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Diagnostic Tests for Lung Cancer
Diagnostic Tests for Lung Cancer
PHILIP R. KARSELL, M.D., Department of Diagnostic Radiology; JOHN C. McDOUGALL, M.D., Division of Thoracic Diseases and Internal Medicine
The goals of diagnostic testing in patients with suspected lung cancer are to establish the diagnosis and to determine the stage of the disease so that appropriate therapy can be initiated. Unless a patient has hemoptysis, fever, or a change in cough as an initial manifestation, resectable lung cancer will seldom be diagnosed on the basis of the history. Screening tests-particularly chest roentgenography-have usually identified the abnormality. The managing physician should then select diagnostic procedures that are associated with low risk and that will provide further diagnostic and staging information. A biopsy will almost always be necessary before definitive therapy can be planned. In many cases, a single procedure-for example, a needle biopsy of a hepatic lesion or biopsy of a supraclavicular lymph node-will provide a definitive diagnosis and establish the stage of the disease. The roles of cytology, histopathologic examination, radiologic studies, and various types of biopsy in the diagnosis of lung cancer are reviewed in this report.
The prognosis for a patient with lung cancer is primarily based on the type of tumor and its stage at the time of diagnosis. Currently, 25 to 40% of lung tumors are considered resectable at the time of initial assessment, I and overall, only 11 to 13% of patients with lung cancer survive 5 years." Symptomatic lung cancer is advanced-and probably unresectable. Early diagnosis and accurate staging of lung cancer are essential for selection of appropriate curative or palliative therapy. Lung cancer may be diagnosed on the basis of the history, physical examination, and radiographic studies. No firm diagnosis can be made, however, without cytologic or histopathologic confirmation of the disease, and suspected lung cancer should always be pathologically confirmed if therapeutic intervention is planned. In this report, we present an overview of available diagnostic tests and techniques for obtaining tissue for pathologic confirmation of lung cancer and discuss the application of these tests and techniques at the Mayo Clinic. Individual reprints of this article are not available. The entire Symposium on Intrathoracic Neoplasms will be available for purchase as a bound booklet from the Proceedings Circulation Office at a later date. Mavo
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HISTORY AND PHYSICAL EXAMINATION The myriad symptoms of lung cancer range from none to cough, hemoptysis, dyspnea, fever, hoarseness, bone pain, weight loss and anorexia, confusion, neuropathic pain, generalized weakness, headache, ataxia, and symptoms of stroke (Table 1). Unless a patient has hemoptysis, fever, or a change in cough as the initial symptom, resectable lung cancer will seldom be diagnosed on the basis of the history. Physicians should have a high index of suspicion for lung cancer in patients who have a history of cigarette smoking or who have been exposed to asbestos, radon gas, or polycyclic aromatic hydrocarbons. The physical findings in patients with lung cancer parallel the symptoms. They range from none to supraclavicular adenopathy, Homer's syndrome, signs of pleural effusion, localized wheezing, hepatic enlargement, cachexia, tenderness over shins and ankles, localized bone tenderness, signs of peripheral motor or sensory neuropathy (or both), and focal deficit of the central nervous system attributable to metastatic involvement. CYTOLOGY AND HISTOPATHOLOGY Sputum cytology is most often useful in screening for lung cancer, primarily detecting centrally located squamous cell 288
© /993 Mayo Foundation for Medical Education and Research
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Table I.-Range of Symptoms and Potential Causes in Patients With Lung Cancer Symptom Cough Hemoptysis Dyspnea Fever Stridor Hoarseness Bone pain Weight loss and anorexia Neuropathic pain Weakness Confusion Headache, stroke Ataxia *SIADH
Potential cause Obstruction, compression, tumor infiltration, or infection of the airway Tumor infiltration of the airway Major airway obstruction, pleural effusion, paralysis of diaphragm Obstructive pneumonia Tracheal narrowing Involvement of recurrent laryngeal nerve Skeletal metastatic lesion or hypertrophic pulmonary osteoarthropathy Hepatic metastatic lesion, advanced cancer Peripheral neuropathy, invasion or compression of nerves Myasthenic syndrome Hyponatremia due to SIADH* or hypercalcemia Brain metastatic lesion Cerebellar degeneration
=syndrome of inappropriate antidiuretic hormone.
carcinomas. In patients with pharyngeal and laryngeal carcinomas, results of sputum cytology may also be positive. To date, the cases of lung cancer detected by cytology have been resectable more often than those detected by radiography in screening trials.v' Cytology may be diagnostic in up to 20% of all patients with lung cancer' and in up to 74% of patients with early lung cancer that involves the central airways." Fewer than 5% of peripheral lung cancers, especially adenocarcinoma and large-cell undifferentiated carcinoma, will yield a positive result of sputum cytology. In fact, positive findings on sputum cytology in a patient with a peripheral nodular lesion should suggest the presence of a cancer of the central airway and prompt the performance of bronchoscopy. In 50% of patients with lung cancer who have pleural effusions, results of pleural fluid cytology will be positive.' This critical finding signifies that the cancer is unresectable. A percutaneous needle biopsy specimen of the pleura will reveal positive results in only 58% of patients with malignant pleural effusions; thus, the yield will be an 8% increase over the results of pleural fluid cytology alone." Because the diagnostic yield is only minimally increased and because the risk of pain and hemorrhage and the cost associated with the procedure are increased, pleural needle biopsy is seldom performed in our practice. RADIOLOGIC TESTS AND TECHNIQUES In the diagnosis of lung cancer, medical imaging is used to detect probable pulmonary abnormalities and to guide the
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selection of additional imaging procedures and, oftentimes, interventional procedures to make a definitive diagnosis. Findings on only imaging studies should never preclude histopathologic examination when suspicion of an abnormality remains. Screening.-Chest roentgenography and sputum cytology are complementary in the detection of early lung cancer and are the two screening techniques currently considered effective.' At the Mayo Clinic, however, chest roentgenography has been shown to be 6 times more effective than sputum cytology in the early diagnosis of lung cancer.' Recent reevaluation of data from the Early Lung Cancer trial and case mortality analyses by Chu and Smart (unpublished data, 1991) suggest that "screening radiography alone may reduce lung cancer mortality by 10%, or about 15,000 persons, in the United States annually."? The smallest pulmonary soft tissue nodule detectable roentgenographically is 2 to 3 mm. In radiographic screening of a general hospital population with a tumor prevalence of 5%, a nodule must be at least 8 mm in diameter to achieve a positive predictive value of 90%. In clinical reports, the typical solitary pulmonary nodule is approximately 1 em in diameter (Fig. 1).10 Twelve to 30% of lung carcinomas are missed at chest roentgenography. In the Early Lung Cancer screening trial, 54% of tumors were evident in retrospect on films obtained 1 year earlier at Memorial Sloan-Kettering Cancer Center, and 90% of nodules were present on films obtained 4 months earlier at the Mayo Clinic. In a study by Austin and associates" of 27 patients with bronchogenic carcinoma in whom the diagnosis was missed at initial chest roentgenography, the diameter of the average nodule was 1.6 em. Of their 27 patients, 25 (93%) were cigarette smokers, and, of interest, two-thirds of them were female. Those investigators suggested that additional history made available to the radiologist, including information about respiratory or constitutional symptoms and total pack-years of cigarette smoking, should help decrease the number of false-negative reports. Conventional Chest Roentgenography.-The primary diagnostic procedure for the detection of lung cancer in the United States continues to be conventional chest roentgenography. It is neither the ultimate nor the final examination but the one that identifies the abnormality and suggests subsequent tests to make the definitive diagnosis and to stage the cancer. Throughout the United States, the standard examination consists of a single posteroanterior view and a lateral view. As previously mentioned, chest roentgenography is 70 to 88% accurate in the overall detection of lung cancer. It has been shown to be 61 to 71 % accurate in the detection of hilar adenopathy and 47 to 60% accurate in the detection of mediastinal adenopathy (Fig. 2).12
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Fig. 1. Radiologic studies of asymptomatic 67-year-old woman with enlarging nodule in right lower lobe of lung. The 2-cm mass, which was adjacent to and partially engulfing a densely calcified granuloma, was a grade 1 mucous adenocarcinoma. A, Portion of a chest roentgenogram. B, Localized tomogram.
