Bronchial Adenoma 

Updated: Sep 19, 2019
Author: Charles W Van Way, III, MD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP 

Overview

Practice Essentials

Bronchial adenoma is a descriptive but misleading term for a diverse group of respiratory tract neoplasms that arise beneath the bronchial epithelium or in bronchial glands. They are characterized by a clinical course that is usually more benign than that of bronchogenic carcinoma. Three types make up approximately 95% of bronchial adenomas:

  • Carcinoids (2 types of bronchial neuroendocrine tumors) account for 85% of bronchial gland tumors and 1-2% of all lung malignancies.
  • Adenoid cystic carcinoma (ACC), which commonly arises in a salivary gland, accounts for 10% of bronchial adenomas (0.04-0.2% of all lung cancers). [1]
  • Mucoepidermoid carcinomas (MEC) account for 1-5% of all bronchial gland tumors (0.1-0.2% of all lung tumors). [2]

Mucous gland adenomas (ie, bronchial cysts, papillary cystadenomas) are rare submucosal tumors arising from mucous glands and truly are benign tumors. Mesodermal and other lesions can also arise in the tracheobronchial tree. 

Bronchial carcinoids are part of a spectrum of neuroendocrine tumors (see below), of which only the first 2 are considered bronchial adenomas. Bronchial neuroendocrine tumors, including tumor type and level of malignancy, are as follows:

  • Typical carcinoid (Kulchitsky type I) - (+)
  • Atypical carcinoid (Kulchitsky type II) - (++)
  • Large cell neuroendocrine carcinoma - (+++)
  • Small cell carcinoma (Kulchitsky type III) - (++++)

Up to 60% of patients have no symptoms. This is more likely if the adenoma is located peripherally as opposed to proximally. When present, symptoms are related to the presence and degree of endobronchial occlusion and the vascularity of the tumor. Hemoptysis occurs in 18%, recurrent infection or cough in 17%, dyspnea or wheezing in 2%, and carcinoid syndrome in 1%. As a result of these symptoms, prolonged treatment for another suspected condition (eg, pneumonia, asthma, COPD) frequently precedes the actual diagnosis.

In the absence of distant metastases, the treatment of choice is complete removal of the primary carcinoid with maximal parenchymal preservation. This is based on the knowledge that most bronchial adenomas are only locally invasive.

Although ACC is a low-grade malignant tumor and complete resection is the preferred treatment, surgical intervention is often not possible, because of late diagnosis and tumor location. Radiation therapy is the best option for unresectable tumors. Chemotherapy is not effective for ACC.[3]  

The treatment of MECs is usually surgical, by traditional or sleeve lobectomy, performed with an open or video-assisted technique, especially for low-grade early-stage lesions.[4]

Pathophysiology

Symptoms develop from the growth of the tumors within the tracheobronchial tree, with consequent obstruction leading to cough, hemoptysis, atelectasis, or pneumonia.[5]

Adenoid cystic carcinoma behaves very similarly to major and minor salivary gland tumors. An important aspect of these tumors is that they tend to spread in a submucosal plane along the perineural lymphatics, beyond the obvious endoluminal margins of the tumor. Most do not metastasize; however, total excision by tracheal resection or tracheobronchial resection is not always possible because of extensive submucosal spread, and local recurrence remains a possibility.

Mucoepidermoid carcinoma (MEC) originates from glandular tissue located in the submucosa of the trachea and bronchus. It is characterized by a mixture of mucus-producing, glandular, and squamous epithelial cells, as well as intermediate cells with both properties at various percentages, and by various growth patterns such as cystic, papillary, and solid structures. Mucus-producing cells form lumens in some cases.

MECs are classified as high grade or low grade on the basis of their histologic appearance. Low grade malignant tumors have mostly cystic components. Microscopic invasion into pulmonary parenchyma is unusual. Mild cytologic atypia can be seen. Metastasis to regional lymph nodes is unusual. High-grade tumors more commonly show areas of solid growth. Atypia, mitotic activity, and necrosis are characteristic, and regional lymph node involvement is more frequent in these tumors.[2]  

Tumor location

The location of carcinoid tumors is as follows:

  • Lobar or segmental location - Approximately 60%
  • Main bronchus - Approximately 20%
  • Peripheral - Approximately 20%
  • Carinal or tracheal – Infrequent
  • Multiple sites – Rare

Most cases of ACC arise from the central tracheobronchial regions; approximately 10% arise in the peripheral bronchi.[1] The majority of MECs arise from bronchial glands in the lumen of a main, lobar, or segmental bronchus. 

