Acs0405 Solitary Pulmonary Nodule


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Acs0405 Solitary Pulmonary Nodule

  1. 1. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 4 THORAX 5 SOLITARY PULMONARY NODULE — 1 5 SOLITARY PULMONARY NODULE Shamus R. Carr, M.D., and Taine T.V Pechet, M.D., F.A.C.S. . Assessment of a Solitary Pulmonary Nodule The solitary pulmonary cative of severe obstructive ventilatory impairment are also associ- nodule (SPN) is a common ated with an increased likelihood of malignancy.11 In addition, the finding that is observed in SPNa is < 1.0 cm presence of endemic granulomatous disease has been shown to more than 150,000 persons increase the probability that an SPN is harboring cancer.7 each year in the United Other factors that influence the probability of malignancy in an States.1 An SPN is defined SPN are based on the findings from CT scanning [see Investigative as a single radiographically Studies, Imaging, Computed Tomography, below]. The size, con- visible pulmonary lesion tour, internal characteristics, and growth rate of the nodule are all that is less than 3 cm in potentially significant indicators of malignant disease [see Table 2]. diameter, is completely sur- rounded by pulmonary parenchyma, and is not associated with Age atelectasis or adenopathy.2 Any pulmonary lesion larger than 3 cm Lung cancer is rare before the age of 40 years, but its incidence is considered a mass and as such has a greater likelihood of being steadily increases from that point until the age of 80.5 Above the malignant.3,4 SPNs are detected on routine chest radiography at a age of 70, the likelihood that an SPN is malignant increases.8 After rate of 1 in 500 x-rays, but with the growing use of computed to- the age of 80, the incidence of malignancy in an SPN seems to mographic scanning, they are now being diagnosed with increas- level off or even decrease. ing frequency. The differential diagnosis of an SPN is broad and includes vas- Tobacco Exposure cular diseases, infections, inflammatory conditions, congenital The link between cigarette smoking and lung cancer has been abnormalities, benign tumors, and malignancies [see Table 1]. well established since the 1950s, and the incidence of lung cancer Although most SPNs are benign, as many as one third represent in smokers is directly correlated with the number of pack-years of primary malignancies, and nearly one quarter may be solitary smoking.12 The Surgeon General’s Report from 2004 states that metastases.1,5,6 Various approaches have been developed to aid in “the evidence is sufficient to infer a causal relationship between the characterization and identification of SPNs. Certain clinical smoking and lung cancer.”13 characteristics—such as greater age, history of tobacco use, and previous history of cancer—have been shown to increase the like- Occupational History lihood that the SPN is malignant.7 Some authors have attempted Patients with a history of workplace exposure to a radioactive to use Bayes’s theorem, logistic regression models, or neural net- substance (e.g., uranium or plutonium) are at increased risk for work analysis to predict the likelihood of malignancy.7-9 Such lung cancer, but this association is not as well documented as the methods are highly sensitive and specific, but they are cumber- association of lung cancer with tobacco use. Miners of heavy met- some and of limited practical use in actual clinical evaluation of a als (e.g., nickel, cadmium, and silica) are also at increased risk. patient with an SPN. There is some evidence to suggest that patients with idiopathic pulmonary fibrosis and pneumoconiosis are at increased risk for bronchoalveolar cell carcinoma.14 Radon exposure is the second Clinical Evaluation