DOI: 10.1148/rg.261055057
RadioGraphics 2006;26:41-57
© RSNA, 2006
Neuroendocrine Tumors of the Lung: Clinical, Pathologic, and Imaging Findings1
Semin Chong, MD,
Kyung Soo Lee, MD,
Myung Jin Chung, MD,
Joungho Han, MD,
O Jung Kwon, MD and
Tae Sung Kim, MD
1 From the Department of Radiology and Center for Imaging Science (S.C., K.S.L., M.J.C., T.S.K.), Department of Pathology (J.H.), and Department of Medicine (O.J.K.), Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul 135-710, Korea. Presented as an education exhibit at the 2004 RSNA Annual Meeting. Received March 21, 2005; revision requested April 19 and received May 2; accepted May 4. All authors have no financial relationships to disclose. Supported by the SRC/ERC program of MOST/KOSEF (R11-2002-103).
Address correspondence to K.S.L. (e-mail: kyungs.lee{at}samsung.com).
 |
Abstract
|
|---|
Neuroendocrine tumors of the lung arise from Kulchitzky cells of the bronchial mucosa and comprise typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma (LCNEC), and small cell lung cancer (SCLC). At histopathologic analysis, these tumors demonstrate a progressive increase in the number of mitotic figures per 10 high-power fields of viable tumor and in the extent of necrosis, with typical carcinoid having the lowest values and SCLC having the highest. Typical carcinoid is less aggressive than atypical carcinoid, although these tumors have similar gross pathologic and radiologic features; LCNEC has a prognosis between that of atypical carcinoid and that of SCLC. SCLC is the most aggressive pulmonary neuroendocrine tumor and has the most specific imaging feature: mediastinal or hilar lymphadenopathy. At CT, carcinoid tumors appear as a spherical or ovoid nodule or mass with a well-defined and slightly lobulated border. When nonspherical, the tumor is elongated with its long axis parallel to adjacent bronchi. Calcification or ossification is seen in up to 30% of cases. The CT findings of LCNEC are nonspecific and are similar to those of other non–small cell lung cancers. Although there are some overlapping features between these tumors, integration of the clinical and imaging features may be helpful in differentiation of pulmonary neuroendocrine tumors.
© RSNA, 2006
|
LEARNING OBJECTIVES FOR TEST 2
|
|---|
After reading this article and taking the test, the reader will be able to:
- Describe how pulmonary neuroendocrine tumors are classified according to histopathologic diagnostic criteria.
- List the clinical, pathologic, and imaging features of pulmonary neuroendocrine tumors.
- Discuss features that are helpful in differential diagnosis of pulmonary neuroendocrine tumors.
|
Introduction
|
|---|
Neuroendocrine tumors of the lung arise from Kulchitzky cells that are normally present in the bronchial mucosa and share the common morphologic features of neuroendocrine tumors including organoid nesting, palisading, rosettes, or a trabecular growth pattern. These tumors represent a broad clinical-pathologic spectrum and have variable morphologic features and biologic behaviors. In 1991, Travis et al (1) proposed a new classification of pulmonary neuroendocrine tumors that includes typical carcinoid, which is a low-grade malignancy; atypical carcinoid, which is a medium-grade malignancy; and large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC), which are high-grade malignancies. The prognosis and the behavioral features of neuroendocrine tumors deteriorate according to the listed order (2). These tumors account for over 25% of all pulmonary neoplasms, and the majority of neuroendocrine tumors are SCLCs (3). Treatment is dependent on the histologic features, which reflect differences in clinical behavior and prognosis.
In this article, we describe the spectrum of neuroendocrine tumors of the lung and their clinical, pathologic, and imaging findings. These findings are summarized in the Table.
|
Carcinoid Tumors
|
|---|
Pulmonary or bronchial carcinoid tumors account for over 25% of all carcinoid tumors and for 1%–2% of all pulmonary neoplasms (4). About 10%–20% of pulmonary carcinoids are atypical carcinoids; the remaining 80%–90% are typical carcinoids (5). Most of these tumors (60%–70%) occur centrally and involve the main, lobar, or segmental airways (6). These tumors are known to affect women slightly more frequently than men (7,8). However, some investigators recently have found that carcinoids may affect males and females equally (5) or have a male predominance with a male-to-female ratio of up to 3.6:1 (9). Patients with atypical carcinoids are more frequently men (10). The mean presenting age is 46 years with a wide age range (11). Patients with carcinoid tumors are younger than those with common primary lung cancer.
The centrally located tumors, being more frequently typical carcinoids than atypical carcinoids, tend to manifest earlier with central airway obstruction symptoms and signs than do peripherally located atypical carcinoids. Therefore, patients with atypical carcinoids are about 10 years older than those with typical carcinoids (59 years in atypical carcinoids and 49 years in typical carcinoids) (12,13). Carcinoids are the commonest primary pulmonary neoplasm of children, mostly being seen in late adolescence (14,15). Common presenting symptoms include a cough, wheezing, and hemoptysis caused by bronchial obstruction (16). However, about 25% of patients are asymptomatic, and thus bronchial carcinoids may be found incidentally (17).
