Vol 3 The Netter Collection of Medical 1 - Epidemiologia (2025)

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158 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONSPlate 4-48 Respiratory SystemLUNG CANCER OVERVIEWLung cancer is the most common cause of cancer death in the world, with estimated total deaths of 1.18 million by GLOBOCAN of the International Agency for Research on Cancer (IARC). In the United States, there will be an estimated 222,000 new diagnoses and 157,000 deaths in 2010. Lung cancer is a lethal disease, with only 6% of all new cases surviving 5 years in the United States. The average 5-year survival rate in Europe is 10% and is 8.9% in developing countries. Lung cancer causes more deaths than the four next most common cancers combined (colorectal, breast, prostate, and pan-creas). These numbers are staggering, especially because it was a rare disease in the early 1900s.Cigarette smoking has been identifi ed as the single most common etiologic agent and is estimated to cause 85% to 90% of all cases. Radon is reported to cause 10% of lung cancers. Other etiologic agents are of less frequency and are primarily occupational exposures (e.g., arsenic, asbestos, chromium, nickel, coal, tar). For a complete list of carcinogens to humans, refer to the IARC (http://monographs.iarc.fr). Secondhand smoke increases the risk of lung cancer by 30% or a relative risk of 1.3 versus a never smoker with no secondhand exposure. Lung cancer risk increases with age. Less than 5% of lung cancer occurs before the age of 40 years, and the average age at diagnosis in the United States is 68 years. Family history (genetics) is a risk factor and responsible for a two- to threefold relative risk increase if lung cancer has been diagnosed in a fi rst-degree relative, especially if he or she was at a younger age at diagnosis. The genetic predisposition of lung cancer is a subject of intense research, but to date, a lung cancer gene has not been identifi ed. The gene 15q 24-25 encompasses the nicotinic acetylcholine receptor gene that has a role in nicotine addiction and has been associated with lung cancer risk, but it is cur-rently uncertain if this gene is directly related to lung cancer, independent of nicotine use.Overwhelming evidence suggests that cigarette smoking is the major cause of lung cancer. The lung cancer epidemic in Western countries parallels the inci-dence of smoking but lags by about 20 to 30 years. The relative risk among smokers compared with people who have never smoked is 10 to 15 times higher and is dependent on the age of onset of smoking, dose, and duration (pack-years). Stopping smoking has been shown to decrease the relative risk, but the risk does not return to that of someone who has never smoked unless one quits at an early age. Tobacco smoking increases the risk of all major histologic cell types, but the strong-est association is with small cell and squamous cell and less strongly with adenocarcinoma. The most common histology in a never smoker is adenocarcinoma.The frequency of lung cancer in women has risen dramatically in most Western countries over the past 4 to 5 decades. Globally, it is still a male-predominant disease (male : female ratio, 2-3 : 1). However, in the United States, women constitute 45% of all new lung cancer diagnoses. Lung cancer has surpassed breast cancer as the most common cause of cancer death, which occurred in the United States in the mid 1980s. Currently, 72,000 women die of lung cancer versus 40,000 deaths from breast cancer per year. Although there has been some controversy, recent studies have not shown a difference in risk between men and women who have smoked a similar amount. There is no clear evidence of ethnic differences in susceptibility to this disease.The signs and symptoms of lung cancer are myriad, but the most common are new cough, dyspnea, hemo-ptysis, chest pain, or weight loss. Paraneoplastic symp-toms of lung cancer are discussed later. Symptomatic lung cancer usually results in an abnormal chest radio-graph. Approximately 15% to 20% of lung cancers are asymptomatic when they are detected by an incidental chest radiograph or computed tomography scan done for other reasons. Methods of diagnosis include sputum cytology, thoracentesis if pleural fl uid is present, bron-choscopy, transthoracic needle aspiration, or needle aspiration and biopsy of distant metastatic sites. In some cases, the diagnosis is made at the time of surgical resection.The World Health Organization histologic classifi -cation of lung tumors is the generally accepted stand-ard. Lung cancer is classifi ed as small cell and non–small cell. Non–small cell lung cancer includes squamous cell, adenocarcinoma, large cell, adenosquamous carcinoma, and sarcomatoid carcinoma. Small cell histology gener-ally has the fastest growth rate, but tumor doubling times can vary tremendously within the same cell type. The slowest growing types have been bronchioloalveo-lar carcinoma (subtype of adenocarcinoma) and super-fi cial squamous carcinoma (in situ), but again, the variability in growth rate can be enormous.BreastLung and bronchusPer capita cigaretteconsumptionMale lung cancerdeath rateFemale lung cancerdeath rateStomachUterusPancreasOvary StomachLung and bronchusColon and rectumColon and rectumProstatePancreasLiverLeukemiaSquamous cell Small cell Adenocarcinoma19301008040200*Age-adjusted to 2000 US standard population.Source: US Mortality Data 1960–2004,US Mortality Volumes 1930–1959, National Centerfor Health Statistics, Centers for Disease Controland Prevention, 2006.60Rate per 100,000Cancer death rates* among men, US, 1930–20041935194019451950195519601965197019751980198519901995200019301008040200*Age-adjusted to 2000 US standard population.Source: US Mortality Data 1960–2004,US Mortality Volumes 1930–1959, National Centerfor Health Statistics, Centers for Disease Controland Prevention, 2006.*Age-adjusted to 2000 US standard population.Source: Death rates: US Mortality Data,1960–2004, US Mortality Volumes, 1930–1959,National Center for Health Statistics, Centers forDisease Control and Prevention, 2006. Cigaretteconsumption: US Department of Agriculture,1900–2004.60Rate per 100,000Cancer death rates* among women, US, 1930–20041935194019451950195519601965197019751980198519901995200019005000400045002000250010001500500030003500Per capita cigarette consumptionAge-adjusted lung cancer death rates*Tobacco use in the US, 1900–2004190519101915192019251930193519401945195019551960196519701980197519851990199520000102030405060708090100Large cellCLASSIFICATION OF BRONCHOGENIC CARCINOMA THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 159Plate 4-49 Diseases and PathologyLUNG CANCER STAGINGIn 2010, the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC) published the revised seventh edition of the TNM (tumor, node, metastasis) staging system. This seventh edition was developed on the basis of the Inter-national Association for the Study of Lung Cancer (IASLC) and proposed changes to the classifi cation from analysis of more than 67,000 cases of non–small cell lung cancer from around the world. This was the largest data set ever analyzed for the purpose of devel-oping and validating a new staging system. The pro-posed new TNM staging system has also been validated for small cell carcinoma and bronchial carcinoid tumors. The primary determinant of each T, N, and M descrip-tor, as well as the overall stage grouping, was based on survival. Detailed algorithms were used to identify unique stages in the simplest way with the least overlap. Stages were internallyand externally validated for out-comes across the various databases and geographic regions from which the data were gathered.There were a number of substantial changes made to the former (sixth) staging system:• T1 tumors were divided into T1a (tumors ≤2 cm in greatest diameter) and T1b (tumors >2 cm but ≤3 cm in greatest dimension).