leading cause of lung cancer, and cigarette smoking further Once an SPN has been discovered, the essential task is to deter- increases the risks associated with radon exposure.15 Asbestos mine whether the lesion is benign or malignant. Evaluation and exposure in combination with cigarette smoking also places workup should be governed by the dictum “malignant until patients at significantly increased risk for lung cancer. proven otherwise.” The basis for this initial assumption of malig- nancy is the observation that the average overall 5-year survival rate is quite poor—10% to 15%—once a diagnosis of lung cancer Investigative Studies is made.10 Appropriate evaluation involves careful assessment of SPNa is < 1.0 cm IMAGING the patient’s history and risk factors for malignancy in conjunction with the results of radiographic studies [see Investigative Studies, below] to develop an individualized care plan. Chest Radiography Whereas the prevalence FACTORS INFLUENCING PROBABILITY OF MALIGNANCY of lung cancer is low in Of the various factors that influence the probability that cancer comparison to that of will be found in an SPN before radiographic evaluation, those breast or prostate cancer, most strongly associated with lung cancer are age, smoking histo- the mortality for lung cancer exceeds that for breast, prostate, and ry, and occupational history. Pulmonary function test results indi- colon cancer combined. As noted [see Clinical Evaluation, above],
  2. 2. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 4 THORAX 5 SOLITARY PULMONARY NODULE — 2 SPN is seen on chest x-ray or CT scan Obtain history and perform thorough physical examination. Assessment of a Solitary Review previous diagnostic images (if available). Pulmonary Nodule SPN is < 1.0SPNa is < 1.0 cmis at low risk cm and patient SPN is 1.0–3.0 cm Obtain follow-up CT scan at 3 mo. Assess probability of malignancy on the basis of salient characteristics (age, smoking history, lesion size, lesion margin). Probability of cancer is low Consider PET. Risk of surgical complications is high Consider PET, or obtain tissue diagnosis via TTNB or bronchoscopy, as warranted by clinical situation. SPN is unchanged SPN has grown Consider PET scanning if nature of lesion is indeterminate. Otherwise, assume malignancy and resect lesion via VATS or thoracotomy after staging Tissue diagnosis is obtained investigations. Pathology is indeterminate Consider PET, or proceed to metastatic evaluation, as warranted by clinical situation. PET scan is obtained PET scan is not obtained PET scan is negative PET scan is positive and lesion is suspicious Obtain follow-up CT scans at 3-, 6-, or 12-month intervals. SPN has remained unchanged for > 2 yr SPN has grown Lesion is probably benign; treat appropriately. Consider PET scanning if nature of lesion is indeterminate. Otherwise, assume malignancy and resect lesion via VATS or thoracotomy after staging investigations.
  3. 3. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 4 THORAX 5 SOLITARY PULMONARY NODULE — 3 SPN has arisen or grown since previous images, SPN has remained unchanged for > 2 yr or no previous images are available for review Lesion is probably benign; treat appropriately. Obtain CT scan. SPN is > 3.0 cm Lesion is considered a mass and thus is more likely to be malignant. Probability of cancer is intermediate Probability of cancer is high Risk of surgical complications is low Obtain tissue diagnosis via TTNB or bronchoscopy, or proceed to metastatic evaluation and resection, as warranted by clinical situation. Tissue diagnosis is not obtained Pathology is malignant Carry out metastatic evaluation. If results are negative, resect lesion via VATS or thoracotomy. If results are positive, treat appropriately.
