A 57-year-old man has a 2-month history of a nonproductive cough. He denies weight loss or hemoptysis. His past medical history is significant for hypertension that is treated with a β-blocker. The patient has had no known exposure to asbestos. He has a 30-pack-year history of tobacco use. On examination, the patient is afebrile and has no significant abnormalities. A chest radiograph (CXR) reveals a 2-cm soft tissue mass in the perihilar region of the left lung field, which appears to be a new lesion that was not present on a CXR obtained 2 years previously.
What should be your next steps?
ANSWER TO CASE 34: Pulmonary Nodule
Summary: A 57-year-old male smoker presents with a left lung mass that is highly suggestive of a malignancy.
• Next steps: A contrast-enhanced computed tomography (CT) scan of the chest that includes the liver and adrenal gland should be obtained to better define the mass and narrow the differential diagnosis. Based on the findings, the most efficient diagnostic technique can be selected. Examples that could be offered to this patient include sputum cytology studies, bronchoscopy with or without a transbronchial biopsy, a transthoracic biopsy, or thoracotomy.
1. Be familiar with the strategy for the evaluation and management of a lung mass in patients with and without a known history of malignancy.
2. Be familiar with the staging and treatment of non–small cell and small cell lung cancer.
3. Understand the role of surgery in the management of pulmonary metastasis.
This solitary pulmonary nodule most likely represents non–small cell lung cancer. The presence of a cough, although nonspecific and common in smokers, should prompt further evaluation when it is new and persistent. With typical tumor doubling time, a 2-cm lung cancer would have been present for nearly 1 year; therefore, the identification of a lesion on CXRs not present 2 years earlier helps narrow the differential diagnosis to either an infectious or a malignant process. The absence of clinical evidence of an infection based on history or physical examination further increases the likelihood of a malignancy. A CT scan of the chest should be obtained to further delineate the mass. The presence or absence of calcifications and their radiographic pattern can assist in narrowing the differential diagnosis, and inclusion of the liver and adrenals, common sites of metastatic lung cancer involvement, can provide staging information. A tissue diagnosis will likely be required; the CT can help define the anatomic location of the mass and will assist in choosing the method of tissue procurement with the highest chance of success.
APPROACH TO: Lung Masses
POSITRON EMISSION TOMOGRAPHY (PET) SCAN: Detects the increased rates of glucose metabolism (positron-emitting glucose analogue) that occur commonly in malignant tumors. It can detect primary lung cancers, metastases to the lung, and mediastinal lymph nodes but may lack anatomic details.
A thorough history and physical examination allow the clinician to generate a differential diagnosis. A patient’s cigarette use, known prior or concurrent neoplasms, family history of cancer, exposure to Mycobacterium, and symptoms of ongoing infection as well as symptoms of metastatic disease are important and may help establish the diagnosis. Patients with a history of prior malignancies who develop a new lung mass should be assumed to have metastatic disease until proven otherwise. Similarly, multiple primary lung cancers occur in less than 2% of patients with lung cancer; therefore, the presence of multiple pulmonary tumors results in a greater likelihood of metastasis or a benign condition. New nodules in smokers as revealed by CXR have a very high risk of malignancy, as high as 70% in some series, and should be approached with a high degree of suspicion.
The initial evaluation should begin with a review of prior CXRs. With serial films the radiologist can determine the rate of growth, allowing a differentiation between benign and malignant disease. If the clinical and radiographic presentations suggest pneumonia, a 10- to 14-day course of antibiotics can be attempted with a mandatory radiographic examination on completion. Persistence of the mass demands further evaluation. The next step in evaluation is a contrast-enhanced CT scan of the chest. The presence of specific patterns of calcifications can be pathognomonic of a benign process; however, some calcified lesions and all noncalcified lesions require further investigation (Figure 34–1).
Figure 34–1. Chest CT of an obstructed right main stem lung tumor. Arrow indicates location of right main stem bronchus. (Reproduced with permission from Brunicardi FC, Andersen DK, Billiar TR, et al, eds. Schwartz’s Principles of Surgery. 8th ed. New York, NY: McGraw-Hill;2005:569.)