Unlike typical carcinoids, atypical carcinoids are associated with a history of cigarette smoking (83%–94% of cases) and occur more often in men (2:1) (10). Most typical carcinoids (80%–90%) are stage I, whereas approximately 50% of atypical carcinoids are stage I cancers. The preferred treatments for carcinoid tumors are lobectomy and pneumonectomy. The overall 5-year survival rates for typical carcinoids and atypical carcinoids are 87% and 56%, respectively, and the survival rate for atypical carcinoid is significantly poorer than that for typical carcinoid (2).
Histologic Findings
Typical carcinoids and atypical carcinoids are distinguished by using histologic features. Both tumors consist of small nests or interconnecting trabeculae of uniform cells separated by a prominent vascular stroma and numerous thin-walled blood vessels (Figs 1, 2) (18). In terms of histologic features predictive of prognosis, typical carcinoids show no evidence of necrosis and less than 2 mitoses per 10 high-power fields (HPFs) (or 2 mm2) of viable tumor (Fig 1), whereas atypical carcinoids have areas of necrosis or 2–10 mitoses per 10 HPFs (Fig 2) (2).
Dense core granules in the cytoplasm, which are evident at electron microscopy, are homogeneous in size in both typical carcinoids and atypical carcinoids, but they are more numerous and generally larger in typical carcinoids than in atypical carcinoids (19). Immunohistochemical staining for neurosecretory granules is usually diffuse, and typical carcinoids show the highest percentages, distributions, and intensities (20). The expressions of neuron-specific enolase, chromogranin, and synaptophysin, so-called panneuroendocrine markers, are valuable in terms of identifying neuroendocrine features but do not affect the designation or the prognosis of a given pulmonary neuroendocrine tumor (21).
The histopathologic features that distinguish atypical carcinoid from typical carcinoid are as follows: (a) increased mitotic activity, (b) greater cytologic pleomorphism and higher nuclear-to-cytoplasmic ratios, (c) increased cellularity and architectural irregularities, and (d) more areas of tumor necrosis.
Imaging Findings
The imaging features of typical carcinoids and atypical carcinoids are too similar to be separated. Although the location of carcinoids varies, the majority are centrally located and therefore related to airways. About 16%–40% occur in the peripheral lung (6). Chest radiographs most often show a well-defined hilar or perihilar mass (Fig 3) as an isolated finding or with associated distal parenchymal disease. The associated parenchymal change may be consolidation, which is suggestive of atelectasis, obstructive pneumonitis, or recurrent pneumonia (Fig 4). It may be mucus plugging, which is apparent as a "gloved finger" pattern when multiple contiguous bronchi are dilated (6,22).
View larger version (159K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 3a. Typical carcinoid in a 25-year-old man. (a) Chest radiograph shows a lobulated mass below the right hilum. (b) Axial thin-section (1.0-mm section thickness) computed tomographic (CT) scan of the right middle lobe shows the large (60-mm-diameter) mass with punctate calcifications (arrowheads). (c) Photograph of the gross specimen obtained with right lobectomy shows the large endobronchial mass with central ossification (arrowheads). (d) Photomicrograph (original magnification, x 100; hematoxylin-eosin stain) shows metaplastic bone (arrows) in the tumor.
|
|
View larger version (100K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 3b. Typical carcinoid in a 25-year-old man. (a) Chest radiograph shows a lobulated mass below the right hilum. (b) Axial thin-section (1.0-mm section thickness) computed tomographic (CT) scan of the right middle lobe shows the large (60-mm-diameter) mass with punctate calcifications (arrowheads). (c) Photograph of the gross specimen obtained with right lobectomy shows the large endobronchial mass with central ossification (arrowheads). (d) Photomicrograph (original magnification, x 100; hematoxylin-eosin stain) shows metaplastic bone (arrows) in the tumor.
|
|
View larger version (109K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 3c. Typical carcinoid in a 25-year-old man. (a) Chest radiograph shows a lobulated mass below the right hilum. (b) Axial thin-section (1.0-mm section thickness) computed tomographic (CT) scan of the right middle lobe shows the large (60-mm-diameter) mass with punctate calcifications (arrowheads). (c) Photograph of the gross specimen obtained with right lobectomy shows the large endobronchial mass with central ossification (arrowheads). (d) Photomicrograph (original magnification, x 100; hematoxylin-eosin stain) shows metaplastic bone (arrows) in the tumor.
|
|
View larger version (191K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 3d. Typical carcinoid in a 25-year-old man. (a) Chest radiograph shows a lobulated mass below the right hilum. (b) Axial thin-section (1.0-mm section thickness) computed tomographic (CT) scan of the right middle lobe shows the large (60-mm-diameter) mass with punctate calcifications (arrowheads). (c) Photograph of the gross specimen obtained with right lobectomy shows the large endobronchial mass with central ossification (arrowheads). (d) Photomicrograph (original magnification, x 100; hematoxylin-eosin stain) shows metaplastic bone (arrows) in the tumor.
|
|
View larger version (98K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 4a. Typical carcinoid in a 47-year-old woman. (a) Lateral chest radiograph shows atelectasis of the left lower lobe (arrows) and a central mass (arrowheads). (b) Axial CT scan (5.0-mm section thickness) obtained at the level of the left atrium shows a 20-mm-diameter endobronchial nodule (arrowhead) in the left basal trunk with attendant atelectasis of the left lower lobe (arrow).