Paraneoplastic involvement

Endocrinopathies associated with bronchial carcinoids include Cushing syndrome (with increased corticotropin levels), hyperpigmentation (excess melanocyte-stimulating hormone), syndrome of inappropriate excretion of antidiuretic hormone, and hypoglycemia. In addition, bronchial carcinoids may be associated with multiple endocrine neoplasia syndrome in up to 4% of patients, the majority of whom are female.

Carcinoid syndrome is a clinical entity that includes cardiovascular, gastrointestinal, respiratory, and cutaneous manifestations. Carcinoid syndrome occurs most commonly when gastrointestinal carcinoids metastasize to the liver and less frequently when due to bronchial carcinoids. Serotonin seems to play a major role in the manifestations of carcinoid syndrome. When released into the bloodstream from gastrointestinal carcinoids, serotonin is broken down in the liver. However, in the presence of liver metastasis, serotonin has a diminished opportunity to be exposed to hepatic metabolism.

Bronchial carcinoids seem to produce diminished amounts of serotonin, and carcinoid syndrome is uncommon; however, when it does occur as a result of a bronchial carcinoid, it may be unusually severe. Carcinoid syndrome can be associated with cardiac valvular fibrotic lesions. These are usually on the right side when the syndrome is due to hepatic metastases, but they may be on the left side in the presence of a right-to-left cardiac shunt or carcinoid syndrome due to a bronchial carcinoid.

Cushing syndrome is reported in as many as 6% of patients with bronchial carcinoid, and represents the second most common paraneoplastic syndrome. An occult bronchial carcinoid should be sought in a patient with Cushing syndrome that has no evident adrenal or pituitary source. Cushing syndrome due to bronchial carcinoids is most often the result of peripherally located tumors, many of which may be radiographically occult. Carcinoid metastases maintain a corticotropin hypersecretory status despite resection of the primary tumor.

For more information, see Carcinoid Lung Tumors.

Etiology

Bronchial carcinoids are thought to arise from Kulchitsky cells. These neuroendocrine cells, formerly classified as amine precursor uptake and decarboxylation cells, produce and store biogenic amines and peptides. Typical carcinoids originate as clusters of monotonous polyhedral cells in a fibrovascular stroma. Ultrastructurally and immunoreactively, carcinoids share characteristics with small cell neuroendocrine carcinoma of the lung.

Adenoid cystic carcinoma (ACC) originates from salivary gland tissue. Occasionally, some tumor cells in this variant are of myoepithelial origin. These tumors have several other names, including cylindromas, adenoid cystic basal cell carcinomas, adenomyoepitheliomas, and pseudoadenomatous basal cell carcinomas.

Mucoepidermoid carcinomas originate from trachea and, more commonly, the proximal bronchi. These tumors are of squamous and intermediate elements, with intercellular bridges. They have the same microscopic appearance as mucoepidermoid carcinoma of the salivary glands, arise in glandular submucosa, and manifest as submucosal lesions.[6]

Mucous gland adenomas (ie, bronchial cysts, papillary cystadenomas) are rare submucosal tumors arising from mucous glands and truly are benign tumors.

 

Epidemiology

Bronchial adenomas represent 1-3% of pulmonary malignancies. Carcinoids account for approximately 85% of bronchial adenomas and 1-2% of all lung malignancies. Almost all bronchopulmonary carcinoids are clearly primary tumors, rather than metastatic. Approximately 84% of bronchial carcinoids are typical and 16% are atypical. Adenoid cystic carcinomas (ACCs) account for 10% of bronchial adenomas. Mucoepidermoid carcinomas (MECs) account for 1-5%. The racial distribution is equal, as far as can be determined for these uncommon tumors, and men and women appear to be equally affected.

The prevalence is highest in persons aged 30-50 years, and the mean age at presentation is 43 years. The incidence varies somewhat with the type of bronchial adenoma.

