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Lung Tumors I(EY POIilIS TABLE 33. Fleischner Society Recommendations for . Principles of pulmonary nodule evaluation include the Single Pulmonary Nodule Follow-Up review of imaging history estimating the probability of Risk Factors for Size Recommended Follow-Up malignancy, and discussing management preferences Lung Cancer? with the patient. No (Low-risk <6 mm No follow-up patient) ! r A focal pulmonary opacity larger than 3 cm is presumed 6-8 mm CT at 6-12 months, then i

I(EY POIilIS TABLE 33. Fleischner Society Recommendations for . Principles of pulmonary nodule evaluation include the Single Pulmonary Nodule Follow-Up review of imaging history estimating the probability of Risk Factors for Size Recommended Follow-Up malignancy, and discussing management preferences Lung Cancer? with the patient. No (Low-risk <6 mm No follow-up patient) ! r A focal pulmonary opacity larger than 3 cm is presumed 6-8 mm CT at 6-12 months, then i malignant until proved otherwise. consider CT at 18-24 months l >B mm Consider CT at 3 months, PET/CI or tissue sampling Solid Indeterminate Nodule LargerThan 8 mm Yes (High-risk <6 mm Optional Cf at12 months The first step in evaluating a solid nodule that is larger than patient) B mm in size is to estimate the probability of malignancy 6-8 mm CI at 6-12 months, then CT at 18-24 months Criteria included in tl.re calculation include age. smoking >B mm Consider CT at 3 months, history, nodule size, location lvithin the lung. and presence PEI/CI, or tissue sampling of spiculatecl or lobular border. ( Lung cancer risk calculators Adapted with permission, from MacMahon H, Naid ch DP, Goo JM, et al. Gurde nes can be accessed at https:i,brocku.ca/lung cancer screening {or management of incidental pulmonary nodules detected on CT mages: from the and.risk prediction/risk calculators/.) Solid nodules with Fleischner Society 201 7. Radiology. 201 7 ;284:228-243. lPMlD. 28240562) dor:1 0.1 1 48/radioi.2017 161 659. Copy rlght 20 T 7, RSNA. moderate prclbability of malignancy should be character ized further r.t,ith a PET scan. Il the PET scan is negative for metabolic activity, continued surveillance is warranted an estimation ot'the likelihood of malignancy (https: ' ,brocku. (Table 33). A nodule with moderate or intense uptake is ca lung-cancer-screening and-risk prediction risk calcula suggestive of n.ralignancy and requires relerral fbr further tors ). Nodules of B mm or smaller hare a lon,er probability of evaluation. being malignant, are dilllcult to biopsyl and are not reliably If the probability of malignancy is initially high, the characterized by PET scan. As a result. these small nodules are next step is staging with a PET scan fbllowed by definitive usually ibllorved by serial CT scans. The frequency and dura- management with surgical resection or chemotherapy and tion of follow up is based on the recommendations of the Fleischner Society and endorsed by other professional socie radiation. ties (see Table 33). I(EY POIIII r The first step in evaluating a solid pulmonary nodule Subsolid Nodule larger than B mm in size is to estimate the probability of A subsolid nodule is a focal rounded opacity that is either pure malignancy. ground glass in appearance (fbcal density with underlying lung architecture still preserved) or has a solid component Solid lndeterminate Nodule of 8 mm or Smaller (part solid) but is still more than 50',x, ground glass (Figure 18). Solid indeterminate nodules of 8 mm or smaller are usually These nodules often represent premalignant disease, such as detected incidentally. 'lhe first step, as with larger nodules. is adenocarcinoma in situ, and can be very slow growing.

malignant until proved otherwise. consider CT at 18-24 months l >B mm Consider CT at 3 months, PET/CI or tissue sampling Solid Indeterminate Nodule LargerThan 8 mm Yes (High-risk <6 mm Optional Cf at12 months The first step in evaluating a solid nodule that is larger than patient) B mm in size is to estimate the probability of malignancy 6-8 mm CI at 6-12 months, then CT at 18-24 months Criteria included in tl.re calculation include age. smoking >B mm Consider CT at 3 months, history, nodule size, location lvithin the lung. and presence PEI/CI, or tissue sampling of spiculatecl or lobular border. ( Lung cancer risk calculators Adapted with permission, from MacMahon H, Naid ch DP, Goo JM, et al. Gurde nes can be accessed at https:i,brocku.ca/lung cancer screening {or management of incidental pulmonary nodules detected on CT mages: from the and.risk prediction/risk calculators/.) Solid nodules with Fleischner Society 201 7. Radiology. 201 7 ;284:228-243. lPMlD. 28240562) dor:1 0.1 1 48/radioi.2017 161 659. Copy rlght 20 T 7, RSNA. moderate prclbability of malignancy should be character ized further r.t,ith a PET scan. Il the PET scan is negative for metabolic activity, continued surveillance is warranted an estimation ot'the likelihood of malignancy (https: ' ,brocku. (Table 33). A nodule with moderate or intense uptake is ca lung-cancer-screening and-risk prediction risk calcula suggestive of n.ralignancy and requires relerral fbr further tors ). Nodules of B mm or smaller hare a lon,er probability of evaluation. being malignant, are dilllcult to biopsyl and are not reliably If the probability of malignancy is initially high, the characterized by PET scan. As a result. these small nodules are next step is staging with a PET scan fbllowed by definitive usually ibllorved by serial CT scans. The frequency and dura- management with surgical resection or chemotherapy and tion of follow up is based on the recommendations of the Fleischner Society and endorsed by other professional socie radiation. ties (see Table 33). I(EY POIIII r The first step in evaluating a solid pulmonary nodule Subsolid Nodule larger than B mm in size is to estimate the probability of A subsolid nodule is a focal rounded opacity that is either pure malignancy. ground glass in appearance (fbcal density with underlying lung architecture still preserved) or has a solid component Solid lndeterminate Nodule of 8 mm or Smaller (part solid) but is still more than 50',x, ground glass (Figure 18). Solid indeterminate nodules of 8 mm or smaller are usually These nodules often represent premalignant disease, such as detected incidentally. 'lhe first step, as with larger nodules. is adenocarcinoma in situ, and can be very slow growing. A c

