90: Overview of Benign Lung Disease: Anatomy and Pathophysiology

Benign tumor, bronchogenic cyst, pulmonary hamartoma, pulmonary sequestration, bronchiectasis, and arteriovenous malformation (AVM) are the principal benign and acquired conditions of the lung encountered in thoracic surgery. This chapter reviews the etiology, clinical presentation, diagnosis, and therapeutic modalities for each of these benign and acquired conditions. Established surgical techniques are described in the ensuing chapters of this section.

Definition

Bronchogenic cysts are the most common cystic masses in the mediastinum. They are thought to be congenital lesions arising from the primitive foregut. Usually, they are found within the mediastinum or lungs. The mediastinal lesions may be found in close proximity to the carina, mainstem bronchi, trachea, esophagus, or pericardium. Bronchogenic cysts of the skin and subcutaneous tissue also have been reported.

Etiology

The precise embryonic pathway leading to the development of bronchogenic cysts remains unknown. The respiratory tree develops by an outpouching of the primitive foregut during the first 16 weeks of development. Some have theorized that this process fails when a cyst develops in place of the mature structure. These congenital cystic lesions comprise not only the bronchogenic cyst, but also a heterogeneous group of bronchopulmonary malformations, including congenital cystic adenomatoid malformations, sequestrations, congenital lobar emphysema, bronchial atresia, and congenital parenchymal cysts.¹ As with other structures of the bronchus, bronchogenic cysts are lined by ciliated columnar or squamous epithelial cells (respiratory and gastrointestinal). Mucus-secreting bronchial glands found in the epithelium cause the cysts to fill. As the cysts grow, they exert pressure on surrounding structures, particularly the membranous trachea or bronchi, which may lead to severe respiratory obstruction. Cartilage and smooth muscle cells also are found in the cyst wall.

Clinical Features

These cystic malformations may present in the early neonatal period or they may remain entirely asymptomatic until later in life.¹ Symptoms may be evident in both children and adults depending on many factors such as the presence of a communication between the lumen of the cyst and the airways, infection of the fluid within the cyst, and bleeding. If the cyst grows large enough to cause mediastinal shift¹ and obstruction in adjacent structures, the main symptoms will be cough, dyspnea, dysphagia, and chest pain of varying degrees as a result of irritation of the airways and esophagus or inflammation of the mediastinal or parietal pleura. Infectious complications may cause symptoms of fever, elevated leukocyte count, and cough with purulent sputum. Pneumonia localized to the pericystic parenchyma may accompany chronically recurring cysts. Hemoptysis is a sign of an ulcerative process in the cyst wall. Rare complications include cardiac arrhythmias, superior vena cava syndrome, and cancer.

Diagnosis

Plain chest radiographs are diagnostic only when the cavity of the cyst contains an air–fluid level. This finding, especially when the cyst is located in the mediastinum, excludes enterogenous cysts from the differential diagnosis. Plain chest radiography alone can diagnose accurately approximately 80% to 90% of cases and is useful for initial screening.²

CT scanning and MRI give greater detail regarding anatomic and topographic localization, especially with respect to surrounding structures. These imaging modalities also provide detail about wall composition and content of the cyst (Fig. 90-1).

Ultrasound is useful when the cyst is close to the chest wall because it may give information about wall thickness and internal content. Transesophageal endoscopic ultrasound is indicated with paraesophageal cysts. Moreover, the widespread use of prenatal ultrasonography and improvements in the resolution of echography have progressed to the point that many patients with these lesions are identified in utero.¹

Bronchoscopy performed as part of the diagnostic workup for a bronchogenic cyst usually reveals extrinsic bronchial compression. Occasionally, there is evidence of a fistulous communication between the cyst and the bronchial tree.