Looking specifically at bronchopulmonary carcinoids, a wide age distribution is also seen with bimodal peaks in the fourth and sixth decades of life. Individuals older than 50 years are more likely (25%) to develop atypical carcinoid than those younger than 30 years (< 10%).

Although adenoid cystic carcinoma affects persons of any age, the metastatic variety tends to occur in younger persons.

MECs generally affects younger patients than the more common non–small cell lung cancer (NSCLC). In one series, more than 50% of the patients were under 30 years of age, while in another, the mean age was 34 years.[4] However, mean ages between 50 and 55 years have also been reported.[2] High-grade MEC appear to occur more frequently in older patients, compared with low-grade MEC.[6, 4]  

Prognosis

Carcinoids

The slow growth pattern of carcinoids often prolongs the natural history of the disease process. In typical carcinoids, excellent long-term survival is frequently seen, with only about 15% of deaths being due to the carcinoid tumor. A 5-year patient survival rate of 92% and 10-year survival rate of 88% has been reported for typical carcinoids treated with complete resection and formal mediastinal dissection. These excellent results applied to patients with both N1 and N2 disease, although those with N2 status received adjunctive radiation therapy. Low rates of recurrence (3-5%) are also characteristic of typical carcinoid.

In comparable atypical carcinoids (pN1,2), the survival rate is decreased to 60% at 5 years and 49% at 10 years. Approximately 25% of patients will experience recurrence. Most deaths in patients with atypical carcinoid are due to recurrence.

Adenoid cystic carcinoma

Patients with ACC have an excellent prognosis because the tumor grows slowly and is radiosensitive.The course of the disease is usually 2 to 3 years, and in some cases it can last more than 10 years.[7]  After resection, the 5-year survival rate is approximately 83% and the disease-free survival rate is 60%. The best results are achieved when complete resection is accomplished; however, prolonged patient survival is possible even with incomplete resection.[1]

Mucoepidermoid carcinoma

Metastasis of low grade MEC of the lung is rare and patients with low grade MECs generally have a good prognosis following resection, with a 5-year survival rate of 95%. Adjuvant treatment is considered unnecessary. Effective treatments for high-grade tumors have not been established, and these cases have a poor prognosis.[2] This tumor is known to cause intracranial metastases and chemotherapy and radiation are used mainly for palliation.[6]

 

Presentation

History

Up to 60% of patients with bronchial adenomas have no symptoms. Asymptomatic disease is more likely if the adenoma is located peripherally as opposed to proximally. When present, symptoms are related to the presence and degree of endobronchial occlusion and the vascularity of the tumor. Hemoptysis occurs in 18%, recurrent infection or cough in 17%, dyspnea or wheezing in 2%, and carcinoid syndrome in 1%. As a result of these symptoms, prolonged treatment for another suspected condition (eg, pneumonia, asthma, COPD) frequently precedes the actual diagnosis.

Endobronchial symptoms

Manifestations of endobronchial involvement include the following:

  • Classic triad of cough, hemoptysis, and recurrent infection
  • Dyspnea
  • Wheezing and stridor
  • Sputum production
  • Pneumonia

Mediastinal involvement

Signs and symptoms of mediastinal involvement include the following:

  • Hoarseness due to recurrent laryngeal nerve involvement
  • Chylothorax due to thoracic duct involvement
  • Chest pain

Systemic

Systemic signs include the following:

  • Endocrinopathies
  • Unexplained weight loss
  • Low-grade temperature elevation

Physical

Physical examination generally is unrevealing, but subtle findings may provide clues. In addition, the physical examination may help in finding other confounding disease processes.

Respiratory findings include upper airway obstruction, with stridor and wheezing, dyspnea, and hoarseness. 

Extrapulmonary manifestations are rare, but may include mechanical compressive and obstructive syndromes such as those seen in other thoracic malignancies and include the following:

  • Pancoast tumor - Superior sulcus tumor causing pain (eg, shoulder, forearm, arm, scapula), Horner syndrome, and atrophy of upper extremity musculature

  • Acute spinal cord compression – Paraplegia, sensory deficits, urinary retention/incontinence, and vertebral pain

  • Superior vena cava syndrome – Head congestion/fullness; headache; nasal congestion; dyspnea; cough; orthopnea; dilated veins in the upper extremity, neck, and face; upper extremity and facial edema; papilledema; facial cyanosis; and mental status changes

 

DDx

Diagnostic Considerations

Aspergillosis: This may occur in association with malignant disorders. Uncommonly, it accompanies benign carcinoid and can lead to a delay in diagnosis of the adenoma.

