Abstract Introduction Trastuzumab deruxtecan is used to treat HER2-positive metastatic breast carcinoma. While pneumonitis is a commonly reported adverse clinical manifestation, other possible complications can include interstitial lung disease, organizing pneumonia, and, in rare cases, immune-mediated phenomena such as vasculitis. Manifestations can be as early as 2-4 weeks and as late as 1 year after initiation of therapy. We describe a case of a patient who was found to be afflicted by granulomatosis with polyangiitis (GPA) involving the tracheobronchial tree while on trastuzumab deruxtecan therapy. Case Report A 77-year-old woman with a history of metastatic breast carcinoma to bone on fifth-line systemic therapy with trastuzumab deruxtecan and recurrent admissions for hypoxic respiratory failure attributed to drug-induced pneumonitis presented with progressive dyspnea. On admission, she was tachycardic and febrile. Chest imaging showed interval progression of bilateral pulmonary infiltrates seen on previous admissions, right middle lobe and left lobe bronchial stenoses, and partial atelectasis of the right middle lobe. Bronchoscopy revealed severe stenosis of the left lower lobe bronchus and narrowing of the right middle lobe bronchus. Sequential airway dilation was performed, followed by placement of a stent in the left lower lobe bronchus. Histopathology of the endobronchial biopsies demonstrated granulation tissue with necro-inflammatory debris. Subsequent serologic studies showed positive ANA (1:320) and c-ANCA (1:40) titers, raising suspicion for antineutrophil cytoplasmic antibody-associated vasculitis, specifically GPA. Considering the patient was being treated with targeted biologic chemotherapy therapy for active malignancy, the decision to initiate immunosuppressant therapy was deferred. Discussion Bronchial stenosis remains a rare but serious manifestation of ANCA-associated GPA. Airway involvement can occur in the presence of granulomatous inflammation, leading to fibrosis and a fixed obstruction. The differential diagnosis must remain broad in patients presenting with bronchial stenosis. In the present case, the coexistence of metastatic breast cancer and treatment with trastuzumab deruxtecan complicated the diagnostic picture. While trastuzumab deruxtecan is primarily associated with pneumonitis, rare immune-mediated events such as vasculitis have been previously reported. The demonstration of c-ANCA positivity and bronchial stenosis raised suspicion for bronchial stenosis secondary to GPA. It is hypothesized that the mechanism behind this clinical manifestation centers around chronic inflammation along with necrotizing vasculitis of the bronchial wall, leading to mucosal ulceration, fibrosis, and eventual fixed airway narrowing. In this case, serological investigation of autoimmune markers was instrumental in establishing the underlying diagnosis. However, it should be noteworthy that negative serologies do not rule out the disease. This abstract is funded by: None
Harb et al. (Fri,) studied this question.