Updated: Nov 10, 2006
Secondary lung tumors are neoplastic lesions originating at a site distinct from the primary lesion. The primary tumor can arise within the lung or outside the lung. Metastatic malignant neoplasms are the most common form of secondary lung tumors; benign neoplasms, such as benign metastasizing leiomyomas, are an uncommon exception.
Secondary lung tumor is a term that is also used for the malignancies that arise in lungs as a consequence of therapy (eg, chemotherapy, radiotherapy, bone marrow transplant) for cancer. This article is not intended to cover the description of such tumors.
The differential diagnosis of discrete masslike lesions of the lung appearing 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.
Cancers other than bronchogenic carcinomas frequently metastasize to the lungs.
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 of 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.
The lung metastases can cause no symptoms or they can be the major cause of morbidity in a cancer patient, causing hypoxemia, dyspnea, cough, and hemoptysis. Hypoxemia and dyspnea are most commonly observed in patients with lymphangitic spread of a cancer, and cough and hemoptysis are associated with endobronchial metastases. Palliative general care that addresses the disabling symptoms and local treatment with curative or palliative intent may be indicated, respectively.
Finally, another common clinical scenario is an incidental finding of secondary lung cancer of unknown origin, most commonly adenocarcinoma.
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 when the usual course of continued systemic treatment with chemotherapy for metastatic disease should be accompanied by radiation and/or surgery.
Recognition of secondary pulmonary tumors has increased with advances in chest radiography. The advent of CT scanning enabled the identification of smaller lesions for both primary and secondary lung tumors.
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.
Metabolic imaging of the lungs (eg, positron emission tomography [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.
Secondary lung tumors are neoplastic lesions originating at a site distinct from the primary lesion. They most typically appear as well-circumscribed, noncalcified nodules.
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 when patients are undergoing screening chest radiography or CT scanning.
Hypoxemia is usually not a presenting sign. Presence of hypoxemia is not explained by cancerous process in the absence of lymphangitic spread, major lung collapse, or massive pleural effusion. Presence of hypoxemia in the absence of these conditions should prompt the search for causes such as pulmonary thromboembolism, tumor emboli syndrome, pulmonary veno-occlusive disease associated with certain cancers or chemotherapies, interstitial fibrosis secondary to chemotherapy or radiation, or infections such as Pneumocystis jiroveci pneumonia (PCP).
The clinical decision to pursue tissue diagnosis depends on whether confirmation of clinical findings would alter current or future treatment.
Treatment of secondary lung tumors can reduce or eliminate tumor burden or palliate disease.
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, although prevalence varies based on the type of primary cancer. Benign neoplasms (eg, benign metastasizing leiomyomas) are uncommon exceptions.
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.
In general, the 2 mechanisms of cancer spread into the lungs are direct extension and true metastatic spread. Iatrogenic implantation of a primary tumor is exceedingly rare.
Cancer spread through direct extension is less frequently encountered and most commonly includes direct invasion from a primary neoplasm involving a contiguous organ (eg, thyroid, esophagus, thymus) 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.
True metastases occur via the pulmonary arteries, bronchial arteries, or pulmonary lymphatics; across the pleural cavity; or via the airways.
Spread via pulmonary arteries is by far the most common route for metastases. The 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 might 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.
The 2 methods of lymphangitic spread are (1) 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, and (2) by retrograde spread of tumor from the originally affected mediastinal or hilar lymph nodes, with consequent obstruction of lymphatic flow.
Pleural spread most frequently results in pleural metastases in the caudal and posterior parts of the pleural cavities.
Spread via airways is rare and difficult to prove, except in the case of bronchoalveolar carcinoma.
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.
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 is considered a T4 tumor, according to the 1997 TNM classification scheme. According to the same classification, the presence of 2 malignant nodules of the same histologic type in 2 different lobes is considered stage IV lung cancer. In both cases, surgical management that is 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 in case one 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 is crucial in this 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.
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:
Surgical resection of lung metastasis should not be performed unless the procedure has a significant likelihood of being curative. One notable exception is endotracheal or endobronchial metastasis in which local treatment can result in symptomatic palliation.
Chemotherapy remains the treatment of choice for advanced cancer. Metastatic cancers known to favorably respond to chemotherapy include Hodgkin lymphoma, non-Hodgkin lymphoma, germ cell tumors, and thyroid cancer. A fair response to chemotherapy is expected for carcinomas of the breast, prostate, and ovary. Immunotherapy is an additional option for the treatment of metastatic malignant melanoma.