Recurrent lobar pneumonia: Consider primary endobronchial tumor as the etiology, especially in children.

Asthma: The misdiagnosis of asthma is not an uncommon error with obstructing tracheobronchial lesions.

Differential Diagnoses

  • Bronchogenic carcinomas

  • Granulomatous diseases

  • Hamartoma

  • Metastatic cancer

  • Squamous cell carcinoma of the trachea

 

Workup

Approach Considerations

No single investigative method is adequate to diagnose bronchial tumors in all patients, but most tumors are detectable. Radiographic and procedural techniques are usually required to locate lesions.

Laboratory Studies

Laboratory studies include the following:

  • Complete blood cell count (CBC) - Results are not diagnostic but can help in differentiation of an infiltrate as a pneumonia; it is useful to help quantify volume of hemoptysis associated with endobronchial lesions.
  • Serum electrolytes, BUN, creatinine, and calcium - Results may assist in the evaluation of paraneoplastic involvement.
  • Liver function tests - Results are insensitive as indicators of hepatic metastases. 
  • Arterial blood gases - Results are useful for the detection of respiratory failure (eg, acidosis, hypercarbia, hypoxia).
  • Sputum culture and cytology  - These are rarely helpful in diagnosing bronchial adenomas.

Tumor markers

Tumor markers include the following:

  • Corticotropin
  • Antidiuretic hormone
  • Calcitonin
  • Bombesin
  • Neuron-specific enolase
  • Serotonin
  • Synaptophysin

All the above-mentioned markers also can be identified in small cell lung cancer; therefore, their presence offers no diagnostic value in distinguishing between these 2 tumor types.

Biochemical testing

Neither blood screening nor urine screening for serotonin or 5-hydroxyindoleacetic acid is of diagnostic value, unless carcinoid syndrome is clinically present. If it is, the presence of these biochemical abnormalities portends a more adverse prognosis.

Immunohistochemical staining

This may help detect differences in secretory products between typical carcinoids and others.

Imaging Studies

Chest radiography

Radiological findings are frequently nondiagnostic. Films may demonstrate a nodule, mass, infiltrate or atelectasis, mediastinal or hilar lymphadenopathy, or pleural effusion. Findings may be due to bronchial obstruction. Oblique-view radiographs provide improved detectability of central lesions and may delineate an occult endobronchial component.

Chest radiograph findings are normal in about 5% of patients with bronchopulmonary carcinoid. 

MECs are generally well circumscribed, round, oval or lobulated masses. Signs of bronchial stenosis or obstruction are frequent.[2]

CT scanning

CT scanning is the best imaging modality.  Upon nodule discovery, obtain 10-mm CT cuts through the chest and upper abdomen. Fine cuts (eg, 1- to 2-mm) should be obtained through nodules, looking for calcifications. Tracheobronchial obstruction is suggested by compression of structures in close proximity to the trachea on the chest CT scan. Three-dimensional reconstruction may aid in localization of endobronchial tumors.

CT scanning further delineates endobronchial and parenchymal tumor components. Prior to the development of CT scanning, tomography and bronchography were used to delineate endobronchial obstruction and bronchiectasis distal to the mass. CT scanning supplants both of these tests; neither is currently indicated.

Central lesions are observed as well-defined masses that narrow, deform, or obstruct adjacent airways. Diffuse punctuate calcifications are observed in 30% of cases and are characteristic but not diagnostic of carcinoid.

Peripheral parenchymal atelectasis or bronchiectasis is common. Peripherally located lesions are contiguous with the airway. They are typically described as rounded, homogenous, sharply demarcated, and slow-growing. Despite their peripheral location these lesions are often buried deep within the parenchyma, making wedge resection difficult.

