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From the Archives of the AFIP¹

Thoracic Carcinoids: Radiologic-Pathologic Correlation

¹ From the Departments of Radiologic Pathology (M.L.R., J.R.G.) and Pulmonary and Mediastinal Pathology (W.D.T.), Armed Forces Institute of Pathology, 6825 16th St NW, Bldg 54, Room M-121, Washington, DC 20306-6000; the Department of Radiology and Nuclear Medicine, Uniformed Services University of the Health Sciences, Bethesda, Md (M.L.R.); the Department of Diagnostic Imaging, Brown University School of Medicine, Rhode Island Hospital, Providence (G.F.A.); the Department of Radiology, New Britain General Hospital, New Britain, Conn (W.M.K.); and the Department of Radiology, University of Maryland Medical System, Baltimore (J.R.G.). Address reprint requests to M.L.R.

	Abstract

Top Abstract INTRODUCTION BRONCHIAL CARCINOID THYMIC CARCINOID CONCLUSIONS References

 
Carcinoids are neuroendocrine neoplasms. Bronchial carcinoids are unusual, malignant primary neoplasms that characteristically involve the central airways and typically exhibit well-defined margins and bronchial-related growth. Bronchial carcinoids include low-grade typical carcinoids and the more aggressive atypical carcinoids. These tumors usually affect patients in the 3rd through 7th decades of life who are often symptomatic with cough, hemoptysis, or obstructive pneumonia. Bronchial carcinoids radiologically manifest as hilar or perihilar masses, with or without associated atelectasis, pneumonia, bronchiectasis, or mucoid impaction. At computed tomography, an anatomic relationship of these tumors to a bronchus is usually seen, and they may show contrast material enhancement or calcification. In rare cases, carcinoids occur in the thymus; when they do, they are aggressive tumors that affect adults who usually present with chest pain, cough, and dyspnea. Thymic carcinoids manifest radiologically as anterior mediastinal masses and may mimic thymomas. Thoracic carcinoids are treated by surgical excision. The prognosis for patients with typical bronchial carcinoids is excellent; patients with atypical bronchial or thymic carcinoids have a worse prognosis.

Index Terms: Lung neoplasms, 60.3111, 60.3117 • Thymus, neoplasms, 675.3111

	INTRODUCTION

Top Abstract INTRODUCTION BRONCHIAL CARCINOID THYMIC CARCINOID CONCLUSIONS References

 
Carcinoids occur most frequently (90% of cases) in the gastrointestinal tract. The second most common location is the respiratory tract. Less commonly, they occur in the thymus, biliary tract, or ovary (1). Other anatomic locations are extremely rare. The majority of thoracic carcinoids behave in an indolent manner. However, all have the potential to metastasize and are considered malignant neoplasms (2,3).

The term carcinoid was coined by Oberndorfer in 1907 as "Karzinoide" to denote its resemblance to carcinoma. In 1930, Kramer classified this tumor among the so-called bronchial adenomas to signify its relatively indolent behavior (4,5). Bronchial carcinoids were initially distinguished from other bronchial neoplasms by Hamperl in 1937 (6).

Today, bronchial carcinoids are thought to derive from the neuroendocrine cells of the bronchial and bronchiolar epithelium, which in turn may derive from pluripotent stem cells (3,7,8). The term neuroendocrine refers to the ability of a cell to synthesize, store, and secrete chemical messenger substances such as neuroamines and neuropeptides (9). Neuroendocrine cells occur as solitary cells along the basement membrane of the bronchial and bronchiolar epithelium or as nodular cell clusters called neuroepithelial bodies. Their neuroendocrine function has been demonstrated by means of ultrastructural studies and immunohistochemical markers, and they form part of the diffuse or dispersed endocrine system, which includes gastrointestinal, thymic, and bronchopulmonary components (3,7,10,11).

Bronchial carcinoids are uncommon pulmonary neoplasms and represent 1%–2% of all lung tumors (3,12). Previously, they were classified along with adenoid cystic carcinomas and mucoepidermoid carcinomas as "bronchial adenomas." Today, that term is considered a misnomer, as it implies that these malignant lesions are benign (8,13). The classification and nomenclature of carcinoids has further evolved with our increased understanding of their biologic and clinical behavior. Bronchial carcinoids display a spectrum of clinical behavior and histologic differentiation, ranging from the low-grade typical carcinoids to the intermediate-grade atypical carcinoids to the high-grade large-cell neuroendocrine carcinomas and small cell carcinomas (3,14).

Thymic carcinoids are unusual primary neoplasms of neuroendocrine origin that manifest as anterior mediastinal masses in adult patients, who may present with a clinically evident hormonal syndrome (11). Thymic carcinoids usually exhibit an aggressive behavior.

In this article, the clinical and radiologic features of bronchial and thymic carcinoids are presented and correlated with the gross and histologic characteristics of these lesions.

	BRONCHIAL CARCINOID

Top Abstract INTRODUCTION BRONCHIAL CARCINOID THYMIC CARCINOID CONCLUSIONS References

 
Clinical Features
Bronchial carcinoids are unique among primary malignant neoplasms of the lung in that the affected population has a significantly lower male-to-female ratio. In fact, in an extensive literature review of 2,837 patients with bronchial carcinoid, 52% of patients were females and 48% were males (15). Affected individuals display a wide age range with an average age at presentation of 45.5 years (11,16). In general, patients with bronchial carcinoids are younger than those with common primary pulmonary neoplasms such as bronchogenic carcinoma (15). However, the age of patients with atypical carcinoid is 1 decade greater (6th decade of life) than that of those with typical carcinoid (13,16,17). Bronchial carcinoid represents the most common primary pulmonary neoplasm of children, and most pediatric patients present in late adolescence (18). Bronchial carcinoid affects whites more frequently than blacks, and there is no documented association with cigarette smoking or exposure to other carcinogens or environmental agents (11,13,15,17).

Patients with bronchial carcinoids are often symptomatic and present with cough and recurrent pulmonary infection. Hemoptysis is frequent and occurs in approximately 50% of patients (11,13). Chest pain, shortness of breath, and constitutional symptoms also occur. Cough, hemoptysis, fever, dyspnea, chest pain, and obstructive pneumonia may occur as isolated symptoms or in combination. Wheezing localized to one lung and "asthma" of recent onset have been described as characteristic findings (11). However, up to 19%–51% of patients are asymptomatic, and bronchial carcinoid is diagnosed incidentally because of abnormal findings at chest radiography (3,11,19). Interestingly, pediatric patients are rarely asymptomatic, and most present with cough, hemoptysis, or pneumonia. In fact, wheezing, pneumonia, and atelectasis are presenting signs in 50% of pediatric patients with bronchial carcinoids (18).

The high frequency of symptoms in patients with bronchial carcinoids is probably related to the frequent central location of the tumor. However, symptoms may be present for many years before the diagnosis is established (20). Peripheral lesions are reported to produce symptoms less frequently than central tumors (3).

It should be noted that although hormonal products can be demonstrated within cellular neurosecretory granules in all carcinoids, systemic hormonal manifestations are rare. However, a small number of patients present because of symptoms related to Cushing syndrome, which is seen in approximately 2% of cases of bronchial carcinoids. Approximately 1% of cases of Cushing syndrome are secondary to bronchial carcinoid through the ectopic production of adrenocorticotropic hormone (ACTH) or ACTH-releasing hormone. In fact, bronchial carcinoids represent the most common source of ectopic ACTH production (13). It may be difficult to distinguish carcinoid-induced Cushing syndrome from pituitary-dependent Cushing syndrome (13,21). However, carcinoid-induced Cushing syndrome may be clinically suspected because of its acute onset, high ACTH concentration (> 55 pmol/L), and hypokalemia (the latter is uncommon in other forms of Cushing syndrome) (21,22). It is also characterized by its glucocorticoid response to high-dose dexamethasone or metyrapone (22). The causative bronchial carcinoid is frequently radiologically occult and may require advanced imaging for detection (22). Typical, atypical, and metastatic carcinoids have all been reported as causes of Cushing syndrome. The carcinoid syndrome is rarely seen in association with bronchial carcinoid. It is seen in less than 2%–5% of patients with bronchial carcinoid, is usually encountered only in patients carcinoid metastatic to the liver, and rarely if ever in patients with isolated bronchial tumors (13,23).