At the Mayo Clinic, the standard chest roentgenographic examination for many years has been two posteroanterior stereoscopic views. Several investigators have shown improvement in both the sensitivity and the specificity of detection of pulmonary nodules by using shifted-pair and stereoscopic examinations.P:" The lateral view of the chest is valuable because it provides the third dimension (Fig. 3); in addition, it displays the
Fig. 2. Chest roentgenogram of 60-year-old man with acute superior vena cava syndrome, who had right hilar and right paratracheal adenopathy. In right pulmonary apex, I-em nodule is faintly evident. Patient had grade 4 small-cell carcinoma.
portions of the chest behind the heart and in the posterior costophrenic angles. It will not only confirm and clarify the presence and character of an abnormality noted on the posteroanterior view in up to 26% of cases but also detect abnormalities not evident on the posteroanterior view in up to 2% of cases.':" We believe that the combined stereoscopic pair-lateral view study is the optimal routine chest roentgenographic examination at this time. This approach increases the sensitivity for detection of pulmonary nodules and decreases the problem of overlapping shadows, the latter being a major factor in cases of missed diagnoses oflung cancer." In attempts to improve imaging of the chest, we are currently evaluating a system that varies the exposure required across the chest to provide a uniform image not only of the lung fields but also of the mediastinum. In addition, we are in the preliminary stages of evaluating a digital imaging system that uses x-ray-exposed photostimulable phosphor plates. Fluoroscopy.-Although currently infrequently used in diagnostic chest imaging, image-intensified fluoroscopy can help localize an abnormality and separate it from adjacent overlapping structures. In some cases, it can show that a lesion is not a lung cancer-as in the case of a bone island, a rib fracture, or an arteriovenous malformation with its characteristic changes during respiration. Commonly, fluoroscopy is used to evaluate diaphragmatic motion. Localized Tomography.-At the Mayo Clinic, linear or complex motion localized tomography is frequently the next step inevaluation after the initial detection of a solitary pulmonary nodule (Fig. 1 B). Its ability to visualize an
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abnormality separate from overlying and underlying anatomic structures allows determination of the size, shape, and architectural characteristics of a nodule. In our experience, plain tomography has facilitated the classification of two of three solitary pulmonary opacities-60% benign, 7% highly suggestive of a malignant lesion, and 33% indeterminate." Benign lesions will be linear or angular, and they may contain central or concentric calcification or may be completely calcified. Of the partially calcified lesions, only those with classic patterns of calcification should be considered benign. The probably malignant lesions are minimally or irregularly calcified or are uncalcified, and they are spherical or spiculated. The indeterminate solitary pulmonary opacities on localized tomography appear smooth, round, oval, or lobulated, uncalcified, or cavitated. Thus, they cannot be readily classified as benign or probably malignant. Littleton and coworkers," using complex motion tomography, found that malignant lesions show substantial enhancement in comparison with benign lesions after intravenous administration of contrast material. As in other studies, some lesions were indeterminate after examination. Those lesions considered indeterminate but likely malignant are further evaluated, usually by invasive testing, whereas those thought more likely to be benign are subjected to careful follow-up. The morphologic features and rate of growth of the lesion and the patient's history of smoking are some factors that should be considered in deciding whether observation or further testing is appropriate. Before the widespread availability of computed tomography (CT), anteroposterior, lateral, and 55-degree oblique tomograms were used for assessment of the pulmonary hila to determine the presence of adenopathy or evidence of direct extension of a lung tumor. Oblique hilar tomography has been shown to be 74 to 80% accurate in such assessments. 19 Computed Tomography.-For the diagnosis of pulmonary disease, CT scanning is an extremely valuable procedure. Currently, it is the procedure of choice for the initial assessment of patients with lung cancer (Fig. 3 C).20 It enables radiologists to evaluate not only the lesion itself, its precise site, and its relationship to nearby structures but also the pulmonary hila, mediastinum, chest wall, liver, and adre-
Fig. 3. Radiologic studies of 64-year-old woman with dyspnea and hemoptysis. Dense atelectasis of left upper lobe was caused by obstructive tumor (grade 3 mixed squamous cell carcinoma and adenocarcinoma) of bronchus. A, Posteroanterior chest roentgenogram. B, Lateral chest roentgenogram. C, Computed tomographic scan of chest.