• T2 tumors were divided into T2a (tumors >3 cm but ≤5 cm in greatest diameter) and T2b (tumors >5 cm but ≤7 cm in greatest dimension).• Tumors more than 7 cm in greatest dimension are classifi ed as T3.• Tumors with additional nodule(s) in the same lobe are classifi ed as T3.• Tumors with additional nodule(s) in another ipsi-lateral lobe are classifi ed as T4.• Pleural dissemination (malignant pleural or peri-cardial effusions, pleural nodules) is classifi ed as M1a.• The lymph node classifi cation remained the same, with N1 as intrapulmonary or ipsilateral hilar, N2 as ipsilateral mediastinal or subcarinal, and N3 as contralateral mediastinal or supraclavicular.• Incorporated proposed changes to T and M (affects T2, T3, T4, and M1 categories).• Reclassify T2aN1 tumors (≤5 cm) as stage IIA (from IIB).• Reclassify T2bN0 tumors (>5 cm to 7 cm) as stage IIA (from IB).• Reclassify T3 (tumor >7 cm) N0M0 as stage IIB (from IB).• Reclassify T4N0 and T4N1 as stage IIIA (from IIIB).• Reclassify pleural dissemination (malignant pleural or pericardial effusions, pleural nodules) from T4 to M1a.• Subclassify M1 by additional nodules in contra-lateral lung as M1a.• Subclassify M1 by distant metastases (outside the lung/pleura) as M1b.Because of the addition of new T and M descriptors, the staging defi nitions have clearly become more complex. However, the new system now provides a more validated system for defi ning prognosis. In addi-tion, the system also allows common terminology to be used across the world to describe similar patients, which is critical for accurate communication across the medical community and the conduct of worldwide clinical trials. A future goal is the further refi nement of the classifi cation system to include the biologic behavior of lung tumors, not just anatomic location, which should promote understanding of tumor biology and provide guidance toward more specifi c therapies.Brachiocephalic (innominate) arterySuperior mediastinal nodesInferior mediastinal nodesN1 nodesBrachiocephalic(innominate) veinAortic archTracheaLigamentum arteriosumMediastinal pleural envelopeMediastinal pleural envelopeCarinaEsophagusPulmonary ligamentMain bronchusLobar bronchiRight pulmonary arteryRight primary bronchusLeft pulmonary arterySegmental bronchiLeft primary bronchusBrachiocephalic(innominate) arteryAortic archLigamentum arteriosumMediastinal pleural envelopeRight pulmonary arteryAnatomy of lymph node stations relevant to lung cancer staging. The IASLC proposes grouping the lymphnodes into the zones shown in bold and circled to assist with prognosis.Aortic nodesLeft pulmonary arteryBrachiocephalic(innominate) vein160 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONSPlate 4-50 Respiratory SystemSQUAMOUS CELL CARCINOMA OF THE LUNGSquamous cell carcinoma (SCC) is defi ned as a malig-nant epithelial tumor showing keratinization or intra-cellular bridges (or both) arising from bronchial epithelium. Previously, SCC, sometimes called epider-moid carcinoma, was the most common cell type, but that has changed in the past 1 or 2 decades in the United States, parts of Western Europe, and Japan. Currently, SCCs account for 20% of all lung cancers in the United States (http://seer.cancer.gov). The vast majority of SCC occurs in smokers. Recent Surveil-lance, Epidemiology and End Results (SEER) data report that SCC accounts for 24% of all cancers in men versus 16% in women. The recent decrease in SCC and increase in adenocarcinoma histology has been attributed to the change in the cigarette, from nonfi lter to fi lter, and the decrease in tar. About 60% to 80% of these cancers arise centrally in mainstem, lobar, or seg-mental bronchi, but they may present as a peripheral lung lesion.SCC arises from the bronchial epithelium, and it is thought that the airway abnormality progresses through a series of changes from hyperplasia to dysplasia to carcinoma in situ, which is classifi ed by World Health Organization as preinvasive and a precursor to SCC. Varying degrees of dysplasia have been associated with cumulative genetic alterations, but the critical genetic change(s) before developing frank cancer is still uncertain.Because of the tendency to occur centrally in the airway, SCC presents more commonly with hemopty-sis, new or change in cough, chest pain, or pneumonia caused by bronchial obstruction. The usual radio-graphic presentation is a central mass or obstructing pneumonia with or without lobar collapse. About 10% to 20% of SCCs present as peripheral lesions. Cavita-tion may occur in 10% to 15% of all SCCs and is the most common histology associated with cavitation. The cavities are usually thick walled. Cavitation in the lung may also be caused by obstructive pneumonia and abscess formation.Sputum cytology has the highest diagnostic yield with this cell type because of the predominant central location. Bronchoscopy with brushings and biopsy are diagnostic in more than 90% of SCCs when the cancer is visible endoscopically. The yield for peripheral lesions that are endoscopically negative is signifi cantly less and depends on the size of the tumor. For lesions smaller than 2 cm in diameter, transthoracic needle aspiration has the highest diagnostic yield if a tissue diagnosis is required before surgical resection.SCC in situ (pre invasive lesion) has an unpredictable course, and the treatment is a topic of current debate. Surgery is the treatment of choice for early-stage disease (stage I or II). Combination chemotherapy and radiotherapy are recommended for good performance score patients with unresectable stage III A or B disease. Stage IV (metastatic disease) is generally treated with systemic chemotherapy, but treatment is noncurative (palliative).It was previously believed that SCC was more slow-growing than other cell types, but recent analysis of a large international database that controlled for stage of disease does not demonstrate defi nite survival benefi t of SCC versus other non–small cell histolo-gies. In the past, SCCs have been treated the same as all other non–small cell histologies, but recent data show that optimal treatment depends on specifi c typing.Tumortypicallylocatednear hilus,projectinginto bronchiBronchoscopic viewCarcinoma in peripheral zone ofright upper lobe with cavitationBronchoscopic viewCombined CT/PET image showing a squamouscell