Any patient who presents with clinical findings suggestive of bronchogenic cyst will require a plain chest radiograph followed by a CT scan of the chest. However, despite advances in diagnostic imaging, a definite diagnosis of mediastinal bronchogenic cyst is ultimately made based exclusively on the results of a biopsy of the surgically resected tissue specimens.³

Therapy

Elective treatment by surgical excision is justified to relieve symptoms in symptomatic patients and to prevent complications in asymptomatic patients. Generally, the excision is technically feasible and easy to perform. However, if there are tight adhesions to the membranous portion of the trachea or mainstem bronchus, or if there is severe inflammation, the excision could be challenging.⁴ Video-assisted thoracoscopic surgical (VATS) resection of bronchogenic cysts is now easily performed and can be considered standard therapy for peripheral lesions³ In cases of intrapericardial bronchogenic cysts, the robotic-assisted approach is particularly suitable. Intrapericardial lesions require meticulous dissection and optimal visualization, both of which are significantly improved with a robotic-assisted approach as compared to a standard video thoracoscopic approach⁵ Other techniques, such as aspiration, cyst wall biopsy, and instillation of sclerosant, can be done with mediastinoscopy. Complete resection is preferred over aspiration because removing the entire cyst prevents recurrences and the possibility of malignant degeneration⁴ (Fig. 90-2).

Definition

Pulmonary hamartomas are benign biphasic lesions consisting of epithelial and mesenchymal tissues.

Etiology

Hamartomas arise more often in men than in women. The lesions exhibit extremely slow growth. Although often arising in young adulthood, they usually are not detected until the sixth or seventh decade. Most individuals have a history of smoking.

Clinical Features

Most pulmonary nodules are located peripherally in the lung without preference for a particular lobe. In this location, they are generally asymptomatic. Central endobronchial hamartomas are less common and are associated with signs and symptoms of obstruction that mimic malignant neoplasms or other benign conditions, including pneumonia or atelectasis. The typical hamartoma is less than 2.5 cm in diameter (range 1–8 cm) and contains fat or calcification with fat. Rare giant hamartomas have been reported,⁶ and instances of multiple endobronchial hamartomas also have been reported.⁷

Diagnosis

Pulmonary hamartoma may exhibit distinct characteristics on high-resolution CT scanning that can often distinguish it from lung cancer nodules. The endobronchial hamartoma appears as an endobronchial mass with or without signs of obstructive pneumonia or atelectasia. CT scan is of considerable diagnostic aid in cases of endobronchial hamartoma with high fat content. Stey et al. considered highly indicative the presence on CT scan of a mass at high fat density without contrast uptake. At bronchoscopic examination, the endobronchial hamartoma appears as a polypoid or pedunculated neoplasm, well-circumscribed, with a smooth and yellowish surface, without signs of submucosal infiltration. Biopsy is necessary for the differential diagnosis from other benign neoplasms and from carcinoid. Histology would usually detect the coexistence of connective, epithelial, bone, muscle, fat, and cartilage tissues, the latter usually in high prevalence.⁸

Fine-needle aspirates also have been used as a diagnostic tool. The differential diagnosis for peripheral hamartomas includes other benign or malignant lung tumors, secondary metastasis, infectious granulomas, amyloidoma, or Carney's triad (i.e., gastric epithelioid leiomyosarcoma, extra-adrenal paraganglioma, or pulmonary chondroma). The differential diagnosis for endobronchial hamartomas includes bronchogenic carcinoma, papilloma, granular cell tumor, adenoid cystic carcinoma, mucoepidermoid carcinoma, carcinoid tumor, leiomyoma, lipoma, tracheobronchopathia osteochondroplastica, and secondary metastasis.

Therapy

Elective treatment by surgical excision is justified to relieve symptoms in symptomatic patients and to rule out malignancy or prevent complications, if deemed likely, in asymptomatic patients. Peripheral nodules can be removed surgically via thoracotomy or VATS wedge resection. Endobronchial lesions are removed bronchoscopically.⁸ Laser treatment through rigid bronchoscopy is considered the gold standard treatment for symptomatic patients with bulky masses on radiological examination. The surgical treatment for endobronchial hamartoma is currently indicated only in cases where the endobronchial lesion cannot be approached through endoscopy, or when lung resection is indicated owing to irreversible parenchymal damage from longstanding airway obstruction.⁹ Rarely, hamartomas are observed to undergo malignant transformation, reinforcing the need for surgical resection.