|
|
View larger version (115K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 4b. Typical carcinoid in a 47-year-old woman. (a) Lateral chest radiograph shows atelectasis of the left lower lobe (arrows) and a central mass (arrowheads). (b) Axial CT scan (5.0-mm section thickness) obtained at the level of the left atrium shows a 20-mm-diameter endobronchial nodule (arrowhead) in the left basal trunk with attendant atelectasis of the left lower lobe (arrow).
|
|
Carcinoid tumors are sometimes located distal to segmental bronchi; such tumors are the so-called peripheral carcinoids. These are well-defined round or ovoid lesions with lobulated margins (Fig 5 ) and measure less than 3 cm in diameter (23,24). Atypical carcinoids have been reported to be larger than typical carcinoids with mean diameters of 3.6 cm and 2.3 cm, respectively, and atypical carcinoids are more likely to occur in the lung periphery than typical carcinoids (24,25). Metastases occur in 15% of bronchial carcinoids and usually involve the liver, bone, adrenal glands, and brain (6).
View larger version (162K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 5a. Typical carcinoid in a 48-year-old man. (a) Chest radiograph shows a well-defined round mass in the right upper lobe. (b) Axial CT scan (5.0-mm section thickness) obtained with a mediastinal window shows the homogeneous mass.
|
|
View larger version (81K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 5b. Typical carcinoid in a 48-year-old man. (a) Chest radiograph shows a well-defined round mass in the right upper lobe. (b) Axial CT scan (5.0-mm section thickness) obtained with a mediastinal window shows the homogeneous mass.
|
|
At CT, carcinoid tumors appear as a spherical or ovoid nodule or mass with a well-defined and slightly lobulated border. When nonspherical, the tumors have an elongated shape, with the long axis parallel to adjacent bronchi or pulmonary artery branches. They are typically located close to central bronchi, often near the bifurcation area (Figs 6, 7). Calcification is usually not visible on chest radiographs, but on CT images calcification or ossification can be seen in up to 30% of tumors (Fig 3) and manifests in a punctate or diffuse pattern (26). Moreover, calcification is more frequent in central carcinoids than in peripheral carcinoids (27). Therefore, observation of a central tumor that causes narrowing, deformation, or obstruction of a bronchus and that displays punctate or diffuse calcification should suggest the diagnosis of bronchial carcinoid (Fig 3).
View larger version (102K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 6a. Typical carcinoid in a 24-year-old woman. (a) Axial CT scan (5.0-mm section thickness), obtained at the level of the right middle lobar bronchus, shows a 13-mm-diameter nodule (arrow) in the superior segmental bronchus of the right lower lobe with distal mucus plugging (arrowheads). (b) Same image displayed with a mediastinal window shows significant enhancement of the endobronchial nodule (arrow). (c) Photograph of the gross specimen shows the yellow polypoid endobronchial nodule (arrow). Note the distal mucus plugging (arrowhead).
|
|
View larger version (89K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 6b. Typical carcinoid in a 24-year-old woman. (a) Axial CT scan (5.0-mm section thickness), obtained at the level of the right middle lobar bronchus, shows a 13-mm-diameter nodule (arrow) in the superior segmental bronchus of the right lower lobe with distal mucus plugging (arrowheads). (b) Same image displayed with a mediastinal window shows significant enhancement of the endobronchial nodule (arrow). (c) Photograph of the gross specimen shows the yellow polypoid endobronchial nodule (arrow). Note the distal mucus plugging (arrowhead).
|
|
View larger version (133K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 6c. Typical carcinoid in a 24-year-old woman. (a) Axial CT scan (5.0-mm section thickness), obtained at the level of the right middle lobar bronchus, shows a 13-mm-diameter nodule (arrow) in the superior segmental bronchus of the right lower lobe with distal mucus plugging (arrowheads). (b) Same image displayed with a mediastinal window shows significant enhancement of the endobronchial nodule (arrow). (c) Photograph of the gross specimen shows the yellow polypoid endobronchial nodule (arrow). Note the distal mucus plugging (arrowhead).
|
|
View larger version (79K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 7a. Typical carcinoid in a 41-year-old man. (a) Axial CT scan (5.0-mm section thickness), obtained at the level of the distal left main bronchus, shows a nodule (arrow) in the left upper divisional bronchus. (b) CT scan (mediastinal window) obtained 10 mm inferior to a shows the low-attenuation mass (arrow) in the lingular segmental bronchus. There was no associated atelectasis or obstructive pneumonia.
|
|
View larger version (87K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 7b. Typical carcinoid in a 41-year-old man. (a) Axial CT scan (5.0-mm section thickness), obtained at the level of the distal left main bronchus, shows a nodule (arrow) in the left upper divisional bronchus. (b) CT scan (mediastinal window) obtained 10 mm inferior to a shows the low-attenuation mass (arrow) in the lingular segmental bronchus. There was no associated atelectasis or obstructive pneumonia.
|
|
Carcinoids occasionally manifest as a small nodule entirely located within the lumen of a bronchus (Figs 6, 7). With thin-section CT, the bronchial relationship between the tumor and the bronchus may be evaluated. Even a small nodule, located beyond the origin of a subsegmental bronchus, may be noticed when it abuts a subsegmental bronchus or when a small endoluminal component of the tumor is displayed at thin-section CT (24). Although the endoluminal component may or may not be evident at CT (Figs 6–8), the intraluminal component may be relatively small compared to the bulk of the tumor; thus, when observed, it represents only the tip of the iceberg (28) (Fig 8). Peripheral carcinoids may manifest as a well-defined, lobulated nodule or mass without evidence of a bronchial relationship at CT (Fig 5).