carcinoma (bright area) of the left lung.Tumor typically located nearhilum, projecting into bronchi THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 161Plate 4-51 Diseases and PathologyADENOCARCINOMA OF THE LUNGAtypical adenomatous hyperplasia is classifi ed by the World Health Organization (WHO) as a putative pre-cursor of adenocarcinoma (ACA), especially bron-chioloalveolar carcinoma (BAC). ACA is defi ned as a malignant epithelial tumor with glandular differentia-tion or mucin production. ACA is the most common cell type in the United States and many developed countries. It accounts for 37% of all lung cancers in the Surveillance, Epidemiology and End Results (SEER) database (40% in women; 33% in men; http://seer.cancer.gov). ACA histology is associated with cigarette smoking, but the association is not as strong as it is for squamous cell and small cell carcinoma. ACA is the most common histology of lung cancer in never smokers, especially women.Bronchioloalveolar cell, also called alveolar cell, is classifi ed by the WHO as a subtype of ACA. BACs are mostlymoderate or well-differentiated tumors and grow along preexisting alveolar structures (lepidic growth) without evidence of invasion. If there is evi-dence of invasion, then the tumor is classifi ed as ACA mixed type. Pure BAC by the current classifi cation is a rare tumor; most are ACA mixed type. It is anticipated that pure BAC will be renamed as adenocarcinoma in situ in the new classifi cation.ACAs are usually peripherally located in the lungs. Because of the peripheral location, more of the patients are asymptomatic, and the lesion is detected on an inci-dental chest radiograph. Patients may present with a new cough, chest pain, or less commonly hemoptysis. Presenting symptoms caused by distant metastases to the bone, brain, or liver are common with all cell types, especially ACA and large cell carcinoma. Individuals with BAC may present with an asymptomatic solitary pulmonary nodule, pneumonia such as consolidation of the lung, or rarely with a profound bronchorrhea. Bronchorrhea is usually seen in those with extensive bilateral lung involvement.The most common radiographic presentation is a peripheral lung nodule or mass (mass defi ned as ≥3 cm) in maximum diameter. It may infrequently present as a central mass and rarely cavitates. ACA is the most common cell type to present with a malignant pleural effusion.Sputum cytology results are rarely positive. Diagnos-tic yields with bronchoscopy are less than with squa-mous cell or small cell carcinoma because of the peripheral location. For lesions that are 2 cm in diam-eter or larger, the diagnostic yields are approximately 60% to 70%. Transthoracic needle aspirations (TTNAs) are diagnostic in 85% to 90% of all lesions and are the preferred diagnostic test for lesions smaller than 2 cm in diameter. The benefi ts of TTNA should be balanced against the risk of pneumothorax, especially in patients with chronic obstructive pulmonary disease or emphy-sema. Thoracentesis and pleural fl uid cytology is the preferred diagnostic test in individuals with pleural effusion.The treatment of choice for patients with stage I, II, or IIIA/B is generally the same as for all non–small cell lung cancers. Patients with stage IV (metastatic) disease have generally been treated with systemic chemother-apy as palliative treatment. In recent years, a number of genetic alterations have been identifi ed in the tumor that are changing the treatment approach. Some ACAs have been identifi ed to have a mutation in the intracel-lular domain of the epidermal growth factor receptor (EGFR) gene. The predominant mutations include in frame deletions of exon 19 and missense mutation in exon 21. These mutations have been associated with a high response rate to treatment with the EGFR tyro-sine kinase inhibitors (TKIs) gefi tinib and erlotinib. For reasons that are currently unknown, the frequency of the EGFR tyrosine kinase mutations vary in different ethnic populations. The frequency of mutation in North America and Europe is approximately 15% of all ACA versus 30% of ACA in East Asians. These mutations are almost exclusively limited to the ACA cell type.Recent reports have documented better survival in individuals when these EGFR mutations are treated initially with EGFR TKIs versus conventional chemo-therapy. Other studies have shown that KRAS muta-tions, which occur in 20% to 30% of patients with ACA, confer resistance to treatment with the EGFR inhibitors. Mutations in KRAS and EGFR are almost always mutually exclusive. It is very likely that future identifi cation of genetic mutations or identifi cation of predominant intracellular pathways of malignant cells will infl uence the choice of treatment of ACA and other histologies. Most recently a mutation of anaplastic lym-phoma kinase (ALK) has been identifi ed in 3% to 5% of ACA, and promising new treatment with the tyrosine kinase inhibitor crizotinib has been reported.Small, peripherally placed tumorHistology of adenocarcinoma. Tumor cells form glandlike structureswith or without mucin secretionPeripheral adenocarcinoma with mediastinalnodal metastases seen on combined CT andPET imaging (bright areas)Different histologic types of bronchogenic carcinoma cannot be distin-guished by gross specimens or radiography alone. However, a peri-pherally located tumor 4 cm in diameter is most likely to beadenocarcinoma162 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONSPlate 4-52 Respiratory SystemLARGE CELL CARCINOMAS OF THE LUNGLarge cell carcinoma is a malignant epithelial undif-ferentiated neoplasm lacking glandular or squamous differentiation and features of small cell carcinoma. It is a diagnosis of exclusion and includes many poorly differentiated non–small cell carcinomas. Several variants are recognized, including neuroendocrine differentiation (large cell neuroendocrine carcinoma [LCNEC]) and basaloid carcinoma), but it is uncertain if this differentiation is of prognostic or therapeutic importance. Large cell carcinoma and its variants can only be diagnosed reliably on surgical material; cytol-ogy samples are not generally suffi cient. LCNEC is differentiated from atypical carcinoid tumor by having more mitotic fi gures, usually 11 or more per 2 mm2 of viable tumor, and large areas of necrosis are common. Neuroendocrine differentiation is confi rmed using immunohistochemical markers such as chromogranin, synaptophysin, or CD56. Patients with LCNEC have a worse prognosis than those with atypical carcinoid tumors. Large cell carcinoma is associated with ciga-rette smoking. This cell type accounted for 4% of all lung cancers in the Surveillance, Epidemiology and End Results (SEER) database. The SEER database listed the cell type of 24% of all lung cancers as “other non–small cell.” These other cancers include non–small cell cancers that pathologists specify as NOS (not otherwise specifi ed). As treatment moves toward spe-cifi c treatment for specifi c cell types, it will be impor-tant for pathologists to classify the histology as accurately as possible and to decrease the percentages of cases