eMedicine Specialties > Thoracic Surgery > Tumors

Secondary Lung Tumors

Author: Daniel S Schwartz, MD, FACS, Assistant Clinical Professor of Cardiothoracic Surgery, Mount Sinai School of Medicine; Chief of Thoracic Surgery, Huntington Hospital
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
Contributor Information and Disclosures

Updated: Jan 7, 2010

Introduction

Secondary lung tumors are neoplastic lesions originating at a site distinct from the primary lesion. They develop in another part of the body and then spread to the lung through the bloodstream, through the lymphatic system, or by direct extension. These secondary cancers are identified by the site of origin. Thus, a colon cancer that metastasizes to the lung is still known as a colon cancer. In children, most lung cancers are secondary.1

Almost any cancer has the ability to spread to the lungs, but the tumors that most commonly do so include bladder cancer, colon cancer, breast cancer, prostate cancer, sarcoma, Wilms tumor, and neuroblastoma. Primary lung cancers themselves most commonly metastasize to the adrenal glands, liver, brain, and bone.2

Secondary lung tumor is a term that is also used for the malignancies that arise in the lungs as a consequence of therapy for cancer (eg, chemotherapy, radiotherapy, bone marrow transplant). This article is not intended to cover the description of such tumors.

The differential diagnosis of discrete masslike lesions of the lung that appear in a patient with a known primary tumor includes secondary lung tumors (defined above), unrelated primary malignancy (so-called synchronous second primary tumor), and benign neoplastic or nonneoplastic lesions.

Spread to the lungs is usually the marker of an advanced malignant disease, but spread can occur as an isolated early event. In certain circumstances, surgical resection with curative intent can be performed, with a reported 5-year survival rate as high as 30-40%, depending upon the underlying primary malignancy and the selection criteria for surgery.

Radiographically, secondary lung tumors can manifest as discrete nodules (single or multiple), interstitial infiltrate(s), or endobronchial lesions with or without distal atelectasis or postobstructive pneumonitis. They often have a characteristic round appearance on chest radiograph.3

Lung metastases can commonly cause no symptoms, or they can be the major cause of morbidity. Symptoms include hypoxemia, dyspnea, cough, and hemoptysis. Hypoxemia and dyspnea are most commonly observed in patients with lymphangitic spread, and cough and hemoptysis are associated with endobronchial metastases. Palliative care to address symptoms or local treatment with curative or palliative intent may be indicated.

Another clinical scenario not infrequently encountered is an incidental finding of secondary lung cancer of unknown origin, known as adenocarcinoma of unknown primary (ACUP). Diagnostic strategies of ACUP after the initial clinical and radiologic stepwise evaluation include extensive immunohistochemistry, which may yield a final classifying diagnosis in up to 50% of patients, followed by gene expression (or reverse transcription–polymerase chain reaction [RT-PCR]), which may then be expected to provide additional classifying information in the remaining patients.4,5,6,7

In this article, the approach to secondary lung tumors is discussed, with an emphasis on clinical decision-making to determine whether tissue diagnosis would alter clinical management. Also discussed is the multidisciplinary approach to determine when the continued systemic treatment with chemotherapy for metastatic disease should be accompanied by radiation, surgery, or both.

History of the Procedure

Chest radiography

 Recognition of secondary pulmonary tumors has increased with advances in chest radiography. Chest radiography, consisting of high quality posterior-anterior (PA) and lateral radiographs, remains the most common imaging study in the initial staging evaluation of lung cancer patients. Improvements in techniques, including the use of Advanced Multiple Beam Equalization Radiography (AMBER) and, more recently, a digital slot-scan charge-coupled device (CCD) system, has improved the utility of this simple and inexpensive staging modality.

LJ Kroft showed that AMBER and the newer CCD digital film systems were equivalent in detecting phantom nodules in or around the mediastinum (135/288 or 46.9% and 128/288 or 44%, respectively), but both of these technologies were superior to older Bucky screen film technology (65/288 or 22.6%; P <0.001).8 Other studies using chest CT scans as the criterion standard, however, failed to confirm a significant advantage of these newer techniques over standard chest radiographs.9

Computed tomography

With the introduction of CT scanning in the 1970s, remarkable advances have been made not only in clinicians’ ability to diagnose lung cancer but, more importantly, in clinically staging it. A CT scan can define the location, size, and anatomical characteristics of a tumor far better and more precisely than a chest radiograph9 , and they are used to delineate the locoregional extent and distal spread of a lung tumor.

