Immune Checkpoint Inhibitor-associated Periaortitis Detected on ¹⁸F-FDG PET/CT: A Rare Case of Nivolumab Toxicity

Abstract

We report a case of a 64-year-old male with metastatic non-small-cell lung carcinoma who was undergoing neoadjuvant chemoimmunotherapy with cisplatin, pemetrexed, and nivolumab. Restaging ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) demonstrated segmental, linear ¹⁸F-FDG uptake along the abdominal aortic wall with corresponding crescentic soft-tissue thickening. Differential diagnoses included intramural hematoma, focal aortitis, atherosclerotic plaque, and tumor thrombus. CT angiography revealed a mildly enhancing periaortic soft-tissue rim involving a 5 cm infrarenal aortic segment, consistent with isolated periaortitis, likely induced by immunotherapy. Steroid therapy was initiated. Follow-up ¹⁸F-FDG PET/CT showed complete metabolic resolution, supporting an immune-related etiology. ¹⁸F-FDG PET/CT played a crucial role in early recognition of this immune-related adverse event by sensitively detecting vascular inflammation and guiding further evaluation with CT angiography. Early PET-based detection enabled timely initiation of steroid therapy, preventing potential vascular complications.

Ethics

Informed consent: The consent was obtained for image use.

Figure 1.

A 64-year-old male is a known case of metastatic non-small-cell lung carcinoma. On neoadjuvant chemoimmunotherapy with cisplatin/ pemetrexed/ nivolumab. ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) is performed for restaging. a) ¹⁸F-FDG PET maximum intensity projection image and b-d) cross-sectional PET/CT images show segmental ¹⁸F-FDG uptake in a continuous linear pattern of the abdominal aortic wall with maximum standard uptake values of 7.6, correlating to a crescentic soft-tissue thickening. Findings could represent an intramural hematoma, focal aortitis, or, less likely, an atherosclerotic plaque and tumor thrombus.

Figure 2.

Computed tomography (CT) angiography in the a) arterial and b) delayed phases shows an irregular rim of soft-tissue density around the infra-renal portion of the abdominal aorta, which shows mild enhancement. Length of involvement is ~5 cm. Findings can suggest isolated periaortitis, likely induced by chemo-immunotherapy. The patient was started on steroids. c) Follow-up positron emission tomography (PET)/CT images show metabolic resolution of the previously seen eccentric uptake along the descending thoracic aorta. Immune checkpoint inhibitors (ICIs), including the PD-1 inhibitor nivolumab, have significantly improved outcomes in advanced malignancies such as non-small-cell lung carcinoma (1). However, when they remove inhibitory signals from T-cells, they may provoke a broad spectrum of immune-related adverse events (irAEs). While dermatologic, gastrointestinal, and endocrine toxicities are the most common, vascular irAEs particularly aortitis or periaortitis are increasingly recognized, but remain rare and potentially underdiagnosed. The pathophysiology is attributed to immune activation against vascular wall antigens, leading to T-cell-mediated inflammation, medial destruction, and soft-tissue thickening surrounding the vessel. The overall incidence of irAEs with either CTLA-4 or PD1/PDL1 inhibitors is approximately 15-30% (2).

18F-fluorodeoxyglucose (¹⁸F-FDG) PET is widely utilized for diagnostic staging and restaging, assessing disease extent, monitoring treatment response, and supporting prognostic evaluation (3,4). ¹⁸F-FDG PET/CT serves not only as a tool for staging and treatment response assessment but also as a crucial modality for identifying clinically silent irAEs in patients undergoing chemoimmunotherapy (5,6). Recognizing these imaging patterns allows timely initiation of immunosuppressive therapy, helps prevent serious vascular complications, and supports the safer use of ICIs in oncology practice. This is particularly important in vascular irAEs, as untreated aortitis can progress to aneurysm formation, dissection, or even life-threatening rupture. Because clinical manifestations are often vague or absent, imaging becomes indispensable, and in this setting, ¹⁸F-FDG PET/CT assumes a key diagnostic role. ¹⁸F-FDG uptake corresponds to activated macrophages and lymphocytes within the inflamed aortic wall, allowing ¹⁸F-FDG PET/CT to identify active vasculitis even before structural changes develop. Several case series and imaging reviews have highlighted the role ¹⁸F-FDG PET/CT for detecting large-vessel inflammation in ICI-treated patients, outperforming contrast-enhanced CT when the inflammatory component is subtle and non-occlusive (7,8). This case highlights a rare but clinically significant presentation of nivolumab-induced periaortitis detected incidentally on ¹⁸F-FDG PET/CT during routine restaging. The characteristic linear aortic wall uptake prompted further evaluation with CT angiography, enabling early diagnosis and timely initiation of corticosteroid therapy. Complete metabolic resolution on follow-up PET/CT confirmed the immune-mediated nature of the process. As the use of ICIs continues to expand, awareness of vascular irAEs and the role of ¹⁸F-FDG PET/CT in their early detection is essential for preventing potentially serious complications.