Endoscopic Ultrasound With Fine Needle Biopsy Confirming a Diagnosis of Immune Checkpoint Inhibitor-Related Type 3...

Immune checkpoint inhibitor-related pancreatitis, also known as type 3 autoimmune pancreatitis (AIP), is uncommon and has a widely ranging clinical presentation. We present the biopsy findings of a case consistent with type 3 AIP-an entity recently described in the literature, the pathologic findings of which have not been well characterized.

A 71-year-old male with metastatic mucosal melanoma of the urethra was treated with immune checkpoint inhibitor (ICI) therapy (nivolumab/relatlimab) and developed vague epigastric discomfort. He was found to have an elevated lipase, which increased to > 20x the upper limit of normal. Subsequent imaging showed new infiltrative masses in the pancreatic head and distal body/tail. Endoscopic ultrasound with fine needle biopsy (FNB) was performed. This showed T-lymphocyte predominant infiltrates, in the acini and septal areas, with concomitant acinar, duct, and venular damage, including both CD4 and CD8 lymphocytes, which were considered consistent with type 3 AIP. He was treated successfully with prednisone.

On biopsy, there was no evidence of malignancy or features of type 1 or type 2 AIP. Histologic findings included moderate infiltration and damage to the pancreatic parenchyma, ductal, and vascular structures by CD4 and CD8 lymphocytes, pointing to immune-mediated pancreatic injury, and supportive of ICI-mediated injury to the pancreas of this patient. The clinical presentation of type 3 AIP ranges from asymptomatic lipase elevation to asymptomatic pancreatitis to acute symptomatic pancreatitis. There may be no clear temporal relationship to treatment initiation. Type 3 AIP typically presents along with other immune-related adverse events. Endoscopic ultrasound with FNB contributed to diagnostic certainty in this case and changed our patient's management, allowing for appropriate treatment of his immune-related adverse event.