The options, in order of increasing aggressiveness, include repeated radiographic evaluation, PET imaging, sputum cytologic studies, transthoracic fine-needle aspiration (FNA), bronchoscopic biopsy, and surgical resection.
The decision concerning which method to use is based on a wide variety of patient variables (age, smoking history, prior granulomatous disease, prior or concurrent cancers, and family history of cancers) and tumor variables (size and location). As a general rule, patients with a high risk of malignancy are evaluated with more invasive methods providing more information (ie, some form of biopsy or surgical resection), whereas those with a low risk of cancer or significant concomitant medical problems are evaluated initially with less invasive methods. PET scanning combined with CT imaging can effectively diagnose a malignancy (sensitivity, 82%-100%; specificity, 75%-100%) but is less effective with smaller lesions (<1 cm) or when concomitant infection is present. The use of sputum cytologic studies can assist in obtaining a tissue diagnosis in 10% to 15% of cases, with higher rates of detection for centrally located lesions. Transthoracic FNA and bronchoscopic biopsies are highly effective when applied to appropriately positioned lesions (peripheral and central, respectively). Finally, surgical resection can be used for patients with a high risk of malignancy and a peripherally based lesion. Although it is the most aggressive method, it does have the greatest accuracy and can simultaneously diagnose and treat an early-stage lung cancer. This advantage actually makes it relatively cost-effective in patients with a high risk of lung cancer (eg, a 65-year-old heavy smoker with hemoptysis but otherwise asymptomatic who has a new lung mass).
Once cancer is diagnosed, every effort should be made to obtain accurate clinical staging of the disease. Staging of non–small cell lung cancer uses the tumor-node-metastasis (TNM) system and is outlined in Tables 34–1 and 34–2. The T status is determined using CT scanning as well as any information obtained on bronchoscopy. Magnetic resonance imaging (MRI) of the chest may help with lesions involving the brachial plexus and the spine. The N status is determined by physical examination, CT imaging, the results of any biopsies (FNA of palpable nodes, transbronchial FNA of mediastinal nodes, scalene node biopsy, or mediastinoscopy), and, most recently, PET scanning. The M status is determined by physical examination, radiographic techniques (MRI of the brain, CT scanning of the chest with inclusion of the liver and adrenals), and nuclear medicine techniques (bone scanning and PET scanning). The five most common sites of metastasis should be examined, namely, the contralateral and noninvolved ipsilateral lung, liver, adrenals, bone, and brain. For very-early-stage lesions, evaluation of the bone and brain can be reserved for patients exhibiting symptoms of metastatic involvement of these organs. However, these techniques should not preclude a thorough physical examination because lung cancer can metastasize to any location.
Table 34–1 • DEFINITIONS OF T, N, AND M CATEGORIES FOR CARCINOMA OF THE LUNG
Table 34–2 • AJCC STAGE GROUPING OF TNM SUBSETS
Small Cell Carcinoma
Staging of small cell lung cancer is much less involved because of the advanced nature of this disease at presentation. Patients have limited disease (confined entirely within the chest), extensive disease, or extrathoracic metastasis. Small cell carcinoma is associated with paraneoplastic syndromes, which are effects not related per se to the cancer itself, but due to the immunological or other endocrine effect. These include Eaton-Lambert myasthenia gravis–like effect, hypercalcemia, Cushing syndrome, syndrome of inappropriate antidiuretic hormone (SIADH), and paraneoplastic cerebellar degeneration. Very rarely, small cell lung cancer is incidentally discovered at an early stage, and in these situations it can be treated using the staging system for non–small cell lung cancer.
