Secondary Lung Tumors Workup

  • Author: Daniel S Schwartz, MD, FACS; Chief Editor: John Geibel, MD, DSc, MA   more...
 
Updated: Oct 14, 2011
 

Laboratory Studies

The usual preoperative laboratory workup of any thoracic patient should include a coagulation profile consisting of a platelet count, international normalized ratio, and activated partial thromboplastin time. A complete blood count and electrolyte count should also be performed to screen for any hematogic derangements such as anemia or electrolyte abnormalities (eg, hypokalemia) that could impact anesthesia.

Cancer-specific tumor markers

Follow-up of cancer-specific tumor markers in serum is rarely clinically useful for diagnosis or prognosis. Examples of tumors in which serum markers can help increase the specificity of imaging studies for establishing the diagnosis of pulmonary metastases include the following:

  • Nonseminomatous testicular germ cell tumors in which the elevated levels of alpha-fetoprotein and/or the beta subunit of human chorionic gonadotropin can help predict tumor recurrence
  • Well-differentiated papillary or follicular thyroid cancer (by identification of elevated thyroglobulin levels)
  • Prostate cancer in which any detectable prostate-specific antigen in the serum after initial treatment suggests persistent disease or recurrence
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Imaging Studies

  • Chest radiography
    • Chest radiography is still recommended as the initial imaging procedure for the evaluation of cancer patients for possible pulmonary metastases. However, because of poor yield, it is rarely recommended as a part of the initial workup for common cancers (eg, breast cancer, colon cancer) at an early stage.
    • This is reflected by the observation that lung metastases have been detected using radiography in only 0.1% of the patients with stage I breast cancer. Chest radiographs are limited by the potential to overlook lesions located in the lung apices, posterior sulci, or against the heart or mediastinum and by their overall poor sensitivity for lung nodules of less than 1.6 cm in diameter, which is far less sensitive than CT scanning.
    • Overall, approximately 25% of the total lung volume is not readily accessible for visual examination using plain posteroanterior chest radiography.
  • Conventional CT scanning
    • Conventional CT scanning of the chest from the level of the superior thoracic aperture to the adrenal glands is superior to plain chest radiography for the detection of pulmonary nodules and mediastinal lymph node involvement. Spiral CT scanning further increases the odds of detecting pulmonary nodules.
    • Increased sensitivity comes at the cost of somewhat decreased specificity compared with both standard chest radiography (posteroanterior and lateral) and conventional CT scanning. However, the specificity of a test is strongly influenced by clinical circumstances. Thus, in a highly selected group of patients (eg, those with osteogenic sarcoma or soft tissue sarcoma, tumors that both have a high propensity for metastasizing to the lungs), 95% of nodules on the CT scan have been shown to represent metastases.
    • In a patient with a known extrathoracic malignancy and a solitary pulmonary nodule on the CT scan, the following scenarios have been proposed:
      • With a history of sarcoma or melanoma, the pulmonary nodule is more likely to be a metastasis.
      • In the case of underlying head and neck cancer or breast cancer, a second primary cancer in the lung is more likely.
      • With other malignancies, the nodule is equally likely to be a primary lung cancer or metastatic disease.
    • Malignant lesions account for 3-10% of CT scan–detected pulmonary nodules. In an older patient, a solitary nodule is more likely to be malignant (lung cancer, in particular); in a younger patient, multiple nodules are more likely to be metastases. However, the number of pulmonary nodules is generally not helpful in distinguishing between benign and malignant lesions. Generally, the larger the nodule, the more likely it is to be malignant (80% of solitary nodules >3 cm in diameter were malignant, compared with 20% of nodules < 2 cm), although autopsy data show that 57% of all metastases are 1-5 mm in diameter. Most of the nodules resected at the time of thoracotomy but not seen on a CT scan are small, fibrous lesions.
    • Calcified pulmonary metastases are observed with osteogenic sarcoma, chondrosarcoma, synovial sarcoma, ovarian cancer, breast cancer, colon cancer, and thyroid cancer. Cavitation occurs in pulmonary metastases of sarcomas and squamous cell carcinoma, as well as after treatment. The mass-vessel sign (ie, a vessel entering the medial aspect of a discrete nodule) indicates hematogenous metastasis. Irregular nodule margins indicate a poor prognosis. An ill-defined margin is observed in choriocarcinoma and in other cancers after chemotherapy, indicating hemorrhage.