  4. 4. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 4 THORAX 5 SOLITARY PULMONARY NODULE — 4 Table 1 Differential Diagnosis of Solitary Advocates of CT scanning for assessment of SPNs base their argu- Pulmonary Nodule ment on two central points. First, as many as 83% of CT-detect- ed stage I malignancies are not visible on chest x-ray.22 Second, non–small cell lung cancer (NSCLC) is the malignancy most Arteriovenous malformations Vascular disease Pulmonary artery aneurysm commonly identified, and the survival rate for stage I NSCLC is relatively high. In patients whose SPN proves to be NSCLC, the Tuberculosis 5-year survival rate is 67% for stage IA disease. This figure falls Mycobacterium avium complex infection rapidly as the disease stage rises: the 5-year survival rate is 55% for Aspergilloma stage IIA NSCLC and only 10% for stage IIIA NSCLC with Histoplasmosis mediastinal nodal metastasis.23 Echinococcosis Infection Blastomycosis Numerous studies have evaluated the use of screening CT both Cryptococcosis in the general population and in at-risk groups consisting of older Coccidioidomycosis patients with a smoking history.22,24,25 The greatest drawback to Ascariasis screening CT is the high false positive rate: nodules are identified Benign Dirofilariasis on 23% to 66% of all CT scans, depending on the thickness of the slices,22,26 and nearly 98% of these nodules are eventually deter- Rheumatoid nodule Inflammatory Sarcoidosis mined to be benign. Sequential CT scanning is often required to condition determine whether an SPN is benign or malignant. In 10% to Wegener granulomatosis 15% of patients, however, this determination cannot be made even Congenital when two CT scans are compared. Such patients may be assessed Foregut duplication cyst abnormality with other imaging modalities (e.g., positron emission tomogra- Rounded atelectasis phy [PET]) or may be referred for transthoracic needle biopsy Other Pulmonary amyloidosis (TTNB) or other invasive diagnostic tests. Hamartoma There is currently some controversy regarding the optimal tim- Benign tumor Lipoma ing of follow-up CT scanning after initial identification of an SPN. Fibroma In the literature, the recommended interval between initial CT scanning and repeat CT scanning has ranged from 1 month to 1 Non–small cell lung cancer year.22,25,26 These varying recommendations are based on what is Squamous cell carcinoma Adenocarcinoma considered the doubling time for an SPN. In a study from 2000 Large cell cancer that included 13 patients with a known diagnosis and lesions less Primary lung cancer Bronchoalveolar carcinoma than 10 mm in diameter at initial evaluation, volumetric growth Small cell lung cancer rates were measured to establish the doubling times of the nod- Malignant Carcinoid ules.10 The doubling times ranged from 51 days to more than 1 Lymphoma year. For malignant lesions, the average doubling time was less Colon cancer than 177 days, whereas for benign lesions, it was more than 396 Testicular cancer days. Metastatic cancer Melanoma In addition to delineating the size and contours of an SPN, CT Sarcoma scans provide information on its internal characteristics. Certain Breast cancer lesion characteristics noted on CT, though not absolutely defini- tive, point more toward a benign condition, whereas others point more toward malignancy. For example, although cavitation may the overall 5-year survival rate for lung cancer patients is dismal, occur in either benign or malignant lesions, SPNs with walls thick- in part because lung cancer is typically identified at a more er than 16 mm are much more likely to be malignant, whereas advanced stage than other cancers are. Several trials performed those with walls thinner than 4 mm are much more likely to be before the advent of CT scanning attempted to employ chest radi- benign.27 As another example, the presence of intranodular fat is ography for early screening of lung cancer, but they were unable a reliable indicator of a hamartoma (a benign lesion) and is seen to demonstrate that such screening yielded any better survival in as many as 50% of hamartomas.28 In addition, calcification is than no screening at all.16-18 One explanation for these disappoint- most commonly associated with hamartomas and other benign ing results may be that fewer than 10% of lung cancers are stage I nodules. Unfortunately, between one third and two thirds of be- at presentation.16 nign lesions visualized are not calcified, and as many as 6% of Although chest radiography is ineffective as a screening tool for malignant lesions are calcified.29-31 Finally, increased enhance- early-stage lung cancer, it remains a valuable investigative tool in ment (measured in Hounsfield units [HU]) after injection with the evaluation of SPNs. If