Imaging in Small Cell Lung Cancer
- Author: Abid Irshad, MD; Chief Editor: Kavita Garg, MD more...
Lung cancer is the leading cause of cancer deaths in males and females in the United States. The incidence of lung cancer is about 60 cases per 100,000 population, and small cell lung cancer (SCLC) accounts for about 15-25% cases of lung cancer. Examples of SCLC are presented in the images below.
See Small Cell Lung Cancer: Beating the Spread, a Critical Images slideshow, to help identify the key clinical and biologic characteristics of small cell lung cancer, the staging criteria, and the common sites of spread.
Also, see the Lung Cancer Staging -- Radiologic Options slideshow to help identify stages of the disease process and Clinical Presentations of Lung Cancer: Slideshow to help efficiently distinguish lung carcinomas from other lung lesions, as well as how to stage and treat them.
Historically, the histologic identification of small cell cancer dates back to the 1920s, when the small cell/oat cell tumor was shown to be a carcinoma of the lung and not an oat cell sarcoma of the mediastinum, as thought earlier. This cancer was also noted to occur in patients younger (27-66 y) than those with the other cancers.
Since that time, many histologic subtypes of SCLC have been found, and attempts have been made to classify this tumor. However, disagreement regarding the classifications still exists. In 1998, the International Association for the Study of Lung Cancer (IASLC) classified SCLC into 3 general histologic subtypes: small, mixed, and combined.
According to this classification, the small-cell subtype includes the previous World Health Organization (WHO) variety of oat cell and intermediate types. The mixed variety encompasses mixed cell and large cell cancers. (In the WHO classification, this is considered a combined variety.) The combined variety includes a significant proportion of squamous cell or adenocarcinoma cell cancers in addition to small cell cancers (1-3% of cases of SCLC).
In 1973, the British Medical Research Council reported that patients with SCLC had a poor prognosis and that SCLC was considered a distinct clinicopathologic entity. After that report, different treatment options were considered, and surgery alone was found to be an insufficient method of treatment. A better response was obtained with the addition of chemotherapy and irradiation.
Because SCLC is considered a systemic disease, the clinical course, prognosis, and treatment options are clearly different from those of other lung cancers. Clinically, lung cancers are often categorized into SCLC and non-SCLC (NSCLC).
SCLC is categorized into 2 stages: limited disease and extensive disease. The disease is termed limited when it is confined to an area of the chest that can be encompassed by a single radiation port; supraclavicular nodes may be included. The disease is called extensive when metastasis outside the thorax is present or when intrathoracic disease cannot be contained in a single radiation port.
Patients with SCLC are rarely surgical candidates, and they are usually treated with irradiation and/or chemotherapy. On the contrary, patients with NSCLC are usually evaluated for possible surgical excision, and their disease is staged by using the common tumor, nodes, and metastases (TNM) staging system.
The usefulness of the various imaging examinations largely depends on the clinical findings at the time of presentation and also on the stage of the disease. Many imaging modalities are used to further evaluate the findings seen on the previous imaging and to determine the stage of the disease.
Commonly used imaging modalities start with simple ones, such as chest radiography; progress to more sophisticated modalities, such as computed tomography (CT) scanning and/or magnetic resonance imaging (MRI); and then progress to even more sophisticated and costly ones, such as positron emission tomography (PET) scanning.[2, 3, 4, 5]
Conventional radiography is not helpful in finding early disease. When the mass or mass effect is visible on a radiograph, the disease is almost invariably in an advanced stage. Although some institutions use low-dose CT to detect early non–small cell lung cancer (NSCLC), it is probably not effective in evaluating SCLC. Contrast-enhanced CT is routinely used to further evaluate any suspicious abnormality noted on radiographs. This examination is also routinely used to determine the stage of a known SCLC, to follow up patients after treatment, and to evaluate distant metastatic disease.
Although most centers do not routinely use MRI to evaluate the primary lesion in the chest, it may provide useful information in problematic cases of mediastinal invasion. MRI does have a role in ruling out brain metastatic lesions and in differentiating questionable adrenal masses. In pregnant patients, MRI can also be used instead of CT scanning, to avoid the potential effects of ionizing radiation.
PET scanning with fluorodeoxyglucose (FDG) has received increased attention, and growing evidence suggests its superiority in the staging of lung cancer.[3, 4, 5] However, PET scanning is more frequently used in evaluating patients with NSCLC to identify surgical candidates. It is less commonly used in patients with SCLC because most of these patients are not candidates for surgery. PET is also useful for evaluating cases in which recurrent disease is questionable.
Bone scanning is routinely used to evaluate bony metastatic disease.
In nuclear medicine, imaging with technetium-99m–labeled monoclonal antibody has shown some promising results in the evaluation of SCLC; however, this study is not widely used in clinical practice.