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nal glands. When necessary, it can be used to guide the bronchoscopist to an otherwise obscure lesion. Approximately 1% of lung cancers are multiple and synchronous." CT can determine the presence or absence of other nodules in the chest. When further testing reveals that a pulmonary nodule is a metastatic lesion, imaging of other areas of the body may disclose the primary tumor." Contiguous thick (usually lO-mm) CT slices are taken through the entire chest before or after contrast enhancement (or at both times). Once located, a lesion can be further evaluated by obtaining thin (1- to 2-mm) CT slices through its center. Calcification is detected by CT in 22 to 30% of solitary pulmonary nodules considered indeterminate by conventional tomography; thus, their status is further clarified." (The approach to solitary pulmonary nodules will be reviewed in another article in this symposium.) Approximately 50% of hamartomas, the third most common pulmonary nodule (after granulomas and carcinomas), contain fat, frequently identifiable by CT.24 Twenty-five percent contain "popcorn" calcification. With use of CT, a solitary pulmonary nodule can be compared with a special reference phantom of the same size, in the same site, and under identical technical conditions.P'" Lesions that contain 10% or more calcification and are found to be more dense than the phantom are likely benign and are usually candidates for observation. Those found to be less dense than the phantom are considered indeterminate; for these lesions, more invasive testing or, occasionally, careful follow-up is necessary. In one study of patients with a previous extrathoracic malignant lesion, 80% of solitary pulmonary nodules detected by CT were actually solitary at operation, in comparison with 54% detected by conventional chest roentgenography." Surgical removal of limited pulmonary metastatic tumors is improving survival among patients with several types of malignant lesions. Comparison scanning with a reference phantom can be misleading in patients who have had prior malignant lesions-such as mucinous carcinomas of the gastrointestinal or genitourinary tract, osteogenic sarcomas, chondrosarcomas, and synovial sarcomas-that tend to be associated with development of calcium-containing metastatic tumors.'? In such patients, we do not use this technique. Recent work by Swensen and associates" at the Mayo Clinic suggested that considerable enhancement of a nodule on CT scanning after intravenous administration of contrast material indicates the likelihood of a malignant lesion. This finding confirms that relationship previously demonstrated by Littleton and colleagues" with use of complex motion tomography. CT scanning has been shown to be 78 to 94% accurate in the detection of hilar involvement with lung cancer. In
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contrast, conventional chest roentgenography is 61 to 71% accurate, and 55-degree oblique hilar tomography is 74 to 80% accurate." For evaluation of the pulmonary hila, we use the thin-slice technique and, frequently, bolus contrast enhancement. Although not optimal, CT scanning can help detect endobronchial lesions by disclosing thickening of the bronchial wall or occlusion of the bronchial lumen. It has been shown to be 50% accurate with central lesions" and approximately 37% accurate with lesions within 2 em of the tracheal carina." Mediastinal adenopathy and extension of carcinoma into the mediastinum can be visualized by CT. Extension of tumor into the mediastinum, heart, or great vessels must be more than minimal, however, to be identified with a high degree of accuracy. In general, lymph nodes larger than 1 em in diameter are considered abnormal; hence, a biopsy can be obtained under CT guidance, at bronchoscopy, or at mediastinoscopy. A patient with lung cancer whose mediastinum appears uninvolved on CT scanning often will undergo surgical treatment without a preliminary mediastinoscopy. In a patient with a suspected lung cancer, we almost always extend our CT examination to include the liver and adrenal glands. Biopsy of an abnormality detected in either location not only is often easier to accomplish and safer for the patient than attempting biopsy of the primary pulmonary tumor but also may simultaneously provide the diagnosis of a malignant lesion and prove the presence of metastatic involvement. Magnetic Resonance Imaging.-The newest modality in our imaging armamentarium is magnetic resonance imaging. This procedure provides multiplanar images, offers a variety of imaging sequences for tissue differentiation, and is flow sensitive. It provides excellent anatomic detail in the chest, usually on the Tl-weighted images, when used with respiratory compensation and electrocardiographic gating, and pathologic changes in the chest are usually well demonstrated on the T2-weighted images. Some of the deficiencies of magnetic resonance imaging are as follows: low signal from pulmonary lesions limits their detectability, motion artifacts may obscure detail, and detection of calcification is difficult. In addition, examinations are expensive, and the equipment is not yet widely available nationwide." Magnetic resonance imaging seems particularly useful in distinguishing scar from residual or recurrent tumor, in evaluating a superior sulcus tumor (Fig. 4), and in determining possible involvement of the brachial plexus with tumor. It is equal to or better than CT in distinguishing dense postobstructive atelectasis or infiltrate from the central mass and in evaluating contiguity or invasion of the chest wall,
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pneumonectomy is being considered, pulmonary function can be determined by using 99mTc-macroaggregatedalbumin to assess overall perfusion. If the product of the percentage isotopic uptake in the contralateral lung and the forced expiratory volume in I minute exceeds 0.8 liter, the patient should be able to tolerate the surgical procedure.W" Another application of nuclear medicine studies is the performance of radioisotope bone and liver scans for the detection of metastatic lesions.
Fig. 4. Magnetic resonance image of chest of 57-year-old man with Homer's syndrome, demonstrating large superior sulcus tumor (Pancoast's syndrome) that caused destruction of rib posteriorly and invaded the chest wall. Tumor was grade 4 adenocarcinoma.
heart, and great vessels. It is useful, as well, in the pulmonary hila and mediastinum, although Tl and T2 values overlap in benign hyperplastic and metastatic lymphadenopathy.P" . Magnetic resonance imaging of the liver seems superior to CT scanning with dynamic contrast enhancement for detecting metastatic involvement but not as effective as the combination of CT scanning and arterial portography." With use of magnetic resonance imaging, Krestin and coworkers" were able to distinguish benign cortical adenomas from malignant adrenal metastatic lesions in 91% of their cases. Additionally, such studies with gadolinium enhancement seem superior to CT scanning in the search for intracerebral metastatic tumors." As previously mentioned, magnetic resonance imaging may be helpful in the posttreatment evaluation of fibrosis or scar versus residual or recurrent tumor because a substantial T2 signal difference exists between mature scar and tumor. Moreover, tumor may show enhancement after administration of gadolinium whereas scar should not. In the occasional patient who is allergic to iodinated contrast material, magnetic resonance imaging can be helpful when CT is not. In our lung cancer practice, magnetic resonance imaging is used primarily as a problem-solving technique when CT scanning and other diagnostic modalities are unable to provide answers to a specific question. Finally, CT scanning is already highly developed, but magnetic resonance imaging should advance because of the continual improvements in hardware and software. Nuclear Medicine Studies.-In patients with lung cancer who have chronic obstructive pulmonary disease for whom
TRANSTHORACIC NEEDLE ASPIRAnON In patients with lung cancer in whom a preoperative tissue diagnosis is important, in patients with a prior malignant lesion who currently have a pulmonary nodule or multiple nodules, and in patients who refuse or have contraindications to surgical treatment, transthoracic needle aspiration is a safe and effective biopsy technique. In our practice, however, in the case of a highly suggestive, apparently surgically resectable lesion in a patient at high risk for lung cancer, the surgical resection will be done without prior performance of such a biopsy. Four percent of solitary pulmonary nodules are metastatic lesions from an extrathoracic carcinoma, and 25% of patients with an extrathoracic carcinoma and pulmonary metastatic involvement have only a solitary pulmonary nodule at the time of initial examination." Tissue obtained by transthoracic needle aspiration may provide the first clue that the patient's primary neoplasm is outside the chest. Transthoracic needle aspiration can be up to 95% accurate in the diagnosis of malignant lesions and 88% accurate for benign Iesions.P-" Although we seldom rely on this procedure for establishing a definite benign diagnosis, this is a major indication for transthoracic needle aspiration at some medical centers. Transthoracic needle aspiration is cost-effective in that it minimizes the time from admission to diagnosis, is often done as an outpatient procedure, decreases or eliminates the need for thoracotomy in patients with small-cell lung cancer or with extrathoracic cancer metastatic to the chest, shortens the overall hospital stay, and thereby reduces total cost." A thorough understanding of the procedure by the patient, the physician, and the surgeon, an experienced radiologist, and a skilled cytopathologist are necessary for an optimal outcome. The procedure is performed by a radiologist in the hospital radiology department under fluoroscopic control; occasionally, CT guidance is used (Fig. 5). The shortest safe route for the needle to traverse is usually chosen, crossing as few pleural surfaces as possible. As previously mentioned, when sites of probable extrathoracic metastatic tumors have been identified during the patient's workup, we often perform a needle biopsy of one or more of those lesions, not
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Fig. 5. In 77-year-old woman who had had headaches and subsequently abnormal chest roentgenographic findings, computed tomography-guided needle biopsy revealed non-small-cell anaplastic carcinoma of lingula with mediastinal extension. Note tip of needle in peripheral aspect of thickened wall, avoiding cavitating portion of tumor.