Lung Cancer Treatment
The treatment of lung cancer depends on the histology (small cell versus non–small cell) and the stage of the disease. For non–small cell lung cancer, early-stage disease is primarily treated with surgery, whereas later stages are managed with chemotherapy with or without radiotherapy. However, all treatments depend on the physiologic reserve of the patient. Therefore, concurrent with evaluation of the tumor, a thorough examination of the pulmonary and cardiac systems should be performed. This consists of complete pulmonary function testing and in selected cases a more extensive evaluation, including exercise oxygen consumption studies. Smoking cessation for at least 2 weeks is mandatory, and pulmonary function can be improved dramatically with this single intervention. Patients at risk of cardiac disease should undergo evaluation by a cardiologist, with aggressive examination and treatment of any signs or symptoms of coronary artery disease. For small cell lung cancer, limited disease is treated with combination chemotherapy and radiotherapy, whereas patients with extensive disease are offered palliative chemotherapy with radiation reserved for symptomatic relief only. Figure 34–2 outlines the treatment of small cell and non–small cell lung cancer.
Figure 34–2. Simplified treatment approach for non–small cell and small cell lung cancer.
Patients with early-stage non–small cell lung cancer who are poor candidates for surgery due to comorbidities could be considered for stereotactic ablative radiotherapy (CyberKnife). With this approach, high-dose and focused radiation is delivered to the tumor. Early observations of treatment have resulted in 5-year local disease control rates of 30% to 50% with 5-year survival rates of 10% to 30%.
Management of Pulmonary Metastasis
Patients with metastatic lung disease who primarily receive chemotherapy usually have very poor outcomes. However, in very specific cases, surgical extirpation can lead to a reasonable chance of cure. The minimal necessary criteria include local control of the primary tumor, metastatic disease confined to the lung parenchyma, disease that is resectable, and adequate pulmonary reserve to tolerate the planned resection. When these criteria are used, 5-year survival rates approximate 30%. Other criteria that can be considered before surgical resection is recommended include tumor doubling time, disease-free intervals, and the number of metastases.
Lung Cancer Screening
The screening of high-risk patients with sputum cytology or by CXR is not sensitive enough to reliably identify lung cancers at the resectable stages. A current trial involving the screening of high-risk patients using CT scans is ongoing.
34.1 A 45-year-old nonsmoker is found to have a 2-cm soft tissue mass in the left lung. Which of the following is the most appropriate next step?
A. Perform a CT-guided biopsy of the mass.
B. Obtain sputum samples.
C. Evaluate all previously obtained CXRs.
D. Obtain a repeated CXR in 6 months.
E. Perform a video-assisted thoracoscopic resection
34.2 A 45-year-old man with a persistent cough was noted to have a suspicious lesion on a CXR. The physician orders a CT scan of the chest. Which of the following describes the main purpose of CT imaging of chest masses?
A. Discern between a pleural effusion and transudate.
B. Differentiate between malignant and benign neoplasm.
C. Determine if the mass is infectious in etiology.
D. Differentiate between primary and metastatic masses.
E. Determine the anatomic location of the mass.
34.3 Which of the following patients is the best candidate to undergo resection of pulmonary metastases?
A. A 33-year-old woman, who is a nonsmoker presenting with two isolate left lung nodules measuring 3 cm in diameter. Biopsy of one of the lesions has revealed adenocarinoma of unknown primary source.
B. A 46-year-old man with a history of left thigh soft tissue sarcoma, who underwent complete resection of the primary tumor. He has remained without evidence of disease recurrence for 3 years. Recently developed a 2-cm mass in the left lung that has been confirmed at sarcoma by FNA.
C. An 86-year-old woman with history of chronic obstructive pulmonary disease (COPD) who underwent treatment of rectal cancer (T3 N1) 3 years ago, and she presents with a newly discovered 5-cm mass in the left lung that is in the left lower lobe.
D. A 23-year-old man with a pigmented skin lesion on the left shoulder. Biopsy has revealed malignant melanoma, and imaging studies have identified 1-cm suspicious mass in the left frontal lobe of his brain and a 2-cm mass in his right lung.
E. A 45-year-old man with a 6-cm left lung small cell carcinoma.
34.4 A 53-year-old man with 20-pack-year smoking history presents with 2-week history of productive cough. The chest x-ray reveals a right middle lobe infiltrate. Which of the following is the most appropriate management?