malignant until proved otherwise. consider CT at 18-24 months l >B mm Consider CT at 3 months, PET/CI or tissue sampling Solid Indeterminate Nodule LargerThan 8 mm Yes (High-risk <6 mm Optional Cf at12 months The first step in evaluating a solid nodule that is larger than patient) B mm in size is to estimate the probability of malignancy 6-8 mm CI at 6-12 months, then CT at 18-24 months Criteria included in tl.re calculation include age. smoking >B mm Consider CT at 3 months, history, nodule size, location lvithin the lung. and presence PEI/CI, or tissue sampling of spiculatecl or lobular border. ( Lung cancer risk calculators Adapted with permission, from MacMahon H, Naid ch DP, Goo JM, et al. Gurde nes can be accessed at https:i,brocku.ca/lung cancer screening {or management of incidental pulmonary nodules detected on CT mages: from the and.risk prediction/risk calculators/.) Solid nodules with Fleischner Society 201 7. Radiology. 201 7 ;284:228-243. lPMlD. 28240562) dor:1 0.1 1 48/radioi.2017 161 659. Copy rlght 20 T 7, RSNA. moderate prclbability of malignancy should be character ized further r.t,ith a PET scan. Il the PET scan is negative for metabolic activity, continued surveillance is warranted an estimation ot'the likelihood of malignancy (https: ' ,brocku. (Table 33). A nodule with moderate or intense uptake is ca lung-cancer-screening and-risk prediction risk calcula suggestive of n.ralignancy and requires relerral fbr further tors ). Nodules of B mm or smaller hare a lon,er probability of evaluation. being malignant, are dilllcult to biopsyl and are not reliably If the probability of malignancy is initially high, the characterized by PET scan. As a result. these small nodules are next step is staging with a PET scan fbllowed by definitive usually ibllorved by serial CT scans. The frequency and dura- management with surgical resection or chemotherapy and tion of follow up is based on the recommendations of the Fleischner Society and endorsed by other professional socie radiation. ties (see Table 33). I(EY POIIII r The first step in evaluating a solid pulmonary nodule Subsolid Nodule larger than B mm in size is to estimate the probability of A subsolid nodule is a focal rounded opacity that is either pure malignancy. ground glass in appearance (fbcal density with underlying lung architecture still preserved) or has a solid component Solid lndeterminate Nodule of 8 mm or Smaller (part solid) but is still more than 50',x, ground glass (Figure 18). Solid indeterminate nodules of 8 mm or smaller are usually These nodules often represent premalignant disease, such as detected incidentally. 'lhe first step, as with larger nodules. is adenocarcinoma in situ, and can be very slow growing. A c I I F t Part-solid nodule 1 year later 6 years later

A c I I F t Part-solid nodule 1 year later 6 years later FIGURE 18. Radiographsshowtheevolutionof apart-solidnodulefromadenocarcinomainsitut0invasiveadenocarcinoma: part'solid,part-gr0und-glassnoduleinthe left upper lobe (/); growth in the solid component of the nodule 1 year after initial imaging (8); an increase in size in the ground-glass component 4 years after initial nodule and demonstrates why patients with this finding musl be followed for at least 5 yean. 46

Lung Tumors I 4-* q' tIGURE 1 9. Metastaticsquamous cell carcinoma can be seen as an B'cm right hilar mass with invasion into the trachea on CTscan (/) and as tumor invasion into the distal trachea and occlusion of the right main stem on bronchoscopy (B).

I 4-* q' tIGURE 1 9. Metastaticsquamous cell carcinoma can be seen as an B'cm right hilar mass with invasion into the trachea on CTscan (/) and as tumor invasion into the distal trachea and occlusion of the right main stem on bronchoscopy (B). Observed doubling times can range between 400 and 800 days. Approximately B0'7, ol lung cancer cases are NSCLC, which is This has implications for both the frequency and the duration divided into adenocarcinoma, squamous cell carcinoma, and of follow up. Subsolid nodules are not reliably characterized large cell carcinoma. Adenocarcinoma is the most common by PET scans, and nonsurgical biopsies also have limited sen NSCLC and accounts for almost all lung cancer diagnoses in sitivity. Development of a solid component in a pure ground nonsmokers. The most frequent location of adenocarcinoma is glass nodule or enlargement of the solid component suggests in the peripheral aspects of the lung parenchyma as a solitary malignancy (see Figure 18). Recommendations for nonsolid nodule or mass. Squamous cell carcinoma is the second most and part-solid nodule follow up are in Table 34. common subtype of NSCLC. [t correlates highly with smoking history and usually originates in the central airways (trachea, main stem bronchi, lobar and segmental bronchi) (Figure 19). Lung Cancer Individuals with squamous cell carcinoma often have symp Lung cancer is the leading cause of cancer death worldwide. In toms of cough and hemoptysis caused by central airway the United States. it is estimated that 230.000 new cases will involvement. Radiographical ly, squamous cell carcinoma may be diagnosed and more than 135,000 deaths will occur annu- present with postobstructive pneumonia or lobar collapse. ally. The overall 5 year survival rate remains low, at 17.7'/.. Large cell carcinoma is an undifferentiated carcinoma and However, much progress has been made recently regarding characteristically presents as a peripheral mass with promi screening, diagnosis, and treatment. nent necrosis (Figure 20). In the past decade, the development oftargeted therapy I(EY POIlIT for specific gene mutations has allowed for the individuali- o Lung cancer is the leading cause of cancer death world- zation oftherapy and improved survival. Testing for epider wide. mal growth lactor receptor (EGFR) mutation, anaplastic