View larger version (72K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 8a. Typical carcinoid in a 60-year-old woman. (a) Axial CT scan (2.5-mm section thickness), obtained at the level of the left lower lobar bronchus, shows a multilobulated mass in the lingular segmental bronchus and at the lingular division. The mass has both endobronchial (arrow) and extrabronchial (arrowheads) components, producing a so-called iceberg tumor. (b) CT scan (mediastinal window) obtained 10 mm inferior to a shows the slightly heterogeneous parenchymal mass (arrowheads) at the lingular division. (c, d) Coronal reformatted images (2.5-mm section thickness) show the endobronchial (arrow in c) and extrabronchial (arrowheads in d) components of the tumor.
|
|
View larger version (105K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 8b. Typical carcinoid in a 60-year-old woman. (a) Axial CT scan (2.5-mm section thickness), obtained at the level of the left lower lobar bronchus, shows a multilobulated mass in the lingular segmental bronchus and at the lingular division. The mass has both endobronchial (arrow) and extrabronchial (arrowheads) components, producing a so-called iceberg tumor. (b) CT scan (mediastinal window) obtained 10 mm inferior to a shows the slightly heterogeneous parenchymal mass (arrowheads) at the lingular division. (c, d) Coronal reformatted images (2.5-mm section thickness) show the endobronchial (arrow in c) and extrabronchial (arrowheads in d) components of the tumor.
|
|
View larger version (82K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 8c. Typical carcinoid in a 60-year-old woman. (a) Axial CT scan (2.5-mm section thickness), obtained at the level of the left lower lobar bronchus, shows a multilobulated mass in the lingular segmental bronchus and at the lingular division. The mass has both endobronchial (arrow) and extrabronchial (arrowheads) components, producing a so-called iceberg tumor. (b) CT scan (mediastinal window) obtained 10 mm inferior to a shows the slightly heterogeneous parenchymal mass (arrowheads) at the lingular division. (c, d) Coronal reformatted images (2.5-mm section thickness) show the endobronchial (arrow in c) and extrabronchial (arrowheads in d) components of the tumor.
|
|
View larger version (100K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 8d. Typical carcinoid in a 60-year-old woman. (a) Axial CT scan (2.5-mm section thickness), obtained at the level of the left lower lobar bronchus, shows a multilobulated mass in the lingular segmental bronchus and at the lingular division. The mass has both endobronchial (arrow) and extrabronchial (arrowheads) components, producing a so-called iceberg tumor. (b) CT scan (mediastinal window) obtained 10 mm inferior to a shows the slightly heterogeneous parenchymal mass (arrowheads) at the lingular division. (c, d) Coronal reformatted images (2.5-mm section thickness) show the endobronchial (arrow in c) and extrabronchial (arrowheads in d) components of the tumor.
|
|
Carcinoids tend to be vascular and may demonstrate intense enhancement (Fig 6). This is particularly helpful for distinguishing the tumor from obstructive atelectasis or an adjacent mucus plug (28). Also, in a dynamic contrast-enhanced CT study, typical carcinoid (Fig 9) and atypical carcinoid (Fig 10) show high enhancement, that is, more than 30 HU of net enhancement (29). Both typical and atypical carcinoids may be associated with hilar or mediastinal lymphadenopathy due to reactive hyperplasia from recurrent pneumonia or to lymph node metastasis (22). Lymph node metastases occur more frequently from atypical carcinoids (30).
View larger version (66K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 9. Typical carcinoid in a 42-year-old man. Dynamic contrast-enhanced CT scans (2.5-mm section thickness), obtained after intravenous injection of 120 mL of contrast medium (iodine concentration, 36 g), show an 18-mm-diameter enhancing nodule in the right lower lobe. The attenuation of the nodule is 48 HU on the unenhanced image (T0), 102 HU (54 HU of net enhancement) on the 2-minute image (T120), and 92 HU (10 HU of wash-out) on the 15-minute image (T900).
|
|
View larger version (72K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 10. Atypical carcinoid in a 44-year-old woman. Dynamic contrast-enhanced CT scans (2.5-mm section thickness), obtained after intravenous injection of 120 mL of contrast medium (iodine concentration, 36 g), show a 28-mm-diameter enhancing nodule in the right middle lobe. The attenuation of the nodule is 39 HU on the unenhanced image (T0), 80 HU (41 HU of net enhancement) on the 90-second image (T90), and 66 HU (14 HU of wash-out) on the 15-minute image (T900).
|
|
Carcinoid tumors have high numbers of somatostatin receptors, which allow scintigraphic imaging with the radiolabeled somatostatin analog octreotide (31). Accordingly, octreotide scanning has been found to be helpful for detecting occult tumors, particularly those with paraneoplastic symptoms (32). At positron emission tomography (PET) performed with fluorine 18 fluorodeoxy-glucose (FDG), most carcinoid tumors do not exhibit increased activity (Fig 11) and usually have lower FDG uptake than expected for malignant tumors (33). However, it was recently reported that carcinoid tumors show increased FDG uptake and thus high metabolic activity and malignant potential (33,34). We have also observed increased FDG uptake in atypical carcinoid (Fig 12). Therefore, conservative management such as follow-up imaging should be performed only when PET shows no or little FDG uptake, although results of imaging studies suggest carcinoid tumors.
