Abstract Introduction CDK4/6 inhibitors like palbociclib have transformed the treatment landscape for hormone receptor-positive metastatic breast cancer. Despite their clinical efficacy, these agents are associated with hematologic toxicity and increased susceptibility to infection. Pulmonary complications, though uncommon, are an emerging concern. Sarcoid-like reactions (SLRs), a form of granulomatous inflammation mimicking sarcoidosis, have been reported with various cancer therapies, including immune checkpoint inhibitors. However, SLRs associated with palbociclib are extremely rare. We present a case of biopsy-confirmed non-necrotizing granulomatous inflammation in the lung of a patient on palbociclib, which improved following cessation of therapy. Case report A 78-year-old woman with metastatic ER+/PR+/HER2-negative breast cancer, initially diagnosed in 2013, experienced recurrence in 2017 with widespread metastases. She was started on fulvestrant and palbociclib, leading to long-term disease stability. In April 2024, a surveillance CT chest revealed a new 2.5 cm lingular lung mass concerning for metastatic disease. Despite radiographic concern, the patient remained asymptomatic. Bronchoscopic biopsy in May 2024 of the lingular mass revealed non-necrotizing granulomas with multinucleated giant cells, chronic inflammation, and no evidence of malignancy or infection (negative GMS and Fite stains). Follow-up imaging in July 2024 demonstrated progression of inflammatory changes, including new tree-in-bud opacities in the right lower lobe. Given persistent imaging abnormalities, palbociclib was held. By October 2024, CT chest revealed significant radiographic regression of the lingular mass and resolution of right lower lobe findings. The patient remained asymptomatic throughout. By February 2025, the lesion had stabilized, appearing as residual nodular scarring. There was no recurrence of disease progression on continued fulvestrant therapy alone. The clinical and temporal association between palbociclib and the development and resolution of the granulomatous lung findings supported a diagnosis of a palbociclib-induced sarcoid-like reaction. Discussion SLRs are non-caseating granulomatous responses that may occur secondary to medications, infections, or malignancies. While drug-induced SLRs have been reported with several therapies, palbociclib has been reported twice. The pathophysiology may involve immune dysregulation and T-cell activation. In this case, the lung findings radiographically mimicked metastatic disease, risking inappropriate escalation of therapy. However, biopsy revealed non-necrotizing granulomas without malignancy or infection. Regression of the lesions after stopping palbociclib supported a drug-induced etiology. This aligns with previous reports where drug withdrawal alone led to resolution. SLRs should be considered in the differential diagnosis of new pulmonary lesions in cancer patients, especially when asymptomatic. Histologic confirmation is essential to guide appropriate management. This abstract is funded by: None
Landry et al. (Fri,) studied this question.