The major advantages of CT are related to its axial format, its higher density resolution, and its wider dynamic range. Continuous technical improvements and the development of more powerful and faster computers are responsible for the fact that today’s CT examinations of the chest result in a large amount of detailed imaging information obtained in a very short time. Because of this evolution in technique, and the development of new therapeutic strategies for lung cancer, and the recent introduction of positron emission tomography (PET), the contribution of CT to the staging of patients with lung cancer is fluid.10  

Identification of smaller lesions offers the opportunity for improved diagnosis and earlier treatment of metastatic disease. The impact of early intervention is likely to be beneficial. However, the magnitude of benefit has not been clearly documented by the literature. The increased sensitivity of CT scanning has also resulted in an increased frequency of identification of nonmalignant lesions, which must be distinguished from true malignancies, as outlined below.

Magnetic resonance imaging

Magnetic resonance imaging (MRI) of pulmonary pathology offers little improvement over CT scanning with a few exceptions. MRI is often superior to other imaging modalities in the investigation of paravertebral tumors and superior sulcus tumors. In paravertebral tumors, imaging of the spinal canal without contrast media is possible. The use of routine MRI for all lung cancer is probably superfluous and not cost-efficient. Its use should be reserved for times when local tumor invasion of the mediastinum, thoracic inlet, or paravertebral region is questioned on CT scanning.11

Positron emission tomography

Positron emission tomography (PET) is a physiologic imaging modality that is fundamentally based on the detection of positrons emitted by isotopes of atoms with low atomic weights. Fluorodeoxyglucose (FDG), a D-glucose analogue, is the compound most commonly used for PET imaging. It is a D-glucose labeled with a positron emitting18 F. Cells uptake and phosphorylate FDG as if it were glucose. However, FDG is not metabolized further and tends to accumulate intracellularly.

In general, malignant cells typically have a higher rate of glucose metabolism than normal cells. Thus, the intracellular accumulation of FDG, coupled with the preferential accumulation of glucose or its analog in malignant cells, leads to the visualization of malignancies on PET scan. PET scanning is currently used as a diagnostic and staging tool in cancer. In particular, in recent years, PET scanning has been applied to staging lung cancer.12 It has a high likelihood of assessing the malignant potential in a pulmonary nodule, particularly if it is solid and larger than 1 cm in diameter. A standard uptake value of greater than 3is sensitive and specific for cancer.13

Metabolic imaging of the lungs (eg, PET scanning) is now widely used in clinical practice. The ultimate aim of various advances in lung cancer imaging is to enable clinicians to distinguish between malignant and nonmalignant lesions without the need for tissue sampling. This goal has not yet been achieved. However, these newer imaging modalities play an increasingly important role in clinical decision-making algorithms, research, and drug development.12 14 13

PET/CT scan combination
As previously discussed, PET has been shown to be more accurate than CT scanning; however, inaccuracies remain, including a high incidence of false positives.15 The combination of PET with CT scanning into a single image modality, known as a PET-CT scan, has enhanced the ability to spatially identify structures that could more accurately evaluate the stage as well as the individual T, N, and M status in patients with non-small cell lung cancer (NSCLC).16

The terminology for PET-CT software and hardware can be confusing. The 3 primary modalities of PET-CT scanners are hybrid, fusion, and visually correlated. The hybrid or integrated PET-CT scanner create 2 images: one relies on CT, the other on PET. A computer then merges the 2 scans into a single image. This is the most accurate and specific system to date for the staging of NSCLC. It is more expensive than PET, CT, or fusion software alone. Fusion PET-CT scanners use software to create a 3D model of the CT study, a 3D model of the PET transmission study, and then an algorithm to compare and provide an overlay of images. It is less costly but may not be as accurate as integrated PET-CT for NSCLC.17 With fusion software, the CT and PET scans may be obtained on different dates; however, this increases the artifact because of different positioning, respiration, and other movement between scans. The fusion software can also be used with MRI. With visually correlated PET-CT scans, the radiologistvisuallyand manually compares CT and PET scans side by side. The examinations can be performed on different dates or at different facilities; however, this modality has been shown in several studies to be far less accurate.17,18

With any PET-CT modality, the clinical stage often differs from the pathologic stage. In other words, significant false positives and negatives remain. The value of PET-CT scans helps direct the surgeon toward targets for biopsies to rule out nodal or systemic disease. All suspicious areas should be biopsied, but the practice of calling a positive PET or PET-CT scan definite evidence of cancer is absolutely wrong.

The application of PET-CT to the future of lung cancer staging is hopeful. With the advent of newer technologies, more advanced machines with enhanced resolution are on the horizon. Currently only FDG-18 is used, but new radiopharmaceuticals and the prospects for developing other new radiotracers for imaging seems to be promising.19 As previously, any new radiotracer must be carefully assessed to determine its accuracy at each nodal station and at each metastasis site.

Problem

Secondary lung tumors are neoplastic lesions originating at a site distinct from the primary lesion. They most typically appear as well-circumscribed, noncalcified nodules.2

Secondary lung tumors are identified when patients are evaluated for symptoms such as chest pain, dyspnea, cough, or hemoptysis; when patients with known primary tumors are being staged for metastases; or incidentally when patients are undergoing screening chest radiography, CT scanning, or PET/CT scanning.

