The right operation for the wrong reason in multi-focal non-small cell lung cancer

1. Introduction 

The diagnosis and pre-operative assessment of multi-focal intrapulmonary non-small cell lung cancer (NSCLC) poses particular challenges for the lung cancer multi-disciplinary team. Disease confined to the lungs, without nodal or distant metastases can often be treated surgically and a good long-term outcome expected. This is inconsistent with the current TNM classification of NSCLC which classifies multi-focal NSCLC as stage IIIB (T4 disease: deposits in the same lobe as the primary) or stage IV (M1 disease; deposits in a separate lobe), implying a poor long-term survival and discouraging lung resection surgery.

The case we report highlights this limitation of the current staging system and discusses particular difficulties encountered in using integrated FDG-PET/CT scanning in the pre-operative assessment of multi-focal intrapulmonary NSCLC, particularly when the bronchioalveolar sub-type is involved as in this case.

2. Case history 

A sixty-seven year old female was referred to our unit by the local pancreato-biliary team following the detection of a right lower lobe mass on abdominal computed tomography (CT) scanning performed for another reason. The patient was an ex-smoker, having stopped 4 years ago. When assessed in the respiratory clinic she described a new non-productive cough but no other symptoms. Clinical examination was unremarkable and her WHO performance status was estimated at 0.

Review of her recent CT scan demonstrated a 6.5×4.1cm pleural-based mass in the right lower lobe which appeared to encase the medial and inferior aspects of the vascular pedicle of the right hilum and the inferior pulmonary vein. There was no evidence of mediastinal lymphadenopathy but the appearances were highly suspicious of direct mediastinal invasion. Standard fibreoptic bronchoscopy revealed no mucosal abnormality although the medial basal sub-segment of the right lower lobe appeared externally compressed. Cytological samples were taken from this sub-segment by bronchial brush biopsy and saline lavage. Microscopy of the bronchial aspirate demonstrated several groups of large atypical cells with pleomorphic nuclei and distinct cytoplasm consistent with NSCLC. Immunocytochemistry was unhelpful in confirming an origin in lung. Pulmonary function testing revealed mild airflow obstruction (forced expiratory volume in one second 1.55litres, 65% of predicted) and a corrected diffusion capacity for carbon monoxide that was 67% of predicted.

The case was discussed at our multi-disciplinary lung cancer meeting with a view to clarifying the T-staging of the primary tumour and deciding on the patient's suitability for surgical treatment. On review of the CT images it remained impossible to delineate the tumour within the enhancing mass. Since the patient was otherwise an operable candidate an integrated 18F-FDG Positron Emission Tomography (PET)/CT scan was arranged to help clarify the T-staging and screen for mediastinal nodal disease or distant metastases (see Fig. 1). This revealed intense FDG uptake (SUV 12.0g/ml) within the inferolateral aspect of the soft tissue mass, presumed to represent the viable tumour. However, in the medial aspect of the mass, adjacent to the left atrium there was a rim of soft tissue that showed no significant FDG activity. This was presumed to be collapsed lung lying adjacent to the tumour and separating it from the mediastinum. There was no evidence of nodal disease or distant metastases. Therefore, the patient was pre-operatively staged as cT3N0M0 and proceeded to exploratory thoracotomy.

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Fig. 1 An integrated 18F-FDG Positron Emission Tomography/Computerised Tomography (PET/CT) scan was performed to clarify the T-staging of the tumour visible on conventional CT imaging. (a) FDG-PET component demonstrating focal avid FDG activity in the right lower lobe. (b) Co-registered non-contrast enhanced CT scan demonstrating the 6.5×4.1cm pleural-based soft tissue mass in the right lower lobe. (c) Integrated FDG-PET/CT image demonstrating a rim of non-FDG avid tissue between the tumour and the mediastinum, presumed to be collapsed lung.

At thoracotomy a large tumour was found in the right lower lobe. In keeping with the results of integrated FDG-PET/CT scanning, there was no evidence of mediastinal invasion. However, the tumour was adherent across the major fissure into the upper lobe and a wedge resection of the adjacent area of the upper lobe was performed in addition to a right middle and lower bilobectomy.

The patient made an uneventful post-operative recovery and histology from the resected lung tissue revealed a moderately differentiated adenocarcinoma located centrally within the visible tumour mass (see Fig. 2(a)). The periphery of the mass was occupied by bronchioalveolar cell carcinoma (BAC) of mucinous type and there were several other small foci of BAC some distance from the primary tumour mass within the right lower lobe (see Fig. 2(b)). The right upper lobe wedge resection sample showed moderately differentiated adenocarcinoma with clear resection margins and the right middle lobe was free of tumour. Neither vascular nor lymphatic invasion were identified and all 17 of the lymph-nodes sampled (right pulmonary artery, hilar and peribronchial nodes) were negative. Although the surgeon was confident that the entire tumour had been removed, she will be considered for adjuvant therapy given her final pathological staging of pT4N0M1 multi-focal adenocarcinoma/BAC.

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Fig. 2 (a) Central region of main tumour showing poorly differentiated adenocarcinoma with an acinar pattern (H&E, 40×). (b) Periphery of the main tumour showing a bronchioalveolar pattern, mucinous type (H&E, 20×).

3. Discussion 

Following FDG-PET/CT scanning this patient was pre-operatively staged as cT3N0M0 and proceeded to exploratory thoracotomy with a view to potentially curative surgical resection. Although there was no evidence of direct mediastinal invasion at thoracotomy, as shown by the pre-operative FDG-PET/CT scan, there were small multi-focal deposits of BAC surrounding the central tumour mass in the right lower lobe and a deposit of adenocarcinoma in the right upper lobe.

This case highlights the limitations of the current TNM classification of NSCLC when applied to patients with multi-focal intrapulmonary NSCLC without nodal or distant metastases. It also emphasises the relative strengths and weakness of integrated FDG-PET/CT scanning, which is becoming an increasingly well established and widely available part of pre-operative lung cancer assessment.

Conflicts of interest Statement 

The authors have no statements of interest to declare.