only to establish the diagnosis but also to substantiate the presence of metastatic involvement. When the biopsy procedure is successful, no malignant cells are found in the material obtained, and no evidence of an endobronchial lesion is noted at bronchoscopy, the lesion may be considered benign, and careful follow-up should be initiated." At the Mayo Clinic, when a biopsy is unsuccessful or when no evidence of a malignant lesion is found at transthoracic needle aspiration, a mediastinoscopy, thoracoscopy, or even thoracotomy is usually performed to determine the definitive diagnosis. Transthoracic needle aspiration is contraindicated in only a few situations-in patients who will receive no obvious benefit, even when a diagnosis is made; in uncooperative patients; in those with a bleeding diathesis, possible vascular lesion, or hydatid cyst; and, in our practice, in patients with a cavitating pulmonary lesion.t'-" Hemoptysis, pneumothorax, air embolism, and death are the potential complications of transthoracic needle aspiration. Hemoptysis is usually minimal. In our experience, approximately a third of the patients will have a pneumothorax, and only 5 to 10% will require a chest tube." For the past several years, we have treated many such pneumothoraces with a small chest tube (7 to 8 F) and a oneway Heimlich valve, placed by the radiologist with use of fluoroscopic guidance. Usually, the tube is removed in 24 hours.
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BRONCHOSCOPY AND BRONCHOSCOPIC BIOPSY Specimens obtained at bronchoscopy are often the means of establishing a cytologic or histopathologic diagnosis of lung cancer. Results of biopsies of central, bronchoscopically visible cancers are almost always positive. In large necrotic tumors or in cases of carcinoma with predominantly submucosal involvement, positive results of a biopsy may be difficult to obtain. Transbronchoscopic needle aspiration of these lesions will often yield positive findings, however." In addition, transbronchoscopic needle aspiration is useful for diagnosing spread of lung cancer to paratracheal, subcarinal, or hilar lymph nodes.tv" During bronchoscopy, fluoroscopically guided needles, biopsy forceps, and cytology brushes can usually be advanced into peripheral lesions that are larger than 2 ern in diameter; thus, diagnosis is possible in 65 to 75% of cases." In peripheral lung cancers smaller than 2 cm in diameter, a positive result of biopsy or cytologic brushing can seldom be obtained." Lung cancer detected only on sputum cytology in patients with normal chest roentgenographic findings can virtually always be localized bronchoscopically by careful visual inspection and biopsy and brushing of suspicious mucosal abnormalities. As previously mentioned, pharyngeal and laryngeal carcinomas as a source of malignant cells must be excluded in these patients. If the cancer is not detected on routine examination with a flexible bronchoscope, we proceed to "long bronchoscopy." General anesthesia is used for the procedure. If no endobronchial lesion is noted on further careful inspection, bronchial biopsy specimens and brushings are obtained from each lobe and from each segment of each lobe of both lungs. These specimens are then submitted separately to the pathologist. Definite localization. is established by positive results of brushings from the same site on two separate bronchoscopies or by one biopsy specimen with positive findings. During bronchoscopy, hematoporphyrin derivative photostimulation can effectively localize occult lung cancer. In our experience, however, this technique is rarely necessary." LYMPH NODE BIOPSY If a palpable supraclavicular (or other) lymph node is found, a biopsy specimen should be obtained. A positive result of biopsy not only establishes the diagnosis of lung cancer but also indicates unresectability and spares the patient an unnecessary thoracotomy. MEDIASTINOSCOPY Mediastinoscopy can be performed as a staging procedure in anticipation of a need for thoracotomy for curative resection
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of a lung cancer. If mediastinal lymph nodes are involved, the tumor is usually unresectable, and nonsurgical therapy should be considered. If the position of the lymph nodes makes biopsy by means of a mediastinoscopy difficult, a limited thoracotomy (Chamberlain procedure) can be performed; thus, the diagnosis can be established without the need for a standard lateral thoracotomy. In this circumstance, an alternative biopsy method may be a needle biopsy with use of fluoroscopic or CT guidance (see previous discussion).
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In certain patients, thoracoscopy may allow a limited surgical procedure for visualization of the pleural space and directed biopsy of pleural and peripheral lung lesions. Thoracoscopic biopsy can be performed through a 2-cm incision in the chest wall. It is particularly useful in diagnosing pleural metastatic lesions that cannot be adequately sampled with pleural fluid cytology or by needle biopsy.
THORACOTOMY Thoracotomy for diagnosis and possibly subsequent resection may be done if the following criteria are fulfilled: (1) the patient has a high risk of lung cancer, (2) a workup for metastatic involvement is unrevealing, and (3) the lung lesion is highly suggestive of cancer on radiographic imaging.
CONCLUSION An effort to diagnose lung cancer will usually be made after a screening chest roentgenogram reveals abnormal findings or when a patient has symptoms of pain, hemoptysis, or a new or changed cough. Diagnostic procedures should prove the presence of the tumor, determine the cell type, and establish the stage. A careful diagnostic approach can accomplish all these goals while minimizing the cost, the discomfort, and the risk to the patient. A single procedure such as a needle biopsy of a hepatic metastatic lesion may prove the diagnosis and establish both the cell type and the unresectability. Appropriate therapy can then be planned.
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ventilation-perfusion scanning. Radiol Clin North Am 1990 May; 28:657-663 Coppage L, Shaw C, Curtis AM. Metastatic disease to the chest in patients with extrathoracic malignancy. J Thorac Imaging 1987 Oct; 2:24-37 Khouri NF, Meziane MA, Zerhouni EA, Fishman EK, Siegelman SS. The solitary pulmonary nodule: assessment, diagnosis, and management. Chest 1987; 91:128-133 Khouri NF, Stitik FP, Erozan YS, Gupta PK, Kim WS, Scott WW Jr, et al. Transthoracic needle aspiration biopsy of benign and malignant lung lesions. AJR Am J Roentgenol 1985; 144:281-288 Gobien RP, Bouchard EA, Gobien BS, Valicenti JF, Vujic I. Thin needle aspiration biopsy of thoracic lesions: impact on hospital charges and patterns of patient care. Radiology 1983; 148:65-67 Weisbrod GL. Transthoracic percutaneous lung biopsy. Radiol Clin North Am 1990 May; 28:647-655 Berquist TH, Bailey PB, Cortese DA, Miller WE. Transthoracic needle biopsy: accuracy and complications in relation to location and type oflesion. Mayo Clin Proc 1980; 55:475481 Shure D, Fedullo PF. Transbronchial needle aspiration in the diagnosis of submucosal and peribronchial bronchogenic carcinoma. Chest 1985; 88:49-51 Wang KP, Brower R, Haponik EF, Siegelman S. Flexible transbronchial needle aspiration for staging of bronchogenic carcinoma. Chest 1983; 84:571-576 Shure D, Fedullo PF. The role of transcarinal needle aspiration in the staging of bronchogenic carcinoma. Chest 1984; 86:693-696 Cortese DA, McDougall Je. Biopsy and brushing of peripheral lung cancer with fluoroscopic guidance. Chest 1979; 75:141-145 Edell ES, Cortese DA. Bronchoscopic localization and treatment of occult lung cancer. Chest 1989; 96:919-921
End of Symposium on Intrathoracic Neoplasms, Part II.
