Continuing Education Activity

Pulmonary sequestration is thought to account for less than 6 percent of congenital lung malformations. In this condition, there is a nonfunctional segment or lobe of dysplastic lung tissue that does not communicate with the rest of the tracheobronchial tree and receives an anomalous vascular supply. Apart from incidental diagnosis on computed tomographic chest scans, the most common clinical presentation of intralobar sequestration is recurrent pneumonia in a localized segment of the lung. Alternative presentations include persistent cough, back pain, hemoptysis, or persistent exertional dyspnea. This activity explains when this condition should be considered on differential diagnosis, articulates how to properly evaluate for this condition, and highlights the role of the interprofessional team in caring for patients with this condition.

Objectives:

• Describe the epidemiology of pulmonary sequestration.
• Review the typical presentation of a patient with intralobar pulmonary sequestration and compare it to that of a patient with extralobar pulmonary sequestration.
• Summarize the treatment and management options available for pulmonary sequestration.
• Identify interprofessional team strategies for improving care coordination and communication to enhance the detection of pulmonary sequestration.

Introduction

Pulmonary sequestration is a condition in which a segment or lobe of dysplastic lung tissue exists with no communication with the rest of the tracheobronchial tree and receives an anomalous systemic vascular supply, separate from the rest of the lung. It is, therefore, a nonfunctional tissue.[1] The condition was first described by Pryce as early as 1946.[2] Although Rokitansky and Rektorik described a similar clinical finding way back in 1861.

Anatomy

Pryce originally divided pulmonary sequestration into

• Intralobar and extralobar
• They further subdivided Intralobar into 3 types

Intralobar Sequestration

Intralobar sequestration is characterized by its presence within the visceral pleura of the functioning lung. Venous drainage is into the pulmonary vein.  It is more common in the left lower lobe. Approximately two-thirds of intralobar sequestrations are found in the posterior basal segment of the left lower lobe. It is more common and has a reported incidence of 75% to 86% among all cases of sequestration. An exception to the left-sided preponderance is pulmonary sequestrations associated with Scimitar syndrome (partial anomalous pulmonary venous connection), where right-sided lesions are more common.[3]

Extralobar Sequestration

Extralobar sequestration has a separate visceral pleura and venous drainage. Venous drainage is into the systemic veins, frequently the lower lobe vein, azygos vein, or hemiazygos vein. There have been reported cases of drainage into the subclavian or portal vein as well.

Arterial supply is from systemic vessels–most commonly descending thoracic aorta (73%)  as reported by Savic et al.,[4] the cranial portion of the abdominal aorta, celiac trunk, splenic artery (21%), as well as intercostal arteries. Rare cases of arterial supply from pericardiophrenic, right coronary artery, subclavian, and internal thoracic arteries have been reported.[5]

They are often found between the diaphragm and the lower lobes and rarely infra- diaphragmatically. In spite of the overall male prevalence of pulmonary sequestration, intraabdominal sequestration is most often found in women (75%), usually as a left retroperitoneal mass.[6]

Etiology

Pulmonary sequestration is a congenital anomaly of the primitive foregut. The most plausible theory is the formation of an accessory supernumerary lung bud below the normal lung bud.[7] It continues to migrate caudally with the esophagus in extra lobar sequestration and then derives its blood supply from the primitive splanchnic vessels surrounding the foregut.[8] If lung bud arises before the development of pleura, it results in intralobar sequestration.

Epidemiology

Pulmonary sequestration accounts for 0.15% to 6.40% of all congenital lung malformations.

Sixty percent of intralobar sequestrations are diagnosed at age 20 or younger. It is rarely ever found in the age group older than 50.[9] However, it is the predominant variant in adults. In a case series from Mayo Clinic, reviewing adult patients with pulmonary sequestration from 1997 through 2016, the median age at diagnosis was 42 years.[10] There is a 4:1 male: female ratio for extra lobar pulmonary sequestration prevalence. Thirty percent of pulmonary sequestrations are incidental findings.[11]

Histopathology

Histologically, lung parenchyma in the sequestered segment displays evidence of lymphocytic inflammation and fibrosis. There can be a presence of cystic air spaces lined by cuboidal or columnar epithelium. There may also be alveoli with emphysema-like hyperinflation.

A granulomatous reaction in response to superimposed infection can sometimes be seen.

History and Physical

Nearly half of adults with intralobar sequestration are asymptomatic.

If significant in size and location, extralobar sequestration is usually manifest clinically in early infancy with respiratory distress, high output congestive heart failure (due to right-to-left shunt), and occasional spontaneous pulmonary or pleural hemorrhage. Extralobar sequestrations rarely get infected as they are separated from the tracheobronchial tree by their pleural investment.