The presence of hypoxemia cannot be explained by a cancerous process in the absence of lymphangitic spread, major lung collapse, or massive pleural effusion. Thus, it is usually a finding in patients with advanced disease. The presence of hypoxemia in the absence of these conditions should prompt the search for causes such as pneumonia, pulmonary thromboembolism, tumor emboli syndrome, pulmonary venoocclusive disease associated with certain cancers or chemotherapies, interstitial fibrosis secondary to chemotherapy or radiation, or an infectious etiology.

The clinical decision to pursue tissue diagnosis depends on whether confirmation of clinical findings would alter treatment. Treatment of secondary lung tumors can be performed for curative intent, to reduce or eliminate tumor burden, or to palliate disease.

Frequency

The primary tumor can arise within the lung or outside the lung. Metastatic malignant neoplasms are the most common form of secondary lung tumors. Lung metastases are identified in 30-55% of all cancer patients, though prevalence varies based on the type of primary cancer. Benign neoplasms (eg, benign metastasizing leiomyomas) are uncommon exceptions.

Etiology

Any cancer can metastasize to the lungs, and the following neoplasms are most likely to spread to the lungs:

The finding of a solitary pulmonary nodule is not specific, and the differential diagnosis includes any type of cancer and a number of nonmalignant etiologies.

Multiple pulmonary nodules of cannonball appearance are associated with colorectal cancer and sarcoma. Thyroid cancer and ovarian cancer are more commonly associated with a miliary pattern. Both types of pulmonary nodules are associated with renal cell cancer and melanoma.

Endotracheal and endobronchial metastases are more likely to be found in patients with breast cancer, colorectal cancer, pancreatic cancer, renal cell cancer, and melanoma. Isolated airway metastases are considered rare; 6.3% of all endobronchial malignant lesions observed by bronchoscopy are metastatic tumors. Autopsy series reported macroscopic involvement of the trachea and bronchi in 19-51% of all carcinomas metastatic to the lungs. The mean time from excision of the primary tumor to diagnosis of the endobronchial metastasis is 33.9 months (range, 9-156 mo).

The cancers most commonly associated with lymphangitic spread into the lungs include breast cancer, stomach cancer, pancreatic cancer, prostate cancer, and lung cancers, particularly small cell cancer and adenocarcinoma.

Pathophysiology

The mechanisms of cancer spread into the lungs are direct extension and true metastatic spread through the bloodstream, airway, or lymphatic system. Iatrogenic implantation of a primary tumor is exceedingly rare.

Direct extension

 Cancer spread through direct extension is not frequently encountered and most commonly includes direct invasion from a primary neoplasm involving a contiguous organ or structure (eg, thyroid, esophagus, thymus, chest wall) or from a neoplasm metastatic to another intrathoracic structure (eg, rib or mediastinal lymph node, commonly causing an obstructive lesion of the trachea or bronchus). Direct extension can also occur through a vascular route, such as the spread of renal cell cancer or testicular germ cell cancer as tumor thrombus into the lung via the inferior vena cava and right side of the heart.

Metastatic spread

True metastases occur via the pulmonary arteries or bronchial arteries, via the pulmonary lymphatics, across the pleural cavity, or, infrequently, via the airways.
  • Arterial  
    • The pulmonary arteries are the most common route for metastases. Cancers most likely to metastasize to the lungs include those with a rich vascular supply draining directly into the systemic venous system. 
    • Spread via bronchial arteries may be responsible for some endobronchial metastases. Other proposed modes of endobronchial spread include bronchial invasion from parenchymal lesions, via involved mediastinal or hilar lymph nodes, and extension along the proximal bronchus.
  • Lymphatic
    • Lymphangitic spread can be in association with hematogenous dissemination, which is subsequently followed by invasion of the adjacent interstitium and lymphatics, with subsequent tumor spread toward the hila or toward the periphery of the lung.
    • Lymphangitic spread can also be via retrograde spread of tumor from the originally affected mediastinal or hilar lymph nodes, with consequent obstruction of lymphatic flow.
  • Pleural: Pleural spread most frequently results in pleural metastases in the caudal and posterior parts of the pleural cavities.
  • Airway: Spread via airways is rare and difficult to prove, except in the case of bronchoalveolar carcinoma.

Presentation

Solitary pulmonary nodules occurring as the single site of distant metastatic spread is frequently the presenting finding; patients with this type of spread are most commonly asymptomatic. This is particularly common in renal cell cancer, Wilms tumor, testicular cancer, and sarcomas, but the finding of a solitary nodule is not specific and can be observed in any type of cancer.