reported as NOS.The signs and symptoms of this cell type are similar to those of other non–small cell carcinomas. The most common radiographic fi nding is a large peripheral lung mass. Because of the peripheral location, these cancers may be asymptomatic and detected on an incidental chest radiograph. Because of the rapid growth of this cell type, the radiographic lesion may appear rather suddenly (within a few months) or enlarge rapidly.Diagnostic procedures are similar to those of other histologic types. Sputum cytology is not generally helpful because of the peripheral location, and bron-choscopic diagnostic yields are similar to those for peripheral adenocarcinomas and squamous cell carcino-mas (∼60%-70%). Transthoracic needle aspiration is diagnostic in the majority of cases. These cancers are usually aggressive tumors with a strong tendency for early metastases. Nevertheless, surgery is still the treat-ment of choice for patients with early-stage disease. Currently, there is no convincing evidence that patients with LCNEC should be treated differently than those with any other large cell carcinoma. Patients with stage III and IV disease are treated the same as those with other non–small cell types. Patients with stage III are treated with combined chemotherapy and thoracic radiotherapy. Survival is similar to that of patients with other non–small cell lung cancers, and patients with stage IV are treated with chemotherapy with palliative intent.Tumors are variable in locationTumor composed of large multinucleated cellwithout evidence of differentiation toward glandformation or squamous epithelium. These cellsproduce mucin (stained red). Some tumors may becomposed of large clear cells containing glycogenLarge cell carcinoma in middle of right upper lobe withextensiveinvolvement of hilar and carinalnodes. Distortion of tracheaand widening of carinaTHE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 163Plate 4-53 Diseases and PathologySMALL CELL CARCINOMAS OF THE LUNGSmall cell carcinoma is defi ned as a malignant epithelial tumor consisting of small cells with scant cytoplasm. If other histologic types of non–small cell carcinoma are also present, then it is classifi ed as combined small cell carcinoma. The cells contain neuroendocrine granules, and it is usually considered as a neuroendocrine tumor at the most malignant end of the neuroendocrine spec-trum. It usually stains positive for the neuroendocrine markers CD56, chromogranin, and synaptophysin. This cell type has the strongest association with ciga-rette smoking and rarely occurs in people who have never smoked. Small cell histology accounts for 14% of all lung cancers (13% in men; 15% in women) in the Surveillance, Epidemiology and End Results database (http://seer.cancer.gov). This cell type generally has the fastest growth rate and a tendency to early spread.Small cell carcinoma is centrally located in the large majority of cases and therefore present with symptoms of cough, hemoptysis, chest pain, or obstructive pneu-monia. Because of the tendency for early spread, many individuals present with signs and symptoms of regional or distant metastasis. Mediastinal lymph node spread may result in hoarseness or a change in voice caused by vocal cord paralysis, dysphagia caused by esophageal compression, or superior vena cava syndrome (dis-cussed later). Symptoms caused by brain, bone, or liver metastases may be the fi rst signs of the disease. Small cell carcinoma is the most common cell type associated with paraneoplastic syndromes (discussed later).Ten percent or fewer of small cell carcinomas present as a peripheral mass or solitary pulmonary nodule. Supraclavicular lymph node metastases may be present and are an easy source for tissue diagnosis. Sputum cytology is rarely positive. Bronchoscopy is the most common method of diagnosis. The tumor is frequently located submucosally, and bronchoscopic biopsies may not yield a diagnosis if deep submucosal samples are not obtained. Pleural fl uid cytology may be diagnostic; however, in many cases, the pleural fl uid is due to a parapneumonic effusion and not caused by malignant seeding of the pleural space.Small cell carcinoma is usually staged as limited or extensive stage disease. Limited disease is defi ned as disease confi ned to one hemithorax and mediastinal lymph nodes with or without ipsilateral supraclavicular nodes. It is generally disease that can be safely confi ned within a thoracic radiotherapy fi eld of treatment. Extensive stage is defi ned as spread of disease beyond the hemithorax with distant metastases. Malignant pleural effusion, cytologically documented, is consid-ered to be extensive stage.The treatment of limited stage disease is combined concurrent chemotherapy and thoracic radiotherapy in patients with a good performance score and minimal weight loss. Recent cooperative group trials of concurrent treatment have resulted in median survival times of 18 to 20 months and 5-year survival rates of 20% to 25%. For patients with extensive stage disease, the usual treatment is chemotherapy for four to six cycles with a platinum based doublet. The median sur-vival time is 8 to 10 months with 10% or less 2-year survival and virtually no 5-year survivors. Chemother-apy treatment for small cell carcinoma has plateaued with no major advances for the past 2 decades.Tumor withmetastasis to hilar andcarinal nodesand collapse ofright upper lobeIntrapulmonary lymphatic spread of neoplasmSmall cellcarcinoma seen by chest CTillustratingextensive hilarinvolvement andcollapse at leftupper lobeMasses of small cellswith hyperchromaticround to oval nucleiand scant cytoplasmBiopsy specimen.Cells elongated164 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONSPlate 4-54 Respiratory SystemSUPERIOR VENA CAVA SYNDROMESuperior vena cava (SVC) syndrome is caused by extrin-sic compression or internal thrombosis of the SVC, which compromises the venous drainage from the head and upper extremities. Lung cancer is responsible for the large majority of SVC syndrome in adults older than age 40 years. Lymphoma is the most common cause in younger individuals. Patients complain of a sensation of fullness in the head, cough, or dyspnea. They may experience lightheadedness, especially when bending over, or have edema and swelling in the head, neck, and arms. Edema of the larynx or pharynx may result in stridor, and cerebral edema may result in head-aches or confusion.Physical fi ndings include dilated neck veins and sub-cutaneous veins of the chest that persist with the patient in an upright position. Facial edema and a plethoric appearance may be present. Computed tomography chest scans with contrast injected through the arm veins show the mass with narrowing or obstruction of the SVC and the extensive venous collateral circulation of subcutaneous and mediastinal veins. If the SVC syn-drome is caused by a benign condition such as fi brosing mediastinitis, then a lung mass will not be identifi ed.Small cell carcinoma is the classic histology to cause SVC syndrome, but any histologic type may do so. Although SVC syndrome is a serious condition, it