Abstract
The most common primary tumors associated with endobronchial metastasis (EBM) are colorectal, breast, and renal. When EBM is present, respiratory symptoms such as shortness of breath or hemoptysis accompanied by coughing usually appear. Herein, we report a case of atelectasis caused by EBM of renal cell carcinoma (RCC) in a 53-year-old man who underwent laparoscopic radical nephrectomy for RCC 5 years ago. The patient’s primary RCC stage was pT1b, and the histological cell type was clear cell RCC with Fuhrman nuclear grade 3/4. At the time of EBM diagnosis, the patient was classified as “favorable” according to IMDC (International mRCC Database Consortium) risk calculator. The patient refused surgical treatment and received targeted therapy with sunitinib. A tumor mass spontaneously detached and came out through the airway during targeted therapy. Subsequently, the patient’s respiratory symptoms were alleviated, and his atelectasis disappeared. This case shows that when there is atelectasis due to EBM of RCC, the obstructed bronchus may be reopened with targeted therapy without any interventional treatment.
Introduction
The most common primary tumors associated with endobronchial metastasis (EBM) are colorectal, breast, and renal cancers [1, 2]. When EBM is present, respiratory symptoms such as shortness of breath or hemoptysis accompanied by coughing usually appear. It is important to distinguish EBM from other malignant tumors because the treatment method may differ depending on the type of primary cancers [3, 4]. The use of electrosurgical snaring method as a palliative therapy for endobronchial metastatic tumor has become widespread, especially to treat obstructive endobronchial tumors [5]. Even if EBM is widespread, these endoscopic surgical procedures are useful for prevention of hemoptysis, atelectasis, or post-obstructive pneumonia [6, 7]. Herein, we report a case of atelectasis due to EBM of renal cell carcinoma (RCC) in a 53-year-old man who underwent laparoscopic radical nephrectomy for RCC 5 years ago. In addition, we describe a unique case in which a tumor mass spontaneously detached and came out through the airway during targeted therapy, and patient’s respiratory symptoms were alleviated.
Case Report
A 53-year-old man with a history of renal cancer surgery 5 years ago visited a local private internal medicine clinic with symptoms such as coughing, intermittent hemoptysis, and shortness of breath that had occurred about 2 months earlier. When the doctor performed auscultation, breathing sounds were not heard in the right lower lung area, and right lower atelectasis was confirmed on a chest X-ray (Fig. 1a). The patient was immediately transferred to a tertiary medical institution and underwent additional imaging studies and flexible bronchoscopy. On bronchoscopy, a bronchial mass completely occluding the right lower bronchus was observed (Fig. 2).
a Chest X-ray shows atelectasis of the right lower lung. b Chest X-ray shows that the atelectasis disappears following the targeted therapy using sunitinib.
a Chest X-ray shows atelectasis of the right lower lung. b Chest X-ray shows that the atelectasis disappears following the targeted therapy using sunitinib.
Flexible bronchoscopic image reveals a polypoid mass occluding the right lower bronchus (yellow arrows).
Flexible bronchoscopic image reveals a polypoid mass occluding the right lower bronchus (yellow arrows).
Metastasis of RCC was confirmed on histological examination performed by bronchoscopic biopsy. A PET-CT scan confirmed metastases to the bronchus, mediastinal lymph nodes, and lumbar spine (Fig. 3). The authors suggested right lung segmentectomy plus targeted therapy for the purpose of palliation, but the patient refused the operation and wanted targeted therapy only. The patient started treatment with sunitinib 50 mg, and after 3 months of administration, a tumor mass spontaneously protruded out of the body through the airway with cough accompanied by hemoptysis (Fig. 4). Fortunately, the symptoms of hemoptysis resolved spontaneously. The patient’s respiratory symptoms were alleviated, and atelectasis of the right lower lobe, which was seen on a simple chest radiograph prior to the therapy, disappeared (Fig. 1b). After 9 months of the targeted therapy, however, new metastatic lesions appeared in both the lungs and skull, and the size of the previously existing metastatic lesions increased. Accordingly, the authors recommended other secondary targeted agents or immune checkpoint inhibitors, but the patient refused all medical treatments, saying that he would be treated with oriental folk remedies that strengthen immunity. Unfortunately, the patient eventually died 7 months later.
PET-CT scan shows multiple metastatic tumors in the right lower bronchus (yellow arrow), mediastinal lymph node (red arrow), lumbar vertebra (blue arrow). It also shows atelectasis on right lower lung field.
PET-CT scan shows multiple metastatic tumors in the right lower bronchus (yellow arrow), mediastinal lymph node (red arrow), lumbar vertebra (blue arrow). It also shows atelectasis on right lower lung field.