Patients with multiple pulmonary nodules as a result of metastatic spread can be asymptomatic, especially those with indolent, slow-growing cancers such as papillary thyroid cancer or adenoid cystic carcinoma of the salivary gland. However, the clinical presentation of patients with pulmonary metastatic lesions occurring late in the course of advanced extrapulmonary cancer is commonly dominated by the signs and symptoms of advanced/terminal malignant disease and by signs and symptoms associated with the primary cancer.

Lymphangitic spread of the cancer into the lungs is associated with the recent onset of rapidly progressive dyspnea at rest and, occasionally, dry cough. This pattern is usually encountered in patients with a known history of cancer, most commonly of the breast, stomach, pancreas, or prostate.

Endotracheal and endobronchial metastases can be associated with new-onset cough, shortness of breath, and, occasionally, hemoptysis and chest pain. Upon physical examination, signs of atelectasis, postobstructive pneumonitis, or postobstructive air-trapping can be evident. However, most patients are asymptomatic.

Indications

Surgical treatment of secondary lung tumors should be considered for a pulmonary metastasis of primary lung cancer and, infrequently, for metastases of nonlung primary cancers.

A metastatic nodule in the same lobe as the primary lung tumor was considered a T4 tumor, according to the 1997 TNM classification scheme and now according to the International Association for the Study of Lung Cancer revised 7th edition TNM staging system is considered a T3 lesion. According to the old classification, the presence of 2 malignant nodules of the same histologic type in 2 different lobes on the ipsilateral side of the lung was considered a considered metastatic disease or stage IV lung cancer; now, according to the newly revised staging system, this is considered a T4 lesion and potentially resectable.20

In both cases, surgical management more aggressive than otherwise recommended for the same stage of the disease has recently been advocated. Every effort should be made to document the diagnosis of both individual nodules if located in different lung lobes because the approach is more aggressive if 2 separate synchronous lung cancers are documented. (Synchronous lung cancers are staged separately, but the overall prognosis is poorer than for a single lung cancer of a similar stage.) This becomes particularly important if of the lesions proves benign.

Surgical procedures of choice for the treatment of primary lung cancer tend to be lobectomy or pneumonectomy, depending on the size and the location of the tumor. Surgical decisions are also dictated by the involvement of regional lymph nodes. Meticulous preoperative lung function evaluation with pulmonary function testing (PFT), possibly pulmonary perfusion scanning and possibly cardiopulmonary exercise testing (CPET), is crucial in the marginal group of patients.

Surgery is also indicated for patients with selective primary extrapulmonary cancers in which the lung is identified as the sole site of metastatic disease and in which alternative therapy alone would not likely be effective, provided the patient is otherwise able to tolerate the required lung resection. Favorable outcomes have been reported in cases of resection of multiple lung nodules for select tumors.

The procedure of choice for the treatment of secondary lung tumors is metastasectomy (wedge resection of the malignant nodule) by means of thoracotomy or video-assisted thoracoscopic surgery (VATS). In the case of bilateral metastasis, median sternotomy may be preferable to staged thoracotomy, particularly if VATS is contraindicated. Surgical resection of pulmonary metastasis is always performed with a curative intent. Some authors believe that a thoracotomy is preferred to VATS for the sole reasoning that tactile evaluation is important to the resection of all metastatic disease.21 A prospective study to further examine this issue is underway.21 This is counter-argued by the fact that the efficiency of multislice CT scanning has improved the ability to detect even subcentimeter lesions.

Local control by bronchoscopic intervention is reserved for symptomatic patients with tracheobronchial metastasis, provided that a reasonable life expectancy may be anticipated with successful resection. Options are as follows:

  • Nd:YAG laser resection of the endoluminal tumor
  • Electrocautery
  • Argon plasma coagulation
  • Cryotherapy
  • Brachytherapy
  • Mechanical removal of obstruction with rigid bronchoscopy
  • Endoluminal stent placement

Contraindications

Surgical resection of lung metastasis should not be performed unless the procedure has a significant likelihood of being curative and not disabling based upon predictive postoperative pulmonary function test or cardiopulmonary exercise testing.

More on Secondary Lung Tumors

Overview: Secondary Lung Tumors
Workup: Secondary Lung Tumors
Treatment: Secondary Lung Tumors
Follow-up: Secondary Lung Tumors
References
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Further Reading

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Keywords

secondary lung tumors, secondary pulmonary tumors, metastatic malignant neoplasms, metastatic lung tumors, neoplastic lesions, leiomyomas, adenocarcinoma, melanoma, thyroid cancer, breast cancer, colorectal cancer, head cancer

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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.

Medical Editor

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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

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.

CME Editor

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 Chairman, Professor, Department of Surgery, Section of Gastrointestinal Medicine and Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director of 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 Other

 
 
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