Part III will appear in the April issue.
PHILIP R. KARSELL, M.D., Department of Diagnostic Radiology; JOHN C. McDOUGALL, M.D., Division of Thoracic Diseases and Internal Medicine
The goals of diagnostic testing in patients with suspected lung cancer are to establish the diagnosis and to determine the stage of the disease so that appropriate therapy can be initiated. Unless a patient has hemoptysis, fever, or a change in cough as an initial manifestation, resectable lung cancer will seldom be diagnosed on the basis of the history. Screening tests-particularly chest roentgenography-have usually identified the abnormality. The managing physician should then select diagnostic procedures that are associated with low risk and that will provide further diagnostic and staging information. A biopsy will almost always be necessary before definitive therapy can be planned. In many cases, a single procedure-for example, a needle biopsy of a hepatic lesion or biopsy of a supraclavicular lymph node-will provide a definitive diagnosis and establish the stage of the disease. The roles of cytology, histopathologic examination, radiologic studies, and various types of biopsy in the diagnosis of lung cancer are reviewed in this report.
The prognosis for a patient with lung cancer is primarily based on the type of tumor and its stage at the time of diagnosis. Currently, 25 to 40% of lung tumors are considered resectable at the time of initial assessment, I and overall, only 11 to 13% of patients with lung cancer survive 5 years." Symptomatic lung cancer is advanced-and probably unresectable. Early diagnosis and accurate staging of lung cancer are essential for selection of appropriate curative or palliative therapy. Lung cancer may be diagnosed on the basis of the history, physical examination, and radiographic studies. No firm diagnosis can be made, however, without cytologic or histopathologic confirmation of the disease, and suspected lung cancer should always be pathologically confirmed if therapeutic intervention is planned. In this report, we present an overview of available diagnostic tests and techniques for obtaining tissue for pathologic confirmation of lung cancer and discuss the application of these tests and techniques at the Mayo Clinic. Individual reprints of this article are not available. The entire Symposium on Intrathoracic Neoplasms will be available for purchase as a bound booklet from the Proceedings Circulation Office at a later date. Mavo
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HISTORY AND PHYSICAL EXAMINATION The myriad symptoms of lung cancer range from none to cough, hemoptysis, dyspnea, fever, hoarseness, bone pain, weight loss and anorexia, confusion, neuropathic pain, generalized weakness, headache, ataxia, and symptoms of stroke (Table 1). Unless a patient has hemoptysis, fever, or a change in cough as the initial symptom, resectable lung cancer will seldom be diagnosed on the basis of the history. Physicians should have a high index of suspicion for lung cancer in patients who have a history of cigarette smoking or who have been exposed to asbestos, radon gas, or polycyclic aromatic hydrocarbons. The physical findings in patients with lung cancer parallel the symptoms. They range from none to supraclavicular adenopathy, Homer's syndrome, signs of pleural effusion, localized wheezing, hepatic enlargement, cachexia, tenderness over shins and ankles, localized bone tenderness, signs of peripheral motor or sensory neuropathy (or both), and focal deficit of the central nervous system attributable to metastatic involvement. CYTOLOGY AND HISTOPATHOLOGY Sputum cytology is most often useful in screening for lung cancer, primarily detecting centrally located squamous cell 288
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Table I.-Range of Symptoms and Potential Causes in Patients With Lung Cancer Symptom Cough Hemoptysis Dyspnea Fever Stridor Hoarseness Bone pain Weight loss and anorexia Neuropathic pain Weakness Confusion Headache, stroke Ataxia *SIADH
Potential cause Obstruction, compression, tumor infiltration, or infection of the airway Tumor infiltration of the airway Major airway obstruction, pleural effusion, paralysis of diaphragm Obstructive pneumonia Tracheal narrowing Involvement of recurrent laryngeal nerve Skeletal metastatic lesion or hypertrophic pulmonary osteoarthropathy Hepatic metastatic lesion, advanced cancer Peripheral neuropathy, invasion or compression of nerves Myasthenic syndrome Hyponatremia due to SIADH* or hypercalcemia Brain metastatic lesion Cerebellar degeneration
=syndrome of inappropriate antidiuretic hormone.
