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:
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Carcinoids (2 types of bronchial neuroendocrine tumors) account for 85% of bronchial gland tumors and 1-2% of all lung malignancies.
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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]
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:
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Typical carcinoid (Kulchitsky type I) - (+)
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Atypical carcinoid (Kulchitsky type II) - (++)
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Large cell neuroendocrine carcinoma - (+++)
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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. [4]
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. [5]
Pathophysiology
Symptoms develop from the growth of the tumors within the tracheobronchial tree, with consequent obstruction leading to cough, hemoptysis, atelectasis, or pneumonia. [6]
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:
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Lobar or segmental location - Approximately 60%
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Main bronchus - Approximately 20%
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Peripheral - Approximately 20%
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Carinal or tracheal – Infrequent
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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. [7]
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. [5] 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. [7, 5]
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.
Tumor genetic profiles associated with poor prognosis in patients with bronchial carcinoids include MEN1 mutations and ATRX mutation. [8]
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. [9] 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. [7]
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Bronchoscopy: Carcinoid tumor (Left Lower Lobe - Anteromedial Basal)
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Bronchoscopy: Carcinoid tumor (Left Lower Lobe - Anteromedial Basal)