Observed doubling times can range between 400 and 800 days. Approximately B0'7, ol lung cancer cases are NSCLC, which is This has implications for both the frequency and the duration divided into adenocarcinoma, squamous cell carcinoma, and of follow up. Subsolid nodules are not reliably characterized large cell carcinoma. Adenocarcinoma is the most common by PET scans, and nonsurgical biopsies also have limited sen NSCLC and accounts for almost all lung cancer diagnoses in sitivity. Development of a solid component in a pure ground nonsmokers. The most frequent location of adenocarcinoma is glass nodule or enlargement of the solid component suggests in the peripheral aspects of the lung parenchyma as a solitary malignancy (see Figure 18). Recommendations for nonsolid nodule or mass. Squamous cell carcinoma is the second most and part-solid nodule follow up are in Table 34. common subtype of NSCLC. [t correlates highly with smoking history and usually originates in the central airways (trachea, main stem bronchi, lobar and segmental bronchi) (Figure 19). Lung Cancer Individuals with squamous cell carcinoma often have symp Lung cancer is the leading cause of cancer death worldwide. In toms of cough and hemoptysis caused by central airway the United States. it is estimated that 230.000 new cases will involvement. Radiographical ly, squamous cell carcinoma may be diagnosed and more than 135,000 deaths will occur annu- present with postobstructive pneumonia or lobar collapse. ally. The overall 5 year survival rate remains low, at 17.7'/.. Large cell carcinoma is an undifferentiated carcinoma and However, much progress has been made recently regarding characteristically presents as a peripheral mass with promi screening, diagnosis, and treatment. nent necrosis (Figure 20). In the past decade, the development oftargeted therapy I(EY POIlIT for specific gene mutations has allowed for the individuali- o Lung cancer is the leading cause of cancer death world- zation oftherapy and improved survival. Testing for epider wide. mal growth lactor receptor (EGFR) mutation, anaplastic Lung Cancer Types There are tvvo major classes of lung cancer: non small cell lung cancer (NSCLC) and small cell lung cancer (SCLC).

Observed doubling times can range between 400 and 800 days. Approximately B0'7, ol lung cancer cases are NSCLC, which is This has implications for both the frequency and the duration divided into adenocarcinoma, squamous cell carcinoma, and of follow up. Subsolid nodules are not reliably characterized large cell carcinoma. Adenocarcinoma is the most common by PET scans, and nonsurgical biopsies also have limited sen NSCLC and accounts for almost all lung cancer diagnoses in sitivity. Development of a solid component in a pure ground nonsmokers. The most frequent location of adenocarcinoma is glass nodule or enlargement of the solid component suggests in the peripheral aspects of the lung parenchyma as a solitary malignancy (see Figure 18). Recommendations for nonsolid nodule or mass. Squamous cell carcinoma is the second most and part-solid nodule follow up are in Table 34. common subtype of NSCLC. [t correlates highly with smoking history and usually originates in the central airways (trachea, main stem bronchi, lobar and segmental bronchi) (Figure 19). Lung Cancer Individuals with squamous cell carcinoma often have symp Lung cancer is the leading cause of cancer death worldwide. In toms of cough and hemoptysis caused by central airway the United States. it is estimated that 230.000 new cases will involvement. Radiographical ly, squamous cell carcinoma may be diagnosed and more than 135,000 deaths will occur annu- present with postobstructive pneumonia or lobar collapse. ally. The overall 5 year survival rate remains low, at 17.7'/.. Large cell carcinoma is an undifferentiated carcinoma and However, much progress has been made recently regarding characteristically presents as a peripheral mass with promi screening, diagnosis, and treatment. nent necrosis (Figure 20). In the past decade, the development oftargeted therapy I(EY POIlIT for specific gene mutations has allowed for the individuali- o Lung cancer is the leading cause of cancer death world- zation oftherapy and improved survival. Testing for epider wide. mal growth lactor receptor (EGFR) mutation, anaplastic Lung Cancer Types There are tvvo major classes of lung cancer: non small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). TABLE 34. Fleischner Society Recommendations for Solitary Subsolid Lung Nodule Follow-Up lmaging Findings Size Recommended Follow-Up Pure ground glass <6 mm No follow-up >6 mm CT at 6-12 months to confirm persistence, then CT every 2 years until 5 years

TABLE 34. Fleischner Society Recommendations for Solitary Subsolid Lung Nodule Follow-Up lmaging Findings Size Recommended Follow-Up Pure ground glass <6 mm No follow-up >6 mm CT at 6-12 months to confirm persistence, then CT every 2 years until 5 years Part solid nodule <6 mm No follow-up >6 mm CT at 3-6 months to confirm persistence; if unchan ged and solid component remains <6 mm, annual CT should be performed for 5 years Adapted wlth permission, from MacMahon H, Nald ch DR Goo JM, et al. FIGURE 20. Large cellcarcinoma with predominant necrosis can be seen on CT Guidelines for management of incidental pulmonary nodules detected on CT scan as a large necrolic tumorthat has completely replaced the right upper and images: from the Fleischner Society 20 1 7. Radiology. 20 1 7;284:228'243. IPMID: middle lobes, with deviation of the central airway structures to the left. Necrosis is 282405621 doi:1 0.1 148/rad o1.2017161 659. Copyright 201 7, RSNA. noted by the mixed attenuation of the mass, as noted on CT. 47

Lung Tumors number of pack years of smoking and other carcinogenic exposures. Any reduction in lung cancer mortality will be linked to an overall reduction of cigarette smoking. Other risk factors that have been associated with lung cancer include previous radiation therapy, exposure to environmental toxins (asbestos, radon. metals, and diesel fumes). pulmonary fibro- sis, HIV infection. family history of lung cancer, and alcohol abuse.