is not generally an emergency situation. Accordingly, a tissue diagnosis should be obtained before treatment begins. It is important to know if it is caused by lymphoma, small cell carcinoma, or non–small cell lung cancer before the appropriate treatment is instituted. SVC syndrome may occasionally be caused by other tumors (e.g., breast cancer, germ cell tumor), fi brosing medias-tinitis, or an infectious process (rarely). Bronchoscopy has a high diagnostic rate when SVC syndrome is caused by lung cancer. If bronchoscopy results are negative, then mediastinoscopy is the next logical pro-cedure in most cases.Treatment of patients with SVC syndrome should include stenting of the SVC early on in the process. This treatment quickly relieves the obstruction in more than 90% of cases. Chemotherapy alone as initial treat-ment is indicated for cases caused by small cell carci-noma or lymphoma, and radiotherapy or combined chemoradiotherapy is used for non–small cell lung cancer. Treatment should rarely be given without a tissue diagnosis. In patients with SVC syndrome caused by lung cancer, the long-term prognosis is related to the histologic type and stage of the disease at the time of initial diagnosis.Obstruction of superior venacava by cancerous invasion ofmediastinal lymph nodes withdistension of brachiocephalic(innominate), jugular, andsubclavian veins and tributariesEdema and rubor offace, neck, and upper chest. Arm veins fail to empty on elevationTHE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 165Plate 4-55 Diseases and PathologyPANCOAST TUMOR AND SYNDROMESuperior sulcus tumors are located at the apical pleuro-pulmonary groove adjacent to the subclavian vessels. Superior sulcus tumors received notoriety in reports by Henry Pancoast and are commonly referred to as Pan-coast tumors. Lung cancer is by far the most common cause of Pancoast and superior sulcus tumors. It is more commonly associated with adenocarcinoma but may be caused by any histologic type. A variety of other rare tumors or infectious diseases have occasionally been reported to cause a Pancoast tumor.Tumors of the superior sulcus may cause shoulder and arm pain (in the distribution of the C8, T1, and T2 dermatomes), Horner syndrome, and weakness of the muscles of the hand. This complex is referred to as Pancoast syndrome. Shoulder pain is the usual presenting symptom and is caused by tumor invasion of the tumor into the chest wall, fi rst and second ribs, vertebralbody, and possibly the brachial plexus. Pain may radiate up to the head and neck or to the axilla and arm in the dis-tribution of the ulnar nerve. The cause of the pain is frequently misdiagnosed for months as osteoarthritis or bursitis of the shoulder. Horner syndrome consists of ipsilateral ptosis, miosis, enophthalmos, and anhidrosis of half of the face and head and is caused by involve-ment of the paravertebral sympathetic chain and the inferior cervical (stellate) ganglion. Contralateral facial sweating and fl ushing have been reported.Tumor involvement of the C8 and T1 nerve roots may result in weakness and atrophy of the intrinsic muscles of the hand or pain or paresthesias of the fourth and fi fth digits and medial aspect of the arm and forearm. Abnormal sensation or pain in the axilla and medial aspect of the upper arm caused by T2 nerve root involvement may be an early symptom. As these tumors progress, they may invade the intervertebral foramina and cause spinal cord compression and paraplegia. This may especially be a problem for patients with progres-sive disease who have failed local treatment. Tumors with progressive mediastinal involvement may result in phrenic nerve or laryngeal nerve paralysis.The classic radiographic fi nding is that of an apical mass or unilateral apical cap. Occasionally, the abnormality will not be obvious on a chest radiograph; therefore if the diagnosis is suspected, a computed tomography (CT) scan of the chest is required. The CT will demonstrate greater detail and is more likely to elucidate the extent of the tumor locally. Magnetic resonance imaging (MRI) is better at demonstrating brachial plexus involvement and evaluating the spinal canal for tumor extension. MR angiography is better for demonstrating subclavian vessel involvement. Bron-choscopy may be diagnostic for larger tumors, but transthoracic needle aspiration is the most common method of diagnosis of these apical tumors. The usual staging tests include a positron emission computed tomography (PET) scan and MRI of the brain because of the propensity for brain metastases.The treatment of patients with superior sulcus tumors caused by non–small cell lung cancer with no evidence of mediastinal nodal metastases is initial con-current chemotherapy and radiotherapy followed by surgical resection 3 to 5 weeks after induction therapy. The 5-year survival with this trimodality treatment is approximately 40%. Patients with documented medias-tinal lymph node involvement at initial presentation are treated with defi nitive chemoradiotherapy alone with somewhat inferior long-term survival. Patients with stage IV or metastatic disease at presentation are treated with palliative radiotherapy and systemic chemotherapy similar to other patients with stage IV disease.Vagus nerveSympathetic trunkBrachial plexusRecurrent nerveTumorSubclavian artery and veinPancoast syndrome. Horner syndrome, pluspain, paresthesias, and paresis ofarm and handCombined CT/PET images of Pancoast tumor(bright area) seen in coronal and axial viewsAxial CoronalPancoast tumor166 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONSPlate 4-56 Respiratory SystemPARANEOPLASTIC MANIFESTATIONS OF LUNG CANCERParaneoplastic effects of tumors are remote effects that are not related to direct invasion, obstruction, or metas-tases. Paraneoplastic syndromes occur in 10% to 15% of all lung cancers. The following are some of the most common.The syndrome of inappropriate antidiuretic hormone secretion (SIADH) may be caused by pulmonary infec-tions, central nervous system (CNS) disease or trauma, drugs, or lung tumors. Small cell lung cancer is the most common malignancy to cause SIADH. The tumor secretes ectopic antidiuretic hormone (ADH; vaso-pressin), which exerts its action on the kidneys and enhances the fl ow of water from the lumen of the renal collecting ducts to the medullary interstitium with resulting concentration of the urine. Patients present with hyponatremia that is associated with low plasma osmolality and elevated urine sodium and osmolality. To make the diagnosis of SIADH, patients must also have normal renal, adrenal, and thyroid function. The symptoms of hyponatremia may include anorexia, nausea, vomiting, irritability, restlessness, confusion, coma, or seizures. The severity of symptoms is related to the degree of hyponatremia and the rapidity of the decrease in serum sodium. The treatment for mildly symptomatic patients is to restrict fl uid intake to 500 to 1000 mL/24 hours. For more severe or life-threatening symptoms, treatment consists of intravenous fl uids with normal saline and loop diuretics. For severe symptoms, some experts