Typical carcinoid is marked by homogeneous contrast enhancement; atypical carcinoid is associated with less contrast enhancement and frequent irregular contours; regional adenopathy is common.

Stromal osseous metaplasia due to tumor-induced necrosis of bronchial cartilage is observed on CT scans as intratumoral calcification.

CT is highly accurate in the assessment of ACC tumor location, extra luminal extensions, carinal involvement and distant metastasis. ACC appears as a focal mass in the trachea or main bronchi with a smooth border as it arises from submucosa. It may involve more than half of the airway circumference. This tumor can also be differentiated from MEC because of its frequent extra-luminal extension. Lymphadenopathy and distant metastases are uncommon and the local recurrence is most common.[8]

The majority of MECs arise from bronchial glands in the lumen of a main, lobar, or segmental bronchus, and CT findings are similar to those of bronchial carcinoid tumors.[2]

MRI

This is probably most often used when CT scan findings are equivocal.

Positron emission tomography

The positron emission tomography (PET) tracer F-18-fluorodeoxyglucose (FDG) has been used to detect bronchogenic carcinoma. Because of their low metabolic rate, carcinoid tumors may not consistently "light up" with PET-FDG scanning. Sensitivities range from 14-100%. Thus, the reliability of a positive or negative test result is unknown and, therefore, the routine use of PET scans is discouraged.

Radiolabeled peptides

Because carcinoid tumors, like other neuroendocrine tumors, may contain somatostatin receptors, the radiolabeled peptides may be useful. The 2 reported to be of greatest merit are [(111In0-DPTA(0)] octreotide (Octreoscan, Mallinckrodt; Petten, The Netherlands) and 99m technetium Tc depreotide single-photon emission CT scanning (NeoTect, Diatide; Londonderry, NH). However, about one third of carcinoid tumors are somatostatin-negative whereas the rest are weakly positive and, thus, difficult to distinguish from inflammation.

Furthermore, octreotide scan results are positive in almost all patients with lung cancer (NSCLC and SCLC), pneumonia, and lymphoma. Therefore, given the relatively high cost and low clinical yield, routine use of octreotide scanning is not recommended in bronchopulmonary carcinoid.

Nuclear imaging

This can include bone scanning when applicable.

Other Tests

Spirometry

Peak expiratory flow is a good bedside detector of significant airflow obstruction. Flow volume loops indicate truncation of the expiratory limb.

Procedures

Fine-needle aspiration

Fine-needle aspiration (FNA) biopsy of peripheral lesions may yield a diagnosis, including revision of incorrect interpretations (eg, bronchial carcinoid misinterpreted as small cell carcinoma).

FNA biopsy may be part of the bronchoscopic examination of submucosal lesions. Frozen section examination of FNA biopsy specimens may be misleading because of the tumors' similarity to small cell carcinoma. Permanent hematoxylin and eosin preparations usually lead to the correct diagnosis, although confusion regarding atypical carcinoid still may lead to an inaccurate diagnosis.

Bronchoscopy

Eighty percent of bronchial adenomas are visible under bronchoscopy, which is usually successful in localizing within and proximal to segmental orifices. See the images below.

Bronchoscopy: Carcinoid tumor (Left Lower Lobe - A Bronchoscopy: Carcinoid tumor (Left Lower Lobe - Anteromedial Basal)
Bronchoscopy: Carcinoid tumor (Left Lower Lobe - A Bronchoscopy: Carcinoid tumor (Left Lower Lobe - Anteromedial Basal)

Flexible bronchoscopy represents the main diagnostic tool for MECs, because it allows direct visualization of the lesions and biopsies, although extraluminal or peripheral lesions cannot be assessed.[4] Typical appearance is that of a smooth, reddish-brown lesion often covered by mucosa. Accurate identification requires bronchial biopsy; biopsy should be performed.[4]

Bleeding can occur, but reports of massive hemorrhage associated with biopsy are exaggerated. Most episodes of postbronchoscopy hemorrhage have followed attempts at partial or complete removal rather than simple biopsy. The submucosal location necessitates a biopsy deeper than usual. Dilute epinephrine is a helpful adjunct to prevent bleeding. General anesthesia and rigid bronchoscopy may be required for airway control if persistent hemorrhage occurs following fiberoptic bronchoscopy.