Histologic Features
Histologically typical carcinoid is composed of uniform cells with an organoid growth pattern in a rich fibrovascular stroma (Fig 1) (3,9). The cells are polygonal with an eosinophilic granular cytoplasm and are arranged in nests or solid sheets. The nuclei are central and rounded and contain a fine stippled chromatin and inconspicuous nucleoli (Fig 1). Typical carcinoids exhibit a wide spectrum of histologic variability including spindle cell, trabecular, palisading, glandular, rosette-like, and sclerosing papillary patterns. Necrosis should be absent, and most tumors exhibit more than one pattern. Mitoses are fewer than two per 2 mm² (3,24–26). Most carcinoids are richly vascular. They may exhibit dystrophic calcification, ossification, or amyloid deposition (13).

View larger version (232K): [in this window] [in a new window] [Download PPT slide]   Figure 1a.  Typical carcinoid. (a) Low-power photomicrograph (original magnification, x100; hematoxylin-eosin [H-E] stain) of a typical carcinoid demonstrates uniform cells with an organoid nesting pattern. (b) High-power photomicrograph (original magnification, x400; H-E stain) of a typical carcinoid shows uniform cells with granular cytoplasm and stippled nuclear chromatin growing in an organoid nesting pattern.

View larger version (212K): [in this window] [in a new window] [Download PPT slide]   Figure 1b.  Typical carcinoid. (a) Low-power photomicrograph (original magnification, x100; hematoxylin-eosin [H-E] stain) of a typical carcinoid demonstrates uniform cells with an organoid nesting pattern. (b) High-power photomicrograph (original magnification, x400; H-E stain) of a typical carcinoid shows uniform cells with granular cytoplasm and stippled nuclear chromatin growing in an organoid nesting pattern.

View larger version (229K): [in this window] [in a new window] [Download PPT slide]   Figure 2a.  Atypical carcinoid. (a) High-power photomicrograph (original magnification, x200; H-E stain) of an atypical carcinoid shows a characteristic punctate focus of necrosis. (b) High-power photomicrograph (original magnification, x400; H-E stain) of an atypical carcinoid demonstrates one mitotic figure (arrow).

View larger version (214K): [in this window] [in a new window] [Download PPT slide]   Figure 2b.  Atypical carcinoid. (a) High-power photomicrograph (original magnification, x200; H-E stain) of an atypical carcinoid shows a characteristic punctate focus of necrosis. (b) High-power photomicrograph (original magnification, x400; H-E stain) of an atypical carcinoid demonstrates one mitotic figure (arrow).

View larger version (201K): [in this window] [in a new window] [Download PPT slide]   Figure 3.  Typical carcinoid. High-power photomicrograph (original magnification, x400) of a typical carcinoid stained with immunohistochemistry for chromogranin A shows cytoplasmic staining.

Gross Pathologic Features
Typical and atypical carcinoids are indistinguishable on the basis of gross pathologic features (24). Tumors are frequently classified according to their location as central or peripheral. However, the definitions of central and peripheral vary greatly in the literature. Central tumors are sometimes defined as those involving the mainstem, lobar, or segmental airways, and peripheral tumors as those that involve subsegmental airways or more distal bronchi (6). Central tumors have also been defined as those located within reach of the bronchoscope, those associated with obstructive features, or those resectable by using bronchoplasty or pneumonectomy; peripheral tumors, by this definition, are not visible with endoscopy and are resectable by using lobectomy (9). In addition, lesion location has also been described on the basis of computed tomographic (CT) findings as central or peripheral. Central lesions have been described as those visualized on CT scans in the medial one-third of the lung and peripheral lesions as those in the outer two-thirds (3,27). A 1976 review of 203 bronchial carcinoids classified the lesions according to their sites of origin and found that 10% occurred in the mainstem bronchi, 75% in the lobar bronchi, and 15% at the level of segmental bronchi and beyond (28). Although the location of carcinoids varies, most investigators agree that the majority are central and are related to an airway and that 16%–40% occur in the lung periphery. Others postulate that carcinoids are evenly distributed throughout the lung, with one-third of lesions located centrally, one-third in the middle portion of the lung, and one-third in the peripheral lung (3,14).

Macroscopically, bronchial carcinoids are well-circumscribed nodules or masses. Central lesions have a red-brown endoluminal polypoid component with a focal or broad attachment to the bronchial wall. The bronchial mucosa is often intact over the lesion and results in a smooth, glistening tumor surface (Fig 4) (3,9,13,29). The cut surface of bronchial carcinoids is yellow-tan or pale pink, depending on the degree of tumor vascularity (Fig 5) (3,20,25). Although some carcinoids grow exclusively within the bronchial lumen, invasion through the bronchial wall and its cartilaginous rings is common (Fig 5) (6). Completely endoluminal carcinoids manifest as polypoid or exophytic masses without gross evidence of extension through the cartilage. However, most carcinoids exhibit a dumbbell shape and have parenchymal (extrabronchial) components of variable size (3,6,20). In these cases, a large parenchymal mass may have a very small endoluminal component (Fig 6). Some lesions simply abut the bronchial lumen without gross endoluminal involvement (Fig 7). Central tumors may partially or completely occlude the bronchus and may produce distal obstruction and inflammation (Fig 8) (9,24).

View larger version (127K): [in this window] [in a new window] [Download PPT slide]   Figure 4. Figures 4, 5. (4) Typical carcinoid in a 38-year-old man with a 2-year history of recurrent pneumonia. Photograph of the resected specimen shows a completely endobronchial ovoid tumor in the left mainstem bronchus. A smooth glistening mucosa covers the lesion. (5) Typical carcinoid in a 28-year-old woman with a 6-month history of dyspnea. Photograph of a cut section of the surgical specimen shows a polypoid carcinoid tumor occluding the main bronchus and focally invading the bronchial wall (arrows).

View larger version (118K): [in this window] [in a new window] [Download PPT slide]   Figure 5. Figures 4, 5. (4) Typical carcinoid in a 38-year-old man with a 2-year history of recurrent pneumonia. Photograph of the resected specimen shows a completely endobronchial ovoid tumor in the left mainstem bronchus. A smooth glistening mucosa covers the lesion. (5) Typical carcinoid in a 28-year-old woman with a 6-month history of dyspnea. Photograph of a cut section of the surgical specimen shows a polypoid carcinoid tumor occluding the main bronchus and focally invading the bronchial wall (arrows).

View larger version (116K): [in this window] [in a new window] [Download PPT slide]   Figure 6. Figures 6–8. (6) Typical carcinoid in a 36-year-old woman with a 1-year history of recurrent left lower lobe pneumonia. Photograph of a cut section of the surgical specimen shows that although the bulk of the tumor is parenchymal, an endoluminal component is also present (*). (7) Typical carcinoid in a 38-year-old man with recurrent right lower lobe pneumonia. Photograph of a cut section of the surgical specimen shows a well-circumscribed, fleshy, ovoid mass abutting the bronchovascular bundle. A mucus plug is seen adjacent to the tumor (*). (8) Typical carcinoid in a 50-year-old woman with an 8-month history of cough and recurrent pneumonia. Photograph of a cut section of the surgical specimen shows an endobronchial tumor (*) occluding the bronchus intermedius with consolidation and bronchiectasis of the right middle and lower lobes.

View larger version (123K): [in this window] [in a new window] [Download PPT slide]   Figure 7. Figures 6–8. (6) Typical carcinoid in a 36-year-old woman with a 1-year history of recurrent left lower lobe pneumonia. Photograph of a cut section of the surgical specimen shows that although the bulk of the tumor is parenchymal, an endoluminal component is also present (*). (7) Typical carcinoid in a 38-year-old man with recurrent right lower lobe pneumonia. Photograph of a cut section of the surgical specimen shows a well-circumscribed, fleshy, ovoid mass abutting the bronchovascular bundle. A mucus plug is seen adjacent to the tumor (*). (8) Typical carcinoid in a 50-year-old woman with an 8-month history of cough and recurrent pneumonia. Photograph of a cut section of the surgical specimen shows an endobronchial tumor (*) occluding the bronchus intermedius with consolidation and bronchiectasis of the right middle and lower lobes.

