cases up to 10 mm or more. Implants are often located at the edges of perforations [40].
●Liver or other organ protrusions through the diaphragm are rare.
Microscopic — Endometrial implants are histologically similar to that of endometrium in the uterine cavity; they share two major features, endometrial glands and stroma. However, unlike endometrium, endometrial implants often contain fibrous tissue, blood, and cysts (see "Endometriosis in adults: Pathogenesis, epidemiology, and clinical impact", section on 'Histology and lesion phenotypes'):
●Endometrial implants – Tissue samples from lung, bronchus, pleura, diaphragm, and/or pericardium may identify endometrial stroma and/or glands that stain positively with estrogen and/or progesterone receptors (ie, histologically-proven thoracic endometriosis) [3,32,39]. However, small sample size, the effects of inflammation, and/or decidualization of endometrial tissue due to hormone withdrawal frequently result in the observation of endometrial stroma without hormone receptor positivity, or stroma with hemosiderin-laden macrophages (from breakdown of red blood cells) (ie, histologically "probable" thoracic endometriosis). (See "Clinical features, diagnostic approach, and treatment of adults with thoracic endometriosis", section on 'Diagnosis'.)
Although these features are typically seen on tissue derived from biopsy material, case reports also suggest that some of these features may be identified on pleural fluid cytology and image-guided or bronchoscopic-guided needle aspiration of lung masses (eg, stroma with hemosiderin-laden macrophages) [41-44].
●Endometriomas – Endometriomas are rounded, cyst-like lesions that, in our experience, are only found in the pelvis or peritoneum of patients with pelvic disease. There are no reports of similar lesions in the thorax. (See "Endometriosis: Management of ovarian endometriomas".)
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
●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 the thoracic cavity (eg, pleura, parenchyma, diaphragm, bronchus). (See "Clinical features, diagnostic approach, and treatment of adults with thoracic endometriosis", section on 'Terminology'.)
●Pathogenesis - Several hypotheses have been proposed to explain the pathogenesis of thoracic endometriosis, of which Sampson's theory of auto-transplantation of endometrium via retrograde menstruation is the most popular. Microembolization and coelomic metaplasia are alternate plausible theories. (See 'Pathogenesis' above.)
●Epidemiology - Thoracic endometriosis is a rare disease that primarily affects young women. It is a significant cause of primary spontaneous pneumothorax (3 to 6 percent), recurrent pneumothorax or pneumothorax requiring surgery (6 to 20 percent), and catamenial pneumothorax (65 to 89 percent). It is present in <1 percent of women undergoing pelvic surgery for suspected or known pelvic disease. (See 'Epidemiology' above.)
●Risk factors - Although specific risk factors for the development of endometriosis have been described (eg, nulliparity, early menarche/late menopause, short menstrual cycles, prolonged menses, tall thin body habitus), it is unknown whether or not the same factors increase risk for thoracic involvement. (See 'Risk factors' above.)
●Pathology – Findings include the following:
•Gross pathology findings consistent with thoracic endometriosis include the visualization of endometrial implants as raised red or purple lesion(s) on pleural, diaphragmatic, and pericardial surfaces. During bronchoscopy, similar lesions may also be seen in the tracheobronchial tree. Diaphragmatic perforations and, rarely, liver or other organs herniating through the diaphragm may be seen. (See 'Gross' above.)
•Endometrial implants are histologically similar to that of endometrium in the uterine cavity in that they share two major features, endometrial glands and stroma. However, unlike endometrium, endometrial implants often contain fibrous tissue, blood, and cysts. (See 'Microscopic' above.)
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