Photograph shows a spontaneously protruded tumor mass out of the body through the airway with cough accompanied by hemoptysis.
Photograph shows a spontaneously protruded tumor mass out of the body through the airway with cough accompanied by hemoptysis.
Discussion
EBM was found in only 2–5% of autopsies performed on patients who died of solid tumors [3, 8]. A retrospective analysis of 438 cases of endobronchial malignancies biopsied in Korea over a period of 10 years revealed only 18 (4.1%) to be of extrapulmonary in origin [1]. So far, there has been no paper that has analyzed the EBM frequency of RCC in detail, but one paper reported that 14% of EBM origins were RCC [9]. Although it is difficult to explain exactly how EBM develops, it may occur when renal cancer cells invade the bronchial lining and form secondary tumors within the bronchial airways. This condition is relatively rare but can occur in advanced stages of kidney cancer. It has been reported to occur predominantly in the right lung in approximately 80% of cases, similar to our patient [10].
Symptoms of EBM may include persistent cough, shortness of breath, wheezing, chest pain, recurrent lung infections, and hemoptysis [11, 12]. Radiological changes of atelectasis are usually the earliest indication of endobronchial disease, and obstructive atelectasis is most often associated with occlusion of a lobar bronchus [13]. In our case, the patient visited a private clinic with symptoms of cough, shortness of breath, and intermittent hemoptysis. Upon auscultation, the doctor found no breath sounds in the right lower lung area, checked a chest X-ray, and found right lower atelectasis. Most endobronchial lesions are within the view and grasp of the bronchoscopist [14, 15]. In our patient, bronchoscopy was also performed to find a solid tumor blocking the lumen of the bronchus, and a biopsy confirmed that RCC had metastasized.
Treatment methods for EBM of RCC include surgical resection of the bronchi or part of the lung, electrosurgical snaring [5], conservative minimally invasive treatment using Nd:YAG laser through bronchoscopy [6, 7], or systemic treatment using targeted therapies or immunotherapies immuno-oncology (IO)-based combinations [16, 17]. Our patient refused surgical treatment and wanted medical treatment only; therefore, targeted treatment with sunitinib 50 mg, a tyrosine kinase inhibitor (TKI), was initiated. The authors chose sunitinib as the alternative therapy even though TKI-IO or IO-IO combination therapies are recommended as the 1st-line therapy for metastatic RCC patients in the National Comprehensive Cancer Network (NCCN) guideline [18]. Korea has a national medical insurance system. The combination therapy of immuno-oncologic drugs was not covered by national health insurance at the time of patient treatment.
In the third month of treatment, the tumor protruded through the airway while coughing. Subsequently, the patient reported that breathing became easier, and atelectasis disappeared on a simple chest X-ray. In addition, spontaneously separated endobronchial tumors were ejected through the airways twice more at intervals of about 1 month thereafter. The authors believe that this is a phenomenon caused by tumor necrosis due to targeted therapy. Hemoptysis may be a worrisome side effect after targeted therapy in cases of EBM of renal cancer. Targeted therapies may shrink tumors or cause necrosis, further increasing the risk of bleeding from the tumor [19]. Fortunately, our patient did not experience severe or persistent hemoptysis even though the tumor spontaneously fell out of the airway.
The prognosis of EBM of RCC depends on various factors, such as the stage of primary renal cancer, the degree of metastasis, and the response to treatment. In our subject, multiple metastatic lesions progressed in both lungs, mediastinal lymph nodes, spines, and skull after 9 months of targeted therapy. The authors recommended other second-line targeted agents or immune checkpoint inhibitors, but the patient refused further drug treatment, saying that he would undergo treatment that naturally enhances immunity by relying on folk remedies. However, the patient eventually died 7 months later. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary Figure 1 (for all online suppl. material, see https://doi.org/10.1159/000533893).
Conclusion
We suggest that bronchial obstruction due to EBM of RCC may be spontaneously reopened with targeted therapy alone without any interventional treatment. To the best of our knowledge, this type of case reports are not yet reported in the literature. Further studies are needed to clarify the role of targeted therapy in EBM of RCC.
Statement of Ethics
This study protocol was reviewed, and the need for approval was waived by the Institutional Review Board of Jeonbuk National University Hospital. Written informed consent was obtained from the patient’s spouse for publication of this case report and any accompanying images.
Conflict of Interest Statement
The authors have no conflicting interests to declare.
Funding Sources
This study was supported by the Jeonbuk National University research grant 2022–2023.
Author Contributions
J.H. You wrote the manuscript, and Y.B. Jeong supervised the study.
Data Availability Statement [1–19]
All data generated or analyzed during this study are included in this article and its online supplementary material. Further inquiries can be directed to the corresponding author.