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Dr. Froudarakis is Lecturer of Pneumonology, Dr. Bouros is Associate Professor of Pneumonology, and Dr. Siafakas is Professor of Pneumonology, Medical School, University of Crete, Greece.
Correspondence to: Marios E. Froudarakis, MD, FCCP, Department of Pneumonology, Medical School, University of Crete, 71110 Heraklion, Crete, Greece; e-mail: mfroud{at}med.uoc.gr
Metastatic spread to the lungs from other than bronchopulmonary tumors is a common clinical problem. The incidence of lung metastases is estimated to from 20 to 50% in nonpulmonary primary tumors. This is thought to be because of the role of the lungs as the primary capillary filter of the drainage of most organs. Tumors more likely to give lung metastases are breast, renal, GI, thyroid, germ cell, carcinomas, as well as sarcomas and malignant melanomas.1 2
A major clinical problem in patients with nonpulmonary primary tumors is the endoluminal metastasis to the tracheobronchial tree. The incidence of such a metastasis is estimated to be approximately 2%.3 4 However, it seems that endoluminal metastases are underestimated. A study5 reported a higher incidence (28%) of endobronchial metastases in patients with metastatic disease. The main cause of this discrepancy is that fiberoptic bronchoscopy is not performed systematically in all patients with pulmonary metastasis.6 Patients with endoluminal metastasis may also have parenchymal lesions, and the diagnosis is provided by means other than bronchoscopic procedures, such as transthoracic biopsy or fine-needle aspiration or even open-lung biopsy.7 In addition, these patients may have low performance status as well as poor prognosis; physicians, aware of their patients’ quality of end of life, deny performing invasive techniques.8 Thus, there is an evident selection bias in the estimation of the incidence of endoluminal metastasis to the tracheobronchial tree.
The differential diagnosis of endotracheal/endobronchial metastasis and primary lung cancer may be difficult.5 9 Presenting symptoms, such as cough, hemoptysis and dyspnea, as well as chest radiograph findings, are indistinguishable from those reported in centrally located bronchogenic carcinoma.10 11 12 The patient’s physical examination reveals nonspecific signs, such as weight loss, performance status degradation, hepatomegalia, and peripheral lymph node enlargement.10 12 In some cases, the mean time for the appearance of endoluminal lesions is long (approximately 5 years) after the diagnosis of the primary tumor12 13 14 ; therefore, a carefully taken history is essential to detection of metastatic disease.5 11 In a recent study,15 it was reported that a patient’s smoking history and the histologic characteristics of the extrapulmonary neoplasm are the factors that determine the likelihood of a primary lung cancer vs a metastasis. CT of the thorax should be performed, although it is not always sensitive in demonstrating endoluminal lesions, as it may reveal associated parenchymal lesions or lymph node involvement.7
Fiberoptic bronchoscopy is a simple technique, essential in the diagnosis of all endoluminal lesions, including metastases.16 Its diagnostic accuracy is almost 100% for centrally located lesions.11 14 16 Results of histopathology from bronchoscopic biopsies and/or cytology from bronchial washing or brushing will differentiate endobronchial metastasis from bronchogenic carcinoma, especially in patients with previously undetected carcinoma.17 18 During the procedure, endobronchial metastatic disease could be suspected when the lesion has characteristics such as a thrombus-like pattern, a strong tendency to bleed, or obstruction of adjacent bronchial orifices.18 Flexible fiberoptic bronchoscopy also helps in the therapeutic approach by assessing the endoluminal lesions as to their number, or their central or peripheral location.19
Classical developmental modes of pulmonary metastases are lymphatic and hematogenous.1 2 However, other modes have been described specific to the endoluminal character, such as invasion or penetration from surrounding tissues, as well as direct seeding in the lumen.18 In this issue of CHEST (see page 768), Kiryu et al report a series of 16 patients with endotracheal/endobronchial metastases, with specific emphasis in the developmental modes. They use findings from fiberoptic bronchoscopy, chest radiography, CT, and histopathology to classify their patients into four categories: type I, direct metastasis to the bronchus; type II, bronchial invasion by a parenchymal metastatic lesion; type III, bronchial invasion by mediastinal or hilar lymph node metastasis; and type IV, peripheral lesion extending along the proximal bronchus. The authors, using developmental mechanisms described by previous reports,2 18 classify the endotracheal/endobronchial metastases in a morphologic way. Thus, we note that type II, type III, and type IV are lesions occurring by secondary invasion of the central airways, from the adjacent parenchyma, or from the adjacent lymph node or the distal airways, respectively. The type I lesions are explained by primary lymphatic or hematogenous spread to the central airways.
Therapeutic approach of pulmonary metastases is under debate. When pulmonary metastases occur, the patient’s prognosis is poor, as it is likely that extrapulmonary metastases exist elsewhere.7 8 14 This is particularly true for tumors widely disseminated, such as malignant melanomas and breast carcinomas, and tumors with short doubling time.1 20 The management of endotracheal/endoluminal metastases is usually in accordance with the histology of the primary tumor, their number and the anatomic location, the evidence of other metastatic sites, and the patient’s performance status.8 Although none of the published studies reported criteria of operability in patients with endotracheal/endobronchial metastases, in some individuals with good performance status, where an endobronchial metastasis represents the single metastatic site, surgical resection seems to offer a longer survival.5 6 However, it is doubtful whether this is the result of aggressive local treatment or whether it reflects the natural history of a slowly progressing tumor.11
Kiryu et al attempted to correlate their classification to the patients’ survival. However, the small number of patients within the different categories does not permit one to draw firm conclusions. All of their operable cases were of type IV, the type with the longest survival (31 months), while type III had the shortest survival (2 months); it is well known that lymph node metastasis is a factor of poor prognosis.21
In located obstructive lesions, external radiation beam is another therapeutic option with good response and acceptable survival.11 13 The effect of systemic chemotherapy is difficult to evaluate, because the published series have limited numbers of patients. However, it seems that chemotherapy does not offer a significant improvement in survival, and it is reserved for multiple metastatic disease.8 11 13 Palliative therapies include endoscopic treatment of symptomatic and/or obstructive metastases by Nd-YAG laser,12 16 22 cryotherapy,16 23 brachytherapy,22 24 or simply mechanical resection and stent placement.16 25
In conclusion, the management of endotracheal/endobronchial metastases is difficult. If surgical resection of the endoluminal lesion will improve patients’ survival, one should take into account different parameters not always easy to be determined. The classification of Kiryu et al is an effort to put together findings from imaging, fiberoptic bronchoscopy, and histopathology. Will this classification define patients with better prognosis? Is this classification going to help us to select patients for surgery? Will this classification contribute to better treatment of endotracheal/endobronchial metastases? It is obvious that further studies are needed in order to answer those questions. From this point to that of better management of patients with active metastatic disease, the way is long, but still there is no way out.
References
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