Abstract Introduction Kaposi sarcoma (KS) is a malignant vascular neoplasm caused by human herpesvirus-8 (HHV-8) infection. Although KS is well described in solid organ transplant recipients, pulmonary involvement of the lung allograft is exceedingly rare and associated with high mortality. We report a case of HHV-8-positive pulmonary Kaposi sarcoma following bilateral lung transplantation. Case Presentation A 74-year-old man with interstitial lung disease underwent bilateral sequential lung transplantation (BSLT) in October 2024. His post-transplant course was notable for prolonged hospitalization due to respiratory failure requiring tracheostomy, empyema, Clostridioides difficile colonization, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) viremia, Aspergillus infection, Pseudomonas aeruginosa pneumonia, and chronic kidney disease. Eight months post-transplant, he developed progressive dyspnea and hypoxia, presenting to the hospital. CT chest revealed diffuse bibasilar ground-glass and nodular opacities with persistent bilateral bronchial stenosis. Serial bronchoscopies demonstrated modest secretions, mucus plugging, and recurrent left lower lobe stent occlusions, requiring repeated dilations and tracheostomy. Despite broad antimicrobial coverage, immunosuppression adjustment, and supportive measures, he succumbed to progressive hypoxic respiratory failure and shock.At autopsy, microscopy revealed spindle-cell proliferations throughout both right and left lung parenchyma. Immunohistochemistry was positive for HHV-8 nuclear antigen. The histomorphology and immunohistochemical profile are diagnostic of Kaposi’s Sarcoma involving bilateral lung allografts (Figure 1). Donor testing was requested but is unavailable. Discussion Post-transplant KS typically involves the skin, lymph nodes, or gastrointestinal tract; isolated pulmonary disease is rare. HHV-8 reactivation or donor-derived infection may occur months to years post-transplant, with augmented immunosuppression and persistent CMV viremia serving as key risk factors. CMV coinfection may enhance HHV-8 replication and endothelial tropism, amplifying oncogenic potential. Bronchoscopy may show non-specific findings such as edematous, inflamed mucosa. Diagnosis is challenging and requires an endobronchial or transbronchial biopsy, which was not performed in this case given poor clinical status. Therapeutic strategies include reducing immunosuppression and converting to sirolimus, an mTOR inhibitor with both immunosuppressive and anti-KS properties. Systemic chemotherapy (e.g., liposomal doxorubicin or paclitaxel) can achieve 50-60% response rates in transplant-associated KS. However, outcomes are generally worse in those with visceral or pulmonary involvement, where complete remission remains uncommon.This case illustrates the diagnostic and therapeutic challenges of post-transplant pulmonary KS, emphasizing the importance of maintaining a high index of suspicion for HHV-8-related malignancy in transplant recipients with unexplained pulmonary infiltrates, particularly with persistent CMV viremia and intense immunosuppression. Early identification and prompt modification of immunosuppressive regimens may improve outcomes in this rare but often fatal complication. This abstract is funded by: None
Burke et al. (Fri,) studied this question.