an SPN’s appearance on chest x-rays intravenous contrast is strongly suggestive of malignancy. Lesions has not changed for more than 2 years, the SPN will be benign in that enhance by less than 15 HU are most likely benign (positive more than 90% of cases. In such cases, only yearly follow-up is predictive value, 99%), whereas lesions that enhance by more than typically required; additional diagnostic tests are usually unneces- 20 HU are typically malignant (sensitivity, 98%; specificity, sary.19,20 Therefore, an effort should always be made to obtain old 73%).32 Lesions that enhance by 15 to 20 HU should be consid- chest radiographs if they are known to exist. ered indeterminate. Because most SPNs are benign and because the risk of misdi- Computed Tomography agnosing a malignant lesion is so great, it is important to make use The advent of CT scanning has led to an increase in the num- of all of the data obtained from CT scanning in the effort to make ber of SPNs detected21—but of course, it has also led to an cost-effective, logical decisions regarding further evaluation or increase in the number of SPNs found that prove to be benign. treatment. Careful evaluation of the size, contours, and internal
  5. 5. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 4 THORAX 5 SOLITARY PULMONARY NODULE — 5 characteristics of an SPN on successive CT scans—in conjunction 1.0 cm) may have an SUV lower than 2.5 and still be malignant. with thoughtful consideration of the patient’s age, smoking histo- The reason is that their small volume causes their true activity ry, and occupational exposure—provides the framework for ap- concentration to be underestimated, with the result that their SUV propriate treatment. Because the doubling time is considerably drops below the threshold value for malignancy. In one prospec- shorter for malignant lesions than for benign lesions, a repeat CT tive study of patients with SPNs, the overall sensitivity of FDG- scan should be performed 3 months after the initial study. If the PET scanning was 79%, and the overall specificity was 65%.46 lesion is visibly larger on the repeat scan, it is probably malignant, When the SPN was smaller than 1.0 cm, however, all of the scans and further diagnostic evaluation should be carried out with an were negative, even though 40% of the nodules were malignant. eye toward resection. If, however, the lesion is still present and has In cases where the SPN is larger than 1.0 cm and no previous not grown, a follow-up CT scan between 3 months and 12 radiographs or CT scans are available for comparison, PET scan- months is warranted; the precise timing remains controversial and ning can provide information that may facilitate the decision should be determined on the basis of individual patient and SPN whether to follow the lesion closely or to proceed with biopsy. PET characteristics. New volumetric modeling methods have been scanning has a definite place in the evaluation of SPNs, but it is developed that may be capable of detecting conformational not appropriate for every patient. A study that examined the cost- changes over much shorter intervals, but at present, they are not effectiveness of PET in the evaluation of SPNs concluded that it frequently used.33 was cost-effective for patients who had an intermediate pretest probability of a malignant SPN and who were at high risk for sur- Positron Emission Tomography gical complications.47 In all other groups, PET was not cost-effec- PET is an imaging modality that employs radiolabeled isotopes tive, and CT led to similar outcomes (in terms of quality-adjusted of fluorine, carbon, or oxygen; the most commonly used isotope is life years) and to lower costs. 18F-fluorodeoxyglucose (FDG). The rationale for FDG-PET BIOPSY scanning in the evaluation of SPNs is based on the higher meta- bolic rate of most malignancies and the preferential trapping of If an SPN demonstrates characteristics suggestive of malignan- FDG in malignant cells.34 However, increased FDG activity can cy, a tissue diagnosis should be obtained. There are several alter- also occur in benign SPNs,35,36 especially those arising from active native biopsy techniques that may be performed in place of resec- granulomatous diseases37,38 or inflammatory processes.39 These tion, including TTNB and bronchoscopy.Traditionally, open lung benign diseases can produce false positive PET scans and thereby biopsy was performed for an SPN, but this approach has the draw- reduce the sensitivity of the test. Conversely, some malignancies— back of the morbidity associated with a thoracotomy. For periph- bronchoalveolar carcinoma and carcinoid tumors, in particular— eral lesions, video-assisted thoracoscopic surgery (VATS) has now have low metabolic activity and commonly