Limitations of techniques
Small cell lung cancer (SCLC) is a histologic diagnosis that is always based on findings in tissue biopsy samples. Imaging only shows suspicious abnormalities that are invariably examined at subsequent biopsy to establish the tissue diagnosis.[7, 8]
Chest radiography has limited usefulness in detecting early SCLC. In most cases in which an abnormality is visible on a radiograph, the cancer has already metastasized. Radiography has poor sensitivity and specificity, and almost all suspicious abnormalities require further evaluation with other modalities, most often CT.
CT shows the anatomic details of the lesion well. CT may have lower sensitivity than MRI in detecting mediastinal invasion. Because CT staging involves criteria based on the size of the lymph nodes, CT has an inherent limitation. Disease may be overstaged if enlarged benign lymph nodes are measured, or disease may be understaged if the microscopically involved normal-sized nodes are classified as being benign.
The spatial resolution of MRI is generally considered to be lower than that of CT. For this reason, a group of nodes may sometimes be falsely mistaken as a single large node. Also, because of the inability to detect calcium with MRI, enlarged and calcified benign nodes may be mistaken for pathologic nodes. The cost of MRI and the artifacts due to cardiac and vascular pulsation and respiratory movements limit its usefulness in evaluating primary lung cancer in most cases; however, MRI may be useful in special circumstances.
Although PET is emerging as a popular modality for evaluating many cancers, the usefulness of PET is limited because of its cost and unavailability in many clinical practices. Generally, the resolution of PET is not considered good for lesions smaller than 1 cm. The PET results can also overlap with the standard uptake values (SUVs) in some benign lesions and malignant lesions.
CT scanning is generally used to guide biopsy of suspicious lesions. It can be used to guide transbronchial biopsy by demonstrating the location of the lesions, or it can be used to direct CT scan–guided percutaneous transthoracic biopsy. Similarly, ultrasonography can also be used to guide biopsy of suspicious intra-abdominal or pelvic lesions.
Chest radiographs may show unilateral hilar enlargement, increased hilar opacity, a perihilar mass, mediastinal mass, or a combination of these. Less commonly, small cell lung cancer (SCLC) may appear as a solitary pulmonary nodule. (See the images below.)
Compression of the bronchi is relatively common in SCLC because of the central location of the tumor in most cases. About 30-50% of SCLCs show evidence of obstructive pneumonitis on the initial presentation. SCLC can appear as segmental or lobar atelectasis with or without an obvious hilar mass. The S sign of Golden is seen when a collapsed upper lobe forms a meniscus concave toward the hilum and when an enlarged hilar mass forms the convex meniscus of the S. Occasionally, endobronchial growth or bronchial compression may be appreciated as a bronchial cutoff or filling defect.
Thickening of the right paratracheal stripe may be an indication of right paratracheal lymphadenopathy. With massive subcarinal lymphadenopathy, widening of the carinal angle may occasionally be observed. Subtle changes of hilar asymmetry, increased opacity, a convex or lobulated outer hilar border, or any change from a previous radiograph should be viewed with suspicion.
Involvement of pleura or pericardium may result in pleural or pericardial effusions. Rarely, involvement of a pulmonary artery may result in compression of the artery with oligemia in the area of distribution. Invasion of pulmonary artery may result in pulmonary metastatic lesions. Large mediastinal masses may lead to lymphatic obstruction, which may result in reticulonodular opacities in the lung. Lateral views are complementary to the frontal views and help in assessing the mediastinal abnormalities, especially in the retrosternal and hilar regions. Paratracheal masses and thickening of the posterior wall of the bronchus intermedius may be seen on the lateral view.
The degree of confidence in radiography is low, because a bulky mediastinal mass may also be seen in a variety of conditions other than small cell lung cancer.
CT scanning is the modality most commonly used for the evaluation and characterization of an abnormality depicted on a chest radiograph. CT is used to assess the size or volume of the tumor, mediastinal involvement, pathologically enlarged lymph nodes, and vascular invasion. It is also sensitive in detecting pleural and pericardial effusion or thickening. Nodularity of pleura or pericardium is the hallmark of metastatic involvement. (See the images below.)
Contrast-enhanced CT can sometimes be used to differentiate a tumor mass from the adjacent collapsed lung or pneumonitis, which usually enhances more than the tumor. Sometimes, air bronchograms are observed. Three-dimensional (3D) images reconstructed from thin sections through the mass improve the sensitivity in detecting invasion of adjacent organs. Chest-wall invasion can be demonstrated with evidence of rib destruction (the most specific finding), pleural thickening, and obliteration of the extrapleural fat line. An obtuse angle of the mass with the chest wall may also suggest invasion. Pain in the chest wall is a more specific sign of involvement.
