Practice Essentials
Carcinoid tumors of the lung are a fascinating but uncommon group of pulmonary neoplasms. In the past, these tumors were grouped with benign or less aggressive malignant pulmonary tumors. Together they were placed in a category of neoplasms called bronchial adenomas.
This unfortunate label, still used by many today, creates the impression that such tumors are benign neoplasms. Subsequent study has revealed, however, that carcinoid lung tumors represent the most indolent form of a spectrum of bronchopulmonary neuroendocrine tumors (NETs) that includes small cell carcinoma of the lung as its most malignant member, as well as several other forms of intermediately aggressive tumors, such as atypical carcinoid. [1]
Laennec's description of an intrabronchial mass in 1831 was the first written description of what was likely a bronchial carcinoid tumor. Mueller described the first so-called bronchial adenoma in detail in 1882. This probably was a carcinoid tumor because the patient was young and had symptoms of cough with hemoptysis for 8 years.
In 1914, Chevalier Jackson performed bronchoscopic resection of a large intrabronchial tumor. At that time, the tumor was labeled with the pathologic diagnosis of endothelioma, but, after reexamination a number of years later, it was determined to be an adenoma. In 1937 and again in 1945, C L Jackson reported on 12 and 20 cases of bronchial adenomas, respectively. He stated that none of these exhibited signs of metastases or any other evidence of malignant activity. Other experts, however, began to question the apparent benign nature of these tumors.
In 1944, Alexander and Weller classified bronchial adenomas as grade 1 malignancies and reported that they had observed metastases in two of 13 cases. In 1939, Eloesser performed the first bronchotomy for resection of a bronchial tumor. The tumor was called a benign carcinoma at the time but was likely a carcinoid or cylindroma.
Bjork, Axen, and Thorsen in 1952 described the first report of carcinoid syndrome and its relation to metastatic carcinoid tumor; it was associated with an intestinal carcinoid tumor. The first report of this syndrome in association with a bronchial carcinoid tumor was by Stanford, Davis, Gunter, and Hobart in 1958.
In 1972, Arrigoni et al reported a subset of pulmonary carcinoid tumors that had an atypical histologic appearance and behaved more aggressively. They named this group of tumors atypical carcinoid and reported that the tumors often were larger at presentation and developed distant metastases in as many as 70% of cases. Since this study, the idea that a spectrum of neuroendocrine tumors of the bronchopulmonary tree exists has become more accepted. [2]
Typical carcinoid tumors of the lung represent the most well differentiated and least biologically aggressive type of pulmonary NET. These tumors characteristically grow slowly and tend to metastasize infrequently.
Atypical carcinoid tumors have a more aggressive histologic and clinical picture. They metastasize at a considerably higher rate than do typical carcinoid tumors and, therefore, carry a worse prognosis.
Carcinoid syndrome has been reported in association with very large bronchopulmonary carcinoid tumors or in the presence of metastatic disease. It is noted much less frequently in association with carcinoids of pulmonary origin than those originating within the gastrointestinal (GI) tract. (For more information, see Intestinal Carcinoid Tumor.)
Endocrine syndromes found in association with small cell carcinoma of the lung are found less commonly with carcinoid tumors of the lung; however, some endocrine abnormalities have been attributed to both typical and atypical pulmonary carcinoid tumors.
All pulmonary carcinoid tumors should be treated as malignancies. No medical therapy exists for the primary treatment of carcinoid tumor of the lung. Because surgical resection is the only treatment known to achieve cure, all pulmonary carcinoid tumors without evidence of distant metastatic disease should be resected completely as long as no contraindication to surgery exists. Total resection should be the primary goal of any form of surgical therapy. Lymph node dissection should accompany resection.
For patient education resources, see the Procedures Center and Cancer and Tumors Center, as well as Bronchoscopy, Bronchial Adenoma, and Understanding Lung Cancer Medications.
Anatomy
Gross anatomic features of carcinoid tumors include the following:
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Tumors most commonly are found within the cartilaginous portion of the tracheobronchial tree
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Tumors usually are soft masses covered with intact bronchial epithelium
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Tumors are very vascular and pink-to-purplish in color
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Tumors usually are attached to the bronchus by a broad base but occasionally are polypoid with a distinct stalk
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Tumors may be associated with the presence of tumorlets (small foci of atypical hyperplastic bronchial epithelium in adjacent locations), which may represent local metastatic disease or an entirely different histologic abnormality and, when present, may indicate a more aggressive tumor and a poorer prognosis
Pathophysiology
Local
Between 25% and 39% of patients with a carcinoid pulmonary tumor are asymptomatic.
The vast majority of symptomatic patients have symptoms directly involving the bronchopulmonary tree. Carcinoids developing within large airway structures grow slowly and can become quite large. Because of their location and size, these central carcinoids can cause bronchial obstruction. All of the sequelae resulting from bronchial obstruction can follow, including persistent atelectasis, recurrent pneumonia, pulmonary abscess, and bronchiectasis.
Carcinoids characteristically are vascular tumors and can bleed secondary to bronchial irritation.
Although most tumors are broad-based intrabronchial lesions, a few present on a mobile stalk and have a polypoid appearance. If large enough, this latter form can create a ball-valve mechanism within the bronchus, producing hyperinflation in the pulmonary parenchyma distal to the tumor.
Peripheral pulmonary carcinoid tumors most often are asymptomatic and usually are discovered incidentally. They are one of the differential diagnoses considered in evaluation of a solitary pulmonary nodule.