Definition

Pulmonary sequestrations are rare congenital malformations of the lung (see Chapter 93). They consist of masses of nonfunctioning pulmonary tissues that lack normal communication with the bronchial tree.¹⁰ The condition may occur within the lobar lung tissue (intralobar sequestration) or external to the lobe (extralobar sequestrations), but each type has a direct arterial blood supply from the thoracic or abdominal aorta or from one or more of the intercostal branches of the aorta. Extralobar sequestrations are peculiar because they can be surrounded by pleura, similar to an accessory pulmonary lobe; differentiation is based on the lack of normal communications with the bronchial tree. Although there is no single unifying embryonic hypothesis, it is nonetheless thought that these lesions arise as an accessory bud that then migrates with the developing esophagus. Others have suggested an acquired etiology (inflammatory) for pulmonary sequestrations.

Congenital cystic adenomatoid malformations have been observed within extralobar pulmonary sequestrations, suggesting similar etiologic factors. Eighty-five percent of pulmonary sequestrations are localized in the lower lung zones, more often on the left side. Twenty-eight percent of intralobar sequestrations have a homogeneous appearance, 33% are inhomogeneous, and 39% are cystic. Seventy-seven percent of extralobar sequestrations are homogeneous, and 23% are cystic. Extralobar sequestrations sometimes are associated with diaphragmatic hernias (16%), lung hypoplasia (25%), bronchogenic cysts, and cardiovascular malformations.

Pathophysiology

The macroscopic characteristics of intralobar sequestrations do not differ from those of the normal surrounding tissues. Sequestration is suspected when severe adhesions between mediastinal or diaphragmatic structures or parietal pleura and lung are found. Extrapulmonary sequestrations have a more typical pathologic appearance consisting of a pyramidal or ovoid lesion of approximately 0.5 to 15 cm in length surrounded by its own pleura. Cystic lesions secondary to chronic inflammation and fibrosis that replaces normal lung tissue may be observed in the extralobar sequestration.

The inner layer of the cyst consists of respiratory epithelium or, on rare occasion, squamous epithelium with an eosinophilic amorphous fluid-filled center. In extralobar sequestrations, bronchus/alveolar-like structures lined with respiratory epithelium may be observed. Both types have their own systemic arterial supply, but venous flow occurs through the pulmonary veins for the intralobar type and through the systemic veins for the extralobar type. The arteries that supply the sequestrations have a large caliber (up to 0.5 cm in diameter). In 80% of cases, they arise both from the thoracic and abdominal aorta. In this event, the arteries run through the triangular ligament toward the lower lobes. Abnormal origin in a sequestration arising from the coronary artery has been reported.¹¹

Clinical Features

The two main forms of pulmonary sequestration are associated with different symptoms. In elderly patients, sequestration may be asymptomatic and observed as an incidental finding on chest radiographs, especially the extralobar sequestration. The intralobar types, because of their bronchial communications, may lead to recurrent pneumonia and respiratory distress symptoms (i.e., dyspnea, cyanosis). Hemoptysis is rare but has been reported as an acute symptom.

Diagnosis

Plain chest radiography is nonspecific in the diagnosis of sequestration. Sometimes it shows the presence of a mass in the lower lobes or, if there is communication with the tracheobronchial tree, a cystic lesion. CT scan of the chest is the standard diagnostic tool, and it can demonstrate the presence of a systemic artery supplying the sequestration. Ultrasonography is noninvasive and safe, making its use ideal in prenatal and postnatal settings.¹⁰ Duplex Doppler ultrasound may be used to demonstrate the abnormal systemic vessel that feeds the sequestration. MRI can be useful in the differential diagnosis (bronchogenic cyst versus bronchiectasis versus solitary lung abscess) and for demonstrating mediastinal structures.