carcinomas. In patients with pharyngeal and laryngeal carcinomas, results of sputum cytology may also be positive. To date, the cases of lung cancer detected by cytology have been resectable more often than those detected by radiography in screening trials.v' Cytology may be diagnostic in up to 20% of all patients with lung cancer' and in up to 74% of patients with early lung cancer that involves the central airways." Fewer than 5% of peripheral lung cancers, especially adenocarcinoma and large-cell undifferentiated carcinoma, will yield a positive result of sputum cytology. In fact, positive findings on sputum cytology in a patient with a peripheral nodular lesion should suggest the presence of a cancer of the central airway and prompt the performance of bronchoscopy. In 50% of patients with lung cancer who have pleural effusions, results of pleural fluid cytology will be positive.' This critical finding signifies that the cancer is unresectable. A percutaneous needle biopsy specimen of the pleura will reveal positive results in only 58% of patients with malignant pleural effusions; thus, the yield will be an 8% increase over the results of pleural fluid cytology alone." Because the diagnostic yield is only minimally increased and because the risk of pain and hemorrhage and the cost associated with the procedure are increased, pleural needle biopsy is seldom performed in our practice. RADIOLOGIC TESTS AND TECHNIQUES In the diagnosis of lung cancer, medical imaging is used to detect probable pulmonary abnormalities and to guide the
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selection of additional imaging procedures and, oftentimes, interventional procedures to make a definitive diagnosis. Findings on only imaging studies should never preclude histopathologic examination when suspicion of an abnormality remains. Screening.-Chest roentgenography and sputum cytology are complementary in the detection of early lung cancer and are the two screening techniques currently considered effective.' At the Mayo Clinic, however, chest roentgenography has been shown to be 6 times more effective than sputum cytology in the early diagnosis of lung cancer.' Recent reevaluation of data from the Early Lung Cancer trial and case mortality analyses by Chu and Smart (unpublished data, 1991) suggest that "screening radiography alone may reduce lung cancer mortality by 10%, or about 15,000 persons, in the United States annually."? The smallest pulmonary soft tissue nodule detectable roentgenographically is 2 to 3 mm. In radiographic screening of a general hospital population with a tumor prevalence of 5%, a nodule must be at least 8 mm in diameter to achieve a positive predictive value of 90%. In clinical reports, the typical solitary pulmonary nodule is approximately 1 em in diameter (Fig. 1).10 Twelve to 30% of lung carcinomas are missed at chest roentgenography. In the Early Lung Cancer screening trial, 54% of tumors were evident in retrospect on films obtained 1 year earlier at Memorial Sloan-Kettering Cancer Center, and 90% of nodules were present on films obtained 4 months earlier at the Mayo Clinic. In a study by Austin and associates" of 27 patients with bronchogenic carcinoma in whom the diagnosis was missed at initial chest roentgenography, the diameter of the average nodule was 1.6 em. Of their 27 patients, 25 (93%) were cigarette smokers, and, of interest, two-thirds of them were female. Those investigators suggested that additional history made available to the radiologist, including information about respiratory or constitutional symptoms and total pack-years of cigarette smoking, should help decrease the number of false-negative reports. Conventional Chest Roentgenography.-The primary diagnostic procedure for the detection of lung cancer in the United States continues to be conventional chest roentgenography. It is neither the ultimate nor the final examination but the one that identifies the abnormality and suggests subsequent tests to make the definitive diagnosis and to stage the cancer. Throughout the United States, the standard examination consists of a single posteroanterior view and a lateral view. As previously mentioned, chest roentgenography is 70 to 88% accurate in the overall detection of lung cancer. It has been shown to be 61 to 71 % accurate in the detection of hilar adenopathy and 47 to 60% accurate in the detection of mediastinal adenopathy (Fig. 2).12
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Fig. 1. Radiologic studies of asymptomatic 67-year-old woman with enlarging nodule in right lower lobe of lung. The 2-cm mass, which was adjacent to and partially engulfing a densely calcified granuloma, was a grade 1 mucous adenocarcinoma. A, Portion of a chest roentgenogram. B, Localized tomogram.
At the Mayo Clinic, the standard chest roentgenographic examination for many years has been two posteroanterior stereoscopic views. Several investigators have shown improvement in both the sensitivity and the specificity of detection of pulmonary nodules by using shifted-pair and stereoscopic examinations.P:" The lateral view of the chest is valuable because it provides the third dimension (Fig. 3); in addition, it displays the
Fig. 2. Chest roentgenogram of 60-year-old man with acute superior vena cava syndrome, who had right hilar and right paratracheal adenopathy. In right pulmonary apex, I-em nodule is faintly evident. Patient had grade 4 small-cell carcinoma.
portions of the chest behind the heart and in the posterior costophrenic angles. It will not only confirm and clarify the presence and character of an abnormality noted on the posteroanterior view in up to 26% of cases but also detect abnormalities not evident on the posteroanterior view in up to 2% of cases.':" We believe that the combined stereoscopic pair-lateral view study is the optimal routine chest roentgenographic examination at this time. This approach increases the sensitivity for detection of pulmonary nodules and decreases the problem of overlapping shadows, the latter being a major factor in cases of missed diagnoses oflung cancer." In attempts to improve imaging of the chest, we are currently evaluating a system that varies the exposure required across the chest to provide a uniform image not only of the lung fields but also of the mediastinum. In addition, we are in the preliminary stages of evaluating a digital imaging system that uses x-ray-exposed photostimulable phosphor plates. Fluoroscopy.-Although currently infrequently used in diagnostic chest imaging, image-intensified fluoroscopy can help localize an abnormality and separate it from adjacent overlapping structures. In some cases, it can show that a lesion is not a lung cancer-as in the case of a bone island, a rib fracture, or an arteriovenous malformation with its characteristic changes during respiration. Commonly, fluoroscopy is used to evaluate diaphragmatic motion. Localized Tomography.-At the Mayo Clinic, linear or complex motion localized tomography is frequently the next step inevaluation after the initial detection of a solitary pulmonary nodule (Fig. 1 B). Its ability to visualize an
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abnormality separate from overlying and underlying anatomic structures allows determination of the size, shape, and architectural characteristics of a nodule. In our experience, plain tomography has facilitated the classification of two of three solitary pulmonary opacities-60% benign, 7% highly suggestive of a malignant lesion, and 33% indeterminate." Benign lesions will be linear or angular, and they may contain central or concentric calcification or may be completely calcified. Of the partially calcified lesions, only those with classic patterns of calcification should be considered benign. The probably malignant lesions are minimally or irregularly calcified or are uncalcified, and they are spherical or spiculated. The indeterminate solitary pulmonary opacities on localized tomography appear smooth, round, oval, or lobulated, uncalcified, or cavitated. Thus, they cannot be readily classified as benign or probably malignant. Littleton and coworkers," using complex motion tomography, found that malignant lesions show substantial enhancement in comparison with benign lesions after intravenous administration of contrast material. As in other studies, some lesions were indeterminate after examination. Those lesions considered indeterminate but likely malignant are further evaluated, usually by invasive testing, whereas those thought more likely to be benign are subjected to careful follow-up. The morphologic features and rate of growth of the lesion and the patient's history of smoking are some factors that should be considered in deciding whether observation or further testing is appropriate. Before the widespread availability of computed tomography (CT), anteroposterior, lateral, and 55-degree oblique tomograms were used for assessment of the pulmonary hila to determine the presence of adenopathy or evidence of direct extension of a lung tumor. Oblique hilar tomography has been shown to be 74 to 80% accurate in such assessments. 19 Computed Tomography.-For the diagnosis of pulmonary disease, CT scanning is an extremely valuable procedure. Currently, it is the procedure of choice for the initial assessment of patients with lung cancer (Fig. 3 C).20 It enables radiologists to evaluate not only the lesion itself, its precise site, and its relationship to nearby structures but also the pulmonary hila, mediastinum, chest wall, liver, and adre-
Fig. 3. Radiologic studies of 64-year-old woman with dyspnea and hemoptysis. Dense atelectasis of left upper lobe was caused by obstructive tumor (grade 3 mixed squamous cell carcinoma and adenocarcinoma) of bronchus. A, Posteroanterior chest roentgenogram. B, Lateral chest roentgenogram. C, Computed tomographic scan of chest.