    • Patterns of calcification strongly suggestive of a benign nature of a nodule are diffuse homogenous calcification, central calcification, laminated concentric calcification, and popcorn calcification. A doubling time from 20-400 days is consistent with a malignant lesion. Doubling of the volume means that a nodule of 0.5 cm in diameter increases by 0.12 cm in diameter, a nodule of 1 cm increases by 0.26 cm in diameter, a nodule of 2 cm increases by 0.52 cm in diameter, a mass of 3 cm in diameter increases by 0.78 cm in diameter, and so forth. Absence of any changes in size over a 2-year follow-up period is generally accepted as evidence of the benign nature of the nodule. Thin-section CT scanning with 3-dimensional reconstruction of the nodule is a particularly accurate method for assessing size changes.
      • Mediastinal nodes are considered positive on CT scans by size criteria, namely, if the short axis is 1 cm or greater. Nineteen percent of nodes from 0.5-1 cm have been reported positive for micrometastases. Seventy-five percent of lymph nodes with cancer involvement are 1 cm or greater in diameter.
      • High-resolution CT scanning is the imaging procedure of choice for lymphangitic carcinomatosis. Characteristic findings include thickened septal lines, prominent reticular patterns, nodular thickening of bronchovascular bundles, polygonal lines, and beaded septa. Hilar or mediastinal lymphadenopathy, lung masses, and lung nodules are also commonly identified. Compared with sarcoidosis (a model of benign interstitial lung disease), lymphangitic carcinomatosis is more commonly unilateral or markedly asymmetric and is associated with fewer nodules and less distortion of surrounding lung parenchyma.
  • Whole-body positron emission tomography scanning (oncologic PET-CT scan)
    • PET scanning has an increased specificity for cancer compared with CT scanning. This investigative tool takes advantage of the increased metabolic activity of the cancer cells, which are known to use glucose substrate more intensely than most of the normal cells.
    • Limitations include an inability to detect brain metastases, false-negative results in diabetic patients and in patients with malignant lung nodules less than 1 cm in diameter (size has not been shown to play a role in the detection of mediastinal lymph node metastases), and false-positive results in persons with granulomatous or inflammatory diseases. Cost remains an important consideration when ordering this test.
    • Fusion of CT scan and PET scan images (integrated CT-PET) is now widely available and very commonly used in clinical practice. Integrated CT-PET has been shown to be superior in anatomic localization and metabolic characterization of lesions when compared with CT scan alone, PET alone, or using both CT scan and PET scan and visually correlating the abnormalities.
    • In a retrospective study of 50 patients who underwent integrated CT-PET for staging of lung lesions suspicious for lung cancer, CT-PET correctly predicted T status in 86% of patients, N status in 80% of patients, M status in 98% of patients, and TNM status in 70% of patients. Correct prediction rates with CT scan alone were 68%, 66%, 88%, and 46%, respectively. With PET scan alone, the correct prediction rates were 46%, 70%, 96%, and 30%, respectively. With CT scan and PET visual correlation, the correct prediction rates were 72%, 68%, 96%, and 54%, respectively.
  • Technetium Tc 99m–labeled somatostatin analog depreotide single-photon emission CT scanning is used for evaluation of pulmonary nodules and staging of lung cancer, with reported sensitivity and specificity comparable to that of PET scanning.
  • Indium In 111–labeled somatostatin analog octreotide scanning is recommended for localization of carcinoid tumors.
  • Whole body iodine I 131 scanning is recommended for the diagnosis of metastatic thyroid cancer.
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Other Tests

  • Immunohistochemistry: The combination of a stepwise approach, with initial clinical and radiological evaluation and a biopsy procedure, followed by histologic evaluation with extensive immunohistochemistry may yield a final classifying diagnosis in up to 50% of the patients who are not otherwise diagnosed.[4]
  • Gene expression: In the remaining patients who are not otherwise diagnosed, further classification based on gene expression may then be expected to provide additional classifying information.[22, 23] {Ref53}[24] The other approach would be a rather simultaneous method in which the gene expression profile is determined up front. Complete replacement of histologic and immunohistochemical evaluation by these methods has been suggested. Both strategies may have pros and cons in terms of accuracy, time frames, and costs. These different aspects are currently being investigated in a diagnostic trial by a collaborative group within the European Organization for Research and Treatment for Cancer (EORTC CU003CR).
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Diagnostic Procedures