Therapy

Medical therapy is based on anti-inflammatory and antimicrobial drugs. Elective treatment is surgical. Anatomic lobectomy is the treatment for intralobar sequestrations. Posterolateral thoracotomy through the lower intercostal spaces is performed for sequestrations of the lower lobes, although a VATS approach has been reported.¹² Retroperitoneal or abdominal sequestrations may require a laparotomy or a thoracoabdominal approach. Robots have been introduced into surgical procedures in an attempt to facilitate surgical performance. The three-dimensional view with depth perception is a marked improvement over the conventional thoracoscopic camera view. All of this creates images with increased resolution, which when combined with the increased degrees of freedom and enhanced dexterity, could enhance the dissection of anomalous vessels.^13–14

Definition

Bronchiectasis was first described by Laennec (Paris, France) in the 1800 s as a bronchial dilatation. This definition is still valid, but it must be added that it is always associated with an alteration of the structural layers of the bronchial wall. The surgical management of bronchiectasis is presented in Chapter 94.

Pathophysiology

Various congenital and acquired disease processes can lead to bronchiectasis. During pulmonary infections, obstructive endobronchial processes localized to the peripheral lung may cause bronchial dilatation. Repeated infections damage the epithelial cilia, mucoelastic tissue, and even cartilage. Healing and replacement of these tissues with fibrous tissue results in loss of elasticity with contraction of the peribronchial tissues and traction on the bronchial tree leading to bronchial dilatation.¹⁵ True bronchiectasis is distinct from pseudobronchiectasis (bronchocele). This latter form of bronchial dilatation is reversible and lasts only a few weeks or months after an episode of bronchopneumonia. The epithelial damage is not severe and is without necrosis.

Sometimes bronchiectasis is caused by bronchial obstruction. The obstruction is created by tiny aspirated endoluminal foreign bodies,¹⁶ benign lymphoadenomatoid-bronchial syndromes, or slow-growth tumorlets such as carcinoids.¹⁷

Bronchial obstruction also can be caused by extrinsic compression from the peribronchial lymph nodes (middle lobe or lingula) in the case of neoplasms or by chronic infections (e.g., histoplasmosis, coccidioidomycosis, aspergillosis, tuberculosis, and AIDS-related infections); see Chapters 102 and 103.¹⁸ Three steps are implicated in the pathophysiology of extrinsic obstruction, namely, secretion retention, chronic infection, and bronchiectasis, as seen before.

Congenital and familial diseases are an uncommon cause of bronchiectasis (Table 90-1). The most important is Kartagener syndrome, or primary ciliary dyskinesia, a rare autosomal recessive disorder involving the combination of situs inversus, bronchiectasis, and sinusitis. A dynein deficiency leads to ciliary dyskinesia. The yellow nail syndrome is a rare clinical entity that combines three main features: yellow discoloration of the nails, chronic lymphedema, and pleural effusion. This syndrome is often complicated by bronchiectasis.¹⁹ The classification of bronchiectasis is morphologic, consisting of three types: (1) cylindrical or tubular, (2) saccular or cystic, and (3) varicose. Cylindrical bronchiectasis has a uniform caliber of dilatation and often is associated with tuberculosis. Saccular bronchiectasis is characterized by an evident dilatation at the distal end, often associated with postinfectious and postobstructive bronchiectasis. Varicose bronchiectasis is a mixed form and presents with alternating areas of saccular and cylindrical dilatation. The subclassification of bronchiectasis is based on blood perfusion. Two types of bronchiectasis are recognized: perfused and nonperfused. Whereas perfused bronchiectasis has intact pulmonary artery flow and cylindrical bronchiectatic changes, the nonperfused type is characterized by a lack of pulmonary artery flow, retrograde filling of the pulmonary artery through the systemic circulation, and cystic bronchiectatic changes.

The location of the bronchiectasis may reveal its pathogenesis. Bronchiectasis related to congenital and familial diseases is always bilateral and involves different segments of the lung. Bronchiectasis related to tuberculosis is located primarily in the upper lobes. Obstructive and inflammatory bronchiectasis is found in the lower lobes. The middle lobe syndrome is a selective localized form of bronchiectasis. The middle lobe bronchus arises with a 30-degree downward open angle from the intermediate bronchus and runs for approximately 2 cm. Lymph node hypertrophy of the angle can easily compress the middle bronchus, leading to atelectasis and bronchiectasis.²⁰

Clinical Features

Bronchiectasis may be symptomatic or asymptomatic.²¹ Bronchiectasis should be considered in all adults who have persistent productive cough (>90% of patients).