produce false negative supplanted thoracotomy as the procedure of choice. For central PET scans.40-44 Thus, a negative PET scan is not a particularly lesions that cannot be diagnosed by means of less invasive tech- helpful result, and it is necessary to follow the lesion with serial CT niques, more invasive approaches will still be required. scans. Efforts have been made to increase the sensitivity and specifici- Transthoracic Needle Biopsy ty of PET scanning in the diagnosis of SPNs. One such effort Lesions that are between 1.0 and 3.0 cm in diameter should be involves the use of the standardized uptake value (SUV), which is considered for TTNB. The diagnostic yield of this procedure for a numerical indication of the activity concentration in a lesion, SPNs is excellent, reaching 95% in some studies. The reported normalized for the injected dose.45 In many studies, an SPN is sensitivity ranges from 80% to 95%, and the specificity ranges considered malignant when its SUV is higher than 2.5. Because of from 50% to 88%.48-50 A study of 222 patients who underwent the method used to calculate the SUV, however, small tumors (< TTNB for an SPN reported a positive predictive value of 98.6% and a negative predictive value of 96.6%51; however, several other studies reported false negative rates ranging from 3% to 29%.48,52 Table 2 Factors Affecting Malignant Probability The complication rate associated with TTNB is relatively high— of Solitary Pulmonary Nodule8 potentially as high as 30% and rarely lower than 10%, in even the most experienced hands.49,53 Most commonly, a pneumothorax Factor Likelihood Ratio for Malignancy results; however, chest tube placement is required only if the patient becomes symptomatic, a situation that occurs in approxi- Spiculated margins on CT scan 5.54 mately 50% of cases. In the absence of symptoms, observation Age > 70 yr 4.16 with serial chest x-rays is generally appropriate. If no increase in the size of the SPN is observed, the patient can be discharged with Lesion size 2.1–3.0 cm 3.67 the expectation that the pneumothorax will resolve. Doubling time < 465 days 3.40 For lesions smaller than 1.0 cm, the risk-to-benefit ratio of TTNB rises to the point where other techniques are typically pre- History of smoking 2.27 ferred.The utility of TTNB depends primarily on the characteris- Age 50–69 yr 1.90 tics of the SPN—in particular, its location. Nodules that are cen- Lesion size 1.1–2.0 cm tral or close to the diaphragm or the pericardium are less well suit- 0.74 ed to this technique than those at other sites are. Lesion size < 1 cm 0.52 Bronchoscopy Smooth margins on CT scan 0.30 Bronchoscopy has a well-established role in the evaluation of No history of smoking 0.19 central SPNs, which are amenable to direct visualization and biop- Doubling time > 465 days 0.01 sy. Most SPNs, however, are not central. Various adjunctive mea- sures, including transbronchial needle biopsy and cytology brush-
  6. 6. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 4 THORAX 5 SOLITARY PULMONARY NODULE — 6 Small Cell Lung Cancer ings, are employed to improve the yield of bronchoscopy. Newer techniques, including the use of endobronchial ultrasonography, Small cell carcinoma accounts for approximately 20% of lung are currently under active investigation. cancers. Typically, it presents as a central mass in association with For SPNs between 2.0 and 3.0 cm in diameter, the diagnostic significant nodal disease, often accompanied by distant metas- yield of bronchoscopy ranges from 20% to 80%, depending on the tases.62 Small cell carcinoma typically has a very short doubling size of the lesion, the incidence of malignancy in the study popu- time. Paraneoplastic syndromes are more common with small cell lation, and the proximity of the lesion to the bronchial tree.54,55 For lung cancer than with NSCLC. SPNs smaller than 1.5 cm, the yield drops to 10%.56 Even though bronchoscopy has a low complication rate (about 5%), its low Pulmonary Carcinoid diagnostic yield for malignancy limits its utility in the evaluation of Pulmonary carcinoid tumors are uncommon neuroendocrine SPNs. neoplasms that account for 1% to 2% of lung cancers.63 They are classified as either typical or atypical, depending on their histol- Excisional Biopsy ogy.64 Either type of carcinoid may present as an SPN, usually in The decision whether to proceed to excisional lung biopsy the fifth or sixth decade of life. Typical carcinoid tumors have a (open or thoracoscopic) must be carefully considered.The risk-to- very long doubling time—up to 80 months—and thus may be mis- benefit ratio of excisional biopsy is determined by clinical charac- taken for benign lesions.65 Atypical carcinoid tumors have a much teristics affecting perioperative morbidity and mortality, as