Sarcoid-like reaction mimicking nodal progression after neoadjuvant pembrolizumab-based chemoimmunotherapy in non-small cell lung cancer: a case report

Combining chemotherapy with immune checkpoint inhibitors (ICIs) has improved the resectability and survival in patients with resectable non-small cell lung cancer. Increasing ICI use has led to increasing recognition of immune-related adverse events, including drug-induced sarcoid-like reactions (DISR). DISR are uncommon and manifest as non-caseating granulomatous inflammation which may mimic disease progression on imaging. Differentiating DISR from true progression is essential to avoid inappropriate changes in plans for curative treatment. A 44-year-old man with Stage IIIA (cT2bN2aM0) right upper lobe lung adenocarcinoma underwent four cycles of carboplatin, paclitaxel, and pembrolizumab as neoadjuvant therapy. Post-treatment imaging showed bilateral enlargement and increased fluorodeoxyglucose uptake in the hilar and mediastinal lymph nodes, and regression of the primary tumor and #11s node. Although these findings were initially interpreted as progressive disease, a sarcoid-like reaction was suspected. Preoperative endobronchial ultrasound-guided transbronchial needle aspiration of the #7 node showed granulomatous changes without signs of malignancy. Intentional first dissection of the #7 node and frozen section analysis during surgery confirmed these findings. The patient subsequently underwent right upper lobectomy with ND2a-2 lymph node dissection. The final pathology revealed ypT1cN0M0 solid adenocarcinoma and granulomatous findings consistent with DISR. This case demonstrates the importance of cautious interpretation of nodal enlargement after immunotherapy. Bronchoscopic evaluation and intraoperative pathological evaluation ruled out progression and enabled curative surgery. When hilar lymph node enlargement is encountered after ICI therapy, clinicians should consider the possibility of DISR and perform appropriate pathological evaluation to ensure accurate disease staging.