Similarly, contact with the mediastinum of more than 3 cm, contact with aorta of more than 90°, invasion of the mediastinal fat, and pleural or pericardial thickening are considered signs of mediastinal invasion. CT scans can also show endobronchial growth and the degree of compression of the bronchi or vessels.
The size of lymph nodes is generally estimated for staging purposes by measuring the short axis of the lymph nodes. Compared with the long axis, the short axis is a more accurate predictor of the volume. For practical purposes, a short-axis measurement greater than 1 cm is generally considered abnormal in the chest. However, some have observed different measurements in different groups of patients.
CT of the chest routinely includes imaging of the adrenal glands, which are common sites for of small cell lung cancer metastases. A lesion with an attenuation value less than 10 HU (Hounsfield units) on a nonenhanced CT scan most likely represents an adenoma (90% accuracy). CT of the abdomen and pelvis is also generally indicated in staging of small cell lung cancer to rule out metastases to the liver, nodes, or other organs. CT of the head helps in ruling out brain metastasis, which is also common in small cell lung cancer. CT is also routinely used to follow up patients with small cell lung cancer after irradiation and chemotherapy.
High-resolution CT (HRCT) features of peripherally located small cell lung cancer (SCLC) were retrospectively reviewed in 33 patients with peripherally located SCLC measuring 30 mm or less. The authors found that a non-round shape and thickening of the bronchovascular bundle (BVB) were common, while marginal ground-glass opacity (GGO) and air bronchogram were less common in small-sized, peripherally located SCLC. In addition, the vermiform/branching shape and thickening of the BVB suggested relatively advanced disease.
Degree of confidence
CT scanning is reasonably accurate in depicting suspicious or indeterminate masses and for staging small cell lung cancers.
With CT scanning, criteria based on the size of the lymph nodes are used for staging the disease. This method has inherent limitations. False-positive findings are due to enlarged benign reactive nodes, and false-negative findings are due to microscopically involved normal-sized metastatic nodes.
Magnetic Resonance Imaging
MRI is not routinely used for detecting the primary tumor or for staging. However, it may sometimes help in problematic cases because MRI offers improved tissue contrast resolution and a multiplanar imaging capability (see the image below). In primary tumors, MRI can sometimes help in differentiating tumor from surrounding atelectasis or pneumonitis, which has relatively high signal intensity on T2-weighted images, as opposed to the relatively low signal intensity of the tumor.
Gadolinium-enhanced MRI may also be helpful because the lung enhances rapidly, whereas the tumor usually enhances relatively slowly. MRI is also good for detecting nodes in the aortopulmonary window or for detecting subcarinal nodes, because it can provide images in the sagittal and coronal planes. With chemical shift imaging, MRI is reliable in differentiating adrenal adenomas from possible metastasis because it shows decreases in signal intensity on out-of-phase images as compared with in-phase images.
Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the Medscape Drugs & Diseases topic Nephrogenic Systemic Fibrosis.
NSF/NFD has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see Medscape Alert Use of Gadolinium in MRI and MRA Linked to NSF/NFD in Patients With Renal Failure.
In a study in which diffusion-weighted imaging (DWI) and short tau inversion recovery (STIR) turbo spin-echo imaging were compared in differentiating small cell lung cancer (SCLC) from non-SCLC (NSCLC), DWI was found to be more useful than STIR. The specificity and accuracy were each 85.7% for DWI, whereas for STIR, specificity was 63.3% and accuracy was 66.1%. However, the accuracy was 94.6% when the 2 modalities were combined.
Degree of confidence
MRI may be more sensitive than CT scanning for the assessment of mediastinal, vascular, or chest wall invasion. MRI is considered superior to CT scanning for detecting brain metastatic lesions and for evaluating the adrenal masses.
Because of the relatively low spatial resolution of MRI compared with that of CT, a cluster of small lymph nodes may occasionally be mistaken for a single enlarged node. This observation can lead to a false-positive finding. Also, calcifications may be missed on MRIs.
Chest ultrasonography has no primary role in the diagnosis or staging of lung cancer. However, abdominal scans sometimes reveal metastatic lesions in the liver, adrenal glands, lymph nodes, or other abdominal or pelvic organs. This finding indicates extensive disease.
As previously mentioned, imaging with technetium-99m–labeled monoclonal antibody has shown some promising results in the evaluation of small cell lung cancer (SCLC); however, this study is not widely used in clinical practice.
Bones are the most common sites for metastatic disease in SCLC. Bone scanning is used as one of the tools for staging the SCLC as well as for follow-up. (See the image below.)
Because an SCLC metastasizes early in its course, bone scanning is an important modality for ruling out bony metastatic disease. Metastatic disease is usually seen as multiple asymmetric areas of increased uptake, mostly in the axial skeleton.