View larger version (130K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 11a. Typical carcinoid in a 56-year-old man. (a) Coronal reformatted image (2.5-mm section thickness) shows a 41-mm-diameter, moderately enhancing, homogeneous mass (arrow) in the right lower lobe. (b) On a PET image, the mass demonstrates little FDG uptake (arrow).
|
|
View larger version (109K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 11b. Typical carcinoid in a 56-year-old man. (a) Coronal reformatted image (2.5-mm section thickness) shows a 41-mm-diameter, moderately enhancing, homogeneous mass (arrow) in the right lower lobe. (b) On a PET image, the mass demonstrates little FDG uptake (arrow).
|
|
View larger version (79K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 12a. Atypical carcinoid in a 42-year-old woman. (a) Axial CT scan (5.0-mm section thickness) obtained at the level of the basal segmental bronchi shows a small (10-mm-diameter), well-defined nodule (arrow) in the left lower lobe. (b) CT scan (mediastinal window) obtained at the level of the left basal trunk shows enlarged left hilar lymph nodes (arrows). (c) FDG PET image shows a hypermetabolic lesion (standardized uptake value = 11.2) at the left hilum (arrow), a finding suggestive of malignancy. The small pulmonary nodule shown in a demonstrated little FDG uptake. At histopathologic analysis of the specimen obtained with left pneumonectomy, the small pulmonary nodule was an atypical carcinoid and the ipsilateral hilar lymph nodes were metastatic with extracapsular invasion.
|
|
View larger version (83K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 12b. Atypical carcinoid in a 42-year-old woman. (a) Axial CT scan (5.0-mm section thickness) obtained at the level of the basal segmental bronchi shows a small (10-mm-diameter), well-defined nodule (arrow) in the left lower lobe. (b) CT scan (mediastinal window) obtained at the level of the left basal trunk shows enlarged left hilar lymph nodes (arrows). (c) FDG PET image shows a hypermetabolic lesion (standardized uptake value = 11.2) at the left hilum (arrow), a finding suggestive of malignancy. The small pulmonary nodule shown in a demonstrated little FDG uptake. At histopathologic analysis of the specimen obtained with left pneumonectomy, the small pulmonary nodule was an atypical carcinoid and the ipsilateral hilar lymph nodes were metastatic with extracapsular invasion.
|
|
View larger version (120K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 12c. Atypical carcinoid in a 42-year-old woman. (a) Axial CT scan (5.0-mm section thickness) obtained at the level of the basal segmental bronchi shows a small (10-mm-diameter), well-defined nodule (arrow) in the left lower lobe. (b) CT scan (mediastinal window) obtained at the level of the left basal trunk shows enlarged left hilar lymph nodes (arrows). (c) FDG PET image shows a hypermetabolic lesion (standardized uptake value = 11.2) at the left hilum (arrow), a finding suggestive of malignancy. The small pulmonary nodule shown in a demonstrated little FDG uptake. At histopathologic analysis of the specimen obtained with left pneumonectomy, the small pulmonary nodule was an atypical carcinoid and the ipsilateral hilar lymph nodes were metastatic with extracapsular invasion.
|
|
|
Large Cell Neuroendocrine Carcinoma
|
|---|
LCNEC was recently proposed as the fourth category of pulmonary neuroendocrine tumors due to its distinct clinical and pathologic findings versus typical carcinoid, atypical carcinoid, and SCLC (1). LCNEC is defined as a poorly differentiated and high-grade neuroendocrine tumor that morphologically is between atypical carcinoid and SCLC (1,35). The age of patients is 60-some years, and men are much more frequently involved than women (more than 2.5 times). More than 60% of patients are smokers (35–39). However, the clinical features and optimal treatment of LCNEC have yet to be established.
LCNEC has a reported prevalence of 2.9% among surgically resected lung cancers (35), 19% among pulmonary neuroendocrine tumors (2), and 12% among all large cell undifferentiated carcinomas (36). Several reports suggest that the prognosis of LCNEC is poor, with a variable overall 5-year survival rate ranging from 13% to 45% (35,37). In a series of 87 patients with LC-NEC, Takei et al (38) reported no significant difference in the overall survival rate between patients with LCNEC and those with other poorly differentiated non–small cell lung cancers (NSCLCs); however, a significantly worse (P = .003) difference was found in survival between patients with stage I LCNEC (67% 5-year survival rate) and those with the same stage of other poorly differentiated NSCLCs (88% 5-year survival rate). In a recent 10-year clinicopathologic study, Paci et al (39) reported that LCNEC has a poorer prognosis than NSCLC, even at an early stage, with an overall 5-year survival rate of 21%.