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nal glands. When necessary, it can be used to guide the bronchoscopist to an otherwise obscure lesion. Approximately 1% of lung cancers are multiple and synchronous." CT can determine the presence or absence of other nodules in the chest. When further testing reveals that a pulmonary nodule is a metastatic lesion, imaging of other areas of the body may disclose the primary tumor." Contiguous thick (usually lO-mm) CT slices are taken through the entire chest before or after contrast enhancement (or at both times). Once located, a lesion can be further evaluated by obtaining thin (1- to 2-mm) CT slices through its center. Calcification is detected by CT in 22 to 30% of solitary pulmonary nodules considered indeterminate by conventional tomography; thus, their status is further clarified." (The approach to solitary pulmonary nodules will be reviewed in another article in this symposium.) Approximately 50% of hamartomas, the third most common pulmonary nodule (after granulomas and carcinomas), contain fat, frequently identifiable by CT.24 Twenty-five percent contain "popcorn" calcification. With use of CT, a solitary pulmonary nodule can be compared with a special reference phantom of the same size, in the same site, and under identical technical conditions.P'" Lesions that contain 10% or more calcification and are found to be more dense than the phantom are likely benign and are usually candidates for observation. Those found to be less dense than the phantom are considered indeterminate; for these lesions, more invasive testing or, occasionally, careful follow-up is necessary. In one study of patients with a previous extrathoracic malignant lesion, 80% of solitary pulmonary nodules detected by CT were actually solitary at operation, in comparison with 54% detected by conventional chest roentgenography." Surgical removal of limited pulmonary metastatic tumors is improving survival among patients with several types of malignant lesions. Comparison scanning with a reference phantom can be misleading in patients who have had prior malignant lesions-such as mucinous carcinomas of the gastrointestinal or genitourinary tract, osteogenic sarcomas, chondrosarcomas, and synovial sarcomas-that tend to be associated with development of calcium-containing metastatic tumors.'? In such patients, we do not use this technique. Recent work by Swensen and associates" at the Mayo Clinic suggested that considerable enhancement of a nodule on CT scanning after intravenous administration of contrast material indicates the likelihood of a malignant lesion. This finding confirms that relationship previously demonstrated by Littleton and colleagues" with use of complex motion tomography. CT scanning has been shown to be 78 to 94% accurate in the detection of hilar involvement with lung cancer. In
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contrast, conventional chest roentgenography is 61 to 71% accurate, and 55-degree oblique hilar tomography is 74 to 80% accurate." For evaluation of the pulmonary hila, we use the thin-slice technique and, frequently, bolus contrast enhancement. Although not optimal, CT scanning can help detect endobronchial lesions by disclosing thickening of the bronchial wall or occlusion of the bronchial lumen. It has been shown to be 50% accurate with central lesions" and approximately 37% accurate with lesions within 2 em of the tracheal carina." Mediastinal adenopathy and extension of carcinoma into the mediastinum can be visualized by CT. Extension of tumor into the mediastinum, heart, or great vessels must be more than minimal, however, to be identified with a high degree of accuracy. In general, lymph nodes larger than 1 em in diameter are considered abnormal; hence, a biopsy can be obtained under CT guidance, at bronchoscopy, or at mediastinoscopy. A patient with lung cancer whose mediastinum appears uninvolved on CT scanning often will undergo surgical treatment without a preliminary mediastinoscopy. In a patient with a suspected lung cancer, we almost always extend our CT examination to include the liver and adrenal glands. Biopsy of an abnormality detected in either location not only is often easier to accomplish and safer for the patient than attempting biopsy of the primary pulmonary tumor but also may simultaneously provide the diagnosis of a malignant lesion and prove the presence of metastatic involvement. Magnetic Resonance Imaging.-The newest modality in our imaging armamentarium is magnetic resonance imaging. This procedure provides multiplanar images, offers a variety of imaging sequences for tissue differentiation, and is flow sensitive. It provides excellent anatomic detail in the chest, usually on the Tl-weighted images, when used with respiratory compensation and electrocardiographic gating, and pathologic changes in the chest are usually well demonstrated on the T2-weighted images. Some of the deficiencies of magnetic resonance imaging are as follows: low signal from pulmonary lesions limits their detectability, motion artifacts may obscure detail, and detection of calcification is difficult. In addition, examinations are expensive, and the equipment is not yet widely available nationwide." Magnetic resonance imaging seems particularly useful in distinguishing scar from residual or recurrent tumor, in evaluating a superior sulcus tumor (Fig. 4), and in determining possible involvement of the brachial plexus with tumor. It is equal to or better than CT in distinguishing dense postobstructive atelectasis or infiltrate from the central mass and in evaluating contiguity or invasion of the chest wall,
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pneumonectomy is being considered, pulmonary function can be determined by using 99mTc-macroaggregatedalbumin to assess overall perfusion. If the product of the percentage isotopic uptake in the contralateral lung and the forced expiratory volume in I minute exceeds 0.8 liter, the patient should be able to tolerate the surgical procedure.W" Another application of nuclear medicine studies is the performance of radioisotope bone and liver scans for the detection of metastatic lesions.
Fig. 4. Magnetic resonance image of chest of 57-year-old man with Homer's syndrome, demonstrating large superior sulcus tumor (Pancoast's syndrome) that caused destruction of rib posteriorly and invaded the chest wall. Tumor was grade 4 adenocarcinoma.
heart, and great vessels. It is useful, as well, in the pulmonary hila and mediastinum, although Tl and T2 values overlap in benign hyperplastic and metastatic lymphadenopathy.P" . Magnetic resonance imaging of the liver seems superior to CT scanning with dynamic contrast enhancement for detecting metastatic involvement but not as effective as the combination of CT scanning and arterial portography." With use of magnetic resonance imaging, Krestin and coworkers" were able to distinguish benign cortical adenomas from malignant adrenal metastatic lesions in 91% of their cases. Additionally, such studies with gadolinium enhancement seem superior to CT scanning in the search for intracerebral metastatic tumors." As previously mentioned, magnetic resonance imaging may be helpful in the posttreatment evaluation of fibrosis or scar versus residual or recurrent tumor because a substantial T2 signal difference exists between mature scar and tumor. Moreover, tumor may show enhancement after administration of gadolinium whereas scar should not. In the occasional patient who is allergic to iodinated contrast material, magnetic resonance imaging can be helpful when CT is not. In our lung cancer practice, magnetic resonance imaging is used primarily as a problem-solving technique when CT scanning and other diagnostic modalities are unable to provide answers to a specific question. Finally, CT scanning is already highly developed, but magnetic resonance imaging should advance because of the continual improvements in hardware and software. Nuclear Medicine Studies.-In patients with lung cancer who have chronic obstructive pulmonary disease for whom
TRANSTHORACIC NEEDLE ASPIRAnON In patients with lung cancer in whom a preoperative tissue diagnosis is important, in patients with a prior malignant lesion who currently have a pulmonary nodule or multiple nodules, and in patients who refuse or have contraindications to surgical treatment, transthoracic needle aspiration is a safe and effective biopsy technique. In our practice, however, in the case of a highly suggestive, apparently surgically resectable lesion in a patient at high risk for lung cancer, the surgical resection will be done without prior performance of such a biopsy. Four percent of solitary pulmonary nodules are metastatic lesions from an extrathoracic carcinoma, and 25% of patients with an extrathoracic carcinoma and pulmonary metastatic involvement have only a solitary pulmonary nodule at the time of initial examination." Tissue obtained by transthoracic needle aspiration may provide the first clue that the patient's primary neoplasm is outside the chest. Transthoracic needle aspiration can be up to 95% accurate in the diagnosis of malignant lesions and 88% accurate for benign Iesions.P-" Although we seldom rely on this procedure for establishing a definite benign diagnosis, this is a major indication for transthoracic needle aspiration at some medical centers. Transthoracic needle aspiration is cost-effective in that it minimizes the time from admission to diagnosis, is often done as an outpatient procedure, decreases or eliminates the need for thoracotomy in patients with small-cell lung cancer or with extrathoracic cancer metastatic to the chest, shortens the overall hospital stay, and thereby reduces total cost." A thorough understanding of the procedure by the patient, the physician, and the surgeon, an experienced radiologist, and a skilled cytopathologist are necessary for an optimal outcome. The procedure is performed by a radiologist in the hospital radiology department under fluoroscopic control; occasionally, CT guidance is used (Fig. 5). The shortest safe route for the needle to traverse is usually chosen, crossing as few pleural surfaces as possible. As previously mentioned, when sites of probable extrathoracic metastatic tumors have been identified during the patient's workup, we often perform a needle biopsy of one or more of those lesions, not
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Fig. 5. In 77-year-old woman who had had headaches and subsequently abnormal chest roentgenographic findings, computed tomography-guided needle biopsy revealed non-small-cell anaplastic carcinoma of lingula with mediastinal extension. Note tip of needle in peripheral aspect of thickened wall, avoiding cavitating portion of tumor.
