Abstract
We describe a first suspected case of fibrosing mediastinitis following anti–programmed death (PD)-1 therapy, pembrolizumab. Multimodality imaging, including cardiac magnetic resonance imaging, and a multidisciplinary team approach were integral to the diagnosis. If further substantiated, systematic surveillance after anti–PD-1 therapy for fibrosing mediastinitis may be warranted. (Level of Difficulty: Intermediate.)
Key Words: anti–programmed death-1, cardiac magnetic resonance, fibrosing mediastinitis, fibrosis, immunotherapy, positron emission tomography
Abbreviations and Acronyms: CHF, congestive heart failure; CMR, cardiac magnetic resonance; LGE, late gadolinium enhancement; FDG, fluorodeoxyglucose; PD-1, programmed death-1; PET, positron emission tomography
Central Illustration
History of presentation
A 58-year-old man with a history of hypertension and diabetes mellitus without known coronary artery disease was diagnosed with anorectal melanoma upon discovery of an ulcerated rectal mass. The patient declined surgical resection and received anti–programmed death (PD)-1 therapy with pembrolizumab. After 1 year of pembrolizumab (ie, after 9 cycles), he developed acute renal failure and was discovered to have diffuse soft tissue densities in the abdomen and retroperitoneum on computed tomography. Biopsy of the retroperitoneal mass showed retroperitoneal fibrosis. Pembrolizumab was discontinued and prednisone was initiated. However, over the following year, the patient had recurrent myocardial infarction events requiring multiple coronary stenting complicated by in-stent restenosis and several hospitalizations for congestive heart failure (CHF).
Investigations
Two years after pembrolizumab discontinuation, the patient presented to our institution with acute CHF. Echocardiogram showed preserved biventricular systolic function and circumferential pericardial thickening measuring up to 6.3 cm abutting the right ventricle and a pericardial mass. Cardiac magnetic resonance (CMR) imaging (Siemens 1.5-T) showed a near-circumferential mediastinal mass from cardiac base to apex (Figure 1A). The mass was isointense with patchy areas of hyperintensity on T1- and T2-weighted sequences, respectively. There was early, diffuse enhancement on first-pass perfusion images, and both early and late gadolinium enhancement (LGE) of the mass (Figures 1B to 1D). Subendocardial LGE was also noted (Figure 1C). 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) showed extensive soft tissue infiltration with diffuse low-level FDG uptake from the mediastinum to the peritoneum, which was mildly increased in comparison to the adjacent organs and did not meet the threshold for focal hypermetabolic activity (Figures 1E and 1F). No focal FDG avid regions were present in the mediastinum or abdomen. The infiltrating structure in the mediastinum seen on CMR correlated with the PET images. This mass in the retroperitoneum and mediastinum was not present on a previous PET scan obtained at the time of cancer diagnosis before pembrolizumab initiation. Based on these findings, the patient was diagnosed with fibrosing mediastinitis. Although biopsy of the mediastinal tissue was not performed due to patient risk, the previous biopsy confirming retroperitoneal fibrosis, continuity of the retroperitoneal mass with the mediastinal mass seen on computed tomography, and CMR and PET findings were all highly indicative of fibrosing mediastinitis. Furthermore, rapidly progressing coronary artery disease necessitating recurrent revascularization over 13 months suggested that this could have been exacerbated by pericoronary inflammatory fibrosis.
Figure 1.
Fibrosing Mediastinitis Associated With Pembrolizumab Presenting as Inflammatory Fibrosis Encasing the Heart and Great Vessels on CMR and Contiguous Retroperitoneal Fibrosis on FDG PET
(A) Cardiac magnetic resonance (CMR) sagittal localizer image showing a large structure encasing the base of the heart and great vessels (red asterisks). (B) CMR phase-sensitive inversion recovery image shows late gadolinium enhancement (LGE) of the same structure (red asterisks). (C) CMR 4-chamber phase-sensitive inversion recovery image shows a structure with LGE circumscribing the heart (asterisks) and subendocardial LGE at the left ventricular apex, apical septum, and anteroseptum (arrowheads). (D) CMR short-axis mid left ventricular view shows LGE surrounding the left ventricle (red asterisks). (E) Fluorodeoxyglucose (FDG)–18 positron emission tomography (PET) coronal view shows a large, ill-defined structure with low metabolic activity in the mediastinum and abdomen. (F) Fused FDG PET/computed tomography coronal view shows low-to-moderate level FDG activity in the soft tissue structure that infiltrates the mediastinum surrounding the heart and peritoneal space. The standardized uptake value (SUV) scale is shown on the left, where yellow (at 49.20 SUV) represents the highest FDG uptake.
Management
The patient underwent diuresis with improvement in symptoms. Oncology, radiology, and cardiothoracic surgery teams were consulted. The patient was deemed to have prohibitive surgical risk for a pericardial resection. It was also revealed that he had inadvertently discontinued prednisone in between the prior recurrent hospitalizations. Prednisone and guideline-directed medical therapy for CHF were initiated.
Conclusions
Although cases of retroperitoneal and pulmonary fibrosis associated with anti–PD-1 have been previously described, this is the first reported case of fibrosing mediastinitis following anti–PD-1 immunotherapy.1, 2, 3 If our finding is further substantiated, systematic surveillance for fibrosing mediastinitis may be warranted after anti–PD-1 use.
Funding and Author Disclosures
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
References
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