well as shorter doubling time and are more likely to show an increase in by the risk of malignancy. size on serial CT scans.Typical carcinoid tumors have an extreme- Resection is the definitive diagnostic technique. The morbidity ly low incidence of recurrence and are not usually associated with associated with VATS is less than that associated with thoracotomy; nodal metastasis. accordingly, when VATS lung biopsy is technically feasible, it is preferable to open lung biopsy.The overall morbidity is lower than Metastatic Malignancies 1% for VATS wedge resection, compared with 3% to 7% for the Metastases to the lung frequently appear as smooth, round, equivalent open procedure.57 Patients who have undergone VATS well-demarcated lesions. They often are multiple and rarely are lung biopsy experience less pain, have shorter hospital stays, and associated with mediastinal adenopathy. Most pulmonary metas- recover sooner than those who have undergone open biopsy.57,58 tases derive from the lungs, the colon, the testicles, the breasts, A technical consideration that must be taken into account when melanomas, or sarcomas. Treatment tends to be palliative, based VATS is planned is possible conversion to a thoracotomy.The con- on the diagnosis of the primary tumor, but it may be curative in version rate for VATS to thoracotomy has been reported to be as cases of metastatic sarcoma or testicular carcinoma. In patients high as 33%, but there is evidence to suggest that this rate can be with these cancers, limited wedge resection of a metastasis to the significantly reduced with careful patient selection and increasing lung has been shown to confer a survival advantage; this measure experience in minimally invasive techniques.59,60 may also be beneficial for patients with metastatic colon or head Peripheral SPNs more than 1.0 cm in diameter are the lesions and neck cancer and, occasionally, for those with metastatic best suited to VATS excision. As SPNs become smaller and more melanoma.66 central, they become harder to identify, and the rate of conversion BENIGN LESIONS to thoracotomy rises. A wide variety of techniques have been employed to improve the identification of SPNs for VATS, ranging from radioisotope use through guide-wire localization. None of Pulmonary Hamartoma these techniques have achieved wide acceptance, and most sur- Pulmonary hamartomas are the most common benign pul- geons rely on simple finger palpation through one of the port sites. monary tumors and the third most common cause of SPNs over- all. Most (90%) arise in the periphery of the lung, but endo- bronchial hamartomas are seen as well. Because they are most Differential Diagnosis common in the periphery, hamartomas are usually asymptomatic. When a potential hamartoma appears as an SPN on a chest x-ray, MALIGNANT LESIONS CT scanning is warranted for further evaluation. Certain typical CT findings suggest that the SPN is likely to be Non–Small Cell Lung Cancer a hamartoma. One such finding is a particular pattern of calcifica- As noted, NSCLC is the malignancy most frequently identified tion. Calcification is more common in benign lesions than in in an SPN. Most lung cancer patients are asymptomatic, and those malignant tumors. There are four patterns of calcification that are who are symptomatic usually have advanced disease, including considered benign: central, diffuse, laminated, and “popcornlike.” mediastinal lymph node involvement. Arterial invasion has also The first three patterns are most commonly associated with an been shown to have an adverse effect on survival in patients with infectious condition (e.g., histoplasmosis or tuberculosis). The early-stage NSCLC.61 The most common sites of metastases are popcornlike pattern, however, indicates that the lesion is probably the lungs, the brain, the bones, and the adrenal glands. a hamartoma. Unfortunately, calcification is present in only about Accordingly, it is essential to perform a metastatic workup that 50% of benign lesions, and only about 50% of hamartomas are focuses on these areas to identify metastatic disease before pro- calcified.29 It is important to remember that pulmonary carcinoid ceeding with resection. tumors and metastases to the lung (especially those from osteosar- Bronchoalveolar carcinoma is a subtype of NSCLC that is well comas, chondrosarcomas, or synovial cell sarcomas) may also have differentiated and has a prolonged doubling time. Because of its calcifications. slow growth rate, it may be missed by PET scanning.42 Broncho- Another reliable marker of a hamartoma is the finding of fat alveolar carcinoma may present as an SPN, as airspace disease, or within the lesion on a CT scan; however, fewer than 50% of as multiple nodules. hamartomas demonstrate this characteristic.