number of pack years of smoking and other carcinogenic exposures. Any reduction in lung cancer mortality will be linked to an overall reduction of cigarette smoking. Other risk factors that have been associated with lung cancer include previous radiation therapy, exposure to environmental toxins (asbestos, radon. metals, and diesel fumes). pulmonary fibro- sis, HIV infection. family history of lung cancer, and alcohol abuse. Screening Until recently, screening for lung cancer was not widely per formed, as previous studies had not shown that early detection resulted in any mortality benefit for lung cancer. The National Lung Screening Trial demonstrated a 20'l. reduction in lung cancer mortality in hear,y smokers who r,rere screened annu ally for 3 years. As a result, the U.S. Preventive Services Task Force has given annual lung cancer screening in high risk tIGURE 21. Small cell lung cancercan beseen on chestCTwith a right patients a grade B recommendation. Screening should be per paratracheal mass (arow). Ihis patient initially presented with encephalitis (paraneoplastic syndrome). formed in patients aged 50 through B0 years who have no symptoms of Iung cancer and at least a 2O-pack year smoking history and who are current smokers or have quit within the lymphoma kinase receptor tyrosine kinase (ALK) transloca- last 15 years. Cessation of screening is recommended once a tion, and ROS proto oncogene 1 receptor tyrosine kinase person has not smoked for 15 years and in those with limited (ROSI) translocation is recommended in advanced stage Iife expectancy or those who would not be candidates for or adenocarcinoma or mixed cancers. The role for immuno willing to undergo surgery. therapy in the treatment of lung cancer is also promising. SCLC accounts for about 15% ofall lung cancers. It is the rtY PolxT most strongly associated with cigarette smoking and tlpically . The U.S. Preventive Services Task Force recommends occurs adjacent to the central airways with extensive lymphad- annual lung cancer screening using low dose CT scan for enopathy and distant metastasis at diagnosis. Imaging com those who are aged 50 to 80 years and have at least a monly shows a large mediastinal mass that encompasses ll,rnph 2O-pack year smoking history and who are either current nodes with an uncertain primary site of origin (Figure 21). smokers or have quit smoking within the last 15 years. Paraneoplastic syndromes are most commonly associated with SCLC, including hyponatremia resulting from the syn drome of inappropriate antidiuretic hormone secretion (rare in other lung tumors), hlpertrophic pulmonary osteoarthropathy (Figure 22), inflammatory myopathies, Cushing slmdrome caused by ectopic adrenocorticotropic hormone secretion, and other hematologic and neurologic slmdromes.

Screening Until recently, screening for lung cancer was not widely per formed, as previous studies had not shown that early detection resulted in any mortality benefit for lung cancer. The National Lung Screening Trial demonstrated a 20'l. reduction in lung cancer mortality in hear,y smokers who r,rere screened annu ally for 3 years. As a result, the U.S. Preventive Services Task Force has given annual lung cancer screening in high risk tIGURE 21. Small cell lung cancercan beseen on chestCTwith a right patients a grade B recommendation. Screening should be per paratracheal mass (arow). Ihis patient initially presented with encephalitis (paraneoplastic syndrome). formed in patients aged 50 through B0 years who have no symptoms of Iung cancer and at least a 2O-pack year smoking history and who are current smokers or have quit within the lymphoma kinase receptor tyrosine kinase (ALK) transloca- last 15 years. Cessation of screening is recommended once a tion, and ROS proto oncogene 1 receptor tyrosine kinase person has not smoked for 15 years and in those with limited (ROSI) translocation is recommended in advanced stage Iife expectancy or those who would not be candidates for or adenocarcinoma or mixed cancers. The role for immuno willing to undergo surgery. therapy in the treatment of lung cancer is also promising. SCLC accounts for about 15% ofall lung cancers. It is the rtY PolxT most strongly associated with cigarette smoking and tlpically . The U.S. Preventive Services Task Force recommends occurs adjacent to the central airways with extensive lymphad- annual lung cancer screening using low dose CT scan for enopathy and distant metastasis at diagnosis. Imaging com those who are aged 50 to 80 years and have at least a monly shows a large mediastinal mass that encompasses ll,rnph 2O-pack year smoking history and who are either current nodes with an uncertain primary site of origin (Figure 21). smokers or have quit smoking within the last 15 years. Paraneoplastic syndromes are most commonly associated with SCLC, including hyponatremia resulting from the syn drome of inappropriate antidiuretic hormone secretion (rare in other lung tumors), hlpertrophic pulmonary osteoarthropathy (Figure 22), inflammatory myopathies, Cushing slmdrome caused by ectopic adrenocorticotropic hormone secretion, and other hematologic and neurologic slmdromes. TEY FOIXTS . There are t\,vo major classes of lung cancer: non-small cell lung cancer and small cell lung cancer; non-small cell lung cancer accounts for 80% of lung cancers and is divided into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. o Testing for epidermal growth factor receptor mutation, anaplastic lymphoma kinase receptor tyrosine kinase translocation, and ROS proto oncogene 1 receptor tyrosine kinase translocation is recommended in advanced-stage adenocarcinoma or mixed cancers.

TEY FOIXTS . There are t\,vo major classes of lung cancer: non-small cell lung cancer and small cell lung cancer; non-small cell lung cancer accounts for 80% of lung cancers and is divided into adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. o Testing for epidermal growth factor receptor mutation, anaplastic lymphoma kinase receptor tyrosine kinase translocation, and ROS proto oncogene 1 receptor tyrosine kinase translocation is recommended in advanced-stage adenocarcinoma or mixed cancers. Risk Factors tIGURE 22. Clubbing is a partofthetriad ofthe paraneoplasticsyndrome The main risk factor for lung cancer is smoking tobacco hypertroph ic pu I mona ry osteoa rth ropathy ( H POA). The other featu res of H POA are (voluntary or secondhand). This risk increases based on the periostitis of long bones and a painful polyarthritis. 48

Lung Tumors TABLf; 35. CT Findings Suggestive of Lung Malignancy Treatment of lung cancer is discussed in MKSAP 19 Oncologr. lrregular or spiculated borders Upper-lobe location XEYPOIIIS - : i Thick-walled cavitation o The definitive diagnosis of lung cancer requires tissue Solid component within a ground-glass lesion histopatholory.

