Abstract Introduction HER2-targeted therapies, such as trastuzumab deruxtecan, rarely cause pulmonary toxicity. Diffuse alveolar damage (DAD), the histologic correlate of ARDS, is nonspecific and can result from infection, toxins, or drug-induced injury. We report a fatal case notable for a strikingly elevated Fungitell (β-D-glucan) in the absence of fungal infection, highlighting a rare diagnostic challenge. Case Presentation A 62-year-old woman with stage IV HER2-positive invasive ductal carcinoma, COPD, and hyperlipidemia presented after being found down at home with acute hypoxemia. Chest CT revealed diffuse bilateral ground-glass opacities with multifocal consolidations. Oxygen requirements escalated to high-flow nasal cannula and BiPAP support. Her Fungitell was markedly elevated at 7360 pg/mL, raising concern for Pneumocystis jirovecii pneumonia (PJP). She was started on high-dose TMP-SMX and intravenous corticosteroids, and trastuzumab was held. Despite broad-spectrum antibiotics and intensive care support, her condition deteriorated, requiring intubation. Infectious workup which included viral panel, bronchoalveolar lavage cultures, and cytology remained negative. Autopsy revealed severe acute-phase DAD on a background of emphysematous and fibrotic changes. There was no evidence of PJP, other fungal infections, or residual malignancy, and no fibroblast foci were present, confirming the absence of ongoing fibrosis. Discussion This case illustrates a rare diagnostic scenario: markedly elevated Fungitell without fungal infection. While β-D-glucan is usually a marker for invasive fungal disease, false positives at such extreme levels are uncommon and may occur in critically ill patients receiving therapeutic antibodies. In this patient, the elevation likely reflected severe acute lung injury and systemic inflammation rather than infection. Clinicians should be aware that drug-induced pneumonitis can mimic infectious processes, and biomarkers must always be interpreted in the full clinical and radiographic context. Conclusion Trastuzumab-induced pneumonitis, though rare, can rapidly progress to fatal DAD. Markedly elevated Fungitell may mislead, simulating PJP, and reinforces the importance of integrating clinical findings, imaging, and pathology. Early recognition, discontinuation of the offending agent, and careful evaluation of atypical biomarker results are essential, and autopsy remains invaluable in confirming etiology in complex pulmonary cases. Disclosure AI assistance was used for drafting and language refinement. All case content and interpretations were written and confirmed by the authors. This abstract is funded by: None
Batra et al. (Fri,) studied this question.