View larger version (135K): [in this window] [in a new window] [Download PPT slide]   Figure 8. Figures 6–8. (6) Typical carcinoid in a 36-year-old woman with a 1-year history of recurrent left lower lobe pneumonia. Photograph of a cut section of the surgical specimen shows that although the bulk of the tumor is parenchymal, an endoluminal component is also present (*). (7) Typical carcinoid in a 38-year-old man with recurrent right lower lobe pneumonia. Photograph of a cut section of the surgical specimen shows a well-circumscribed, fleshy, ovoid mass abutting the bronchovascular bundle. A mucus plug is seen adjacent to the tumor (*). (8) Typical carcinoid in a 50-year-old woman with an 8-month history of cough and recurrent pneumonia. Photograph of a cut section of the surgical specimen shows an endobronchial tumor (*) occluding the bronchus intermedius with consolidation and bronchiectasis of the right middle and lower lobes.

Central lesions are larger than peripheral tumors, with mean diameters of 3.1 and 2.4 cm, respectively (3). Atypical carcinoids are larger, on average, than typical carcinoids, with mean diameters of 3.6 and 2.3 cm, respectively (3,10). Atypical carcinoids are more likely to exhibit hemorrhage and necrosis. Both typical and atypical carcinoids may metastasize to regional lymph nodes, but atypical tumors do so more frequently (48%) (30). Although both may invade the adjacent lung, atypical tumors do so more aggressively and are more likely to invade vascular or lymphatic structures and to establish distant metastases (10). Metastases occur in 15% of bronchial carcinoids and typically affect the liver, bone, adrenal glands, and brain (20).

Radiologic Features
Radiography.—Typical and atypical bronchial carcinoids share similar imaging features. The most frequent radiographic manifestation of bronchial carcinoid is a hilar or perihilar mass, which may represent an isolated finding or may be associated with distal parenchymal disease (19,31). These lesions may occur in any parenchymal location, and, when they occur distal to the hila, they are generally distributed equally throughout the pulmonary lobes. The mass is characteristically well circumscribed, is rounded or ovoid, and may have a notched or lobulated contour (Fig 9). Masses with irregular or ill-defined margins are rarely seen. These lesions typically range in size from 2 to 5 cm. Atypical carcinoids are reported to be larger on average than typical carcinoids (32). Calcification is rarely visible radiographically. Multifocal tumors have been reported but are also rare. Cavitation has not been reported in bronchial carcinoids (19,33,34). In rare cases, the chest radiographs of patients with bronchial carcinoids are read as normal (19,33).

View larger version (133K): [in this window] [in a new window] [Download PPT slide]   Figure 9a.  Typical carcinoid in an asymptomatic 38-year-old woman. (a, b) Posteroanterior (PA) (a) and lateral (b) chest radiographs show a well-circumscribed, spherical left hilar mass. (c) Chest CT scan (lung window) demonstrates the lobular, partially endobronchial mass. Note the convex appearance of the lesion within the bronchial lumen. (d) Photograph of a cut section of the resected left upper lobe demonstrates the relationship of the lesion to the bronchus (arrow). Scale is in centimeters.

View larger version (132K): [in this window] [in a new window] [Download PPT slide]   Figure 9b.  Typical carcinoid in an asymptomatic 38-year-old woman. (a, b) Posteroanterior (PA) (a) and lateral (b) chest radiographs show a well-circumscribed, spherical left hilar mass. (c) Chest CT scan (lung window) demonstrates the lobular, partially endobronchial mass. Note the convex appearance of the lesion within the bronchial lumen. (d) Photograph of a cut section of the resected left upper lobe demonstrates the relationship of the lesion to the bronchus (arrow). Scale is in centimeters.

View larger version (125K): [in this window] [in a new window] [Download PPT slide]   Figure 9c.  Typical carcinoid in an asymptomatic 38-year-old woman. (a, b) Posteroanterior (PA) (a) and lateral (b) chest radiographs show a well-circumscribed, spherical left hilar mass. (c) Chest CT scan (lung window) demonstrates the lobular, partially endobronchial mass. Note the convex appearance of the lesion within the bronchial lumen. (d) Photograph of a cut section of the resected left upper lobe demonstrates the relationship of the lesion to the bronchus (arrow). Scale is in centimeters.

View larger version (89K): [in this window] [in a new window] [Download PPT slide]   Figure 9d.  Typical carcinoid in an asymptomatic 38-year-old woman. (a, b) Posteroanterior (PA) (a) and lateral (b) chest radiographs show a well-circumscribed, spherical left hilar mass. (c) Chest CT scan (lung window) demonstrates the lobular, partially endobronchial mass. Note the convex appearance of the lesion within the bronchial lumen. (d) Photograph of a cut section of the resected left upper lobe demonstrates the relationship of the lesion to the bronchus (arrow). Scale is in centimeters.

View larger version (128K): [in this window] [in a new window] [Download PPT slide]   Figure 10a. Figures 10, 11. (10) Typical carcinoid in a 21-year-old woman who was being evaluated for pyelonephritis. PA (a) and lateral (b) chest radiographs demonstrate atelectasis of the right middle lobe and an incidental right apical pneumothorax. Bronchography revealed a mass obstructing the bronchus intermedius. (11) Typical carcinoid in an 18-year-old man with a 4-month history of recurrent pneumonia. PA chest radiograph demonstrates right middle and lower lobe consolidation, a parapneumonic pleural effusion, and cut-off of the bronchus intermedius (arrow).

View larger version (123K): [in this window] [in a new window] [Download PPT slide]   Figure 10b. Figures 10, 11. (10) Typical carcinoid in a 21-year-old woman who was being evaluated for pyelonephritis. PA (a) and lateral (b) chest radiographs demonstrate atelectasis of the right middle lobe and an incidental right apical pneumothorax. Bronchography revealed a mass obstructing the bronchus intermedius. (11) Typical carcinoid in an 18-year-old man with a 4-month history of recurrent pneumonia. PA chest radiograph demonstrates right middle and lower lobe consolidation, a parapneumonic pleural effusion, and cut-off of the bronchus intermedius (arrow).

View larger version (110K): [in this window] [in a new window] [Download PPT slide]   Figure 11. Figures 10, 11. (10) Typical carcinoid in a 21-year-old woman who was being evaluated for pyelonephritis. PA (a) and lateral (b) chest radiographs demonstrate atelectasis of the right middle lobe and an incidental right apical pneumothorax. Bronchography revealed a mass obstructing the bronchus intermedius. (11) Typical carcinoid in an 18-year-old man with a 4-month history of recurrent pneumonia. PA chest radiograph demonstrates right middle and lower lobe consolidation, a parapneumonic pleural effusion, and cut-off of the bronchus intermedius (arrow).

View larger version (129K): [in this window] [in a new window] [Download PPT slide]   Figure 12a.  Typical carcinoid in a 22-year-old man with a 2-year history of hemoptysis. (a) PA chest radiograph demonstrates a well-marginated, endoluminal mass within the right mainstem bronchus. (b) Chest CT scan (lung window) demonstrates the well-defined, endoluminal tumor.

View larger version (105K): [in this window] [in a new window] [Download PPT slide]   Figure 12b.  Typical carcinoid in a 22-year-old man with a 2-year history of hemoptysis. (a) PA chest radiograph demonstrates a well-marginated, endoluminal mass within the right mainstem bronchus. (b) Chest CT scan (lung window) demonstrates the well-defined, endoluminal tumor.

View larger version (169K): [in this window] [in a new window] [Download PPT slide]   Figure 13a.  Typical carcinoid in a 23-year-old woman with hemoptysis. (a) PA chest radiograph demonstrates left upper lobe atelectasis. (b) Chest CT scan (lung window) helps confirm the left upper lobe collapse and shows a lesion (*) obstructing the left upper lobe bronchus. (c) Photograph of a cut specimen of the resected left upper lobe shows the obstructing endobronchial tumor (*) and the distal bronchiectasis and mucoid impaction.