TABLf; 35. CT Findings Suggestive of Lung Malignancy Treatment of lung cancer is discussed in MKSAP 19 Oncologr. lrregular or spiculated borders Upper-lobe location XEYPOIIIS - : i Thick-walled cavitation o The definitive diagnosis of lung cancer requires tissue Solid component within a ground-glass lesion histopatholory. Detection of growth on follow-up imaging . In patients with radiographic evidence ofadvanced-stage HVC lung cancer, diagnosis and staging are best accomplished with a single invasive test at a location that will establish Diagnosis and Staging both the diagrrosis and the stage of disease. When evaluating a patient who has a lung nodule or mass for possible lung cancer, two questions must be answered: first, Other Pulmonary Neoplasms what is the cell type? And second, what is the stage? Carcinoid tumors are low-grade neoplasms comprised of Initial evaluation should start with a full history physical neuroendocrine cells; they account for 1'l. to 2'X, of all lung examination, complete blood count, serum chemistries, and cancers. Smoking is not a risk factor. Arising in the proxi- CT scan of the chest. Most lung cancers present at a late stage. mal airways, the predominant symptoms or signs are those Symptoms result from the local effects of the tumor, metastatic of an obstructing mass (cough, dyspnea, monophonic spread involving other organs, or paraneoplastic syndromes. wheezing) or bleeding. Bronchial obstruction may cause The most common symptoms at presentation include cough, Iobar atelectasis and recurrent episodes of pneumonia in dyspnea, chest pain, weight loss, and hemoptysis. NSCLC and the same pulmonary segment or may be asymptomatic SCLC present with similar symptoms. Similarly, the presence (Figure 23). Misdiagnosing carcinoid tumors as asthma or of findings on physical examination (consolidation, effusion, pneumonia is responsible for delayed diagnosis. Lung carci- bone tenderness, neurological findings) will indicate advanced noid tumors are rarely associated with carcinoid syndrome. disease. CT scan findings that are suggestive ofmalignancy are Surgical resection is often curative, and l0-year survival listed in Table 35. PET scans can be very helpful in the initial rates are higher than 90%. evaluation of potential lung cancer, as several studies have Adenoid cystic carcinoma is a salivary gland tumor that demonstrated that PET identifies unsuspected mediastinal occurs in the lower respiratory tract and accounts for less than involvement, distant disease, or both, which informs staging 17, ofall lung cancers. Surgical resection is the preferred treat- biopsies and reduces futile (noncurative) surgery. The sensitiv- ment. Hamartomas are the most common benign lung neo ity of a PET scan to detect Iung cancer is affected by the mass plasm. These rare lesions are a combination of cartilage, of the nodule and its metabolic rate, with increased potential connective tissue, smooth muscle, fat, and respiratory epithe- for false-negative results for cancers smaller than 1 cm and lium. On imaging they tend to be smooth-bordered nodules, slow-growing cancers, such as carcinoid tumors. which may contain fat. The definitive diagnosis of lung cancer requires tissue histopathologz. In patients with radiographic evidence of advanced stage disease, diagnosis and staging are best accom- plished with a single invasive test at a location that will estab- lish both the diagnosis and the stage of disease. Because there are many techniques available for tissue diagnosis, the strategr will depend on the size and location of the tumor, patient characteristics, and local expertise. In general, mediastinal and central lesions are best approached with bronchoscopy and smaller peripheral lesions are best approached with a trans- thoracic needle aspiration. Definitive staging of lung cancer is essential, allows for accurate prognostication, and serves as a guide for treatment decision making. NSCLC is staged on the basis of the TNM staging system, taking into account the characteristics of the primary tumor (T), regional lymph node involvement (N), and metastatic disease (M). SCLC is generally staged as either "limited" or'extensive" disease. Limited disease is defined as disease limited to one hemithorax and ipsilateral supraclavicular lymph nodes. ; I G U R E 2 3 . Endobronchial carcinoid can be seen on bronchoscopy as a smooth, The presence of disease outside these locations defines exten polypoid, vascular-appearing mass that completely occludes a subsegmental airway sive stage disease. of the right lower lobe.

Detection of growth on follow-up imaging . In patients with radiographic evidence ofadvanced-stage HVC lung cancer, diagnosis and staging are best accomplished with a single invasive test at a location that will establish Diagnosis and Staging both the diagrrosis and the stage of disease. When evaluating a patient who has a lung nodule or mass for possible lung cancer, two questions must be answered: first, Other Pulmonary Neoplasms what is the cell type? And second, what is the stage? Carcinoid tumors are low-grade neoplasms comprised of Initial evaluation should start with a full history physical neuroendocrine cells; they account for 1'l. to 2'X, of all lung examination, complete blood count, serum chemistries, and cancers. Smoking is not a risk factor. Arising in the proxi- CT scan of the chest. Most lung cancers present at a late stage. mal airways, the predominant symptoms or signs are those Symptoms result from the local effects of the tumor, metastatic of an obstructing mass (cough, dyspnea, monophonic spread involving other organs, or paraneoplastic syndromes. wheezing) or bleeding. Bronchial obstruction may cause The most common symptoms at presentation include cough, Iobar atelectasis and recurrent episodes of pneumonia in dyspnea, chest pain, weight loss, and hemoptysis. NSCLC and the same pulmonary segment or may be asymptomatic SCLC present with similar symptoms. Similarly, the presence (Figure 23). Misdiagnosing carcinoid tumors as asthma or of findings on physical examination (consolidation, effusion, pneumonia is responsible for delayed diagnosis. Lung carci- bone tenderness, neurological findings) will indicate advanced noid tumors are rarely associated with carcinoid syndrome. disease. CT scan findings that are suggestive ofmalignancy are Surgical resection is often curative, and l0-year survival listed in Table 35. PET scans can be very helpful in the initial rates are higher than 90%. evaluation of potential lung cancer, as several studies have Adenoid cystic carcinoma is a salivary gland tumor that demonstrated that PET identifies unsuspected mediastinal occurs in the lower respiratory tract and accounts for less than involvement, distant disease, or both, which informs staging 17, ofall lung cancers. Surgical resection is the preferred treat- biopsies and reduces futile (noncurative) surgery. The sensitiv- ment. Hamartomas are the most common benign lung neo ity of a PET scan to detect Iung cancer is affected by the mass plasm. These rare lesions are a combination of cartilage, of the nodule and its metabolic rate, with increased potential connective tissue, smooth muscle, fat, and respiratory epithe- for false-negative results for cancers smaller than 1 cm and lium. On imaging they tend to be smooth-bordered nodules, slow-growing cancers, such as carcinoid tumors. which may contain fat. The definitive diagnosis of lung cancer requires tissue histopathologz. In patients with radiographic evidence of advanced stage disease, diagnosis and staging are best accom- plished with a single invasive test at a location that will estab- lish both the diagnosis and the stage of disease. Because there are many techniques available for tissue diagnosis, the strategr will depend on the size and location of the tumor, patient characteristics, and local expertise. In general, mediastinal and central lesions are best approached with bronchoscopy and smaller peripheral lesions are best approached with a trans- thoracic needle aspiration. Definitive staging of lung cancer is essential, allows for accurate prognostication, and serves as a guide for treatment decision making. NSCLC is staged on the basis of the TNM staging system, taking into account the characteristics of the primary tumor (T), regional lymph node involvement (N), and metastatic disease (M). SCLC is generally staged as either "limited" or'extensive" disease. Limited disease is defined as disease limited to one hemithorax and ipsilateral supraclavicular lymph nodes. ; I G U R E 2 3 . Endobronchial carcinoid can be seen on bronchoscopy as a smooth, The presence of disease outside these locations defines exten polypoid, vascular-appearing mass that completely occludes a subsegmental airway sive stage disease. of the right lower lobe. 49

