eMedicine Specialties > Thoracic Surgery > Tumors

Carcinoid Lung Tumors

Author: Mary C Mancini, MD, PhD, Professor, Department of Surgery, Louisiana State University Health Sciences Center
Contributor Information and Disclosures

Updated: Oct 23, 2008

Introduction

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 grouped as a category of neoplasms called bronchial adenomas. This unfortunate label, still used by many today, creates the impression that such tumors are benign neoplasms. Recent study has revealed that carcinoid lung tumors represent the most indolent form of a spectrum of bronchopulmonary neuroendocrine tumors that includes small cell carcinoma of the lung as its most malignant member and several other forms of intermediately aggressive tumors, such as atypical carcinoid.

History of the Procedure

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 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 2 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 and associates 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.¹

Problem

Typical carcinoid tumors of the lung represent the most well differentiated and least biologically aggressive type of pulmonary neuroendocrine tumor. 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 tract. (For more information, see eMedicine Oncology article Carcinoid Tumor, Intestinal.)

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.

Frequency

• The gastrointestinal tract is the most common area in which carcinoid tumors arise.
• Bronchopulmonary carcinoid tumors are reported to represent about 10% of all carcinoid tumors.
• One to 6% of all lung tumors are carcinoid tumors.
• Carcinoid tumors occur in equal numbers of males and females.
• 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.
• Eighty to 90% of tumors develop within a bronchus of subsegmental size or greater.
• Ten to 15% of tumors arise in a mainstem bronchus; however, they rarely appear in the trachea.
• Ten to 20% of tumors are located in the pulmonary periphery.
• Atypical carcinoid tumors comprise about 10% of all pulmonary carcinoid tumors.
• Carcinoid syndrome occurs in about 2% of cases of pulmonary carcinoid tumors, much less frequently than in cases associated with gastrointestinal carcinoid tumors.²

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.

Pathophysiology

Local pathophysiology

Twenty-five to 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.²

Systemic pathophysiology

As neuroendocrine tumors, carcinoids are capable of producing a variety of biologically active peptides and hormones, including serotonin, adrenocorticotropin 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 less 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, although 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.

Presentation

About 25% of patients with pulmonary carcinoid tumors are asymptomatic at the time of discovery.

In symptomatic patients, the most common clinical findings are those associated with bronchial obstruction, such as persistent cough, hemoptysis, and recurrent or obstructive pneumonitis. Wheezing, chest pain, and dyspnea also may be noted.

Although uncommon, various endocrine or neuroendocrine syndromes can be initial clinical manifestations of either typical or atypical pulmonary carcinoid tumors. Carcinoid syndrome, hypercortisolism and Cushing syndrome, inappropriate secretion of ADH, increased pigmentation secondary to excess MSH, and ectopic insulin production resulting in hypoglycemia are some of the endocrinopathies that can be produced by a pulmonary carcinoid tumor in a patient who is otherwise asymptomatic.

In cases of malignancy, the presence of metastatic disease can produce weight loss, weakness, and a general feeling of ill health. Carcinoid syndrome is observed most commonly when metastatic disease to the liver is present.

Indications

All pulmonary carcinoid tumors should be treated as malignancies. 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. While the most commonly used procedures are formal lobectomy, segmentectomy, or pneumonectomy, a variety of parenchymal-sparing bronchoplastic procedures, including sleeve resections, has been utilized with good long-term results. Patients with marginal pulmonary reserve may be good candidates for complete resection and cure if a bronchoplastic or parenchymal-sparing procedure can be performed.

Thoracoscopic or open wedge resection of a peripheral carcinoid tumor should be reserved for patients with limited pulmonary reserve who cannot tolerate anatomic resection. Appropriate lymph node dissection also should be performed in these cases.

Bronchoscopic resection of an intrabronchial carcinoid tumor only is recommended in selected cases. These include preoperative management of symptomatic bronchial obstruction prior to formal resection and palliative treatment in patients who would otherwise not tolerate formal pulmonary resection. Complete tumor removal is extremely unlikely using this method because these obstructing intrabronchial tumors usually have penetrated the bronchus and invaded the local pulmonary parenchyma by the time they are discovered. In addition, lymph node staging cannot be accomplished. Palliation, not cure, is the goal of this technique.

Neodymium:yttrium-aluminum-garnet (Nd:YAG) laser photoresection of intrabronchial carcinoid tumors also has been proposed. This form of therapy should not be considered primary and should be reserved for the same types of cases indicated for bronchoscopic resection. Its limitations are similar to those of bronchoscopic resection with one additional drawback. Transbronchial photocoagulation destroys at least a portion of the resected tumor and thwarts thorough analysis of a completely resected specimen. Incomplete specimen analysis may have significant bearing on prognostic determination because the histologic features of pulmonary carcinoid tumors must be scrutinized carefully in order to determine whether typical or atypical carcinoid is present.

Resection of distant metastatic lesions is indicated in a select group of patients in whom thorough evaluation has revealed isolated lesions in areas amenable to resection.

Relevant Anatomy

Gross anatomic features of carcinoid tumors

• Tumors most commonly are found within the cartilaginous portion of the tracheobronchial tree.
• Tumors usually are soft masses covered with intact bronchial epithelium.
• Tumors are very vascular and pink to purplish in color.
• Tumors usually are attached to the bronchus by a broad base, but, occasionally, they are polypoid with a distinct stalk.
• Tumors may be associated with the presence of tumorlets, which are small foci of atypical hyperplastic bronchial epithelium in adjacent locations. Tumorlets may represent local metastatic disease or an entirely different histologic abnormality and, when present, may indicate a more aggressive tumor and a poorer prognosis.

Contraindications

Formal resection of carcinoid tumors of the lung only is contraindicated in patients who would not otherwise tolerate the operative procedure or who are found to have widespread metastatic disease.

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