recommend 300 mL of 3% saline intra-venously, but extreme caution must be used because too rapid correction of serum sodium may be associated with central pontine myelinolysis, which is a devastat-ing CNS process that is often fatal. For patients with less severe symptoms from hyponatremia but requiring more than fl uid restriction, oral demeclocycline can be used. The onset of action may take from a few hours to a few weeks, and renal function should be monitored. The best treatment for SIADH, if the patient is stable, is to treat the small cell lung cancer with systemic chemotherapy. Regression of the tumor results in nor-malization of the sodium in most cases.Cushing syndrome may be related to ectopic produc-tion of corticotropin (adrenocorticotropic hormone) or corticotropin-releasing hormone by small cell carci-noma. It has also been reported with bronchial carci-noid tumors or carcinoid tumors of the thymus or pancreas. Small cell lung cancer accounts for 75% of all cases of Cushing syndrome caused by ectopic hormone secretion. Because of the rapid growth of small cell lung cancer, patients are more likely to present with edema, hypertension, and hyperglycemia with or without muscle weakness. This is in contrast to the classic fea-tures of Cushing syndrome that include truncal obesity, rounded (moon) facies, buffalo hump (dorsocervical fat pad), and diabetes mellitus. The best screen for Cushing syndrome caused by ectopic hormone secretion is the 24-hour urine free cortisol measurement. Marked ele-vation of cortisol production and plasma corticotropin levels are highly suggestive of ectopic corticotropin as the cause of Cushing syndrome.Treatment of patients with ectopic corticotropin production includes metyrapone, aminoglutethimide, mitotane, or ketoconazole given alone or in combina-tion. Ketoconazole is the most commonly used agent. If the patient is stable with no superimposed infection, then systemic chemotherapy is the best treatment for histologically confi rmed small cell lung cancer. If the Cushing syndrome is caused by carcinoid tumor, then surgical resection, if possible, is the treatment of choice.Hypercalcemia in relation to lung cancer may be caused by bone metastases, or less commonly, secretion of parathyroid hormone–related protein (PTHrP) or other cytokines. The most common cancers to cause paraneoplastic hypercalcemia are kidney, lung, breast, myeloma, and lymphoma. For lung cancers, squamous cell carcinoma is the most common cell type associated with hypercalcemia. Symptoms of hypercalcemia include anorexia, nausea, vomiting, constipation, leth-argy, polyuria, polydipsia, and dehydration. Confusion and coma are late manifestations. A shortened QT interval on electrocardiography, ventricular arrhyth-mia, heart block, and asystole may occur. Renal failure and nephrocalcinosis are also possible. Elevated PTHrP levels may be detected in the serum of about half of patients with hypercalcemia of malignancy that is not caused by bony metastasis. Patients with mild elevation of calcium do not require treatment. Treatment is determined by symptoms and includes intravenous fl uids to correct dehydrationcaused by polyuria and vomiting. Intravenous treatment with bisphosphonates inhibits osteoclast activity, and one dose achieves a normal calcium level in 4 to 10 days in most individuals. If rapid partial correction of hypercalcemia is needed, calcitonin will rapidly lower the calcium level by 1 to 2 mg/dL, but the effects are short lived. If the lung cancer is localized, then the treatment of choice, after the patient has been stabilized, is surgical resection. However, the usual situation is that the patient has metastatic disease. For these individuals with hypercal-cemia, the average life expectancy, even with treatment, is 1 month.Paraneoplastic neurologic syndromes (PNSs) are most commonly associated with small cell lung cancer ENDOCRINE MANIFESTATIONS OF LUNG CANCERCorticotropic effectsAntidiuretic hormone (ADH) effectsParathyroid hormone–like effectsSmall cell carcinomaof lungCorticotropic substance elaboratedCortical hormonesAtypical Cushing syndrome with edema hypertensionand hyperglycemiaHypokalemic alkalosisHypercalcemia Lethargy Polyuria Polydipsia Constipation Abdominal pain Coma if extremeSmall cell carcinoma of lungHigh urine osmolalityHyponatremiaIrritability Confusion Weakness Seizures if extremeParathyroidhormone–likesubstanceSquamous cell carcinomaADHAdrenal cortex hyperplasiaLow serum osmolalityTHE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 167Plate 4-57 Diseases and Pathologyand are quite variable. They include Lambert-Eaton myasthenic syndrome (LEMS), sensory neuropathy, encephalomyelopathy, cerebellar degeneration, auto-nomic neuropathy, retinal degeneration, and opso-clonus. Limbic encephalitis (dementia with or without seizures) has frequently been observed. The neurologic syndromes may precede the diagnosis of lung cancer by months to years.PNSs are thought to be immune mediated on the basis of identifying autoantibodies. The antineuronal nuclear antibody (ANNA-1), also known as anti-Hu antibody, has been associated with small cell carcinoma and various neurologic syndromes. ANNA-2 (anti-Ri antibody) and CRMP-5 antibody have also been associ-ated with various PNSs. These antibodies predict the patients’ neoplasm but not a specifi c neurologic syn-drome. The ANNA-1 binds to the nucleus of all neurons in the central and peripheral nervous system, including the sensory and autonomic ganglia and mye-nteric plexus.Proximal muscle weakness, hyporefl exia, and auto-nomic dysfunction characterize LEMS. Cranial nerve involvement may be present and does not differentiate LEMS from myasthenia gravis. There is a strong asso-ciation of LEMS with antibodies against P/Q type presynaptic voltage-gated calcium channels of the peripheral cholinergic nerve terminals. These antibod-ies have also been identifi ed in 25% of patients with small cell lung cancers with no neurologic syndrome. Myasthenia gravis, in contrast to LEMS, is associated with antiacetylcholine receptor antibodies. Malignancy is identifi ed in approximately 50% of patients with LEMS, and small cell lung cancer is by far the most common type. The diagnosis of LEMS is based on the characteristic electromyographic (EMG) fi nding that shows a small amplitude of the resting compound muscle action potential and facilitation with rapid, repetitive, and supramaximal nerve stimulation. A single-fi ber EMG is optimal for making the diagnosis. Careful radiographic evaluation of the lungs and mediastinum is indicated, especially in current or former smokers who have a suspected PNS. In many cases, the radio-graphic fi ndings are very subtle. If the patient has a positive paraneoplastic autoantibody blood test result and the computed tomography (CT) chest scan does not reveal an abnormality, then current guidelines rec-ommend that a positron emission computed tomogra-phy (PET) scan be performed to look for an occult malignancy. Strong consideration should be given to biopsy of even subtle abnormalities because without diagnosis and treatment the