Atypical carcinoid tumors can present in the same locations as typical carcinoids, but they occur more commonly as peripheral lesions. At least 50% of pulmonary atypical carcinoid tumors present in the periphery of the lung. They have a more aggressive nature and a greater tendency to metastasize. [3]
Systemic
As NETs, carcinoids are capable of producing a variety of biologically active peptides and hormones, including serotonin, adrenocorticotropic hormone (ACTH), antidiuretic hormone (ADH), melanocyte-stimulating hormone (MSH), and others.
Excess serotonin production has been implicated in the development of carcinoid syndrome. This syndrome is characterized by a constellation of symptoms, including tachycardia, flushing, bronchoconstriction, hemodynamic instability, diarrhea, and acidosis, and is reported in 2-12% of patients with bronchial carcinoid tumors. This syndrome characteristically occurs in the presence of metastatic disease to the liver; however, bronchial carcinoid tumors, especially large ones, are capable of producing the syndrome in the absence of metastatic disease.
Ectopic production of ACTH and Cushing syndrome have been reported in association with typical and atypical carcinoid tumors. Although fewer than 1% of pulmonary carcinoid tumors produce Cushing syndrome, it is the second most common neuroendocrine syndrome produced by these tumors. In addition, these tumors are responsible for the development of about 1% of cases of Cushing syndrome. When a patient is found to have an ectopic source of ACTH production, the lesion is generally a pulmonary neoplasm of some type.
The syndrome of inappropriate AVP (arginine vasopressin) secretion or syndrome of inappropriate secretion of ADH (SIADH) can be produced by pulmonary carcinoid tumors, though it more commonly is associated with small cell lung carcinoma. The production of excess circulating AVP creates hyponatremia secondary to water retention. Patients present with weight gain, weakness, lethargy, and mental confusion and, in severe cases, can develop convulsions and coma.
Etiology
In the past, pulmonary carcinoid tumors were believed to be derived from neural crest cells; however, they currently are understood to be of endodermal origin, arising from stem cells of the bronchial epithelium known as Kulchitsky cells.
Although these neoplasms are capable of producing a variety of substances, including biologically active peptides and hormones, most are inactive.
Unlike carcinoma of the lung, no external environmental toxin or other stimulus has been identified as a causative agent for the development of pulmonary carcinoid tumors.
Epidemiology
The GI tract is the most common area in which carcinoid tumors most commonly arise.
Bronchopulmonary carcinoid tumors are reported to represent about 10% of all carcinoid tumors. Between 1% and 6% of all lung tumors are carcinoid tumors. Some 80-90% of tumors develop within a bronchus of subsegmental size or greater. About 10-15% of tumors arise in a mainstem bronchus; however, they rarely appear in the trachea. About 10-20% of tumors are located in the pulmonary periphery.
Atypical carcinoid tumors account for about 10% of all pulmonary carcinoid tumors. Carcinoid syndrome occurs in about 2% of cases of pulmonary carcinoid tumors, much less frequently than it does in cases associated with GI carcinoid tumors. [3]
The average age of people at occurrence of typical carcinoid tumors is 40-50 years, but typical carcinoid tumors have been reported in virtually every age group. Atypical carcinoid tumors appear in slightly older people than typical carcinoids do. Carcinoid tumors occur in equal numbers of males and females.
Prognosis
Carcinoid tumors of the lung generally have a better prognosis than other forms of pulmonary malignancy. They have an overall 5-year survival rate of 78-95% and a 10-year survival rate of 77-90%.
Typical carcinoid tumors have been found to have a much better prognosis than do the atypical variety. [4] Atypical carcinoid tumors have been associated with a 5-year survival rate of 40-60% and a 10-year survival rate of 31-60%, depending on the series.
Regardless of histologic type, the presence of lymph node metastases at the time of resection has a significant effect on prognosis in many series, [5] producing 5-year survival rates of 37-80% and 10-year rates of 22-80%. This wide variation is likely related to the percent of atypical carcinoid tumors present in each analyzed series. N1 disease does not affect prognosis in typical carcinoids, and it tends to decrease survival in atypical carcinoids; however, N2 disease has a dismal prognosis. [6]
The presence of tumorlets associated with the primary tumor appears to worsen the prognosis. In a retrospective single institution study from Australia, age greater than 60 years and atypical histology were negative predictors of survival; patients in the atypical subgroup were found to be significantly older. [7] Whether or not tumor size is a prognostic risk factor is uncertain.
The presence of carcinoid syndrome or other paraneoplastic syndromes in the absence of lymph node or distant metastases does not seem to affect prognosis adversely. [8, 9, 10, 11, 12]
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Posteroanterior chest radiograph of a 37-year-old woman with a carcinoid lung tumor of the left mainstem bronchus and resultant left upper lobe atelectasis.
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Lateral chest radiograph of a 37-year-old woman with a carcinoid lung tumor of the left mainstem bronchus and resultant left upper lobe atelectasis.
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Computerized tomographic study of a 37-year-old woman with a carcinoid lung tumor of the left mainstem bronchus and resultant left upper lobe atelectasis.
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Posteroanterior chest radiograph showing a carcinoid lung tumor presenting as a coin lesion in the right lower lobe of a 40-year-old, asymptomatic woman.
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Lateral chest radiograph showing a carcinoid lung tumor presenting as a coin lesion in the right lower lobe of a 40-year-old, asymptomatic woman.