View larger version (140K): [in this window] [in a new window] [Download PPT slide]   Figure 13b.  Typical carcinoid in a 23-year-old woman with hemoptysis. (a) PA chest radiograph demonstrates left upper lobe atelectasis. (b) Chest CT scan (lung window) helps confirm the left upper lobe collapse and shows a lesion (*) obstructing the left upper lobe bronchus. (c) Photograph of a cut specimen of the resected left upper lobe shows the obstructing endobronchial tumor (*) and the distal bronchiectasis and mucoid impaction.

View larger version (96K): [in this window] [in a new window] [Download PPT slide]   Figure 13c.  Typical carcinoid in a 23-year-old woman with hemoptysis. (a) PA chest radiograph demonstrates left upper lobe atelectasis. (b) Chest CT scan (lung window) helps confirm the left upper lobe collapse and shows a lesion (*) obstructing the left upper lobe bronchus. (c) Photograph of a cut specimen of the resected left upper lobe shows the obstructing endobronchial tumor (*) and the distal bronchiectasis and mucoid impaction.

View larger version (106K): [in this window] [in a new window] [Download PPT slide]   Figure 14a. Figures 14, 15. (14) Typical carcinoid in a 35-year-old woman with recurrent pneumonia. (a) PA chest radiograph demonstrates consolidation and volume loss of the left lung. (b) Chest CT scan (lung window) demonstrates marked cystic bronchiectasis of the left lung. A carcinoid of the left mainstem bronchus was treated with pneumonectomy. (15) Typical carcinoid in a 48-year-old woman with recurrent right lower lobe pneumonia. (a) PA chest radiograph demonstrates consolidation of the right lower lobe. (b) Follow-up PA chest radiograph shows partial resolution of the consolidation and visualization of an ovoid mass (arrow) in the bronchus intermedius.

View larger version (105K): [in this window] [in a new window] [Download PPT slide]   Figure 14b. Figures 14, 15. (14) Typical carcinoid in a 35-year-old woman with recurrent pneumonia. (a) PA chest radiograph demonstrates consolidation and volume loss of the left lung. (b) Chest CT scan (lung window) demonstrates marked cystic bronchiectasis of the left lung. A carcinoid of the left mainstem bronchus was treated with pneumonectomy. (15) Typical carcinoid in a 48-year-old woman with recurrent right lower lobe pneumonia. (a) PA chest radiograph demonstrates consolidation of the right lower lobe. (b) Follow-up PA chest radiograph shows partial resolution of the consolidation and visualization of an ovoid mass (arrow) in the bronchus intermedius.

View larger version (151K): [in this window] [in a new window] [Download PPT slide]   Figure 15a. Figures 14, 15. (14) Typical carcinoid in a 35-year-old woman with recurrent pneumonia. (a) PA chest radiograph demonstrates consolidation and volume loss of the left lung. (b) Chest CT scan (lung window) demonstrates marked cystic bronchiectasis of the left lung. A carcinoid of the left mainstem bronchus was treated with pneumonectomy. (15) Typical carcinoid in a 48-year-old woman with recurrent right lower lobe pneumonia. (a) PA chest radiograph demonstrates consolidation of the right lower lobe. (b) Follow-up PA chest radiograph shows partial resolution of the consolidation and visualization of an ovoid mass (arrow) in the bronchus intermedius.

View larger version (150K): [in this window] [in a new window] [Download PPT slide]   Figure 15b. Figures 14, 15. (14) Typical carcinoid in a 35-year-old woman with recurrent pneumonia. (a) PA chest radiograph demonstrates consolidation and volume loss of the left lung. (b) Chest CT scan (lung window) demonstrates marked cystic bronchiectasis of the left lung. A carcinoid of the left mainstem bronchus was treated with pneumonectomy. (15) Typical carcinoid in a 48-year-old woman with recurrent right lower lobe pneumonia. (a) PA chest radiograph demonstrates consolidation of the right lower lobe. (b) Follow-up PA chest radiograph shows partial resolution of the consolidation and visualization of an ovoid mass (arrow) in the bronchus intermedius.

View larger version (171K): [in this window] [in a new window] [Download PPT slide]   Figure 16a.  Typical carcinoid in a 20-year-old man with a 3-year history of cough and recurrent pneumonia. (a) PA chest radiograph demonstrates a well-defined, lobular, left hilar mass. Tubular opacities project distal to the lesion. (b, c) Chest CT scans (mediastinal window, with b obtained at a lower level than c) demonstrate the mass, which contains central calcification and produces abrupt bronchial obstruction. Mucoid impaction is seen distal to the lesion in c.

View larger version (111K): [in this window] [in a new window] [Download PPT slide]   Figure 16b.  Typical carcinoid in a 20-year-old man with a 3-year history of cough and recurrent pneumonia. (a) PA chest radiograph demonstrates a well-defined, lobular, left hilar mass. Tubular opacities project distal to the lesion. (b, c) Chest CT scans (mediastinal window, with b obtained at a lower level than c) demonstrate the mass, which contains central calcification and produces abrupt bronchial obstruction. Mucoid impaction is seen distal to the lesion in c.

View larger version (109K): [in this window] [in a new window] [Download PPT slide]   Figure 16c.  Typical carcinoid in a 20-year-old man with a 3-year history of cough and recurrent pneumonia. (a) PA chest radiograph demonstrates a well-defined, lobular, left hilar mass. Tubular opacities project distal to the lesion. (b, c) Chest CT scans (mediastinal window, with b obtained at a lower level than c) demonstrate the mass, which contains central calcification and produces abrupt bronchial obstruction. Mucoid impaction is seen distal to the lesion in c.

View larger version (148K): [in this window] [in a new window] [Download PPT slide]   Figure 17a.  Typical carcinoid in an asymptomatic 68-year-old woman. (a) PA chest radiograph shows an ovoid, solitary, lingular nodule (arrow). (b) Chest CT scan (lung window) demonstrates the sharply marginated, ovoid, lobular pulmonary nodule. (c) Photograph of a cut specimen of the resected lung demonstrates a well-circumscribed, fleshy tumor nodule.

View larger version (134K): [in this window] [in a new window] [Download PPT slide]   Figure 17b.  Typical carcinoid in an asymptomatic 68-year-old woman. (a) PA chest radiograph shows an ovoid, solitary, lingular nodule (arrow). (b) Chest CT scan (lung window) demonstrates the sharply marginated, ovoid, lobular pulmonary nodule. (c) Photograph of a cut specimen of the resected lung demonstrates a well-circumscribed, fleshy tumor nodule.

View larger version (122K): [in this window] [in a new window] [Download PPT slide]   Figure 17c.  Typical carcinoid in an asymptomatic 68-year-old woman. (a) PA chest radiograph shows an ovoid, solitary, lingular nodule (arrow). (b) Chest CT scan (lung window) demonstrates the sharply marginated, ovoid, lobular pulmonary nodule. (c) Photograph of a cut specimen of the resected lung demonstrates a well-circumscribed, fleshy tumor nodule.

View larger version (130K): [in this window] [in a new window] [Download PPT slide]   Figure 18a.  Typical carcinoid in a 35-year-old man with a 3-month history of recurrent pneumonia. (a, b) Contrast-enhanced chest CT scans (lung [a] and mediastinal [b] windows) demonstrate an endobronchial mass in the posterior segmental bronchus of the right lower lobe with a distal tubular mucus plug. The mass enhances and is distinct from the low-attenuation mucus plug. (c) Photograph of a cut specimen of the resected right upper lobe shows the central tumor (*) and distal mucoid impaction.

View larger version (103K): [in this window] [in a new window] [Download PPT slide]   Figure 18b.  Typical carcinoid in a 35-year-old man with a 3-month history of recurrent pneumonia. (a, b) Contrast-enhanced chest CT scans (lung [a] and mediastinal [b] windows) demonstrate an endobronchial mass in the posterior segmental bronchus of the right lower lobe with a distal tubular mucus plug. The mass enhances and is distinct from the low-attenuation mucus plug. (c) Photograph of a cut specimen of the resected right upper lobe shows the central tumor (*) and distal mucoid impaction.

View larger version (128K): [in this window] [in a new window] [Download PPT slide]   Figure 18c.  Typical carcinoid in a 35-year-old man with a 3-month history of recurrent pneumonia. (a, b) Contrast-enhanced chest CT scans (lung [a] and mediastinal [b] windows) demonstrate an endobronchial mass in the posterior segmental bronchus of the right lower lobe with a distal tubular mucus plug. The mass enhances and is distinct from the low-attenuation mucus plug. (c) Photograph of a cut specimen of the resected right upper lobe shows the central tumor (*) and distal mucoid impaction.