A normal bone scan result usually excludes metastatic disease; however, in rare cases, aggressive osteolytic lesions with little bone reaction may not be evident. Similarly, benign conditions such as fractures or degenerative disease may occasionally be confused with metastatic disease.
Positron emission tomography
PET is one of the most rapidly emerging modalities for the evaluation, staging, and posttherapeutic follow-up of cancer. PET combines the functional and anatomic aspects of the lesions. PET primarily depends on the metabolism of glucose, which is usually high in tumor cells. By measuring the standardized uptake values (SUVs) within the lesions, the malignant lesions (which usually have values greater than 2.5) can be reliably differentiated from benign lesions in most cases. However, the values can overlap. (See the images below.)
PET can be used for staging purposes by determining nodal involvement and distant metastasis. CT is usually used along with PET for anatomic comparison. Some studies have shown that PET is more sensitive than CT for staging purposes. Other studies have also shown that PET has good sensitivity in detecting bony metastasis.
The main limitations of PET use are its cost, its limited availability, and the lack of expertise in performing the examination.
Infrequently, when surgery is being considered in the treatment of a peripheral SCLC with limited disease, lung ventilation/perfusion scanning is sometimes helpful for surgical planning to assess the respiratory reserve and perfusion distribution after lobectomy or pneumonectomy.
Monoclonal antibody scanning
Monoclonal antibody study with technetium-99m NRLU-10 whole-body scanning has been shown to be sensitive in detecting SCLC. However, this study has not been widely used in clinical practice.
[Iodine-131]6-beta-iodomethyl-19-norcholesterol nuclear imaging
[Iodine-131]6-beta-iodomethyl-19-norcholesterol (NP-59) nuclear imaging is sometimes used to differentiate adrenal metastasis from adrenal adenomas (which take up the agent).
Angiography generally has no primary role in the diagnosis, staging, or follow-up of small cell lung cancer. However, in some cases, it may be used to evaluate vascular involvement or to plan surgery.
Hirsch FR, Matthews MJ, Aisner S. Histopathologic classification of small cell lung cancer. Changing concepts and terminology. Cancer. 1988 Sep 1. 62(5):973-7. [Medline].
Seute T, Leffers P, ten Velde GP, Twijnstra A. Detection of brain metastases from small cell lung cancer: consequences of changing imaging techniques (CT versus MRI). Cancer. 2008 Apr 15. 112(8):1827-34. [Medline].
van Loon J, Offermann C, Bosmans G, et al. 18FDG-PET based radiation planning of mediastinal lymph nodes in limited disease small cell lung cancer changes radiotherapy fields: a planning study. Radiother Oncol. 2008 Apr. 87(1):49-54. [Medline].
Lee HY, Chung JK, Jeong JM, et al. Comparison of FDG-PET findings of brain metastasis from non-small-cell lung cancer and small-cell lung cancer. Ann Nucl Med. 2008 May. 22(4):281-6. [Medline].
Decker RH, Wilson LD. Advances in radiotherapy for lung cancer. Semin Respir Crit Care Med. 2008 Jun. 29(3):285-90. [Medline].
Boland GW, Lee MJ, Gazelle GS. Characterization of adrenal masses using unenhanced CT: an analysis of the CT literature. AJR Am J Roentgenol. 1998 Jul. 171(1):201-4. [Medline].
Askoxylakis V, Dinkel J, Eichinger M, et al. Multimodal hypoxia imaging and intensity modulated radiation therapy for unresectable non-small-cell lung cancer: the HIL trial. Radiat Oncol. 2012 Sep 14. 7:157. [Medline]. [Full Text].
Dane B, Grechushkin V, Plank A, Moore W, Bilfinger T. PET/CT vs. non-contrast CT alone for surveillance 1-year post lobectomy for stage I non-small-cell lung cancer. Am J Nucl Med Mol Imaging. 2013 Sep 19. 3(5):408-16. [Medline]. [Full Text].
Kreisman H, Wolkove N, Quoix E. Small cell lung cancer presenting as a solitary pulmonary nodule. Chest. 1992 Jan. 101(1):225-31. [Medline].
Kobayashi T, Tanaka N, Matsumoto T, et al. HRCT findings of small cell lung cancer measuring 30 mm or less located in the peripheral lung. Jpn J Radiol. 2015 Feb. 33(2):67-75. [Medline].
Quint LE, Francis IR, Wahl RL, Gross BH. Imaging. Pass HI, Mitchell JB, Johnson DH, Turrisi AT, Minna JD. Lung Cancer: Principles and Practice. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2000. 535-78.
Koyama H, Ohno Y, Nishio M, et al. Diffusion-weighted imaging vs STIR turbo SE imaging: capability for quantitative differentiation of small-cell lung cancer from non-small-cell lung cancer. Br J Radiol. 2014 Jun. 87(1038):20130307. [Medline]. [Full Text].