INTRODUCTION: Despite an overall increase in survival over the last 40 years, lung transplant recipients continue to experience high rates of complications such as rejection, opportunistic infections, and malignancies. The most common malignancies affecting lung transplant recipients are post-transplant lymphoproliferative disorders and skin cancers. Kaposi's sarcoma (KS) has been reported in up to 6% of renal transplant patients, but remains extremely rare in pulmonary transplantation. Herein we report a unique case of aggressive symptomatic allograft involvement by KS in a bilateral lung transplant recipient.
CASE PRESENTATION: A 45-year-old male of Mediterranean descent with cystic fibrosis status-post bilateral lung transplant 7 months prior to presentation was evaluated for fever, fatigue and nonproductive cough of 1 week duration. He also had a 1 month-history of a worsening pruritic rash on his chest, which was diagnosed clinically as Herpes Zoster and treated with valacyclovir. A bronchoscopy with transbronchial biopsies 2 weeks prior to presentation revealed no rejection or infection. The patient's immunosuppressant regimen consisted of prednisone, azathioprine, and tacrolimus. On initial examination, the patient was comfortable, afebrile, with room-air oximetry of 95%. Breath sounds were decreased over the right lung base on auscultation. His skin exam revealed a 10 by 12 cm area of multiple coalescing violacious papular lesions on his thorax. His FEV1 was 1.96 L, reduced from 2.72 L two weeks prior. A chest X-ray revealed new bilateral pleural effusions, right greater than left.The patient was admitted to the hospital with concern for allograft rejection, viral or fungal pulmonary infection, or a lymphoproliferative process. Bronchoscopy showed diffuse airway edema with multiple submucosal hemorrhagic lesions throughout both lungs. Microscopic evaluation of transbronchial biopsies revealed areas of hemorrhage and vascular proliferation as well as focal interstitial collections of spindle-shaped cells staining positive for vimentin, CD31, and factor VIII. An immunoperoxidase stain for human herpesvirus 8 (HHV8) was focally positive. These lesions were consistent with KS. Skin punch biopsies also showed KS. HHV8 was found by PCR in the patient's blood at 393,000 DNA copies/mL and in the hemorrhagic pleural fluid at 226,000 DNA copies/mL.
DISCUSSIONS: Kaposi's sarcoma, related to infection with human herpesvirus 8, is an important complication of transplantation. Tumorigenesis is likely mediated by the upregulation of multiple anti-apoptotic and angiogenic genes. One intriguing proposed mechanism is the lytic-phase expression of a viral chemokine G-coupled receptor homologue (vGCR), which induces the secretion of VEGF, which in turn has angiogenic and cell-transforming properties.Treatment of KS in the transplant population remains controversial and first line therapy may include reduction of immunosuppressant and consideration of an anti-tumor agent. The largest reported experience is a cohort of 15 renal transplant recipients whose cutaneous lesions regressed after discontinuation of calcineurin-inhibitors and treatment with sirolimus. The experience in lung transplantation is very limited and in the four previous reports there was disease regression over several months with reduced immunosuppression. Of these four patients, three had respiratory tract disease, but only one had symptomatic allograft involvement. Our patient presented with unusually aggressive disease and extensive allograft involvement and dysfunction making treatment decisions difficult. Reduced immunosuppression and therapy with sirolimus were initiated.
CONCLUSION: Kaposi's sarcoma is a rare malignancy in lung transplant recipients but should be considered in patients with skin lesions and pulmonary disease. HHV8-rich hemorrhagic pleural effusion can be part of the clinical spectrum of KS in lung transplant recipients. Additionally, given the recent implication of HHV8 in the pathogenesis in KS, pre and post-transplant monitoring for HHV8 may be considered in lung transplantation.
DISCLOSURE: Tereza Martinu, None.