Abstract Introduction In chemotherapy recipients, close surveillance is recommended for life-threatening adverse reactions like drug-induced interstitial lung disease (DIILD) or pneumonitis. Enhertu is an antibody-drug conjugate indicated for metastatic HER-2 positive solid tumors like breast, gastric, and non-small cell lung cancer. Pseudocirrhosis, most commonly seen in metastatic breast cancer, results from desmoplastic response to both chemotherapy and metastases. It mimics the radiology and manifestations of liver cirrhosis. Some complications include hepatic failure, decreased drug clearance (increasing drug toxicity), immunocompromise predisposing to invasive fungal infections, and reduced survival. Description A 49-year-old female with metastatic breast cancer, post-bilateral mastectomy and radiation, presented with disease progression despite chemotherapy and hormonal suppression. Computed tomography (CT) revealed pseudocirrhosis with decompensated hepatic function. Enhertu was initiated. However, 3 weeks later, she presented with fevers, confusion, acute hypoxic respiratory failure requiring high-flow nasal cannula, and cryptococcal bacteremia. Chemoport was removed as a result of the tip being colonized with Cryptococcus. CT chest showed extensive ill-defined airspace opacities bilaterally with interstitial thickening. The acute respiratory distress syndrome (ARDS) progressed subsequently. A week later, despite antifungal treatment to target suspected cryptococcal pneumonia as well, these opacities and high oxygen requirements persisted. After ruling out central nervous system dissemination, benefits of mitigating respiratory compromise with steroids for the now suspected Enhertu-induced pneumonitis, outweighed the delayed resolution of concurrent fungal infection. Thus, moderate-dose intravenous methylprednisone was initiated. Over the next week, she no longer experienced dyspnea and cough, with improvements in oxygen requirements and lung opacities. Patient was discharged on 2 L/min oxygen and a prolonged antifungal treatment regimen. Enhertu was permanently discontinued. Discussion On CT, cryptococcal pneumonia may appear as localized consolidations and nodules or diffuse bilateral confluent opacities in cases that progress to ARDS, resembling various patterns seen with DIILD. DIILD is a diagnosis of exclusion but poses a diagnostic challenge due to overlapping clinical and radiological features with other interstitial diseases, pulmonary infections, radiation pneumonitis, lymphangitis carcinomatosis, or progression of malignancy. For Enhertu, median time to onset of DIILD is 2.8 - 5.5 months, with majority of cases within the first year. Patients need to be advised to report pulmonary symptoms immediately. The mainstay of therapy is chemotherapy dose reduction or dose interruption (Grade 1 ILD), permanent drug discontinuation (Grade 2-4 ILD), along with prompt initiation of steroids until complete clinical and radiological resolution, followed by a slow steroid taper to prevent a flare. ILD grades 3-4 warrant hospitalization. This abstract is funded by: None
Nehete et al. (2026) studied this question.