A 56-year-old Japanese woman was referred to our department of respiratory medicine for intermittent bloody sputum and a tumor shadow in the right lower lobe in chest X-ray and computed tomography (CT) scan (Fig. 1a). She was a current smoker with 55.5 pack-year smoking history. Her medical history was only hyperlipidemia. The tumor was bronchoscopically visible at the right intermediate bronchus. She was diagnosed of squamous cell carcinoma by transbronchial biopsy (Fig. 2a). Tumor proportion score (TPS) of PD-L1 was low expression (TPS 30-40%) (22C3 pharmDx assay) (Fig. 2b). Whole body CT with contrast enhancement and fluorodeoxyglucose positron emission tomography (FDG-PET) revealed a 36 x 28 mm diameter tumor in the right lower lobe with a maximum standardized uptake value (SUVmax) of 6.3, and ipsilateral mediastinal lymph node metastases with SUVmax of 8.8. The cancer was classified as c-stage IIIA, c-T1cN2M0, in the seventh edition staging system of Union for International Cancer Control (UICC)-TNM classification. She received chemo-radiotherapy with two courses of cisplatin and vinorelbine and concurrent thoracic irradiation of once daily 2Gy x 33 fractions, followed by durvalumab consolidation therapy (at a dose of 10 mg/kg of body weight intravenously, every 2 weeks for up to 12 months). Persistent fever, slow moving and incoherent behavior occurred 5 to 6 months after durvalumab. She was diagnosed of an irAE of isolated adrenocorticotropic hormone (ACTH) deficiency. Supplemental hydrocortisone improved her symptoms.
Thereafter, comparison of follow-up CTs of 1 and 1.5 years after durvalumab showed growth of the tumor in the right S6, which had lost intra-tumorous air bronchogram (Fig. 1b-d). PET-CT also revealed abnormal uptake in the tumor in the right S6 (SUVmax, 4.7) (Fig. 3). Neither CT nor FDG-PET found mediastinal and distant metastases (Fig. 1c-d, 3). Based on these images, we suspected loco-regional recurrence of her lung cancer. We did not try endobronchial ultrasound-guided transbronchial needle aspiration biopsy (EBUS-TBNB) at a risk of arterial vessels surrounding the tumor.
She underwent curative-intent right lower lobe lobectomy. The resected right lower lobe macroscopically contained a poorly-marginated and grayish white tumor (Fig. 4a). However, there was no residue of carcinoma cells in the resected tumor and sampled lymph nodes. Histopathologically, the tumor contained widespread organized lesions with infiltration of inflammatory cells, diffuse epithelioid granuloma with partial necrotic lesions, and many multinucleated giant cells (Fig. 4b, c). Immunohistochemical stains showed that CD3 (+) and CD8 (+) T cells predominantly infiltrated, but CD79alpha (+) B cells also appeared. There were few CD4 (+) T cells and a relatively small number of scattered CD20 (+) B cells (Fig. 5a-d). No organism was identified by Ziehl-Neelsen, periodic acid-Schiff and Grocotts stains. A serum T-SPOT TB test and anti-MAC antibody were negative, and angiotensin-converting enzyme were not elevated (11.2 U/L). Thus, we diagnosed her with sarcoid-like granulomatosis of the lung, which might have been induced by durvalumab. We did not administer steroid and other immunosuppressant drug.
Neither feature of systemic sarcoidosis nor cancer relapse appeared 3 months after the surgery.