The Histopathology of Abemaciclib-Induced Interstitial Lung Disease: A First Case Report With Transbronchial Lung Cryobiopsy

Abstract

Abemaciclib, a cyclin-dependent kinase 4/6 inhibitor, is crucial in treating hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic or recurrent breast cancer. However, its association with drug-induced interstitial lung disease (DI-ILD) is concerning. We present an 82-year-old woman with breast cancer receiving abemaciclib, who developed persistent cough and malaise. Initial diagnostics suggested pneumonia, supported by ground-glass opacities and consolidations on chest high-resolution computed tomography. Suspecting DI-ILD, a transbronchial lung cryobiopsy (TBLC) was performed, revealing fibrosing organizing pneumonia and confirming abemaciclib-induced ILD. Discontinuing abemaciclib led to significant symptom improvement, supporting the diagnosis. This case report describes the clinical presentation and diagnostic approach in a patient with suspected abemaciclib-induced ILD, including the use. To our knowledge, this is the first reported case of fibrosing organizing pneumonia as a histopathological pattern in abemaciclib-induced ILD, expanding knowledge of this therapy's pulmonary adverse events. Histopathological features included diffuse lymphocytic infiltration, polypoid intra-alveolar fibrosis, intraluminal granulation tissue plugs with dense hyalinization, hyalinized fibrotic alveolar septa lesions, and obliterative fibrotic processes affecting alveolar ducts. Our case suggests that TBLC might be useful in recognizing DI-ILD by providing detailed lung tissue examination, which can facilitate early diagnosis and guide management. Identifying fibrosing organizing pneumonia indicated a potentially corticosteroid-responsive pathology, suggesting a more favorable prognosis compared with patterns like diffuse alveolar damage. This case highlights the potential for abemaciclib-induced ILD to occur even after prolonged treatment periods, emphasizing the importance of vigilance and consideration of diagnostic intervention for patients on cyclin-dependent kinase 4/6 inhibitors presenting with respiratory symptoms. Timely recognition and appropriate management may mitigate adverse outcomes. Further studies are needed to confirm these findings and to better understand the role of TBLC and histopathological examination in diagnosing and managing abemaciclib-induced ILD.

Keywords: Abemaciclib; breast cancer; drug-induced interstitial lung disease; transbronchial lung cryobiopsy.

Figure 1.

Chest radiography at admission (A). High-resolution computed tomography (HRCT) at admission (B, C) and 3 months later (D, E). Chest radiography revealed consolidation and reticular shadow in the bilateral lower field. At admission, HRCT demonstrated nonsegmental consolidation and ground-glass opacities in both lungs, with a predominance in the lower lobes, particularly in the right lung (B, C). After 3 months, most of the ground-glass opacities had resolved, and the consolidations had significantly improved (D, E).

Figure 2.

Histologic findings from a transbronchial lung cryobiopsy. Low-magnification (A) and high-magnification (B, C, D, E) views with hematoxylin and eosin (H&E) staining (A, B, D) and Elastica Masson-Goldner (EMG) staining (C, E) are shown. The high-magnification images (D, E) provide an enlarged view of the area enclosed by the square in the low-magnification images (B, C). Diffuse lymphocytic infiltration was observed, accompanied by polypoid intra-alveolar fibrosis. Intraluminal plugs of granulation tissue (Masson bodies) with dense hyalinization and fibrosis of the central core were noted (B, C). Hyalinized fibrotic lesions of alveolar septa and obliterative fibrotic processes affecting the alveolar ducts were also observed (black star in D, E), resulting in loss of normal alveolar architecture. Epithelial damage was also evident (arrowhead in D, E).