  • Mediastinoscopy
    • Mediastinoscopy is the criterion standard for the diagnosis of mediastinal lymph node metastatic disease. Reported specificity of the procedure is as high as 100%, with a sensitivity of approximately 90%. Cervical mediastinoscopy by the Carlens method is used for the diagnosis of right-sided paratracheal, precarinal, and subcarinal lymphadenopathy. Left-sided parasternal mediastinoscopy is used for the diagnosis of anterior mediastinal and aortopulmonary window lymph node metastases.
    • Mediastinoscopy is an outpatient procedure with a reported complication rate of 2% and a procedure-related mortality rate of 0.2%.
  • Transthoracic needle aspiration biopsy
    • Transthoracic needle aspiration biopsy (TNAB) remains the initial procedure for the diagnosis of pulmonary nodules.
    • A 1999 meta-analysis of 48 studies reported a pooled sensitivity for malignant lesions of 86.1% (range, 83.8-88.4%), with a pooled specificity of 98.8% (range, 98.4-99.2%).[25] CT-guided TNAB was more sensitive than fluoroscopy-guided TNAB, although other factors are used to determine which procedure is more suitable for an individual patient. Also, aspiration biopsy needles were shown to yield better results than cutting needles.
    • Other authors consider bronchoscopy and TNAB complementary procedures and advocate their sequential use.
    • TNAB has been reported to have a high yield for malignant nodules after an indeterminate bronchoscopy.
    • Pneumothorax is the most consistently reported complication of the procedure. The meta-analysis reported a pooled rate of 24.5% (range, 3.1-41.7%). The pooled rate of pneumothorax requiring chest tube drainage was 6.8% (range, 0-16.6%). Bleeding of varying severity, air embolism, myocardial infarction, and local iatrogenic spread of the tumor have also been reported following the procedure.
  • Transbronchial needle aspiration (TBNA)
    • Bronchoscopy with transbronchial needle aspiration (TBNA) for mediastinal lymphadenopathy or peripheral lung lesions, forceps biopsy, brush biopsy, brush-needle biopsy, bronchial aspirate, bronchial washing, or bronchoalveolar lavage (BAL) is used for the diagnosis of endobronchial tumor, lymphangitic cancer, and pulmonary nodule(s), with decreasing order of yield.
    • The overall yield of noninvasive bronchoscopic specimens (ie, bronchial aspirates, bronchial washings, BAL) for diagnosis of peripheral lesions is just less than 50%. The highest yield of BAL is in lymphangitic carcinomatosis.
    • The diagnostic yield of fiberoptic bronchoscopy depends on the lesion location and size, character of the border, and the ability to perform all sampling methods. Diagnostic yield for lesions less than 2 cm in diameter is 54%, compared with 80% for those more than 3 cm in diameter; for lesions located in the lower lobe basilar segments or in the apical segments of the upper lobes, yield is 58%, compared with 83% for other locations; and for lesions with sharp borders, the yield is 54%, compared with 83% for lesions with fuzzy borders. Only one of the sampling methods was positive in 24% of bronchoscopies.
    • The overall yield of invasive bronchoscopic specimens for diagnosis of peripheral lesions is brush at 52%, transbronchial biopsy at 57%, and transbronchial needle aspiration at 51%.
  • Combining TBNA and PET scanning
    • Combining transbronchial needle aspiration (TBNA) and PET scanning has been shown to obviate the need for mediastinoscopy for mediastinal staging of nonsmall cell lung cancer with mediastinal lymphadenopathy in most patients. In a retrospective study of 113 patients with enlarged mediastinal lymph nodes who underwent both TBNA and PET scanning, 51 patients whose histopathology was confirmed by surgical lymph node dissection, the results of the surgical yield were compared with PET scan and TBNA results.
    • Using histopathology by surgical lymph node dissection as the criterion standard, the combined TBNA and PET scan had 100% sensitivity, 94% specificity, 79% positive predictive value, 100% negative predictive value, and 95% accuracy to detect malignant lymph nodes. For PET alone, these rates were 68%, 89%, 46%, 95%, and 86%, respectively; for TBNA alone, these rates were 54%, 100%, 100%, 91%, and 92%, respectively.
  • Navigation bronchoscopy with biopsy
    • This is a newer technology that allows the operator to approach a peripheral lung mass using electromagnetic navigation based on virtual bronchoscopy and real-time three-dimensional (3D) CT images. This technology has been shown to be capable of reaching peripheral lung masses beyond the reach of the standard bronchoscope in an animal model.[26]
  • Endobronchial ultrasound with biopsy
    • Endobronchial ultrasound (EBUS) has been widely adopted by pulmonologists and thoracic surgeons and is poised to replace mediastinoscopy in the future. For thoracic surgeons, the technique can be easily learned, and it may be important to do so to maintain its traditional and important role in the diagnosis and staging of thoracic malignancies.
    • EBUS has been associated with a low rate of serious adverse effects (< 1%) and the procedure is touted to be highly accurate, with false negative rates reported to be between 6% and 9%. EBUS-guided fine needle aspiration biopsy of mediastinal nodes offers a less invasive alternative for histologic sampling of the mediastinal nodes.
  • Esophagoscopy with ultrasound-guided needle aspiration
    • Esophagoscopy with ultrasound-guided needle aspiration (EUS) of accessible lymph nodes is an alternative to transbronchial needle aspiration of lymph nodes accessible from the esophagus. It appears to be complimentary to EBUS.
  • Video-assisted thoracoscopic surgery
    • Video-assisted thoracoscopic surgery (VATS) with lung biopsy is an inpatient procedure with a high diagnostic yield and a low complication rate; it can also be used for curative resection.
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Contributor Information and Disclosures
Author