Lung Tumors The lung is a frequent site for metastatic disease from primary malignancies, which include head and neck. colon, kidney, breast, thyroid, and melanoma. Metastatic disease can present as solitary or multiple nodules: lymphangitic spread; and endobronchial. pleural, or embolic lesions. Surgical resec- tion may be appropriate when a solitary pulmonary metastasis is identified without evidence of other metastatic disease. rlY P0tltr o Surgical resection of carcinoid tumors is often curative, and lO-year survival rates are higher than 90%.

The lung is a frequent site for metastatic disease from primary malignancies, which include head and neck. colon, kidney, breast, thyroid, and melanoma. Metastatic disease can present as solitary or multiple nodules: lymphangitic spread; and endobronchial. pleural, or embolic lesions. Surgical resec- tion may be appropriate when a solitary pulmonary metastasis is identified without evidence of other metastatic disease. rlY P0tltr o Surgical resection of carcinoid tumors is often curative, and lO-year survival rates are higher than 90%. Mesothelioma Malignant pleural mesothelioma is a rare neoplasm that origi nates from the cells that line the pleural cavity (mesothelium). It can present as small nodules, plaque like masses. or conflu ent sheets that can encase the lung. It is associated with inha- lational exposure to asbestos fibers and has a latency of 20 to 40 years. In addition to malignant pleural mesothelioma and lung cancer, asbestos exposure has been linked to a spectrum of nonmalignant pleuropulmonary diseases (Table 36). Because FIGURE 24. Alateral chest radiograph demonstratesthe anterior(red), middle of environmental control of asbestos. the rate of mesothelioma (yellow), and posterior (b/ue) mediastinal compartments. in the United States has been declining since 2000. Patients with malignant pleural mesothelioma usually ItY POIilIS (cofinued) present with advanced disease. Symptoms include chest r Clinical suspicion for malignant pleural mesothelioma pain, dyspnea, cough, hoarseness, night sweats, or dysphagia. should arise in the setting ofpleural thickening or exu Clinical suspicion for malignant pleural mesothelioma should dative pleural effusion and a history ofasbestos exposure arise in the setting ofpleural thickening or recurrent exudative pleural effusion and a history ofasbestos exposure. The sensi- tivity of pleural fluid cytologr is less than 5'7, and the diagnosis requires a pleural biopsy. Medical or surgical thoracoscopy has Mediastinal Masses a greater than 90'7, sensitivity fbr malignancy. Treatment The mediastinum is anatomically near the center of the options depend on the extent of disease and patient factors thoracic cavity and is bound by the sternum anteriorly, the and preferences and may include surgery radiation therapy, lungs and pleura laterally and the vertebral column poste and systemic chemotherapy. The overall prognosis of malig riorly. Tumors in the mediastinum can be either benign or nant pleural mesothelioma remains poor, with a median sur malignant, and symptoms vary depending on size (mass vival of 6 to 9 months. effect) and systemic effects of the tumor. Dividing the medi astinum into compartments can be useful in developing a TEY POITTI differential diagnosis when a mediastinal mass is discovered o Mesothelioma is associated with inhalational exposure (Figure 24). to asbestos fibers and has a latency of 20 to 40 years. (Continued) Anterior Mediastinum The anterior mediastinal compartment lies between the pos- terior sternum and the great vessels and heart. lt is the most TABLE 36, NonmalignantAsbestos-Related Pleural and common mediastinal location where malignant tumors Pulmonary Diseases occur. Masses in this location are usually remembered as the Disease Characteristics "terrible T's": thymoma, teratoma/germ cell tumor, "terrible" Asbestosis Slowly progressive diffuse pulmonary lymphoma, and thyroid. Thymic Iesions are the most com fibrosis caused by inhalation of asbestos fibers mon and are associated with various paraneoplastic syn dromes such as pure red cell aplasia and myasthenia gravis. Benign asbestos Small unilateral pleural effusion; may pleural effusion be associated with concomitant pleural Myasthenia gravis is an autoimmune disorder of the neuro- plaq ues muscular junction that commonly presents with muscular Pleural plaques Benign circumscribed areas of calcified weakness, fatigability, ptosis, diplopia, and bulbar symp- pleural thickening with linear or nodular toms. Diagnosis can be confirmed with an acetylcholine appearance receptor antibody test.