  7. 7. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 4 THORAX 5 SOLITARY PULMONARY NODULE — 7 Inflammatory Nodules rupture could result in an anaphylactic reaction to the highly anti- Sarcoidosis is known as the great mimicker, but it rarely presents genic contents. Patients may be treated with anthelmintic agents, as an SPN.67 Most commonly, it presents as hilar and mediastinal but the incidence of persistent or recurrent disease is high. Accord- lymphadenopathy and diffuse parenchymal involvement. When it ingly, surgical resection should be considered. does present as an SPN, it is almost invariably a solid lesion, hard- ly ever a cavitary one. The incidence of sarcoidosis is highest in OTHER CONSIDERATIONS African-American women between 20 and 40 years of age. If sar- Pulmonary amyloidosis may present in either a diffuse or a coidosis is suspected during the evaluation of an SPN, an elevated nodular form.The prognosis is most favorable when it presents as angiotensin-converting enzyme level supports the diagnosis, but a an asymptomatic SPN. Typically, the nodule is well defined and normal level does not exclude it. If a biopsy is performed, the pres- between 2 and 4 cm in diameter. Unless the patient exhibits sys- ence of noncaseating granulomas on pathologic evaluation estab- temic manifestations of amyloidosis, the diagnosis can be con- lishes the diagnosis. firmed only by biopsy of the nodule.35 Pulmonary rheumatoid nodules are present in fewer then 1% of Rounded atelectasis usually presents as a pleura-based nodular patients with rheumatoid arthritis.68 They are usually associated density that occurs secondary to pleural scarring and thickening. with rheumatoid nodules in other parts of the body but may pre- An effort should be made to look for associated pleural plaques cede any systemic manifestations of the disease. Pulmonary resulting from asbestos exposure. The CT scan usually demon- rheumatoid nodules, though generally asymptomatic in them- strates an SPN with a “comet tail.” Biopsy is not required unless selves, arise from underlying rheumatoid activity.When the under- mesothelioma is strongly suspected or the SPN is seen to have lying disease is active, the nodules may grow, simulating malignan- grown on successive CT scans.75 cy. An elevated serum rheumatoid factor level is typical and helps confirm the diagnosis. Wegener granulomatosis is a necrotizing vasculitis that affects Management both the upper and the lower respiratory tract, as well as the kid- Currently, there are no evidence-based guidelines that fully neys. It presents with an SPN in approximately 20% of patients.69 delineate a recommended approach to the workup and manage- If vasculitis is suspected during evaluation of an SPN, laboratory ment of SPNs.76 The following is a summary of our preferred studies should include testing for cytoplasmic antineutrophil cyto- approach. plasmic antibodies (c-ANCA); a positive result on this test is high- The ultimate aim in the evaluation of an SPN is to classify the ly suggestive of Wegener granulomatosis. Treatment includes the lesion as either benign or malignant.The first step toward that end cytotoxic drug cyclophosphamide, either alone or in combination is to compare current chest x-rays or CT scans with any previous with corticosteroids. images that are available. An SPN whose size has been stable for Infectious Nodules 2 years on diagnostic images will be benign 90% to 95% of the time. If no previous images are available for comparison, the An SPN can also represent an infectious granuloma caused by patient should undergo a complete evaluation as if the nodule tuberculosis, atypical mycobacterial diseases, histoplasmosis, coc- were an early-stage NSCLC. This evaluation must be individual- cidioidomycosis, or aspergillosis. Such granulomas normally have ized according to the characteristics of the patient and the lesion. a cavitary appearance on CT scans. Occasionally, an upright chest On the basis of the patient’s age and smoking history, the size of x-ray taken with the patient in the lateral decubitus position shows the SPN, and the characteristics of the lesion’s borders, an SPN shifting of the position of the cavity’s contents or a crescent of air for which no previous diagnostic images are available can be ini- around