Our patient is a 66-year-old Japanese man diagnosed with right upper lobe adenocarcinoma of p-stage IIIA (pT2bN2M0; version 8) post right upper lobectomy. After a year of surgical resection, recurrent mediastinal lymph node metastases were confirmed by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Based on the result of immunohistochemical staining (TTF-1+, p40-, Tumor Proportion Score (TPS; PD-L1 IHC 22C3 pharm DX Dako) 100%, EGFR-mutation -, ALK-rearrangement FISH-, ROS1-rearrangement RT-PCR-), The anti-Programmed Death receptor 1 (anti-PD-1) antibody pembrolizumab 200mg/body once every three weeks was initiated. After the sixth cycle of the treatment, the patient presented to the clinic with worsening dyspnea. He was tachypneic without any fever nor desaturation. Lungs were clear to auscultation. Both complete blood count and chemistry panels were normal. Blood culture, sputum culture, serum beta-D glucan, serum galactomannan, serum interferon-gamma release assays (IGRAs) for diagnosing mycobacterium tuberculosis, and serological assay by use of glycopeptide lipid core antigen for diagnosing mycobacterium avium complex came back negative.
High-resolution chest CT (HRCT) revealed bilateral diffuse well-defined 1-2 mm of small granular shadow along with thickened interlobular septa, consistent with perilymphatic distribution (Fig. 1). Given the lack of any evidence of pulmonary infection or any exposure to the stimulants of hypersensitivity pneumonia, an immune reaction to pembrolizumab was suspected and transbronchial random lung biopsy from the left upper lobe anterior segment and the left lower lobe anterior basal segment was performed (see Fig. 2).
Microscopically, type 2 pneumocytes with bizarre enlarged nuclei as well as lymphocytic infiltration in interstitium were identified. Pigmented macrophages suggested the hemorrhage. Most lymphocytes showed CD8+/CD4-, suggesting cytotoxic T lymphocytes. These findings were consistent with T cell-induced lung injury due to pembrolizumab. In addition, those lymphocytes aggregated around lymphatic vessels, which was confirmed by D2-40 immunohistochemistry. Those findings were confirmed in all samples of the random biopsy.
Given the clinical, radiological and pathological findings, pembrolizumab-induced pneumonitis was strongly suspected, thereby the treatment was immediately discontinued. After three-week admission, the patient was discharged with ameliorated symptoms. No corticosteroid was administered during admission to avoid potential interference with the anti-tumor effect of pembrolizumab. Complete remission of his tumor has been maintained throughout the follow-up period; pembrolizumab is still suspended.