View larger version (155K): [in this window] [in a new window] [Download PPT slide]   Figure 19a.  Typical carcinoid in a 35-year-old man with a 1-year history of fever, hemoptysis, and pneumonia. (a) PA chest radiograph demonstrates a lobular, right perihilar mass. (b, c) Chest CT scans (lung window, with b obtained at a slightly higher level than c) demonstrate the partially endobronchial mass. The bulk of the mass is extraluminal with a smaller intraluminal component. (d) Photograph of the bisected specimen demonstrates the ovoid, lobular, endoluminal mass with focal hemorrhage. Note the adjacent bronchial wall (arrow).

View larger version (150K): [in this window] [in a new window] [Download PPT slide]   Figure 19b.  Typical carcinoid in a 35-year-old man with a 1-year history of fever, hemoptysis, and pneumonia. (a) PA chest radiograph demonstrates a lobular, right perihilar mass. (b, c) Chest CT scans (lung window, with b obtained at a slightly higher level than c) demonstrate the partially endobronchial mass. The bulk of the mass is extraluminal with a smaller intraluminal component. (d) Photograph of the bisected specimen demonstrates the ovoid, lobular, endoluminal mass with focal hemorrhage. Note the adjacent bronchial wall (arrow).

View larger version (122K): [in this window] [in a new window] [Download PPT slide]   Figure 19c.  Typical carcinoid in a 35-year-old man with a 1-year history of fever, hemoptysis, and pneumonia. (a) PA chest radiograph demonstrates a lobular, right perihilar mass. (b, c) Chest CT scans (lung window, with b obtained at a slightly higher level than c) demonstrate the partially endobronchial mass. The bulk of the mass is extraluminal with a smaller intraluminal component. (d) Photograph of the bisected specimen demonstrates the ovoid, lobular, endoluminal mass with focal hemorrhage. Note the adjacent bronchial wall (arrow).

View larger version (140K): [in this window] [in a new window] [Download PPT slide]   Figure 19d.  Typical carcinoid in a 35-year-old man with a 1-year history of fever, hemoptysis, and pneumonia. (a) PA chest radiograph demonstrates a lobular, right perihilar mass. (b, c) Chest CT scans (lung window, with b obtained at a slightly higher level than c) demonstrate the partially endobronchial mass. The bulk of the mass is extraluminal with a smaller intraluminal component. (d) Photograph of the bisected specimen demonstrates the ovoid, lobular, endoluminal mass with focal hemorrhage. Note the adjacent bronchial wall (arrow).

View larger version (116K): [in this window] [in a new window] [Download PPT slide]   Figure 20.  Atypical carcinoid in a 54-year-old man with a 2-month history of cough. Thin-section chest CT scan (lung window) demonstrates a well-marginated, spherical pulmonary nodule that is partially endobronchial.

View larger version (156K): [in this window] [in a new window] [Download PPT slide]   Figure 21a.  Typical carcinoid in a 46-year-old man with a 2-month history of hemoptysis and shortness of breath. (a) PA chest radiograph shows a masslike consolidation in the superior segment of the right lower lobe. (b) Contrast-enhanced chest CT scan (mediastinal window) demonstrates mass effect on the lateral wall of the bronchus intermedius with dense distal consolidation. The mass (arrows) enhances minimally with contrast material and can thus be distinguished from the adjacent consolidated lung. (c) Photograph of a cut section of the surgical specimen shows the peribronchial neoplasm with endobronchial extension (arrow) surrounded by consolidated lung.

View larger version (115K): [in this window] [in a new window] [Download PPT slide]   Figure 21b.  Typical carcinoid in a 46-year-old man with a 2-month history of hemoptysis and shortness of breath. (a) PA chest radiograph shows a masslike consolidation in the superior segment of the right lower lobe. (b) Contrast-enhanced chest CT scan (mediastinal window) demonstrates mass effect on the lateral wall of the bronchus intermedius with dense distal consolidation. The mass (arrows) enhances minimally with contrast material and can thus be distinguished from the adjacent consolidated lung. (c) Photograph of a cut section of the surgical specimen shows the peribronchial neoplasm with endobronchial extension (arrow) surrounded by consolidated lung.

View larger version (122K): [in this window] [in a new window] [Download PPT slide]   Figure 21c.  Typical carcinoid in a 46-year-old man with a 2-month history of hemoptysis and shortness of breath. (a) PA chest radiograph shows a masslike consolidation in the superior segment of the right lower lobe. (b) Contrast-enhanced chest CT scan (mediastinal window) demonstrates mass effect on the lateral wall of the bronchus intermedius with dense distal consolidation. The mass (arrows) enhances minimally with contrast material and can thus be distinguished from the adjacent consolidated lung. (c) Photograph of a cut section of the surgical specimen shows the peribronchial neoplasm with endobronchial extension (arrow) surrounded by consolidated lung.

View larger version (104K): [in this window] [in a new window] [Download PPT slide]   Figure 22a.  Atypical carcinoid in a 25-year-old woman. (a) Chest CT scan (lung window) demonstrates an endoluminal mass (*) completely occluding the lumen of the left lower lobe bronchus. Note the overinflation of the left lower lobe secondary to obstruction. A pneumomediastinum is also present. (b) Photograph of the resected endobronchial lesion shows the fleshy, spherical, homogeneous, soft-tissue mass that straddled the left main and left lower lobe bronchi at the time of surgery.

View larger version (104K): [in this window] [in a new window] [Download PPT slide]   Figure 22b.  Atypical carcinoid in a 25-year-old woman. (a) Chest CT scan (lung window) demonstrates an endoluminal mass (*) completely occluding the lumen of the left lower lobe bronchus. Note the overinflation of the left lower lobe secondary to obstruction. A pneumomediastinum is also present. (b) Photograph of the resected endobronchial lesion shows the fleshy, spherical, homogeneous, soft-tissue mass that straddled the left main and left lower lobe bronchi at the time of surgery.

View larger version (124K): [in this window] [in a new window] [Download PPT slide]   Figure 23a.  Typical carcinoid in a 34-year-old woman with a 2-year history of wheezing, shortness of breath, and recurrent bronchitis. (a) Chest CT scan (lung window) demonstrates a well-marginated, ovoid, completely endoluminal nodule in the left mainstem bronchus. (b) Photograph of a cut specimen from a sleeve resection shows the fleshy tumor within the bronchial lumen.

View larger version (121K): [in this window] [in a new window] [Download PPT slide]   Figure 23b.  Typical carcinoid in a 34-year-old woman with a 2-year history of wheezing, shortness of breath, and recurrent bronchitis. (a) Chest CT scan (lung window) demonstrates a well-marginated, ovoid, completely endoluminal nodule in the left mainstem bronchus. (b) Photograph of a cut specimen from a sleeve resection shows the fleshy tumor within the bronchial lumen.

View larger version (160K): [in this window] [in a new window] [Download PPT slide]   Figure 24a.  Typical carcinoid in a 47-year-old woman with a 3-day history of hemoptysis. (a) PA chest radiograph demonstrates a well-marginated, ovoid, peripheral mass in the right lower lobe. (b) Thin-section chest CT scan (lung window) shows the well-defined notched lesion, which abuts a lower lobe bronchus. (c) Photograph of a cut specimen of the resected right lower lobe shows the mass and helps confirm its bronchial relationship (arrow).

View larger version (121K): [in this window] [in a new window] [Download PPT slide]   Figure 24b.  Typical carcinoid in a 47-year-old woman with a 3-day history of hemoptysis. (a) PA chest radiograph demonstrates a well-marginated, ovoid, peripheral mass in the right lower lobe. (b) Thin-section chest CT scan (lung window) shows the well-defined notched lesion, which abuts a lower lobe bronchus. (c) Photograph of a cut specimen of the resected right lower lobe shows the mass and helps confirm its bronchial relationship (arrow).