the mass (the Monod sign).70 This radiographic finding is tially classified as having a low, intermediate, or high probability characteristic of a mycetoma, usually aspergilloma. Depending on the circumstances—in particular, on whether there has been sig- of cancer [see Table 3].7,77,78 This classification governs the subse- nificant hemoptysis and whether pulmonary function is reasonably quent workup. Whereas a patient with a high-probability SPN well preserved—many of these lesions are best treated by means of needs a complete workup, with the goal being resection, the same resection. Others are best diagnosed by noninvasive techniques workup would not be cost-effective for a patient with a low-prob- and treated with antibiotics. ability SPN. It is important not to subject a patient with a high- Pulmonary dirofilariasis is a rare but well-attested cause of probability SPN to studies that will not change clinical manage- SPNs that is the consequence of infestation of human lungs by the ment or outcome: doing so will delay diagnosis and treatment canine heartworm Dirofilaria immitis.This organism is transmitted unnecessarily. to humans in larval form by mosquitoes that have ingested blood At this point in the evaluation, if the nature of the SPN is still from affected dogs.71 Because humans are not suitable hosts for this organism, the larvae die and embolize to the lungs, where they initiate a granulomatous response.Typically, these lesions are pleu- Table 3 Initial Assessment of Probability ra based, and the diagnosis is made at the time of resection.72 Once of Cancer in Solitary Pulmonary Nodule the diagnosis is made, no further therapy is required. Echinococcosis is a hydatid disease caused by the tapeworm Characteristics of Probability of Cancer Echinococcus granulosus. It is endemic to certain areas of the world Patient or Lesion Low Intermediate High where sheep and cattle are raised. Normally, it is ingested inciden- tally; the parasite penetrates the bowel wall and travels to the lungs Patient age < 40 yr 40–60 yr > 60 yr in 10% to 30% of cases.73,74 A complete blood count usually de- Patient smoking history Never smoked < 20 pack-years ≥ 20 pack-years monstrates peripheral eosinophilia. If echinococcosis is suspected, a hemagglutination test, which has a sensitivity of 66% to 100% and Lesion size < 1.0 cm 1.1–2.2 cm ≥ 2.3 cm a specificity of 98% to 99% for Echinococcus, should be performed. Lesion margin Smooth Scalloped Spiculated TTNB should not be performed, because there is a risk that cyst
  8. 8. © 2006 WebMD, Inc. All rights reserved. ACS Surgery: Principles and Practice 4 THORAX 5 SOLITARY PULMONARY NODULE — 8 indeterminate and the lesion is larger than 1.0 cm, there may be a vals for a minimum of 2 years. The rationale for this approach is role for PET scanning. If PET scanning yields negative results, the based on the difficulty of identifying these lesions with VATS, the SPN is probably benign, and follow-up with CT scanning is low likelihood of establishing a diagnosis with TTNB, and the pos- appropriate. If PET scanning yields positive results and the patient sibility that the lesion may be benign. If the lesion has grown visi- is a high surgical risk,TTNB may be performed to establish a diag- bly between scans, it is probably malignant, and proceeding with nosis. If, however, the patient is a reasonable surgical risk, pro- resection for diagnosis and treatment is appropriate.The likelihood ceeding directly to VATS resection (and, potentially, to lobectomy) that nodal metastases will develop in a closely followed SPN small- offers the best chance of a cure. er than 1.0 cm is low.60 If the SPN proves to be malignant, scan- For patients with SPNs smaller than 1.0 cm, the optimal ning at 3-month intervals is unlikely to alter the eventual approach may be to perform serial CT scanning at 3-month inter- outcome. References 1. Leef JL 3rd, Klein JS:The solitary pulmonary nod- Czechoslovakia. Int J Cancer 45:26, 1990 role of positron emission tomography in the man- ule. Radiol Clin North Am 40:123, 2002 19. Lillington GA: Management of solitary pulmon- agement of patients with inflammatory and other ary nodules. Dis Mon 37:271, 1991 benign disorders. Semin Nucl Med 34:313, 2004 2. 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