PNS will progress, fre-quently with devastating consequences.The best treatment for patients with PNS caused by small cell lung cancer is to treat with chemotherapy with or without thoracic radiotherapy, depending on the stage of disease. LEMS may improve with treat-ment, but not always. The other PNSs rarely improve with treatment, but the goal is to treat the lung cancer as soon as possible to try to prevent progressive neuro-logic disease.Skeletal muscular paraneoplastic syndromes include digital clubbing, hypertrophic pulmonary osteoar-thropathy (HPO), and dermatomyositis or polymyosi-tis. Clubbing may involve the fi ngers and toes and consist of selective enlargement of the connective tissue in the terminal phalanges with loss of the angle between the base of the nail bed and cuticle, rounded nails, and enlarged fi ngertips. There are nonmalignant causes of clubbing such as pulmonary fi brosis or congenital heart disease. HPO is uncommon in association with lung cancer and is characterized by painful joints that usually involve the ankles, knees, wrists, and elbows and is most often symmetric. Some patients may complain of pain or tenderness along the shins. The pain and arthropa-thy is caused by a proliferative periostitis that involves the long bones but may involve metacarpal, metatarsal, and phalangeal bones. Clubbing may be present along with HPO. Large cell and adenocarcinoma are the most common types to cause HPO. The cause of HPO is uncertain but is thought to be attributable to a humeral agent. A radiograph of the long bones (tibia and fi bula or radius and ulna) may show the characteristic perio-steal new bone formation. An isotype bone scan or PET scan typically demonstrates diffuse uptake in the long bones. Symptoms of HPO may resolve with thoracot-omy with or without resection of the malignancy. For inoperable patients, treatment with nonsteroidal anti-infl ammatory agents is often of benefi t. Recently, the use of intravenous bisphosphonates has been reported to alleviate the symptoms of HPO.There have been reports of the association of lung cancer with dermatomyositis-polymyositis (DM-PM), but the relationship is uncertain. Patients may present with painful muscles and weakness. Blood tests for the muscle enzymes creatine kinase or aldolase will demon-strate elevated levels. An EMG or muscle biopsy is diagnostic. A CT scan of the chest is warranted in a patient with DM-PM who is at high risk for lung cancer. The treatment of patients with malignancy-related DM-PM is the same as for nonmalignancy-related disease plus appropriate treatment of the underlying lung cancer.Neuromuscular manifestationsConnective tissue manifestationsEdema and/or painful swelling of feet, legs,or handsSubacutecerebellardegeneration;vertigo, ataxiaElectromyographic abnormalityin Lambert-Eaton Myasthenicsyndrome (readings fromhypothenar muscles withstimulation of ulnar nerveat wrist). Note low amplitudeand initial decline.(Normal � 5 mv or morewith no initial decline)30 stim/sec10 stim/sec3 stim/secmv42024mvmv4 4 sec1 sec0.4 sec20242101Lambert-Eaton syndrome; weaknessof proximal muscle groups (oftenmanifested by difficulty in risingfrom chair)Peripheral neuropathy;paresthesias, pain,loss of functionHypertrophicpulmonaryosteoarthropathyClubbing of fingers Subperiosteal new bone formationDementia (may predateonset of pulmonarysymptoms)Swellingof knee joint(synovialeffusionmay bepresent)NEUROMUSCULAR AND CONNECTIVE TISSUE MANIFESTATIONSPARANEOPLASTIC MANIFESTATIONS OF LUNG CANCER (Continued)168 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONSPlate 4-58 Respiratory SystemOTHER NEOPLASMS OF THE LUNGUncommon malignant tumors of the lung include bronchial carcinoid and salivary gland tumors of adenoid cystic carcinomaand mucoepidermoid carci-noma. Bronchial carcinoid tumors account for 1% to 2% of all lung malignancies and 20% of all carcinoid tumors. The annual rates in men and women are 0.52 and 0.89, respectively, per 100,000 population. These tumors are characterized by growth patterns that suggest neuroendocrine differentiation. Bronchial car-cinoids are classifi ed as typical or atypical. Typical car-cinoid tumors are low-grade tumors with fewer than 2 mitoses per 2 mm2 (10 high-power microscopic fi elds) and no necrosis. Atypical carcinoids are intermediate-grade neuroendocrine tumors with 2 to 10 mitoses per 2 mm2 or foci of necrosis. Typical carcinoid tumors are about four times more common than atypical carci-noids. There is no clear relationship to smoking.Approximately 75% of these tumors arise in the central airways. The usual symptoms are cough, wheeze, hemoptysis, and recurrent pneumonia. One-fourth are peripherally located and are usually asymptomatic or present as an obstructive pneumonia. Five percent may present with an endocrine syndrome such as carcinoid syndrome, Cushing syndrome, or acromegaly.Centrally located tumors are likely to cause bronchial obstruction with atelectasis, lobar collapse, or pneumo-nia on chest radiography or computed tomography (CT) scan. Cavitation and pleural effusion, unless related to pneumonia, are rare. The CT scan may show an intraluminal tumor in the central airways. Carcinoid tumors are more commonly smooth bordered but may also be lobulated and are less likely to have irregular borders.Bronchoscopy is able to visually identify an endo-bronchial lesion in a majority of cases because 75% are centrally located. The pink to red vascular-appearing mass is typical. Biopsy is frequently diagnostic. Bleed-ing may be a little more prominent than with non–small cell lung cancer, but serious bleeding complications are uncommon. Sputum cytology and bronchial brushings are usually nondiagnostic. Transthoracic needle biopsy may be diagnostic, but occasionally carcinoid tumor and small cell lung cancer have been confused histologi-cally on small samples from needle biopsy.The treatment of choice is surgical resection for stage I, II, and IIIA disease (the staging system is same as for non–small cell lung cancer). The 10-year survival with typical carcinoid tumors is 80% to 90%. Survival of those with atypical tumors is signifi cantly less but still approximately 50% at 5 years and depends on the stage of disease at the time of diagnosis. Carcinoid tumors, both typical and atypical, are more chemoresistant and radiotherapy resistant than non–small cell lung cancer. Nevertheless, concurrent chemoradiotherapy is the treatment of choice for patients with unresectable stage IIIA/B disease. Stage IV disease is very chemoresistant, but the somatostatin analog octreotide is effective at controlling the symptoms of carcinoid syndrome (fl ush-ing and diarrhea) and may impact survival.Salivary gland tumors of the tracheobronchial tree are histologically similar to their counterparts in the salivary glands. The two most common airway tumors are adenoid cystic carcinoma (cylindroma) and mucoep-idermoid carcinoma; both are less common than carcinoid tumors. There is no clear association of these tumors with smoking. Adenoid cystic carcinoma causes fewer than 1% of all lung tumors, and the vast majority of cases originate