Daniel S Schwartz, MD, FACS  Assistant Clinical Professor of Cardiothoracic Surgery, Mount Sinai School of Medicine; Chief of Thoracic Surgery, Huntington Hospital

Daniel S Schwartz, MD, FACS is a member of the following medical societies: American College of Chest Physicians, American College of Surgeons, Society of Thoracic Surgeons, and Western Thoracic Surgical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Cynthia S Chin, MD  Assistant Professor, Department of Cardiothoracic Surgery, Mount Sinai School of Medicine; Attending Physician, Department of Cardiothoracic Surgery, Mount Sinai Hospital

Cynthia S Chin, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Surgeons, and American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Benson B Roe, MD  Emeritus Chief, Division of Cardiothoracic Surgery, Emeritus Professor, Department of Surgery, University of California at San Francisco Medical Center

Benson B Roe, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Thoracic Surgery, American College of Cardiology, American College of Surgeons, American Heart Association, American Medical Association, American Society for Artificial Internal Organs, American Surgical Association, California Medical Association, Society for Vascular Surgery, Society of Thoracic Surgeons, and Society of University Surgeons

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Shreekanth V Karwande, MBBS  Chair, Professor, Department of Surgery, Division of Cardiothoracic Surgery, University of Utah School of Medicine and Medical Center

Shreekanth V Karwande, MBBS is a member of the following medical societies: American Association for Thoracic Surgery, American College of Chest Physicians, American College of Surgeons, American Heart Association, Society of Critical Care Medicine, Society of Thoracic Surgeons, and Western Thoracic Surgical Association

Disclosure: Nothing to disclose.

Paolo Zamboni, MD  Professor of Surgery, Chief of Day Surgery Unit, Chair of Vascular Diseases Center, University of Ferrara, Italy

Paolo Zamboni, MD is a member of the following medical societies: American Venous Forum and New York Academy of Sciences

Disclosure: Nothing to disclose.

Chief Editor

John Geibel, MD, DSc, MA  Vice Chair and Professor, Department of Surgery, Section of Gastrointestinal Medicine, and Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director, Surgical Research, Department of Surgery, Yale-New Haven Hospital

John Geibel, MD, DSc, MA is a member of the following medical societies: American Gastroenterological Association, American Physiological Society, American Society of Nephrology, Association for Academic Surgery, International Society of Nephrology, New York Academy of Sciences, and Society for Surgery of the Alimentary Tract

Disclosure: AMGEN Royalty Consulting; ARdelyx Ownership interest Board membership

Additional Contributors

We gratefully acknowledge the contributions of previous authors to the development and writing of this article.

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