Mesothelioma Malignant pleural mesothelioma is a rare neoplasm that origi nates from the cells that line the pleural cavity (mesothelium). It can present as small nodules, plaque like masses. or conflu ent sheets that can encase the lung. It is associated with inha- lational exposure to asbestos fibers and has a latency of 20 to 40 years. In addition to malignant pleural mesothelioma and lung cancer, asbestos exposure has been linked to a spectrum of nonmalignant pleuropulmonary diseases (Table 36). Because FIGURE 24. Alateral chest radiograph demonstratesthe anterior(red), middle of environmental control of asbestos. the rate of mesothelioma (yellow), and posterior (b/ue) mediastinal compartments. in the United States has been declining since 2000. Patients with malignant pleural mesothelioma usually ItY POIilIS (cofinued) present with advanced disease. Symptoms include chest r Clinical suspicion for malignant pleural mesothelioma pain, dyspnea, cough, hoarseness, night sweats, or dysphagia. should arise in the setting ofpleural thickening or exu Clinical suspicion for malignant pleural mesothelioma should dative pleural effusion and a history ofasbestos exposure arise in the setting ofpleural thickening or recurrent exudative pleural effusion and a history ofasbestos exposure. The sensi- tivity of pleural fluid cytologr is less than 5'7, and the diagnosis requires a pleural biopsy. Medical or surgical thoracoscopy has Mediastinal Masses a greater than 90'7, sensitivity fbr malignancy. Treatment The mediastinum is anatomically near the center of the options depend on the extent of disease and patient factors thoracic cavity and is bound by the sternum anteriorly, the and preferences and may include surgery radiation therapy, lungs and pleura laterally and the vertebral column poste and systemic chemotherapy. The overall prognosis of malig riorly. Tumors in the mediastinum can be either benign or nant pleural mesothelioma remains poor, with a median sur malignant, and symptoms vary depending on size (mass vival of 6 to 9 months. effect) and systemic effects of the tumor. Dividing the medi astinum into compartments can be useful in developing a TEY POITTI differential diagnosis when a mediastinal mass is discovered o Mesothelioma is associated with inhalational exposure (Figure 24). to asbestos fibers and has a latency of 20 to 40 years. (Continued) Anterior Mediastinum The anterior mediastinal compartment lies between the pos- terior sternum and the great vessels and heart. lt is the most TABLE 36, NonmalignantAsbestos-Related Pleural and common mediastinal location where malignant tumors Pulmonary Diseases occur. Masses in this location are usually remembered as the Disease Characteristics "terrible T's": thymoma, teratoma/germ cell tumor, "terrible" Asbestosis Slowly progressive diffuse pulmonary lymphoma, and thyroid. Thymic Iesions are the most com fibrosis caused by inhalation of asbestos fibers mon and are associated with various paraneoplastic syn dromes such as pure red cell aplasia and myasthenia gravis. Benign asbestos Small unilateral pleural effusion; may pleural effusion be associated with concomitant pleural Myasthenia gravis is an autoimmune disorder of the neuro- plaq ues muscular junction that commonly presents with muscular Pleural plaques Benign circumscribed areas of calcified weakness, fatigability, ptosis, diplopia, and bulbar symp- pleural thickening with linear or nodular toms. Diagnosis can be confirmed with an acetylcholine appearance receptor antibody test. 50

Sleep Medicine Middle Mediastinum TABTE 37. Extrinsic and lntrinsic Causes of Excessive Masses in the middle mediastinum are common and are Daytime Sleepiness attributed to lymphadenopathy, cysts, esophageal disorders, or Extrinsic Causes vascular lesions (aneurysm). Lymphadenopathy is most com lnsufficient sleep duration (or inadequate opportunity for sleep) mon and can be secondary to lymphoma, sarcoid, or meta- Circadian rhythm disturbance (shift work sleep disorder, jet lag) static disease. Drug-, su bstance-, psychiatric-, or medical condition-related hypersomnia Posterior Mediastinum Environmental sleep disorder (ambient noise, pets) Masses in the posterior mediastinum include neurogenic tumors, meningoceles, and spine lesions. Neurogenic neo lntrinsic Causes plasms are most common and are classified on the basis of Sleep-disordered breathing syndromes, such as obstructive sleep apnea and central sleep apnea their neural origin. Narcolepsy t(EY POll{IS ldiopathic hypersomnia . Thymic lesions are the most common tumor in the Restless leg syndrome and periodic limb movement disorder anterior mediastinum and are associated with various Circadian rhythm sleep disorders (misalignment of the intrinsic paraneoplastic syndromes such as pure red cell aplasia circadian timing with the desired sleep schedule; for example, and myasthenia gravis. dementia and blindness) . Lymphadenopathy is the most common mass in the middle mediastinum and can be secondary to ly,rnphoma, sarcoid. or metastatic disease. associated with cardiovascular disease and metabolic disor ders such as glucose intolerance and obesity. o Neurogenic neoplasms are the most common tumors in The initial evaluation of excessive daytime sleepiness the posterior mediastinum and are classified on the basis should include a thorough history to assess the time available of their neural origin. fbr and time spent sleeping before pursuing additional testing. Patients should be questioned about sleep hygiene, the eflf'ect of sleepiness on activities, sleep times and duration, sleep Sleep Medicine environment, napping, caffeine use, and duration of symp toms. In addition, physicians should probe for symptoms of Sleep disorders have six classifications: insomnia, sleep- specific sleep disorders (snoring, apneas, leg discomfort. and related breathing disorders, central disorders of hypersomno sleep attacks). A 1 or 2 week diary of the sleep-wake schedule lence, circadian rhythm sleep wake disorders, parasomnias, is a simple tool that promotes self realization of suboptimal and sleep related movement disorders (including restless leg sleep habits. A more objective assessment of sleep and wake syndrome). For a discussion of insomnia, see MKSAP 19 fulness can be obtained with a wrist actigraph-a device that General Internal Medicine 1. measures movement and ambient light during a period of I or 2 weeks. Wrist worn consumer fitness products using similar technologz may provide useful feedback. Questionnaires such i Excessive Daytime Sleepiness as the Epworth Sleepiness Scale can quanti$r sleepiness and Excessive dal.time sleepiness refers to difficul[z staying awake help gauge the response to treatment. and alert during daytime hours. [-ack of self-recognition is Objective sleep testing, either in lab or at home multi common and poses a safety hazard if sleepiness occurs while channel recordings, is often indicated when a primary sleep driving or operating machinery. Sleepiness, a cardinal symp disorder is suggested by the history and physical examina tom olmany sleep disorders, is different from fatigue, which is tion. In certain cases, a multiple sleep latency test a sleep a lack ofenergr or sense ofexhaustion that prevents mental or laboratory based study that measures the time to sleep dur physical activi$/ at the desired intensity or pace. Fatigue is ing a series of daytime nap opportunities after a normal night untikely to be solely attributable to a sleep disorder and is of sleep provides an objective measure of sleepiness and is more likely to occur in other medical conditions. key to establishing the diagnoses of narcolepsy and idio Causes ofexcessive daytime sleepiness can be categorized pathic hypersomnia. as extrinsic (circumstantial) or intrinsic (disease-related) pro All patients with excessive daytime sleepiness should be cesses (Table 37). counseled about the dangers of drowsy driving and the need Sleepiness can occur acutely r,r'hen a person is deprived of to maintain a routine sleep wake schedule that allows for 7 to the 7 to 8 hours of sleep most adults require. Functional 8 hours of sleep per night. Specific treatment depends on the impairment resulting from an inadequate amount of sleep is underlying condition. Short term management of the occa termed insufficient sleep syndrome. It likely is the most com sional bout of acute sleepiness may include strategically timed mon cause of excessive daytime sleepiness and has been naps or caffeine.