Intralobar sequestration frequently remains asymptomatic and gets diagnosed in adults. Apart from asymptomatic patients with incidental diagnosis in chest CT, the most common clinical presentation is of recurrent pneumonia in a localized segment of the lung. It can also be a persistent cough, back pain, or persistent exertional shortness of breath. Intralobar sequestration tends to present with hemoptysis more often.[12]

Associated congenital anomalies occur more frequently with extralobar sequestration than intralobar. About 50% to 60% of patients have another congenital anomaly. It may include congenital diaphragmatic hernia, congenital cystic adenomatoid malformation, vertebral defect, congenital heart disease, tracheoesophageal fistula, pulmonary hypoplasia, bronchogenic cyst, and congenital megacolon. A congenital diaphragmatic hernia is the commonest.[13] Type II cystic adenomatoid malformation of the lung has been reported in 15% to 25% of patients with extralobar sequestration.

Evaluation

Pulmonary sequestration should be suspected as a possible differential in the following:

• A fetus with evidence of polyhydramnios, fetal hydrops, pleural effusion, or pulmonary mass lesion
• Infants with grunting and recurrent respiratory distress, feeding difficulties
• Both adults and children with recurrent pneumonia, lung abscess, and hemoptysis

Antenatal diagnosis of pulmonary sequestration can be achieved by Doppler ultrasound at 18 to 19 weeks of gestation. However, some of them involute spontaneously and even disappear.[14]

Definitive diagnosis requires the establishment of a systemic arterial supply and venous drainage of the sequestered lung tissue.

Conventionally digital subtraction angiography has been the study of choice to demonstrate the lesions well as the anomalous vascular supply. However, multi-planar CT with 3-dimensional reconstruction has taken over as a better noninvasive diagnostic tool. MR angiography is also a reasonable alternative.

Imaging has 2 main goals:

1. To exclude the presence of other thoracic pathologies.
2. To demonstrate the presence of an abnormal arterial supply.

In a CT chest with contrast, the sequestered lung tissue may have a variety of presentations, including a cyst, a mass, a lamellar lesion, a capsulated lesion with an air-fluid level (and thus, falsely interpreted as hydatid cyst or abscess), focal atelectasis, or bronchiectasis. Isolated emphysematous bleb with no functional lung tissue in an atypical location is also a reported presentation.[15]

However, despite the broad use of invasive and CT-guided angiographic techniques, a retrospective review of 72 cases by Xiao et al. showed that 62.5% of cases were diagnosed after surgery, underlining the extent of misdiagnosis before surgery.

Intraabdominal extralobar pulmonary sequestration is very difficult to differentiate from retroperitoneal tumors. For the few reported cases in adults,  the diagnosis was almost always on histopathological examination of the surgical specimen.[16][17][18]

Biopsy of the pulmonary sequestration for confirmatory tissue diagnosis is an area of controversy because of the high risk of bleeding from aberrant arterial and venous structures.[17][19]

As a part of the initial workup, blood and urine catecholamine, cortisol, and aldosterone levels may help in differentiating from adrenal adenoma, pheochromocytoma, and other neurogenic tumors. There are case reports of elevated tumor markers like CA 19-9, which makes it even more difficult to distinguish from retroperitoneal malignancy.

As far as its impact on pulmonary function is concerned, the obstructive disease has been diagnosed in 8.8% of patients. The severity of obstructive disease was mild to moderate in almost all cases. From a pulmonary function standpoint, surgical resection is tolerated well.[20]

Treatment / Management

Intra or extra lobar sequestration diagnosed perinatally requires complicated management in a hospital equipped to provide vigorous resuscitation and appropriate treatment for pulmonary hypoplasia.

If a fetus is less than 30 weeks gestation and is showing signs of hydrops, thoracoamniotic shunting is recommended. Post-delivery of the baby in large sequestration, supportive management with ventilator support, high-frequency oscillatory ventilation or extracorporeal membrane oxygenation (ECMO) may be necessary. Immediate tube thoracostomy is indicated for large pleural effusions. Surgical resection is indicated for symptomatic infants although thoracotomy is deferred until stabilization is achieved in infants with pulmonary hypoplasia and pulmonary hypertension.[21]

Pulmonary lobectomy is the treatment of choice for established pulmonary sequestration. It is recommended even in asymptomatic patients to avoid infection), and progressive inflammation of the lung parenchyma. However, in the largest retrospective case series in adults by Xiao et al., there was a lack of clear evidence of the benefit between preemptive surgery and a conservative approach in asymptomatic patients.[22]

Resection can be achieved by open thoracotomy or video-assisted thoracoscopic procedures  (VATS). In recent years uniportal VATS guided lobectomy has also been successfully performed.[23][24][10] There is no reported difference between the 2 modalities, in terms of duration of surgery, postoperative hospital stay, and complications.[25]

Anesthetic and surgical risks of resection tend to be lower after 2 months of age.