Histologic Findings
Since Travis et al (1) proposed that LCNEC is a pulmonary neuroendocrine tumor in 1991, the diagnosis of LCNEC has been established by histologic and cytologic evaluations, immunohistochemistry, or electron microscopy. In 1999, the World Health Organization (WHO) proposed histopathologic diagnostic criteria for LCNEC: (a) neuroendocrine morphologic features (organoid nesting, palisading, rosettes, or a trabecular growth pattern) (Fig 13); (b) a high mitotic rate (> 10 per 10 HPFs); (c) necrosis (often large zones); (d) cytologic features different from those of SCLC (large cell size, polygonal shape, a low nuclear-cytoplasmic ratio, finely granular eosinophilic cytoplasm, coarse nuclear chromatin, and frequent nucleoli); and (e) positive immunohistochemical staining for one or more neuroendocrine markers including chromogranin A, synaptophysin, and neural cell adhesion molecule (NCAM/CD56) (40). Because diagnosis with transthoracic fine-needle aspiration or biopsy may be difficult, studies of clinicopathologic or radiologic findings should include only cases of surgically resected LCNEC (38,39,41,42).
View larger version (186K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 13. LCNEC. Photomicrograph (original magnification, x 100; hematoxylin-eosin stain) shows a neuroendocrine appearance with peripheral palisading and rosettes. Note the area of necrosis (arrow).
|
|
The histologic criteria for LCNEC differ from those for atypical carcinoid mainly in two ways: (a) LCNEC has more frequent mitoses (> 10 per 10 HPFs) than atypical carcinoid (2–10 per 10 HPFs), and (b) LCNEC has a lower nuclear-cytoplasmic ratio than atypical carcinoid (2,41).
Imaging Findings
Although the radiologic findings of LCNEC have not been reported in detail, they are similar to those of other common NSCLCs. In the description of the spectrum of radiologic changes in neuroendocrine carcinomas of the lung by Forster et al (43) in 1989, LCNEC was not included because their study was reported before the proposal of the WHO classification. According to the WHO suggestion that the morphologic features of LCNEC represent a spectrum between those of atypical carcinoid and those of SCLC, the radiologic findings of LCNEC may also be speculated to be intermediate between those of atypical carcinoid and those of SCLC.
In the study by Jung and colleagues (41), eight of 11 tumors (73%) appeared as a peripheral mass or nodule (Figs 14–17), whereas three tumors (27%) manifested as a central mass and attendant atelectasis or distal mucus plugging (Fig 18). Mediastinal lymph node enlargement was observed in three of 11 patients (27%) (Fig 16), and extrathoracic metastasis was noted in four patients (36%) over the follow-up period of 15 months. The authors concluded that the CT findings of LCNEC of the lung are nonspecific and similar to those of other NSCLCs. Similarly, in the study by Oshiro et al (42), 32 of 38 tumors (84%) were peripherally located and six (16%) were centrally located.
View larger version (129K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 14. LCNEC in a 52-year-old man. Axial CT scan (5.0-mm section thickness) obtained at the level of the right middle lobar bronchus shows a well-defined, 8-cm-diameter mass abutting the chest wall in the right lower lobe.
|
|
View larger version (66K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 15a. LCNEC in a 64-year-old man. (a) Dynamic contrast-enhanced CT scans (2.5-mm section thickness), obtained after intravenous injection of 120 mL of contrast medium (iodine concentration, 36 g), show a 23-mm-diameter peripheral nodule in the right lower lobe. The attenuation of the nodule is 44 HU on the unenhanced image (T0), 92 HU (48 HU of net enhancement) on the 2-minute image (T120), and 80 HU (12 HU of washout) on the 15-minute image (T900). (b) Photograph of the pathologic specimen shows a well-defined, whitish tan, soft nodule (arrow).
|
|
View larger version (111K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 15b. LCNEC in a 64-year-old man. (a) Dynamic contrast-enhanced CT scans (2.5-mm section thickness), obtained after intravenous injection of 120 mL of contrast medium (iodine concentration, 36 g), show a 23-mm-diameter peripheral nodule in the right lower lobe. The attenuation of the nodule is 44 HU on the unenhanced image (T0), 92 HU (48 HU of net enhancement) on the 2-minute image (T120), and 80 HU (12 HU of washout) on the 15-minute image (T900). (b) Photograph of the pathologic specimen shows a well-defined, whitish tan, soft nodule (arrow).
|
|
View larger version (104K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 16a. LCNEC in a 57-year-old man. (a) Axial CT scan (5.0-mm section thickness) obtained at the level of the thoracic inlet shows a 32-mm-diameter mass with a lobulated margin in the right upper lobe. (b) CT scan obtained at the level of the right upper lobar bronchus shows enlarged lymph nodes in the right lower paratracheal area (arrowhead) and at the right hilum (arrow). At mediastinoscopic examination, the right lower paratracheal nodes contained malignant cells.
|
|
View larger version (84K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 16b. LCNEC in a 57-year-old man. (a) Axial CT scan (5.0-mm section thickness) obtained at the level of the thoracic inlet shows a 32-mm-diameter mass with a lobulated margin in the right upper lobe. (b) CT scan obtained at the level of the right upper lobar bronchus shows enlarged lymph nodes in the right lower paratracheal area (arrowhead) and at the right hilum (arrow). At mediastinoscopic examination, the right lower paratracheal nodes contained malignant cells.
|
|
View larger version (62K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 17a. LCNEC in a 72-year-old man. (a) Axial CT scan (5.0-mm section thickness) obtained at the level of the hepatic dome shows a 20-mm-diameter nodule (arrow) in the right lower lobe. (b) Axial PET image shows that the nodule (arrow) is hypermetabolic (peak standardized uptake value = 8.2).