Middle Mediastinum TABTE 37. Extrinsic and lntrinsic Causes of Excessive Masses in the middle mediastinum are common and are Daytime Sleepiness attributed to lymphadenopathy, cysts, esophageal disorders, or Extrinsic Causes vascular lesions (aneurysm). Lymphadenopathy is most com lnsufficient sleep duration (or inadequate opportunity for sleep) mon and can be secondary to lymphoma, sarcoid, or meta- Circadian rhythm disturbance (shift work sleep disorder, jet lag) static disease. Drug-, su bstance-, psychiatric-, or medical condition-related hypersomnia Posterior Mediastinum Environmental sleep disorder (ambient noise, pets) Masses in the posterior mediastinum include neurogenic tumors, meningoceles, and spine lesions. Neurogenic neo lntrinsic Causes plasms are most common and are classified on the basis of Sleep-disordered breathing syndromes, such as obstructive sleep apnea and central sleep apnea their neural origin. Narcolepsy t(EY POll{IS ldiopathic hypersomnia . Thymic lesions are the most common tumor in the Restless leg syndrome and periodic limb movement disorder anterior mediastinum and are associated with various Circadian rhythm sleep disorders (misalignment of the intrinsic paraneoplastic syndromes such as pure red cell aplasia circadian timing with the desired sleep schedule; for example, and myasthenia gravis. dementia and blindness) . Lymphadenopathy is the most common mass in the middle mediastinum and can be secondary to ly,rnphoma, sarcoid. or metastatic disease. associated with cardiovascular disease and metabolic disor ders such as glucose intolerance and obesity. o Neurogenic neoplasms are the most common tumors in The initial evaluation of excessive daytime sleepiness the posterior mediastinum and are classified on the basis should include a thorough history to assess the time available of their neural origin. fbr and time spent sleeping before pursuing additional testing. Patients should be questioned about sleep hygiene, the eflf'ect of sleepiness on activities, sleep times and duration, sleep Sleep Medicine environment, napping, caffeine use, and duration of symp toms. In addition, physicians should probe for symptoms of Sleep disorders have six classifications: insomnia, sleep- specific sleep disorders (snoring, apneas, leg discomfort. and related breathing disorders, central disorders of hypersomno sleep attacks). A 1 or 2 week diary of the sleep-wake schedule lence, circadian rhythm sleep wake disorders, parasomnias, is a simple tool that promotes self realization of suboptimal and sleep related movement disorders (including restless leg sleep habits. A more objective assessment of sleep and wake syndrome). For a discussion of insomnia, see MKSAP 19 fulness can be obtained with a wrist actigraph-a device that General Internal Medicine 1. measures movement and ambient light during a period of I or 2 weeks. Wrist worn consumer fitness products using similar technologz may provide useful feedback. Questionnaires such i Excessive Daytime Sleepiness as the Epworth Sleepiness Scale can quanti$r sleepiness and Excessive dal.time sleepiness refers to difficul[z staying awake help gauge the response to treatment. and alert during daytime hours. [-ack of self-recognition is Objective sleep testing, either in lab or at home multi common and poses a safety hazard if sleepiness occurs while channel recordings, is often indicated when a primary sleep driving or operating machinery. Sleepiness, a cardinal symp disorder is suggested by the history and physical examina tom olmany sleep disorders, is different from fatigue, which is tion. In certain cases, a multiple sleep latency test a sleep a lack ofenergr or sense ofexhaustion that prevents mental or laboratory based study that measures the time to sleep dur physical activi$/ at the desired intensity or pace. Fatigue is ing a series of daytime nap opportunities after a normal night untikely to be solely attributable to a sleep disorder and is of sleep provides an objective measure of sleepiness and is more likely to occur in other medical conditions. key to establishing the diagnoses of narcolepsy and idio Causes ofexcessive daytime sleepiness can be categorized pathic hypersomnia. as extrinsic (circumstantial) or intrinsic (disease-related) pro All patients with excessive daytime sleepiness should be cesses (Table 37). counseled about the dangers of drowsy driving and the need Sleepiness can occur acutely r,r'hen a person is deprived of to maintain a routine sleep wake schedule that allows for 7 to the 7 to 8 hours of sleep most adults require. Functional 8 hours of sleep per night. Specific treatment depends on the impairment resulting from an inadequate amount of sleep is underlying condition. Short term management of the occa termed insufficient sleep syndrome. It likely is the most com sional bout of acute sleepiness may include strategically timed mon cause of excessive daytime sleepiness and has been naps or caffeine. 51