Factors favoring further investigation are any one of the following:

• Young age at presentation

• History of symptoms over many years

• Absence of smoking history

• Daily expectoration of sputum (the volume of sputum produced may vary widely with mean/median daily volumes of 300, 567, and 200 mL)

• Sputum colonization with Pseudomonas aeruginosa

• Nonproductive cough or unexplained hemoptysis. This latter symptom, even if rare, may occur and has been reported as a symptom of the type of bronchiectasis associated with coronary fistula.²²

Physical examination of the chest may reveal coarse expiratory rhonchi and dullness over localized areas, especially during periods of acute infectious exacerbation.

Diagnosis

Standard chest radiography is often not useful because it shows only nonspecific inflammatory radiographic signs (Fig. 90-3). In the past, the ideal radiographic method was, and in some cases still is, a bronchogram. This procedure provides information about the morphology, localization, and extent of the bronchiectasis (Fig. 90-4). High-resolution, fine-cut CT scan is the procedure of choice for the diagnosis of bronchiectasis.²¹

CT is able to show the extent of the disease bilaterally and gives information about the walls of the bronchioles, including the presence of peribronchial inflammation and parenchymal disease (Fig. 90-5).

Flexible fiberoptic bronchoscopy is useful for evaluating bronchial neoplasms and endoluminal foreign bodies or obtaining samples for bacterial culture to start specific antibiotic therapy. Bronchoscopy permits biopsy of the respiratory mucosa for the diagnosis of hereditary mucociliary disorders.

Therapy

The treatment aims in adult care are to control symptoms and thus enhance quality of life, reduce exacerbations, and maintain pulmonary function. The evidence is clear that patients with bronchiectasis who have more frequent exacerbations have a worse quality of life.²¹

Medical

Postural drainage is the most effective treatment for mobilizing the thick bronchial secretions but it requires the skills of a trained respiratory physiotherapist. To treat infections, a sputum culture should be performed. Targeted antibiotic therapy is started if an acute infection of the lung is present or for a preoperative workup. Patients with primary or secondary immune deficiency should be under joint care with a clinical immunologist.²¹

The conservative therapeutic approach should be continued for several months. Annual vaccination against influenza and pneumococcus is recommended.

Surgical

Indications for surgery reported in the literature have included failure of medical/conservative therapy, recurrent respiratory infections, persistent sputum production, hemoptysis, chronic cough, and persistent lung abscess.^21,23–26

Complete excision of the bronchiectatic parenchyma is the goal of surgery. Patients considered candidates for surgical resection must meet the following criteria: (1) localized bronchiectasis that is completely resectable, (2) adequate respiratory reserve, (3) irreversible process versus an early treatable condition, (4) significant symptoms with a continued chronic productive cough, significant hemoptysis, major recurring episodes of pneumonia sufficiently severe to warrant surgery, and (5) failed prolonged attempts at medical therapy.²⁷

For massive pulmonary hemorrhage, endobronchial suction with balloon tamponade, embolization of the bleeding vessel (usually a bronchial artery), or emergency resection can be lifesaving. The surgical approach involves anatomic resection of all targeted areas. The anatomic resection depends on the origin of the bronchiectasis. Tuberculous bronchiectasis typically requires resection of the upper lobes, whereas postinfective bronchiectasis usually involves resection of the lower lobes or lingula (Fig. 90-6). Abundant mucopurulent secretions must be treated with particular attention to prevent contamination of the normal airways. Lung transplantation is available for end-stage cardiopulmonary disease in children and adults, although there is a paucity of literature on bronchiectasis specifically. As a general guideline, patients are evaluated for lung transplantation if the FEV₁ is <30% or if there is rapid, progressive respiratory deterioration despite optimal medical management. The following additional factors should lower the threshold for considering referral for transplantation assessment: massive hemoptysis, severe secondary pulmonary hypertension, multiple ICU admissions, or respiratory failure (particularly if requiring noninvasive ventilation). It should be noted that antibody deficiency is not an absolute contraindication to transplantation.^21,28–29

Surgical treatment of bronchiectasis is more effective in patients with localized disease. Excision in such patients is satisfactory with an acceptable rate of morbidity and mortality. Mortality and morbidity rates range from 1.7% to 3.5% in different case series (Table 90-2).