Bronchoscopy should be performed in all candidates for a bronchoplastic procedure in order to precisely define the limits of the planned bronchial resection.

If the endoscopist is not prepared to deal with airway bleeding, biopsy should be deferred until the patient has been sent to an appropriate facility.

Thoracentesis

This can aid in diagnosis via cytological studies that confirm other diagnoses in the differential.

Thoracentesis can also be therapeutic when large pleural effusions cause respiratory insufficiency

Ultrasound guidance may be helpful when dealing with small effusions.

Mediastinoscopy

It is of little value in preoperative nodal staging in bronchial adenomas, unless mediastinal involvement is suspected.

It should be reserved for atypical carcinoid or for when evidence of mediastinal involvement is seen with CT scanning.

Even with mediastinal node involvement, resection of a carcinoid with mediastinal lymph node dissection provides excellent local control and 5-year survival.

Histologic Findings

Carcinoids originate from bronchial epithelial stem cells and are not of neural crest origin. Grossly, they appear as soft, highly vascularized, and pink-to-purplish tumors. They are usually covered by intact epithelium, which occasionally has squamous metaplasia, and ulceration can be present. Carcinoids usually are sessile, but they can be polypoid. They may penetrate the bronchial wall and occasionally may show parenchymal or peribronchial nodal extension.

Microscopically, the cells are uniform and round-to-polygonal; however, when they are located peripherally, a spindle shape predominates. The cellular arrangement usually involves small clusters, interlacing cords, or both, separated by well-vascularized connective tissue. Nuclei are small and oval, and finely granular chromatin with abundant eosinophilic cytoplasm is observed. Typical carcinoids, or Kulchitsky cell type I neuroendocrine tumors, have less than 2 mitoses per 2 mm2 and they lack necrosis.

Atypical carcinoids, or Kulchitsky cell type II neuroendocrine tumors, have carcinoid morphology with 2-10 mitoses per 2 mm2 or necrosis. They exhibit malignant histologic features and aggressive behavior. They exhibit pleomorphism, more mitotic activity, nuclear abnormalities, prominent nucleoli with peripheral palisading, and necrosis.

Kulchitsky type III cells are thought to be the cells of origin of small cell carcinoma.

A rare, pigmented, melanocytic variety of carcinoid has been described and is differentiated from melanoma.

An oncocytic type is a rare subtype of typical lesions with mixed cellular content, including typical carcinoid cells and large eosinophilic oncocytes. True oncocytic differentiation occurs.

Adenoid cystic carcinomas are slow-growing tumors with the propensity for submucosal invasion, perineural invasion, and distant metastasis. Numerous prominent mitochondria and serous secretory granules can be observed with electron microscopy.

Mucoepidermoid tumors are characterized by a mixture of mucus-producing, glandular and squamous epithelial cells, as well as intermediate cells with both properties at various percentages, and by various growth patterns such as cystic, papillary, and solid structures.[2]  Low grade malignant tumors have mostly cystic components and mild cytologic atypia . Microscopic invasion into pulmonary parenchyma and metastasis to regional lymph nodes is unusual. High grade tumors presents areas of solid growth, with atypia, mitotic activity and necrosis, and may be difficult to distinguish from lung adenosquamous carcinomas. Regional lymph node involvement is more frequent in these tumors.

Tumorlets are foci of atypical hyperplastic bronchial epithelium less than 5 mm in diameter that appear histologically similar to carcinoid. These lesions are more commonly seen in middle-aged or older individuals with chronic pulmonary pathology. They are usually an incidental finding in a resected specimen or are found during an autopsy. These lesions, present in 7-10% of patients with pulmonary carcinoid, do not represent metastasis and should not alter treatment planning.

Staging

Bronchopulmonary carcinoids are staged according to the AJCC TNM staging classification used for lung cancer. Size, nodal involvement, and presence of metastases have all been shown to be significant predictors of survival. Nodal status becomes particularly important given the relatively smaller size of carcinoid tumors when compared to NSCLC. About 90% of typical carcinoids are pN0 (Stage I) at presentation, as are about 60% of atypical carcinoids.

