A48-01 Metastatic Urothelial Carcinoma Confined to a Transplanted Lung: A Rare Pattern Suggesting Allograft-specific Susceptibility

Introduction Solid organ transplant recipients have an increased risk of malignancy due to chronic immunosuppression, with cancer representing the second leading cause of death in lung transplant recipients. While primary malignancies are more common in the native lung of single-lung transplant recipients, selective metastatic seeding of a transplanted lung is exceedingly rare. We present a case of metastatic urothelial carcinoma (UC) confined to a transplanted lung with complete sparing of the native lung, suggesting possible allograft-specific susceptibility to metastatic seeding. Case Report A 75-year-old man with severe COPD and a 22.5 pack-year smoking history underwent right single-lung transplantation in January 2019. His postoperative course was complicated by donor-derived Pseudomonas infection and rhinovirus. He received basiliximab induction followed by maintenance immunosuppression with a calcineurin-inhibitor-based regimen. In March 2024, he developed gross hematuria. Transurethral resection revealed high-grade papillary UC invading the lamina propria. Intravesical Bacillus Calmette-Guérin (BCG) was contraindicated due to immunosuppression, and he underwent radical cystectomy (pT2N0Mx) in October 2024. Surveillance PET/CT in January 2025 demonstrated a new hypermetabolic right middle-lobe nodule confined to the transplanted lung, with no lesions in the native lung or other organs. Transthoracic needle aspiration confirmed metastatic UC. The patient underwent irreversible electroporation ablation of the transplant lung metastatic mass in March 2025, followed by systemic therapy with Enfortumab Vedotin as pembrolizumab was avoided due to transplant status. Follow-up imaging through September 2025 demonstrated a partial response of numerous pulmonary metastases decreasing in size and disease remaining limited to the transplanted lung. Discussion This case highlights a unique metastatic pattern confined to a transplanted lung, suggesting that allograft tissue may represent a more permissive microenvironment for tumor seeding. UC commonly spreads to the lung, liver, bone, and lymph nodes, but isolated involvement of a transplanted lung is exceptionally uncommon. The pathophysiology of this phenomenon remains unclear. Impaired immune surveillance, pre-metastatic niche formation from tumor-secreted growth factors, and disruption of lymphatic drainage in the allograft may have contributed to this unusual pattern of metastatic spread. In addition, calcineurin inhibitor-mediated suppression of adhesion molecules could have created a permissive microenvironment, promoting metastatic tropism toward the allograft. To our knowledge, this is the first reported case of UC selectively metastasizing to a transplanted lung. Recognition of this pattern may influence oncologic surveillance strategies in lung transplant recipients. This case underscores the need for further research into the biological differences between native and transplanted lungs that influence metastatic tropism.