only to establish the diagnosis but also to substantiate the presence of metastatic involvement. When the biopsy procedure is successful, no malignant cells are found in the material obtained, and no evidence of an endobronchial lesion is noted at bronchoscopy, the lesion may be considered benign, and careful follow-up should be initiated." At the Mayo Clinic, when a biopsy is unsuccessful or when no evidence of a malignant lesion is found at transthoracic needle aspiration, a mediastinoscopy, thoracoscopy, or even thoracotomy is usually performed to determine the definitive diagnosis. Transthoracic needle aspiration is contraindicated in only a few situations-in patients who will receive no obvious benefit, even when a diagnosis is made; in uncooperative patients; in those with a bleeding diathesis, possible vascular lesion, or hydatid cyst; and, in our practice, in patients with a cavitating pulmonary lesion.t'-" Hemoptysis, pneumothorax, air embolism, and death are the potential complications of transthoracic needle aspiration. Hemoptysis is usually minimal. In our experience, approximately a third of the patients will have a pneumothorax, and only 5 to 10% will require a chest tube." For the past several years, we have treated many such pneumothoraces with a small chest tube (7 to 8 F) and a oneway Heimlich valve, placed by the radiologist with use of fluoroscopic guidance. Usually, the tube is removed in 24 hours.
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BRONCHOSCOPY AND BRONCHOSCOPIC BIOPSY Specimens obtained at bronchoscopy are often the means of establishing a cytologic or histopathologic diagnosis of lung cancer. Results of biopsies of central, bronchoscopically visible cancers are almost always positive. In large necrotic tumors or in cases of carcinoma with predominantly submucosal involvement, positive results of a biopsy may be difficult to obtain. Transbronchoscopic needle aspiration of these lesions will often yield positive findings, however." In addition, transbronchoscopic needle aspiration is useful for diagnosing spread of lung cancer to paratracheal, subcarinal, or hilar lymph nodes.tv" During bronchoscopy, fluoroscopically guided needles, biopsy forceps, and cytology brushes can usually be advanced into peripheral lesions that are larger than 2 ern in diameter; thus, diagnosis is possible in 65 to 75% of cases." In peripheral lung cancers smaller than 2 cm in diameter, a positive result of biopsy or cytologic brushing can seldom be obtained." Lung cancer detected only on sputum cytology in patients with normal chest roentgenographic findings can virtually always be localized bronchoscopically by careful visual inspection and biopsy and brushing of suspicious mucosal abnormalities. As previously mentioned, pharyngeal and laryngeal carcinomas as a source of malignant cells must be excluded in these patients. If the cancer is not detected on routine examination with a flexible bronchoscope, we proceed to "long bronchoscopy." General anesthesia is used for the procedure. If no endobronchial lesion is noted on further careful inspection, bronchial biopsy specimens and brushings are obtained from each lobe and from each segment of each lobe of both lungs. These specimens are then submitted separately to the pathologist. Definite localization. is established by positive results of brushings from the same site on two separate bronchoscopies or by one biopsy specimen with positive findings. During bronchoscopy, hematoporphyrin derivative photostimulation can effectively localize occult lung cancer. In our experience, however, this technique is rarely necessary." LYMPH NODE BIOPSY If a palpable supraclavicular (or other) lymph node is found, a biopsy specimen should be obtained. A positive result of biopsy not only establishes the diagnosis of lung cancer but also indicates unresectability and spares the patient an unnecessary thoracotomy. MEDIASTINOSCOPY Mediastinoscopy can be performed as a staging procedure in anticipation of a need for thoracotomy for curative resection
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of a lung cancer. If mediastinal lymph nodes are involved, the tumor is usually unresectable, and nonsurgical therapy should be considered. If the position of the lymph nodes makes biopsy by means of a mediastinoscopy difficult, a limited thoracotomy (Chamberlain procedure) can be performed; thus, the diagnosis can be established without the need for a standard lateral thoracotomy. In this circumstance, an alternative biopsy method may be a needle biopsy with use of fluoroscopic or CT guidance (see previous discussion).
5.
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9.
In certain patients, thoracoscopy may allow a limited surgical procedure for visualization of the pleural space and directed biopsy of pleural and peripheral lung lesions. Thoracoscopic biopsy can be performed through a 2-cm incision in the chest wall. It is particularly useful in diagnosing pleural metastatic lesions that cannot be adequately sampled with pleural fluid cytology or by needle biopsy.
THORACOTOMY Thoracotomy for diagnosis and possibly subsequent resection may be done if the following criteria are fulfilled: (1) the patient has a high risk of lung cancer, (2) a workup for metastatic involvement is unrevealing, and (3) the lung lesion is highly suggestive of cancer on radiographic imaging.
CONCLUSION An effort to diagnose lung cancer will usually be made after a screening chest roentgenogram reveals abnormal findings or when a patient has symptoms of pain, hemoptysis, or a new or changed cough. Diagnostic procedures should prove the presence of the tumor, determine the cell type, and establish the stage. A careful diagnostic approach can accomplish all these goals while minimizing the cost, the discomfort, and the risk to the patient. A single procedure such as a needle biopsy of a hepatic metastatic lesion may prove the diagnosis and establish both the cell type and the unresectability. Appropriate therapy can then be planned.
6. 7.
8.
10.
11.
12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22.
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End of Symposium on Intrathoracic Neoplasms, Part II.
Part III will appear in the April issue.