 

Treatment

Approach Considerations

In the absence of distant metastases, the treatment of choice is complete removal of the primary carcinoid with maximal parenchymal preservation. This is based on the knowledge that most bronchial adenomas are only locally invasive.

Although adenoid cystic carcinoma (ACC) is a low-grade malignant tumor and complete resection is the preferred treatment, often because of late diagnosis and tumor location surgical intervention is not possible. Radiation therapy is the best option for unresectable tumors. Chemotherapy is not effective for ACC.[3]  

The treatment of mucoepidermoid carcinomas (MECs) is usually surgical by traditional or sleeve lobectomy, performed with an open or video-assisted technique, especially for low-grade early-stage lesions.[4]

See Surgical Care, below.

Medical Care

Chemotherapy

Combination therapy, as is used for small cell lung carcinoma, has some effect in treating metastatic carcinoids. However, the response rate is only approximately 50%. Adjuvant chemotherapy along with postoperative radiation has been advocated for atypical lesions associated with mediastinal nodal extension.

Radiation therapy

Carcinoid tumors are generally radioresistant. Anecdotal reports describe tumor responses in inoperable cases. Radiation therapy is recommended for postoperative management of incompletely resected atypical lesions and in the presence of mediastinal nodal involvement. Data supporting the efficacy of this treatment are lacking.

Adenoid cystic tumors are radiosensitive and postoperative radiotherapy is of value.

Surgical Care

Surgical resection is the mainstay of treatment for patients with bronchopulmonary carcinoid. Radical surgery based on lung cancer treatment is performed for MEC, and this operation has increasingly performed using video-assisted thoracic surgery (VATS). MECs of the lung are often treated by lobectomy, sleeve resection, local resection, segmental resection, or endoscopic removal.[2]

Endoscopic resection: bronchoscopic resection

This procedure is plagued by incomplete tumor removal, with frequent recurrence due to extraluminal tumor bulk, often with limited tumor visibility and accessibility via the bronchoscope. It also carries a high risk of hemorrhage. Patient selection is important, as only about 5-10% of carcinoid tumors are polypoid lesions without extension through the cartilaginous wall.

Bronchoscopic resection is warranted to alleviate bronchial obstruction in patients in whom thoracotomy poses prohibitive risk. Additionally, occasional preoperative use of this technique may allow assessment of the reversibility of distal parenchymal damage. Finally, the technique of argon-beam electrocoagulation may be very useful for bronchoscopic control of bleeding prior to definitive resection.

Endoscopic resection: Neodymium:Yttrium-aluminum-garnet laser

The Nd:YAG laser reduces the risk of hemorrhage-related complications by means of photocoagulation. It is not recommended as a primary mode of tumor removal. Rarely, the Nd:YAG laser is applicable to a polypoid, easily accessible lesion on a narrow, uninvolved stalk.

Surgical resection

In the past, as many as 62% of patients with bronchial adenomas underwent lobectomy or pneumonectomy. They frequently had significant delays in their diagnosis and had complete obstruction of a bronchus with distal parenchymal destruction. Complete tumor removal, removal of all destroyed lung parenchyma, nodal dissection, and preservation of functional parenchyma are the goals of resectional therapy.

Surgical procedures overview

Preoperative endobronchial resection may be used as part of the preparation of the patient for surgical resection.

Bronchotomy/bronchial wedge resection

Parenchyma-sparing techniques may be appropriate in cases of typical carcinoid, provided that an R0 resection can be achieved. Polypoid tumors are accessible by bronchotomy and excision, including the involved bronchial wall. Bronchotomy ensures complete resection (as compared with endoscopic removal, which may not), and wedge resection may be appropriate for small lesions lacking atypia. These procedures may be accompanied by nodal sampling.

Lobectomy with or without sleeve resection

This is the most commonly used technique because most tumors occur in or near the origin of lobar bronchi. Concomitant sleeve resection of the main stem is required if the orifice of the lobar bronchus or the adjacent main stem bronchus is involved. Bronchoplastic adjuncts may permit preservation of normal distal parenchyma and are preferred over pneumonectomy when possible. Case reports have demonstrated eventual reinflation of even severely atelectatic lung parenchyma, along with improvement in pulmonary function, when parenchyma-sparing techniques, such as sleeve lobectomy, are used.