View larger version (118K): [in this window] [in a new window] [Download PPT slide]   Figure 24c.  Typical carcinoid in a 47-year-old woman with a 3-day history of hemoptysis. (a) PA chest radiograph demonstrates a well-marginated, ovoid, peripheral mass in the right lower lobe. (b) Thin-section chest CT scan (lung window) shows the well-defined notched lesion, which abuts a lower lobe bronchus. (c) Photograph of a cut specimen of the resected right lower lobe shows the mass and helps confirm its bronchial relationship (arrow).

Enlargement of thoracic lymph nodes associated with carcinoids sometimes represents benign disease. Nodes may become enlarged because of hyperplasia resulting from associated recurrent or chronic distal infection. However, typical and atypical carcinoids may be associated with hilar or mediastinal lymphadenopathy secondary to lymph node metastases (Fig 25) (41). The latter are more frequently encountered in lesions with atypical histologic characteristics (48).

View larger version (109K): [in this window] [in a new window] [Download PPT slide]   Figure 25a.  Atypical carcinoid in a 46-year-old man with a 2-year history of cough and hemoptysis. Contrast-enhanced chest CT scans (mediastinal window, with a obtained at a lower level than b) demonstrate a lobular mass (* in a) that abuts the bronchus intermedius. A large pretracheal lymph node (arrow in b) contained metastatic carcinoid at surgery.

View larger version (113K): [in this window] [in a new window] [Download PPT slide]   Figure 25b.  Atypical carcinoid in a 46-year-old man with a 2-year history of cough and hemoptysis. Contrast-enhanced chest CT scans (mediastinal window, with a obtained at a lower level than b) demonstrate a lobular mass (* in a) that abuts the bronchus intermedius. A large pretracheal lymph node (arrow in b) contained metastatic carcinoid at surgery.

MR Imaging.—Magnetic resonance (MR) imaging of bronchial carcinoids has demonstrated lesions of high signal intensity on T2-weighted images and short T1-inversion-recovery images (Fig 26) (50). Although MR imaging does not allow carcinoids to be differentiated from other central neoplasms, it may be helpful in distinguishing these lesions from adjacent normal vascular structures (51). Ultrafast contrast-enhanced MR imaging studies have shown pronounced signal enhancement in bronchial carcinoids during the systemic phase of circulation, which helps confirm the bronchial arterial supply to these tumors and their highly vascular nature (50).

View larger version (124K): [in this window] [in a new window] [Download PPT slide]   Figure 26a.  Typical carcinoid in an asymptomatic 46-year-old woman. On both T1-weighted (a) and T2-weighted (b) MR images, an ovoid mass of high signal intensity is seen.

View larger version (120K): [in this window] [in a new window] [Download PPT slide]   Figure 26b.  Typical carcinoid in an asymptomatic 46-year-old woman. On both T1-weighted (a) and T2-weighted (b) MR images, an ovoid mass of high signal intensity is seen.

View larger version (111K): [in this window] [in a new window] [Download PPT slide]   Figure 27a.  Typical carcinoid in an 18-year-old woman with a 3-month history of cough and hemoptysis. (a, b) Contrast-enhanced chest CT scans (mediastinal window, with a obtained at a higher level than b) show a mass in the left mainstem bronchus with distal volume loss, bronchiectasis, and consolidation. (c) Octreotide scintigram demonstrates uptake in the central carcinoid tumor. (d) Photograph of a cut section of the resected left lung shows the endobronchial neoplasm and distal consolidated lung.

View larger version (104K): [in this window] [in a new window] [Download PPT slide]   Figure 27b.  Typical carcinoid in an 18-year-old woman with a 3-month history of cough and hemoptysis. (a, b) Contrast-enhanced chest CT scans (mediastinal window, with a obtained at a higher level than b) show a mass in the left mainstem bronchus with distal volume loss, bronchiectasis, and consolidation. (c) Octreotide scintigram demonstrates uptake in the central carcinoid tumor. (d) Photograph of a cut section of the resected left lung shows the endobronchial neoplasm and distal consolidated lung.

View larger version (139K): [in this window] [in a new window] [Download PPT slide]   Figure 27c.  Typical carcinoid in an 18-year-old woman with a 3-month history of cough and hemoptysis. (a, b) Contrast-enhanced chest CT scans (mediastinal window, with a obtained at a higher level than b) show a mass in the left mainstem bronchus with distal volume loss, bronchiectasis, and consolidation. (c) Octreotide scintigram demonstrates uptake in the central carcinoid tumor. (d) Photograph of a cut section of the resected left lung shows the endobronchial neoplasm and distal consolidated lung.

View larger version (119K): [in this window] [in a new window] [Download PPT slide]   Figure 27d.  Typical carcinoid in an 18-year-old woman with a 3-month history of cough and hemoptysis. (a, b) Contrast-enhanced chest CT scans (mediastinal window, with a obtained at a higher level than b) show a mass in the left mainstem bronchus with distal volume loss, bronchiectasis, and consolidation. (c) Octreotide scintigram demonstrates uptake in the central carcinoid tumor. (d) Photograph of a cut section of the resected left lung shows the endobronchial neoplasm and distal consolidated lung.

Positron Emission Tomography.—Positron emission tomography (PET) is a useful imaging modality in the noninvasive evaluation of tumors as it provides physiologic information that may allow distinction between benign and malignant lesions. PET performed with fluorodeoxyglucose-18 (FDG) has proved valuable in the evaluation of pulmonary nodules. In general, malignant nodules display an increased consumption of glucose in contrast with normal tissue and thus are visualized as hypermetabolic lesions at FDG PET. In a recent retrospective review of seven pulmonary carcinoids imaged with FDG PET, however, six of the seven lesions were hypometabolic (56). The authors concluded that FDG PET imaging is not a useful test in the noninvasive characterization of carcinoids as the malignant lesions they represent (56).

Diagnostic Methods
Venous Sampling.—Bilateral petrosal sinus sampling for ACTH before and after stimulation by ACTH-releasing hormone has been considered a reliable test for distinguishing pituitary from ectopic ACTH-producing neoplasms. However, this method does not provide specific information about the anatomic location of the source of ectopic ACTH production.

If the tumor location is suspected based on abnormalities detected with other imaging studies such as CT or MR imaging, targeted venous sampling in these anatomic locations can be undertaken to confirm the diagnosis. However, in the absence of abnormal imaging findings, wide-ranging venous sampling of systemic and portal veins generally yields negative results. Although venous sampling provides functional and anatomic information on lesions seen during advanced imaging studies, it is an invasive procedure (47,51,55).

Bronchoscopy.—Most bronchial carcinoids are within reach of a bronchoscope (29). Central typical bronchial carcinoids have a characteristic endoscopic appearance and manifest as smooth, red-to-pink, lobulated endobronchial lesions that may bleed at the time of bronchoscopic visualization (Fig 28). A small percentage of atypical carcinoids exhibit similar endoscopic characteristics (57).

View larger version (131K): [in this window] [in a new window] [Download PPT slide]   Figure 28.  Typical carcinoid in a 21-year-old woman with cough and fever. Image from bronchoscopy shows a well-defined, red, polypoid mass obliterating the lumen of the bronchus intermedius.

Although endoscopy is reliable in the detection of the endoluminal component of central carcinoids, it fails to provide information about the extraluminal extent of tumor.

Fine-Needle Aspiration Biopsy.—Sampling of typical carcinoids by means of CT-guided fine-needle aspiration biopsy usually yields hypercellular aspirates with loose groupings of cells in a background of single cells. Cellular and nuclear monomorphism is seen in virtually all cases. Rosette formation is observed in approximately 33% of cases. The nuclei are small and round to oval and have a finely granular chromatin. Necrosis and nucleoli are not seen. Immunostaining for chromogranin is usually positive. Therefore, fine-needle aspiration biopsy is considered reliable in the diagnosis of typical bronchial carcinoids.

Atypical carcinoids demonstrate increased pleomorphism and mitoses, hyperchromatic nuclei, irregular coarse chromatin, necrosis, and nuclear molding (60). Thus, these lesions present potential pitfalls in the pathologic diagnosis and introduce difficulty in the differentiation between carcinoid and carcinoma, a distinction that was achieved in only 60% of cases in one study (58).