The presence of metastasis indicates an advanced stage of the malignant process. However, as mentioned above, in certain circumstances, surgical resection with curative intent can be performed with an expected 5-year survival rate of 30-40%, depending upon the underlying primary malignancy and the selection criteria for surgery.
Selection of patient for pulmonary metastasectomy
In general, good surgical candidates meet all of the following criteria:
Sometimes the resection is done to confirm the diagnosis (eg, to rule out a new primary cancer that might require a different approach to therapy).
Other therapies
Several other therapies are used. However, most have limited availability. The value of such therapies has not been evaluated by structured clinical trials. Most of them should be used only in experienced centers for patients who have lung malignancies (primary lung cancer or pulmonary metastases) and who are not candidates for surgery with the intent to resect. These therapies may also be used in conjunction with other treatments (ie, chemotherapy, radiotherapy) for better disease control. Some examples of such therapies include the following:
1. Percutaneous radiofrequency ablation
2. Percutaneous cryoablation
3. Radiofrequency ablation followed by conventional radiotherapy
The following 5-year survival rates have been reported after resection of single pulmonary metastasis of the metastatic cancers known to respond favorably to surgical treatment:
Solitary lung metastasis has a significantly better prognosis compared with any other visceral site in metastatic malignant melanoma, with a median survival of 8.3 months and a 5-year survival rate of 4%. The other important independent outcome predictor in metastatic malignant melanoma is the disease-free interval prior to the identification of metastatic disease ( <12 mo vs >12 mo).
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secondary pulmonary tumors, metastatic malignant neoplasms, metastatic lung tumors, neoplastic lesions, leiomyomas, adenocarcinoma, melanoma, thyroid cancer, breast cancer, colorectal cancer, head cancer, neck cancer, renal cell cancer, choriocarcinoma, testicular cancer, osteosarcoma, Ewing sarcoma, Wilms tumor, rhabdomyosarcoma, prostate cancer, lymphangitic carcinomatosis, chemotherapy, lobectomy, pneumonectomy, metastasectomy, thoracotomy, video-assisted thoracoscopic surgery, VATS, median sternotomy, Nd:YAG laser resection, electrocautery, argon plasma coagulation, cryotherapy, brachytherapy, rigid bronchoscopy, balloon dilatation, endoluminal stent placement
Rebecca Bascom, MD, MPH, Professor of Medicine, Pennsylvania State College of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, Milton S Hershey Medical Center
Rebecca Bascom, MD, MPH is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Physicians, American Industrial Hygiene Association, American Public Health Association, and American Thoracic Society
Disclosure: Nothing to disclose.
Shoaib Alam, MD, Assistant Professor of Medicine, Division of Pulmonary, Allergy and Critical Care, Penn State University and Hershey Medical Center
Shoaib Alam, MD is a member of the following medical societies: American College of Chest Physicians, American Thoracic Society, European Respiratory Society, International Society for Magnetic Resonance in Medicine, Pennsylvania Thoracic Society, and Society of Critical Care Medicine
Disclosure: Nothing to disclose.
Milos Tucakovic, MD, Fellow, Department of Internal Medicine, Sections of Pulmonary Disease, Allergy and Critical Care Medicine, Milton S Hershey Medical Center, Pennsylvania State College of Medicine
Milos Tucakovic, MD is a member of the following medical societies: American College of Physicians and American Medical Association
Disclosure: Nothing to disclose.
William Flood, MD, Professor, Department of Medicine, Division of Hematology/Medical Oncology, Pennsylvania State University
Disclosure: Nothing to disclose.
Sanjay M Mehta, MD, Assistant Professor of Cardiothoracic Surgery, Pennsylvania State University, Surgical Director of Cardiac Transplantation, Department of Surgery, Division of Cardiothoracic Surgery, Milton S Hershey Medical Center
Disclosure: Nothing to disclose.
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, Senior Pharmacy Editor, eMedicine
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Shreekanth V Karwande, MBBS, Chair, Professor, Department of Surgery, Division of Cardiothoracic Surgery, University of Utah School of Medicine and Medical Center
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.
John Geibel, MD, DSc, MA, 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
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