Pneumonectomy

Pneumonectomy may be required if all lobes on the involved side are destroyed because of a proximal obstructing lesion.

Preoperative risk assessment

Preopertive testing is done to assist in risk assessment and to identify areas of concern that can be mitigated prior to surgical intervention. Tests and evaluations other than those listed below may be appropriate as suggested by history, physical examination, and laboratory testing findings, but all of the listed tests are not routinely required.

History (focusing on factors known to affect operative risk) may include the following:

  • Chronic obstructive pulmonary disease
  • Chronic renal failure
  • Cor pulmonale
  • Diabetes mellitus
  • Myocardial infarction within 6 months or unstable ischemic disease
  • Severe cardiac valvular disease
  • Congestive heart failure
  • Bleeding disorders
  • Peripheral vascular disease

Pulmonary function evaluation includes the following:

  • Exercise tolerance - May include informal evaluation using the patient’s history, a stair climbing test, or a formal walk test
  • Areterial blood gases
  • Pulmonary function tests - Spirometry, diffusion capacity, and split-function testing

Pulmonary reserve criteria include the following:

  • Forced expiratory volume in 1 second (FEV1): Mortality risk is inversely proportional to FEV1. With low FEV1, expect prolonged postoperative mechanical ventilation.

  • Forced vital capacity: This value should be greater than 2 liters or at least 3 times the tidal volume. Mortality risk is inversely proportional to forced vital capacity.

  • Ratio of residual volume to total lung capacity: A value of greater than 50% suggests severe chronic obstructive pulmonary disease with airway closing volumes approaching total lung capacity. A contraindication includes a ratio of residual volume to total lung capacity of greater than 50%.

  • Maximum breathing capacity: This should be more than 50% of predicted.

  • PaCO2: A concern is a PaCO2 greater than 40.

Cardiac evaluation includes the following:

  • Electrocardiogram
  • Stress testing
  • Echocardiography

Perioperative management

Routine monitoring, which includes an arterial catheter for blood pressure monitoring and blood sampling, is required.

With regard to positioning, pay special attention to maximize operative exposure and reduce the risk of peripheral nerve injury.

Double-lumen endotracheal tubes and bronchial blockers allow single-lung ventilation, which increases operative safety. Management of one-lung ventilation includes the following:

  1. Using tidal volumes low enough to maintain peak airway pressure at less than 30-35 mm Hg and plateau airway pressures less than 25-30 mm Hg
  2. Limiting the fraction of inspired oxygen to that required to maintain acceptable oxygen saturations
  3. Avoiding auto–positive end expiratory pressure
  4. Maintaining a heightened awareness of the risk for hypoxic pulmonary vasoconstriction

Intraoperative details

The margin of resection for endobronchial lesions frequently requires frozen section examination, especially if bronchoplastic procedures are used. The presence of microscopic tumor at the resection margin mandates wider resection. For atypical carcinoids, nodal staging by frozen section analysis and/or extensive mediastinal nodal dissection is required.

Postoperative details

Pulmonary care frequently includes bronchodilators and chest physiotherapy. Deep venous thrombosis prophylaxis is necessary. Monitoring should include cardiac rhythm and pulse oximetry as well as routine care and surveillance of vital signs.

Pain management

Pain promotes atelectasis, impairs secretion clearance and ventilation, and leads to a restrictive defect. Adjunctive measures such as epidural techniques, patient-controlled analgesia, and nonsteroidal agents all may be of value in addition to standard narcotic-based regimens. Intercostal nerve blocks, both intraoperatively and postoperatively, can be helpful.

Postoperative complications

Postoperative complications can include the following:

  • Delayed hemorrhage
  • Bronchial leak
  • Respiratory failure
  • Cardiac dysfunction

Complications

Perioperative complications include the following:

  • Delayed hemorrhage
  • Bronchial anastomotic leak
  • Bleeding and coagulopathy
  • Myocardial ischemia
  • Atelectasis or pneumonia
  • Respiratory failure, need for persistent mechanical ventilation

Mucoepidermoid carcinoma is known to result in intracranial metastases, even in cases of minimal bronchial wall involvement.  In carcinoid, solid organ metastases (eg, to the liver) are possible.