A New Hepatic Lesion During Immunotherapy: an Unexpected Diagnosis

Background: Hepatic hemangiomas are the most common benign tumors of the liver and typically grow slowly. Rapid growth has been reported with the PD-1 inhibitor camrelizumab, but whether it occurs with other PD-1 inhibitors remains unclear. We report a case of rapid development of a hepatic hemangioma over a two-year period from no detectable lesion on prior imaging during treatment with a different PD-1 inhibitor.

Case Presentation: A 70-year-old woman with relapsed Hodgkin lymphoma, previously treated with CHOP chemotherapy, brentuximab vedotin, and nivolumab, underwent follow-up FDG PET/CT in October 2023. Imaging demonstrated FDG-avid retroperitoneal lymphadenopathy consistent with recurrent lymphoma and a newly detected 7.5-cm well-defined hypodense hepatic lesion without FDG uptake. The lesion was not detectable on the previous PET/CT in 2021, prior to initiation of nivolumab therapy. Given the development of a new hepatic lesion in a patient with active malignancy, core needle biopsy was performed. Histopathological examination confirmed the diagnosis of hepatic hemangioma.

Discussion: Rapid enlargement of a hepatic hemangioma is uncommon and may raise concern for metastatic disease. Despite its unusual growth pattern, dedicated contrast-enhanced liver imaging could have provided a confident noninvasive diagnosis and potentially avoided biopsy. Although causality cannot be established, the temporal association with PD-1 inhibition raises the possibility of accelerated hemangioma growth. While this phenomenon has been reported primarily with camrelizumab, often in combination with other anticancer therapies, whether it represents a class effect of PD-1 inhibition remains uncertain.

Conclusion: Rapid enlargement of a hepatic hemangioma should be considered in the differential diagnosis of newly detected hepatic lesions arising during PD-1 inhibitor therapy. Dedicated contrast-enhanced liver imaging may allow accurate noninvasive diagnosis and help avoid unnecessary biopsy. Further investigation is warranted to clarify the relationship between PD-1 inhibitors and accelerated hemangioma growth.