|
|
View larger version (63K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 17b. LCNEC in a 72-year-old man. (a) Axial CT scan (5.0-mm section thickness) obtained at the level of the hepatic dome shows a 20-mm-diameter nodule (arrow) in the right lower lobe. (b) Axial PET image shows that the nodule (arrow) is hypermetabolic (peak standardized uptake value = 8.2).
|
|
View larger version (76K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 18a. LCNEC in a 63-year-old man. (a) Axial CT scan (5.0-mm section thickness) obtained at the level of the distal right main bronchus shows a 37-mm-diameter mass (arrow) in the right upper lobar bronchus. (b) CT scan (lung window) shows the proximal end of the endobronchial mass (arrow) and peripheral mucus plugging (arrowhead). (c) Photograph of the gross specimen shows the yellow endobronchial mass (arrow) and distal mucus plugging (arrowheads).
|
|
View larger version (103K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 18b. LCNEC in a 63-year-old man. (a) Axial CT scan (5.0-mm section thickness) obtained at the level of the distal right main bronchus shows a 37-mm-diameter mass (arrow) in the right upper lobar bronchus. (b) CT scan (lung window) shows the proximal end of the endobronchial mass (arrow) and peripheral mucus plugging (arrowhead). (c) Photograph of the gross specimen shows the yellow endobronchial mass (arrow) and distal mucus plugging (arrowheads).
|
|
View larger version (83K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 18c. LCNEC in a 63-year-old man. (a) Axial CT scan (5.0-mm section thickness) obtained at the level of the distal right main bronchus shows a 37-mm-diameter mass (arrow) in the right upper lobar bronchus. (b) CT scan (lung window) shows the proximal end of the endobronchial mass (arrow) and peripheral mucus plugging (arrowhead). (c) Photograph of the gross specimen shows the yellow endobronchial mass (arrow) and distal mucus plugging (arrowheads).
|
|
Nodules or masses typically have a well-defined and lobulated appearance (Figs 14–17) but sometimes have a spiculated margin. The internal characteristics of nodules or masses at CT may include air bronchogram, cavity, bubble lucency, or necrosis (41,42). Intratumoral calcifications are seen in 9% of patients with LCNEC (44). Other associated findings may include a pleural tag or surrounding emphysema (41,42). On contrast-enhanced CT scans, tumor attenuation varies from slightly less to more than that of the chest wall muscle, with a homogeneous or heterogeneous pattern. Almost all tumors contain necrotic foci. Tumors of large diameter appear with heterogeneous attenuation at enhanced CT, whereas small tumors do not necessarily show heterogeneous attenuation despite the presence of necrotic foci histopathologically (42) (Figs 15, 17). Pleural effusion is observed in 24% of cases (42).
To our knowledge, there has been no study on PET imaging of LCNEC. We have some experience with PET study of LCNEC. The tumors showed avid FDG uptake at PET (Fig 17).
|
Small Cell Lung Cancer
|
|---|
SCLC accounts for about 20% of bronchogenic carcinomas (45). Approximately 90%–95% of SCLCs occur centrally, apparently arising in a lobar or main bronchus (46). The mean age of patients with SCLC is about 70 years. Tobacco exposure is more closely associated with SCLC than with any other histologic cancer type. Common clinical manifestations are dyspnea, a persistent cough, hemoptysis, and postobstructive pneumonia. The invasion of adjacent structures may cause dysphagia, hoarseness, and superior vena cava syndrome. At the time of diagnosis, patients usually have extensive disease with rapid tumor growth (47).
SCLC is usually classified by using a two-stage system, that is, limited disease or extensive disease. Limited disease is defined as a tumor confined to one hemithorax including regional mediastinal and supraclavicular lymph nodes, whereas extensive disease is defined as disease beyond these bounds. However, the criteria for these two categories remain controversial (48). The widely used Veterans Administration Lung Study Group (VALG) definition of limited disease includes patients with primary tumor and nodal involvement limited to one hemithorax (49). In contrast, the International Association for the Study of Lung Cancer (IASLC) proposes that limited disease should additionally include all patients without distant metastasis (50). Therefore, the IASLC definition includes more patients in the prognostically better limited disease category than the VALG definition. Approximately 60%–70% of patients initially diagnosed with SCLC have extensive disease, and the most common meta-static sites at diagnosis are bone (19%–38%), the liver (17%–34%), the adrenal glands (10%–17%), and the brain (up to 14%) (51).
Limited disease is treated with combination chemotherapy and concurrent thoracic radiation therapy, whereas extensive disease is treated with chemotherapy alone; any radiation therapy in such cases is performed for symptom palliation.
Histologic Findings
The tumor cells are usually small with a round or fusiform shape and have high cellularity with a very high mitotic rate (Fig 19). The architecture of the tumor clusters is poorly preserved, with large areas of necrosis separating small islands of viable tumor (21). At immunohistochemical study, neurosecretory granules such as chromogranin and synaptophysin are usually present, but these are fewer and smaller than those observed in carcinoid tumors.
View larger version (177K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 19. SCLC. Photomicrograph (original magnification, x 400; hematoxylin-eosin stain) shows high cellularity; the small round cells have scanty cytoplasm and coarse chromatin. Note the frequent mitoses.
|
|
Imaging Findings
Most SCLCs are located centrally and manifest as mediastinal (92%) or hilar (84%) lymphad-enopathy (Figs 20, 21) with displacement or narrowing of the tracheobronchial tree (68%) or major vessels (68%). Other intrathoracic CT findings are major (at least lobar) atelectasis (30%), a noncontiguous parenchymal mass (41%) (Fig 22 ), and pleural effusion (38%) (52). In 5%–10% of cases, SCLC manifests as a peripheral nodule without associated lymphad-enopathy (53,54) (Fig 22). Intratumoral calcification may be seen in up to 23% of SCLCs (55).
