This 60-year-old asymptomatic male patient presented in our outpatient department because of a suspicion of primary lung cancer as discovered on a chest X-ray performed by his general practitioner. He was an active smoker and had signs of an old myocardial infarction on electrocardiography (EKG) but no other relevant medical history. His physical examination did not show any abnormalities.
The screening X-ray showed a shadow in the right upper lobe (RUL) for which the patient was referred to a pulmonologist. A subsequent CT-thorax showed two nodules: one in the right lower lobe with a long axis diameter of 30 mm and one in the RUL with a long axis diameter of 17 mm. Both nodules were deemed of sufficient high risk of lung cancer to warrant further analysis. A positron emission tomography (PET)-scan was therefore performed which showed both identified nodules to be fluorodeoxyglucose (FDG)-avid, without mediastinal involvement or other signs of metastatic disease (see Figure 1).
Patient was subsequently referred for minimal invasive biopsy of these nodules. A navigation bronchoscopy was considered most optimal, because both nodules could then be sampled in one procedure. After induction of general anesthesia, an inspection bronchoscopy was performed following the workflow as described above. While it was expected that only the right side was affected, inspection bronchoscopy revealed a third adverse finding. During the routine inspection, a submucosal lesion with dotted vessels of approximately 5 mm was observed in the left upper lobe (LUL). Based on its appearance, sampling for further analysis was believed indicated. Repeated sampling using a forceps biopsy instrument was performed (see Figure 2).
Subsequently, the navigation bronchoscopy procedure ensued. An EWC (Medtronic) with a 180 degrees angulated distal tip was inserted in the target segment of the RUL and a first CBCT spin was performed. The target nodule and route were segmented for further image guided navigation which in this case required several CBCT scans for repositioning of the catheter in order to access this RUL nodule. Lesion access was confirmed with rEBUS and CBCT (Figure 3). Subsequently, this lesion was sampled with transbronchial needle aspiration and (new) forceps biopsy providing both cytological and histological samples. As ROSE was not able to provide a certain diagnosis, the lesion was sampled extensively for histology.
Next, for the second nodule, the EWC was inserted in the target segment of the right lower lobe (RLL) using augmented fluoroscopy for the second nodule and its planned route which were segmented on the initial high dose CBCT. Navigation towards this lesion resulted in immediate access of the nodule and position confirmation was obtained by rEBUS and a new CBCT spin (Figure 3). Both a new TBNA needle and biopsy forceps were used to prevent cross-contamination for sampling of this third target. ROSE did provide a preliminary diagnosis suspicious for malignancy in the second nodule. At the end of the procedure, an X-ray was obtained using the CBCT system to check for signs of a pneumothorax, which were not found. Although there was no imaging based suspicion of lymphadenopathy, a systematic linear EBUS examination of the mediastinal and hilar lymph nodes was performed to check for signs of nodal disease. All lymph node regions showed small lymph nodes (<5 mm) with benign B-mode characteristics, which is why no fine needle aspiration was performed. After observation in day care setting, the patient was discharged the same day without complications.
Pathological analysis of tissue samples revealed the endobronchial lesion in the LUL as a squamous cell carcinoma of the lung based on immunohistochemistry, tropomyosin receptor kinase (TRK) positive, tumor protein 53 (TP53) positive, programmed death ligand-1 (PD-L1) <1%. The RUL nodule was diagnosed as a non-small cell carcinoma of the lung not otherwise specified (NOS), with no further differentiation possible due to a low malignant cell count which precluded further molecular and clonal analysis. The lesion in the RLL was diagnosed as an adenocarcinoma of the lung, thyroid transcription factor 1 (TTF1) positive with PD-L1 <1%. There was insufficient material to perform clonal analysis on the two parenchymal lesions. Based on the pathology findings, and the radiological and clinical presentation of the lesion, the multidisciplinary tumor board including the pathologist concluded that it was most likely that this patient suffered from three separate primary pulmonary malignancies. They were respectively staged as: RUL cT1bN0M0, RLL cT1cN0M0 and endobronchial: cT1aN0M0. Although pathological examination was not able to fully differentiate if the non-small cell lung cancer (NSCLC) NOS of the RUL was a third primary or an ipsilateral metastasis of the RLL lesion, it was decided to not perform repeat biopsy of the RUL nodule to prevent further diagnostic delay.
Due to the uncommon presentation, a cerebral magnetic resonance imaging (MRI) was performed which ruled out cerebral metastases. Subsequently, an additional mediastinoscopy showed no lymph node metastases.
Because the patient did not have the pulmonary reserve to safely undergo a right sided pneumonectomy, a video assisted thoracoscopic surgical lobectomy was performed to resect the RLL. Stereotactic ablative radiotherapy was used to treat the lesion in the RUL, and the endoluminal squamous cell carcinoma was treated with endobronchial cryoablation. Unfortunately, the lymph node dissection performed during surgery of the RLL lesion revealed nodal metastases in levels 10 right and 11 right resulting in a final staging of pT1cN1 PL0 R0. Due to this upstaging, the patient received adjuvant chemotherapy in the form of carboplatin and pemetrexed for four cycles. No severe adverse events took place during the diagnostic process and following treatment. Patient is currently more than 12 months post-treatment and has no signs of recurrence, both on imaging and repeated bronchoscopy and re-biopsy of the endoluminally treated squamous cell carcinoma. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.