Surgical treatment of bronchiectasis is used widely, but there appear to be no randomized, controlled trials. It is not possible to provide an unbiased estimate of its benefit compared with conservative therapy.³⁰ Addition of a vascularized muscle flap should be considered to prevent postoperative infection.

Definition

Pulmonary AVMs are caused by abnormal communications between pulmonary arteries and pulmonary veins and are most commonly congenital in nature (see Chapter 95). Although these lesions are quite uncommon, they are an important part of the differential diagnosis of common pulmonary problems such as hypoxemia and pulmonary nodules. Since their first description at autopsy in 1897, these abnormal communications have been given various names, including pulmonary arteriovenous fistulas, pulmonary arteriovenous aneurysms, hemangiomas of the lung, cavernous angiomas of the lung, pulmonary telangiectasias, and pulmonary AVMs. Abnormal communications among blood vessels of the lung also may be found in a variety of acquired conditions. Right-to-left shunting as a result of communications between pulmonary arteries and pulmonary veins has been reported in many diseases. Communications between bronchial arteries and pulmonary arteries causing left-to-right shunting can develop in chronic inflammatory conditions such as bronchiectasis. Many patients with pulmonary AVMs have hereditary hemorrhagic telangiectasia.

Embryology

By the fourth week of gestation, the respiratory tract can be seen as a groove in the ventral wall of the foregut. The blood vessels of the lung are derived from two sources, namely, the plexiform network of vessels that develops in the pulmonary mesenchyme and the heart. Like bronchi, the vessels may vary in their course based on the eventual development of channels from the preexisting mesenchymal network. During blood vessel development, primitive arteriovenous connections form to initiate the flow of blood. Subsequent vascular remodeling results in normal vessel development. AVMs result from unknown stimuli during the stage of arteriovenous communications in the retiform plexus.

Diagnosis and Clinical Features

Clinical symptoms of AVM are based on the grade of the right-to-left shunt. Hemoptysis,³¹ dyspnea on exertion, congestive heart failure, or a major neurologic event such as stroke or cerebral abscess may be present.³² In patients with Rendu–Osler–Weber syndrome, cutaneous and mucosal spider angiomas are present.^33–34

On physical examination of the thorax, a continuous murmur may be heard over the involved area of the thorax, especially if the AVM is quite large. Standard chest radiographs may reveal a solid round or oval mass of uniform density, frequently lobulated but sharply defined, more commonly located in the lower lobes, and ranging from 1 to 5 cm in diameter. As such, it may be difficult to differentiate from a lung tumor (Fig. 90-7).

CT scan of the chest may provide information about the vascular origin of the mass (Fig. 90-8), but a selective angiogram of the pulmonary artery is essential to localize the AVM, determine its extent, map the AVM for preoperative workup and consideration for therapeutic embolization (Fig. 90-9). Right-to-left shunt entities may be measured by radionuclide perfusion scans of the lung.

Therapy

A small quiescent AVM may be managed conservatively, using the “watch and wait” approach. If the AVM becomes symptomatic, however, the treatment options are embolization or surgery. Localized and large AVMs require a surgical approach. Surgical resection as a mode of treatment for pulmonary AVM carries (at least) the same risks as any other thoracic operation. Surgical resection is not feasible as a primary treatment in patients with masses that are too large and have an overly extensive blood supply. In such cases, preoperative embolization may help to reduce blood flow within the vascular mass and thereby prevent life-threatening intraoperative bleeding. On the downside, lesions that are incompletely excised have a higher risk of recurrence.³⁵

Lobectomy (Fig. 90-10) or wedge resection³⁶ via thoracotomy or VATS is the standard procedure when surgical resection is indicated.³⁷ Multiple bilateral AVMs may require a bilateral approach and multiple resections.³⁸ Small or multiple pulmonary AVMs may be treated conservatively with angiographic embolization using different techniques such as balloons, springs, coils, and thrombogenic materials.^39–40

This section on benign lung diseases concludes with a review of benign and metastatic pediatric pulmonary tumors (Chapter 96).