View larger version (151K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 20a. SCLC in a 55-year-old man. (a) Chest radiograph shows bilateral enlargement at the pulmonary hilum. (b) Coronal contrast-enhanced reformatted CT scan (2.5-mm section thickness) shows enlargement of right hilar and left superior mediastinal (arrowhead) lymph nodes. (c) Coronal PET image shows strong FDG uptake in bilateral hilar (straight arrows), subcarinal (curved arrow), and left lower paratracheal (arrowhead) lymph nodes.
|
|
View larger version (100K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 20b. SCLC in a 55-year-old man. (a) Chest radiograph shows bilateral enlargement at the pulmonary hilum. (b) Coronal contrast-enhanced reformatted CT scan (2.5-mm section thickness) shows enlargement of right hilar and left superior mediastinal (arrowhead) lymph nodes. (c) Coronal PET image shows strong FDG uptake in bilateral hilar (straight arrows), subcarinal (curved arrow), and left lower paratracheal (arrowhead) lymph nodes.
|
|
View larger version (93K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 20c. SCLC in a 55-year-old man. (a) Chest radiograph shows bilateral enlargement at the pulmonary hilum. (b) Coronal contrast-enhanced reformatted CT scan (2.5-mm section thickness) shows enlargement of right hilar and left superior mediastinal (arrowhead) lymph nodes. (c) Coronal PET image shows strong FDG uptake in bilateral hilar (straight arrows), subcarinal (curved arrow), and left lower paratracheal (arrowhead) lymph nodes.
|
|
View larger version (104K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 21a. SCLC in a 59-year-old man. (a) Axial contrast-enhanced CT scan (5.0-mm section thickness) obtained at the level of the aortic arch shows enlarged lymph nodes in the right paratracheal (arrows) and bilateral prevascular (arrowheads) areas with extracapsular invasion. (b) CT scan obtained at the level of the right middle lobar bronchus shows enlarged subcarinal (arrow) and right hilar (arrowhead) lymph nodes.
|
|
View larger version (95K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 21b. SCLC in a 59-year-old man. (a) Axial contrast-enhanced CT scan (5.0-mm section thickness) obtained at the level of the aortic arch shows enlarged lymph nodes in the right paratracheal (arrows) and bilateral prevascular (arrowheads) areas with extracapsular invasion. (b) CT scan obtained at the level of the right middle lobar bronchus shows enlarged subcarinal (arrow) and right hilar (arrowhead) lymph nodes.
|
|
View larger version (91K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 22a. Peripheral SCLC in a 46-year-old man. (a) Axial CT scan (5.0-mm section thickness) obtained at the level of the ventricles shows a 22-mm-diameter nodule with a well-defined margin in the left lower lobe. (b) Photograph of the gross specimen shows the white solid nodule (arrow).
|
|
View larger version (85K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 22b. Peripheral SCLC in a 46-year-old man. (a) Axial CT scan (5.0-mm section thickness) obtained at the level of the ventricles shows a 22-mm-diameter nodule with a well-defined margin in the left lower lobe. (b) Photograph of the gross specimen shows the white solid nodule (arrow).
|
|
Most peripheral SCLCs manifest as a well-defined homogeneous mass with lobulation, marginal ground-glass opacity, and fine spiculation (54). Histopathologically, marginal ground-glass opacities correspond to focal edema and hemorrhage and less commonly to intraalveolar invasion. Fine spiculation corresponds to vascular or lymphatic invasion or to irregular intraalveolar spread. However, these findings are nonspecific and similar to those of NSCLCs.
At dynamic contrast-enhanced CT, the enhancement pattern of peripheral SCLCs is also similar to those of NSCLCs (29) (Fig 23). The extent of enhancement reflects underlying tumor angiogenesis, and a rich bloodstream tumor is presumptively sensitive to proper chemotherapy. Choi et al (56) statistically showed that the more enhanced a tumor is at CT, the better is its response to chemotherapy, and suggested a tumor enhancement of 30 HU as a guide for chemotherapeutic response.
View larger version (70K):
[in this window]
[in a new window]
[Download PPT slide]
|
Figure 23. Peripheral SCLC in a 62-year-old man. Dynamic contrast-enhanced CT scans (2.5-mm section thickness), obtained after intravenous injection of 120 mL of contrast medium (iodine concentration, 36 g), show a 17-mm-diameter peripheral nodule in the right lower lobe. The attenuation of the nodule is 51 HU on the unenhanced image (T0), 101 HU (50 HU of net enhancement) on the 4-minute image (T240), and 98 HU (3 HU of washout) on the 15-minute image (T900).
|
|
Since FDG PET has been used to evaluate NSCLC, its use in SCLC has been reported in a limited number of studies. Pandit et al (57) reported that the sensitivity of PET scanning in detecting SCLC is 100%, and a high standardized uptake value is significantly associated with poor survival (Fig 20). PET is also of value for 
Top
Abstract
LEARNING OBJECTIVES FOR TEST...