Diagnostic Pitfalls.—Potential pitfalls exist in the pathologic diagnosis of bronchial carcinoid. Marked nuclear pleomorphism has been observed in frozen sections of biopsy material of bronchial carcinoids and has resulted in their misdiagnosis as non-small cell carcinomas (61). In one study, the incorrect diagnosis of bronchogenic carcinoma was made in 32% of bronchial carcinoids when small biopsy samples were available (62). Radiologists and other physicians who perform biopsies of these lesions should be aware of these pitfalls. Correlation with imaging findings may be helpful in suggesting the correct diagnosis.

Therapy and Prognosis
The only effective treatment for patients with bronchial carcinoids is complete surgical excision of the primary tumor mass (29,58,59). Surgical technique ranges from radical procedures including pneumonectomy, bilobectomy, and lobectomy to conservative excision such as segmentectomy, wedge resection, sleeve lobectomy, and sleeve bronchectomy (63). Complete excision of the tumor is usually possible, because only 15% of lesions demonstrate regional lymph node metastases. However, the presence of local nodal metastases does not preclude definitive surgical therapy, and in cases of typical carcinoid, excellent results may be achieved (63). Pneumonectomy is typically employed for large central tumors (> 5 cm), central tumors that invade the lung parenchyma, and lesions with extensive hilar or mediastinal involvement (31,64). Pneumonectomy is also used when central tumors have resulted in severe or extensive distal parenchymal infection (29,59).

Although complete tumor excision may also be achieved by conservative resection, only a small percentage of patients (22% in one series) are candidates for such bronchoplastic procedures (31,64). Morbidity is not increased in patients in whom bronchoplastic procedures are employed (63). Preoperative use of thoracic CT has enabled precise surgical planning and selection of those patients who are the best candidates for sleeve resection or other bronchoplastic procedures (49). In all cases, mediastinal lymph node dissection is highly recommended for staging purposes and to ensure that all tumor-bearing tissue is excised at the time of the initial surgical procedure (58).

Although endobronchial resection has also been employed, it should be reserved for patients with centrally located, symptomatic tumors in which there are clinical contraindications to definitive thoracotomy (58). In Europe, a select patient population with predominantly endoluminal typical bronchial carcinoids was successfully treated with bronchoscopic Nd-YAG laser therapy. These patients had no evidence of bronchial wall thickening or lymph node enlargement at thin-section CT and had excellent local tumor control and surgical proof of cure in six of 11 cases (65).

Peripheral bronchial carcinoids have been successfully treated with minimal loss of lung tissue by means of stapled wedge pulmonary resection (5). In recent reports, video-assisted thoracoscopic surgery has been employed to remove and diagnose small peripheral carcinoids when medical or other considerations contraindicate thoracotomy (4).

In the case of atypical carcinoids, an aggressive surgical approach is recommended. Nodal disease is common and is seen in 40%–50% of patients; in one study, 22% of patients had N2 disease at the time of surgery. Thus, the recommended therapy for patients with atypical carcinoids includes at minimum a lobectomy for the resection of the primary tumor as well as systematic regional and mediastinal lymph node dissection. The role of adjuvant chemotherapy is controversial, but this treatment approach has been recommended for patients who have systemic metastases at the time of presentation (30,48). Adjuvant multiagent chemotherapy has been employed with some success in the treatment of advanced and atypical bronchial carcinoids (5).

Long-acting somatostatin analogues such as octreotide have been used to treat hormonally active carcinoids. Therapy is achieved through inhibition of the adenylate cyclase system via type 2 somatostatin receptors and is associated with a decrease in ACTH secretion by the tumor (5,66). Treatment with octreotide is useful in preparation for surgery because it results in preoperative control of hypercortisolism, and prior octreotide imaging is used to identify those tumors that are somatostatin receptor positive and thus likely to respond (66). Although both clinical and biochemical responses have been reported, complete normalization of blood levels has not been achieved (53,66). However, relief of symptoms as well as a decrease in urinary levels of 5-hydroxyindoleacetic acid in patients with the carcinoid syndrome have been reported (52).

Patients with typical bronchial carcinoids have an excellent prognosis, with reported 5-, 10-, and 15-year survivals of 92.4%, 88.3%, and 76.4%, respectively (63). Patients with atypical carcinoids have a less favorable prognosis, with 5- and 10-year survivals of 69% and 24%–52%, respectively (30,58,59). Improved survivals have been reported in female patients as well as those with asymptomatic presentations, peripheral tumors, negative lymph nodes, small primary tumors (< 2 cm), and typical histologic subtype (5).

A recently published retrospective review of 87 surgically treated patients was undertaken to evaluate those features that influenced tumor recurrence and treatment outcome. An overall 4-year actuarial survival rate of 89% was noted in patients with carcinoids, and 92%, 94%, and 96% of patients were free of local, regional, and distant recurrent disease 4 years after therapy. Tumor size, histologic subtype, and nodal involvement at initial diagnosis were the factors that most influenced recurrence and outcome. Although previous studies suggested that tumor size had no influence on outcome, this series found a trend toward an increased likelihood of distant recurrence as well as a significant decrease in survival when tumors were larger than 3 cm. The overall 4-year survival for patients with large tumors was 69%, compared with 96% for patients with tumors measuring less than 3 cm in diameter (58,67). Atypical histologic subtype also influenced local and regional tumor recurrence, which was noted in 17% and 2% of atypical and typical carcinoids, respectively. Local recurrence may also have contributed to the lower 4-year survival rate of 70% found in patients with atypical carcinoid (67). Regional nodal involvement was associated with an increased rate of regional recurrence after surgery. Regional recurrence occurred in 10% of patients with nodal involvement as opposed to 4% in patients without nodal disease. In addition, the 4-year overall survival of patients without nodal disease was 91%, compared with 80% in patients with lymph node involvement (67).

	THYMIC CARCINOID

Top Abstract INTRODUCTION BRONCHIAL CARCINOID THYMIC CARCINOID CONCLUSIONS References

 
Clinical Features
Thymic carcinoids are rare primary malignant thymic neoplasms that affect patients over a wide age range, with the median age being 43 years. Men are more frequently affected than women, with a male-to-female ratio of 3:1. In general, thymic carcinoids exhibit a more aggressive behavior than bronchial carcinoids (11,68,69). This aggressiveness may be related to the fact that most thymic carcinoids are histologically similar to atypical bronchial carcinoids.

The majority of patients present with symptoms related to mass effect on or invasion of mediastinal and other thoracic structures. Presenting symptoms and signs include cough, dyspnea, chest pain, and the superior vena cava syndrome (11,70). Approximately one-third of patients are entirely asymptomatic, and the presence of thymic carcinoid is discovered incidentally because of abnormal chest radiographic findings (69).

Approximately one-half of thymic carcinoids are functionally active and manifest with clinical hormone syndromes. Cushing syndrome is seen in approximately 33%–40% of affected individuals. Another important clinical manifestation relates to the association between thymic carcinoid and the autosomal dominant syndrome of multiple endocrine neoplasia (MEN), specifically type 1 MEN (Wermer syndrome), which is seen in 19%–25% of patients with thymic carcinoids. Type 1 MEN syndrome is characterized by hyperparathyroidism (90% of cases), islet cell tumors of the pancreas (80%), and pituitary adenomas (65%) (70,71,72). Carcinoids, adrenal adenomas or carcinomas, lipomas, or follicular thyroid adenomas are less frequently associated neoplasms (70). The majority of patients with thymic carcinoids and type 1 MEN syndrome are men. Additional associated conditions found in patients with thymic carcinoids include type 2 MEN syndrome, inappropriate secretion of antidiuretic hormone, polymyositis, clubbing, polyarthropathy, and myocarditis (73,74). There are no reports of the carcinoid syndrome in patients with thymic carcinoids (69).

Pathologic Features
Rosai and Higa (75) originally described thymic carcinoids as distinct and separate from thymomas in 1972. Thymic carcinoids exhibit histologic features similar to those of bronchial carcinoids. The tumor cells are disposed in ribbons, solid sheets, or organoid nests of cells separated by fibrous trabecula. The cells are polygonal with central rounded nuclei, stippled nuclear chromatin, and inconspicuous nucleoli. The cytoplasm is granular and eosinophilic (69).