In the retrospective review from Mayo Clinic, 56% of patients underwent surgical resection. The postoperative complication rate was 28%.

Berna et al. also had an equivalent postoperative complication rate of 25% in their sample of 26 adult patients. Complications included prolonged air leak and bronchopleural fistula, hemoptysis, empyema, and arrhythmia.[26]

In the past few years, endovascular embolization and coiling have emerged as a therapeutic alternative.[11] Endovascular embolization reduces blood flow to the sequestered tissue, leading to necrosis, fibrosis and progressive involution. Apart from micro coils, polyvinyl alcohol particles, n-butyl cyanoacrylate glue, Amplatzer plugs, gelatin, and alcohol has been used as embolic agents. A combination of agents has also been reported for use.[11][12][27] Micro coils are preferred in infants as an embolization agent because they can be delivered through smaller diameter catheters.[28] In any setting, more than one vessel needs to be embolized, and more than one coil is necessary to embolize each vessel.[29]

Embolization is associated with a recurrence rate of 25% to 47%. Etiology of recurrence could be:

• Incomplete closure
• Displacement of the embolic agent
• Opening of collaterals
• Formation of shunts

Some authors have explored the role of preoperative embolization of sequestration, to minimize bleeding risk, as the area of sequestration arteries with anomalous blood vessels with fragile wall integrity, thus prone to hemorrhagic complications during surgery.[30]

Differential Diagnosis

1. Cystic adenomatoid malformation
2. Bronchogenic cyst
3. Focal bronchiectasis
4. Congenital lobar emphysema
5. Retroperitoneal tumors in extra lobar abdominal sequestrations

Prognosis

Poor prognostic factors include[21]:

• Presence of fetal hydrops or pulmonary hypoplasia
• Only 22% of fetuses with a large pleural effusion survive
• Extra lobar intraabdominal sequestration tend to have a better prognosis

Complications

Growth abnormalities are often seen with early childhood bronchopulmonary sequestration. Although various theories could explain this, including recurrent infection, high output failure, shunting of blood from the gastrointestinal (GI) tract resulting in malabsorption is possible.[31]

Hemoptysis is the most common complication in adulthood due to high pressure derived from systemic vessels. Hemorrhagic pleural effusion is also common with fibrinoid necrosis in the sequestered tissue.

Recurrent infection is common in intralobar sequestration, and Pseudomonas aeruginosa is the most commonly identified agent. Other agents include tuberculosis, Nocardia, or Aspergillus.[26][22]

Rare cases of extra lobar sequestrations communicating with the GI tract have been reported and need barium studies for diagnosis.[32][31] They are known as congenital bronchopulmonary foregut malformations (CBPFM).

Finally, there has been reported the development of malignant tumors within intralobar sequestration.[33]

Enhancing Healthcare Team Outcomes

Pulmonary sequestration, both intralobar or extralobar, is a rare clinical phenomenon with less than 6% incidence among all congenital lung malformations. Large randomized controlled trials and consensus guidelines regarding diagnostic and management strategies are lacking. Most of the practice standards are based on retrospective case series reviews and single-center experiences.

Management, particularly when diagnosed in infancy, requires a coordinated effort between pulmonologists, radiologists, and thoracic surgeon, in collaboration with an intensive care unit well versed in handling pulmonary emergencies. Once diagnosed, referral to a specialized center equipped for thoracic surgery, interventional radiology, advanced ventilation modalities like high-frequency oscillatory ventilation and extracorporeal membrane oxygenation should be a priority. In adults, the diagnostic workup should establish vascular supply (both arterial and venous), anomalous vessels, coexisting congenital malformations, and any evidence of infection. The establishment of cardiac and pulmonary functional status is essential before definitive treatment, as is the treatment of any underlying infection.

An extensive discussion with the patient (if adult) and family regarding education about the condition, complications, and treatment options are necessary. Although surgery has been historically the standard of treatment, the emergence of embolization as an alternative further requires patient participation in treatment choice, particularly for those with limited pulmonary function or hesitancy toward surgery. Even though surgical resection is the treatment of choice, there is emerging evidence of a neo-adjuvant approach of embolization before surgery to reduce intraoperative hemorrhagic complications.

The exact duration of postoperative surveillance and follow up is yet to be established and is contingent upon individual center standards.