Allergic Fungal Sinusitis Imitating an Aggressive Skull Base Lesion in the Setting of Pembrolizumab Immunotherapy

Abstract

Objectives: We report a case of acutely worsening allergic fungal sinusitis in a patient receiving immunotherapy with pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor. Methods: A 53-year-old man with a history of metastatic melanoma and recent initiation of pembrolizumab therapy presented with acutely worsening headaches, left abducens nerve palsy, and neuroimaging demonstrating an erosive skull base lesion with bilateral cavernous sinus involvement. Results: Intraoperative findings were consistent with non-invasive allergic fungal sinus disease. Microbiology and histopathologic data ruled out malignancy and demonstrated Aspergillus fumigatus without concern for angioinvasion. After treatment with antifungal therapy, the patient’s symptoms and abducens nerve palsy resolved. Symptoms were well-controlled 7 months after his initial presentation. Conclusions: Inflammatory sinusitis in patients receiving anti-PD-1 therapy may be secondary to T-cell infiltration, a similar pathophysiology as immune-related adverse events, and warrants appreciation by otolaryngologists given our increasing exposure to immunotherapy and its head and neck manifestations.

Infections due to dysregulated immunity: an emerging complication of cancer immunotherapy

“… 98 Dysregulated immunity appears to play a role, indicated by dramatic worsening of chronic progressive pulmonary aspergillosis and fulminant deterioration of nasal fungal sinusitis postimmunotherapy. Again, clinical presentation can mimic cancer progression, with pulmonary cavitation, 98 99 erosive skull base lesions with bilateral cavernous sinus involvement 100 and new pulmonary nodules with pleural effusion, 101 and so cases may well be under-reported. In these situations, immune checkpoint blockade may cause an exaggerated immune response to fungal colonisation, which could promote fungal growth similar to recent studies in Mtb infection.…”

Pembrolizumab‐associated chronic rhinosinusitis: A new endotype and management considerations

“…The study supports previous case reports of CRS associated with ICIs. [3][4][5][6] It is hypothesized that the activation of T cells by pembrolizumab and similar medications may lead to local inflammation and CRS. However, the exact mechanism underlying this CRS endotype is yet to be tested.…”

Pembrolizumab-Induced Nasal Polyposis: The First Reported Case

“…To date, there have been no reported cases of pembrolizumab causing CRS with or without nasal polyposis. One previous case has been described of worsening of allergic fungal CRS in the setting of pembrolizumab therapy [5], and there have been reports of nivolumab, another ICI of programmed deathligand 1 (PDL-1), causing CRS with nasal polyposis [5,6]. In one case this occurred years after commencing therapy [6].…”