Most thymic carcinoids are characterized as atypical on the grounds of necrosis or local invasion (Fig 29). Typical thymic carcinoids are very rare (68,76). As with bronchial carcinoids, thymic carcinoids are classified within the spectrum of neuroendocrine neoplasms. The following grading system for thymic carcinoids has been proposed: grade 1 (well differentiated), grade 2 (atypical carcinoid), and grade 3 (small cell carcinoma). Most thymic carcinoids are categorized as grade 2 lesions. Histochemical studies demonstrate argyrophil granules in scattered cells, and immunohistochemical studies are variably positive for chromogranin and neuron-specific enolase. Ultrastructural analysis demonstrates cytoplasmic dense core granules (68,73).

View larger version (234K): [in this window] [in a new window] [Download PPT slide]   Figure 29a.  Thymic carcinoid. (a) Low-power photomicrograph (original magnification, x40; H-E stain) shows a punctate focus of necrosis in the center of a nest of tumor cells. (b) High-power photomicrograph (original magnification, x400; H-E stain) shows a tumor that consists of uniform cells growing in ribbons. A mitotic figure is seen in the center, characteristic of the atypical histologic subtype of this lesion.

View larger version (215K): [in this window] [in a new window] [Download PPT slide]   Figure 29b.  Thymic carcinoid. (a) Low-power photomicrograph (original magnification, x40; H-E stain) shows a punctate focus of necrosis in the center of a nest of tumor cells. (b) High-power photomicrograph (original magnification, x400; H-E stain) shows a tumor that consists of uniform cells growing in ribbons. A mitotic figure is seen in the center, characteristic of the atypical histologic subtype of this lesion.

View larger version (138K): [in this window] [in a new window] [Download PPT slide]   Figure 30a.  Thymic carcinoid in an asymptomatic 84-year-old man. (a, b) PA (a) and lateral (b) chest radiographs show a large, lobular, right-sided anterior mediastinal mass. (c) Contrast-enhanced chest CT scan (mediastinal window) shows the heterogeneous soft-tissue mass intimately related to the heart. The lesion is indistinguishable from a thymoma. (d) Photograph of a cut section of the resected lesion shows the encapsulated mass with central areas of hemorrhage and necrosis.

View larger version (135K): [in this window] [in a new window] [Download PPT slide]   Figure 30b.  Thymic carcinoid in an asymptomatic 84-year-old man. (a, b) PA (a) and lateral (b) chest radiographs show a large, lobular, right-sided anterior mediastinal mass. (c) Contrast-enhanced chest CT scan (mediastinal window) shows the heterogeneous soft-tissue mass intimately related to the heart. The lesion is indistinguishable from a thymoma. (d) Photograph of a cut section of the resected lesion shows the encapsulated mass with central areas of hemorrhage and necrosis.

View larger version (102K): [in this window] [in a new window] [Download PPT slide]   Figure 30c.  Thymic carcinoid in an asymptomatic 84-year-old man. (a, b) PA (a) and lateral (b) chest radiographs show a large, lobular, right-sided anterior mediastinal mass. (c) Contrast-enhanced chest CT scan (mediastinal window) shows the heterogeneous soft-tissue mass intimately related to the heart. The lesion is indistinguishable from a thymoma. (d) Photograph of a cut section of the resected lesion shows the encapsulated mass with central areas of hemorrhage and necrosis.

View larger version (118K): [in this window] [in a new window] [Download PPT slide]   Figure 30d.  Thymic carcinoid in an asymptomatic 84-year-old man. (a, b) PA (a) and lateral (b) chest radiographs show a large, lobular, right-sided anterior mediastinal mass. (c) Contrast-enhanced chest CT scan (mediastinal window) shows the heterogeneous soft-tissue mass intimately related to the heart. The lesion is indistinguishable from a thymoma. (d) Photograph of a cut section of the resected lesion shows the encapsulated mass with central areas of hemorrhage and necrosis.

Radionuclide imaging with [In-111–diethylenetriaminepentaacetic acid (DTPA)-D-Phe¹]-octreotide, which accumulates in thymic carcinoids, has been used in the evaluation of patients with MEN syndrome (78). However, [In-111–DTPA-D-Phe¹]-octreotide has also been shown to concentrate in primary and metastatic thymic tumors, including thymoma, thymic carcinoma, and thymic carcinoid (79). The same study showed no radionuclide accumulation in the thymus of patients with thymic hyperplasia. It has been shown that small lesions may not be detectable with radionuclide imaging, despite the use of single photon emission computed tomography, and that uptake correlates with tumor size and histologic type. Despite the above, it is recognized that octreotide imaging may be useful in the evaluation of patients with MEN, as both thymic carcinoids and thymomas may occur as associated lesions in these individuals (79).

Therapy and Prognosis
Local progression of disease, tumor recurrence, and metastatic disease are common in patients with thymic carcinoids. Thus, the therapy of choice for patients with these neoplasms is complete and aggressive surgical excision of the primary tumor, any recurrent disease, and distant metastases. Thymic carcinoid has an unpredictable behavior and a tendency to metastasize widely and recur locally even years after the initial surgical excision. Thus, adjuvant radiation therapy and chemotherapy have both been employed with some success to treat affected individuals. Although radiation therapy is more commonly used to treat residual and recurrent tumors, the role of chemotherapy is less established (72,73,76).

Thymic carcinoids display a more aggressive behavior in patients with MEN syndromes (68). Although carcinoids are less commonly found in patients with type 1 MEN than parathyroid, endocrine, enteropancreatic, and anterior pituitary neoplasms, they potentially represent a major cause of death in these individuals (71). Because many patients with type 1 MEN (85%) have biochemical hyperparathyroidism, it is customary to use concurrent thymectomy at the time of surgical resection of the parathyroid glands to prevent recurrence from supernumerary glands located in the thymus. These individuals may have a better outcome because tissue at risk for thymic carcinoid is incidentally excised (71).

The prognosis of patients with thymic carcinoids is poor, principally because of the high incidence of tumor recurrence and widespread metastases following surgical excision (73). Three- and 5-year survival rates of 45 and 31%, respectively, have been reported, and all patients in one series died within 18 months of diagnosis (76). However, survivals of up to 12 years have been achieved through aggressive surgical excision of the primary tumor as well as its recurrences and metastases (73). Patients with extracapsular invasion of mediastinal structures at initial surgical exploration and those presenting with Cushing syndrome have a worse prognosis (73). Follow-up consisting of physical examination, chest radiography, thoracic CT, and metastatic work-up every 6–12 months has been recommended for treated individuals. Additional radiation therapy and chemotherapy may be required in patients with recurrent or widespread metastatic disease (73).

	CONCLUSIONS

Top Abstract INTRODUCTION BRONCHIAL CARCINOID THYMIC CARCINOID CONCLUSIONS References

 
Thoracic carcinoids usually occur in symptomatic adults who are usually younger than individuals afflicted by the more common primary bronchogenic carcinomas. Typical bronchial carcinoids produce symptoms related to obstruction of central bronchi. Their well-defined borders, central location, and radiologic evidence of a bronchial relationship characterize these lesions. Surgically treated patients have a favorable prognosis. Atypical bronchial carcinoids have similar gross and radiologic features but exhibit a higher propensity for metastatic spread, and affected patients have a worse prognosis. Thymic carcinoids are aggressive anterior mediastinal neoplasms that usually affect symptomatic male patients. They are often associated with a clinical hormone syndrome and have radiologic features that mimic those of thymoma (Table).

	Footnotes

 
The opinions and assertions contained herein are the private views of the author and are not to be construed as official nor as representing the views of the Departments of the Air Force or Defense.

Abbreviations: ACTH = adrenocorticotropic hormone H-E = hematoxylin-eosin MEN = multiple endocrine neoplasia PA = posteroanterior

This article meets the criteria for 1.0 credit hour in category 1 of the AMA Physician's Recognition Award. To obtain credit, see the questionnaire on pp 737–744.

LEARNING OBJECTIVES After reading this article and taking the test, the reader will be able to: • To describe the varied radiologic features of bronchial and thymic carcinoids on the basis of their underlying histopathologic features. • To enumerate the multiple cross-sectional imaging manifestations of these tumors with special attention to characteristic features that may help suggest the correct diagnosis. • To define clinical and prognostic characteristics of these tumors, which may enable increased understanding of their behavior.

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