A. CT scan of the chest, pulmonary function test, and thorascopic wedge biopsy of the right middle lobe.
B. Antibiotic therapy for 2 weeks, followed by repeat chest x-ray. If infiltrate persists, proceed with CT of chest and bronchoscopy.
C. CT scan with CT-guided biopsy.
D. Right thoracotomy and right middle lobe resection.
E. Bronchoscopy brushings and biopsy.
34.5 Which of the following tumor characteristics of non–small cell lung cancer does contraindicate pulmonary resection?
A. Involvement of the parietal pleura by a 3-cm tumor
B. 2.5-cm tumor with a single 1.5-cm peribronchial node on the ipsilateral side
C. 3-cm left lower lobe tumor with left pleural effusion that contains malignant cells
D. 5-cm tumor involving the right upper and middle lobe
E. 4-cm central lesion involving the right mainstem bronchus
34.1 C. Evaluation of all available CXRs is a reasonable first step in treating any patient with a newly identified lung mass. A new mass will most likely suggest malignancy, whereas a mass that was present and unchanged on numerous prior radiographs is perhaps infectious. Further evaluation or follow-up would still be required after the review of prior CXRs.
34.2 E. The primary purpose of CT imaging of chest masses is to determine the anatomic location of the lesion, not whether it is benign or malignant. CT also provides additional information regarding the presence or absence of mediastinal lymphadenopathy.
34.3 B. This is a 40-year-old man who apparently had complete resection of extremity soft tissue sarcoma 3 years ago, who now presents with a single pulmonary metastasis. Resection of the metastasis is reasonable if no other site of metastasis is identified. The patient in choice A has a pulmonary metastasis without location or treatment of the primary site; therefore resection of the metastasis is not indicated. The patient in choice C has a lesion that may be treatable by surgery, but, because of her advanced age and comorbid conditions, the risk-benefit analysis makes surgery less desirable. The patient presented in choice D has multiple sites of metastases, therefore is unlikely to benefit from the resection of these lesions. The patient presented in choice E has localized small cell lung cancer, which is treated by radiation therapy and chemotherapy.
34.4 B. Initial antibiotic treatment with follow-up of CXR is appropriate for a smoker who presents with a cough. More aggressive follow-up is appropriate, if the infiltrate persists after treatment because the infiltrate and infection can be produced by partial airway obstruction by a tumor.
34.5 C. Pleural effusion associated with lung cancer is common and is not always produced by the tumor; however, in this case the presence of malignant cell indicates extension of the tumor into the pleural space that precludes operative treatment. Isolated parietal pleura involvement by tumor extension can be treated with en bloc resection of the lung, involved pleura, and chest wall. A 2.5-cm primary lung cancer with peribronchial or ipsilateral hilar nodal involvement constitutes stage IIA non–small cell carcinoma, which is best treated by pulmonary resection with chemotherapy + radiation therapy. A patient with tumor involvement of the right upper and middle lobe can still be successfully treated by lung resection if his/her pulmonary reserve is adequate. Isolated lung cancer involving the mainstem bronchus could be completely resected by a pneumonectomy.
Approximately 95% of patients with lung cancer present with symptoms related to the disease, whereas only 5% present with asymptomatic chest findings.
Cough is the initial presenting symptom in 75% of patients with lung cancer, and this cough is produced by endobronchial tumor growth causing inflammation or irritation of the airway.
Approximately 10% to 20% of lung cancer patients are affected by paraneoplastic syndromes, and these syndromes are most commonly associated with small cell and squamous carcinoma.
Gibbs IC, Loo BW. Cyberknife stereotactic ablative radiotherapy for lung tumors. Technol Cancer Res Treat. 2010;9:589-596.
Nason KS, Maddaus MA, Luketich JD. Chest wall, lung, mediastinum, and pleura. In: Brunicardi FC, Andersen DK, Billiar TR, et al, eds. Schwartz’s Principles of Surgery. 9th ed. New York, NY: McGraw-Hill; 2010:513-590.
Robinson CG, Bradley JD. The treatment of early-stage disease. Semin Radiat Oncol. 2010;20:178-185.