intraluminally in the trachea, main-stem, or lobar bronchi. These tumors are typically very slow growing, and the symptoms and presentation are similar to those of centrally located carcinoid tumors. The chest radiograph is frequently normal because of the central endoluminal location of the tumor, but CT usually identifi es the tumor. Bronchoscopy is the most common method of diagnosis.Surgical resection is the treatment of choice, but multiple local recurrences are common before develop-ing distant metastases. The 5- and 10-year survival rates for resected adenoid cystic carcinoma are approximately 70% and 60%, respectively, compared with unresecta-ble disease, in which the 5- and 10-year survival rates are 50% and 30%, respectively.Mucoepidermoid carcinomas account for fewer than 1% of lung tumors. They form a signifi cant proportion of endobronchial tumors in children. These tumors tend to occur centrally in the tracheobronchial tree. Tumors are divided into low- or high-grade types on the basis of histology. High-grade tumors are rare and have a signifi cantly worse prognosis. The clinical and radiographic presentations of this tumor are similar to those of adenoid cystic carcinomas, and bronchoscopy is the most common method of diagnosis. The treat-ment of choice is surgical resection. Low-grade tumors metastasize in 5% or fewer of cases. High-grade tumors are treated similarly to non–small cell lung cancer and have a poor prognosis. The overall survival rate for resected mucoepidermoid carcinoma is 80% to 90% at 5 years. Patients with mucoepidermoid carcinoma have better survival than those with adenoid cystic carcinoma.“Iceberg” type oftumor projectinginto bronchuswith chiefmass belowsurfaceBronchoscopic view of a primarybronchial tumorCentral carcinoid lesionPeripheralcarcinoidlesionCT of mainstem airway carcinoid lesionBronchialcarcinoid.Nests of lightlystaining cellswith centralnuclei andtrend towardtubule formationMucoepidermoidcarcinoma. Manyglandlikeformations(most of whichcontain mucus)resembling a salivary glandtumorAdenoid cysticcarcinoma(cyclindroma).Cylinders oftumor cells withsurroundingand central areasof myxomatoustissueTHE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 169Plate 4-59 Diseases and PathologyBENIGN TUMORS OF THE LUNGPulmonary granulomas are the most common cause of a benign pulmonary nodule and are a sequela of infec-tion. The next most common benign tumor is hamar-toma. It is composed of varying proportions of mesenchymal tissues, including smooth muscle, fat, and connective tissue and cartilage. The incidence in the population is 0.25% with two to four times male pre-dominance. Most hamartomas occur in the periphery of the lung and present as an asymptomatic solitary pulmonary nodule. The edges of the tumor are typically smooth. Approximately 10% may occur endobronchi-ally and may present with symptoms of cough, wheeze, dyspnea, or obstructive pneumonia. The presence of “popcorn” calcifi cation on chest radiography or com-puted tomography (CT) scan is a classic pattern but is present in only a small percentage of cases. The pres-ence of fat on thin-section CT chest images or fat alternating with areas of calcifi cation is diagnostic of this lesion, but many hamartomas do not have either of these fi ndings. Because of the peripheral location, bron-choscopy is typically nondiagnostic. The positron emis-sion tomography (PET) scan is negative for increased metabolic activity. Because of the indeterminate diag-nostic results, many of these tumors are treated with surgical resection, although removal is not necessary for the peripherally located and asymptomatic tumor if it has the diagnostic radiographic appearances discussed above.Solitary fi brous tumors occur in numerous sites, including the pleura, and may present as a mass in the chest. Previously called benign localized mesothelioma (this term is now discouraged), it has no association with asbestos exposure, and 80% to 90% of these lesions are benign and do not spread. It is an uncom-mon tumor of spindle cell mesenchymal growth thought to be of fi broblastic origin and arises from the visceral pleura most commonly but may also arise in the lung parenchyma or mediastinum. The tumor is usually detected as an asymptomatic nodule or mass on chest radiography. Some patients may present with cough, dyspnea, or chest pain. Rarely, patients may present with hypertrophic pulmonary osteoarthropathyor symptomatic hypoglycemia caused by production of insulin-like growth factor. These latter symptoms are more likely when the tumor is quite large. There are no diagnostic radiographic features, and the PET scan results are usually negative or have a low level of uptake. Bronchoscopy is nondiagnostic because of the pleural origin of these lesions, and transthoracic needle biop-sies are unreliable for a defi nitive diagnosis. The treat-ment of choice is surgical resection. Local recurrence may occur in 10% to 15% of cases.Chondromas are a rare tumor of cartilage. They usually occur in female patients with the Carney triad of gastrointestinal stromal tumor, pulmonary chon-droma, and paraganglionoma. Pulmonary chondromas are usually asymptomatic unless they are numerous or of large size. Occasionally, they may cause obstruc-tive pneumonia. Radiographically, they are well-circumscribed tumors, usually multiple, and calcifi ed or may have “popcorn” calcifi cation. If the pulmonary tumors are asymptomatic, then there is no reason for treatment. Symptomatic tumors may require surgical resection.Infl ammatory myofi broblastic tumor, previously called infl ammatory pseudotumor or plasma cell granuloma, is composed of a mixture of collagen, infl ammatory cells, and the cytologically bland spindle cells showing myofi broblastic differentiation. It occurs in all ages, with an equal gender distribution. It is the most common pulmonary tumor of childhood and may have a signifi cant endobronchial component. Symptoms may include cough, dyspnea, fever, and weight loss. Some patients are asymptomatic. The majority of these tumors are solitary in lung parenchyma but occasionally may involve the chest wall or mediastinum. The mass is usually well circumscribed, lobulated, or smooth, but irregular borders occur in 20%. Calcifi cation may be present, and rarely cavitation has been reported. Com-plete surgical resection is the treatment of choice with excellent long-term survival of 90% at 5 years in one reported series. Local recurrence may occur with incomplete resections.HamartomaChondromaSolitary fibrous tumorTumor containing muchcartilage, fibrous andfatty septa, and cysticspaces lined withcuboidal epitheliumCT scan showing“popcorn” calcificationand areas of fat densityin a hamartoma in theright lungSharply circumscribed growth with calcified areasPeripherally located solitary fibrous tumor;these are usually local on the pleural lining.Chest radiographshowing multiplechondroma lesionsTumor composed almost entirely ofcartilage and covered by bronchialepitheliumTumor made up of interlacingcollagen fibers and fibroblastswith no invasive tendencyCT scan of solitaryfibrous tumor