Post-liver transplant Kaposi sarcoma (KS) is a rare but clinically significant condition, most commonly observed in recipients of solid organ transplants who are undergoing long-term immunosuppressive therapy [1]. KS was first described by Moritz Kaposi in 1872 as an idiopathic hyperpigmented sarcoma of the skin [2]. The understanding of KS expanded with the recognition of an iatrogenic form in 1970, which included its occurrence in immunocompromised individuals following transplantation [3]. The infectious etiology of KS was definitively established in 1994, highlighting the pivotal role of immunodeficiency in its pathogenesis [2,4]. Despite these advances, managing post-liver transplant KS remains challenging due to its rarity, variable clinical presentation, and the need to maintain a delicate balance between controlling the neoplasm and preserving graft function.

In this case report, we present long-term follow-up data regarding a 40-year-old Asian woman who developed de novo KS in a liver graft following living donor liver transplantation. The patient was treated with mammalian target of rapamycin (mTOR) inhibitors along with tacrolimus withdrawal. The follow-up period extended over 64 months, and as of the date of this report, the patient’s condition remains stable. This case represents the longest documented follow-up of a patient with KS developing in a liver graft after living donor liver transplantation.

The work received approval from the Institutional Review Board of Republican Scientific Center of Emergency Medicine (IRB No. #476/24). The patient provided written consent for the use of her medical data in scientific research, with the assurance that anonymity would be maintained.

A 38-year-old Asian woman had been diagnosed with hepatitis D virus end-stage liver disease. She was admitted to the hospital due to acute decompensation, presenting with jaundice and moderate ascites. Further investigation and evaluation revealed clinically significant portal hypertension, grade 3 esophageal varices, moderate ascites, splenomegaly, and grade 2 hepatic encephalopathy. A suitable living donor was found in the patient’s 40-year-old sister, who had an unremarkable medical history, no notable somatic diseases or habits, and normal laboratory parameters. Her viral serology tests, including those for human herpesvirus (HHV) and cytomegalovirus, were negative. In March 2019, the patient underwent living donor liver transplantation. Immunosuppressive therapy, initiated on the second day after transplantation, included tacrolimus, prednisolone, and mycophenolate, with the tacrolimus levels maintained between 6–10 ng/mL. Additionally, the patient continued standard antiviral therapy with entecavir. During the second week posttransplant, the patient experienced an episode of T cell rejection, which was managed with pulse therapy using methylprednisolone at 20 mg/kg of body weight. The patient was discharged on the 21st day after surgery with normal liver function tests (LFTs).

Six months later, the patient was readmitted due to the development of late anastomotic biliary stricture leading to graft dysfunction. Upon admission, her vitals were unstable, and she had a fever of 38.7 °C. Ultrasonography revealed significant ascites and mild right-sided hydrothorax. An magnetic resonance imaging scan showed dilated biliary ducts and multiple enlarged lymph nodes in the portal hilum of the liver graft. Consequently, late anastomotic stricture was diagnosed. Computed tomography (CT) imaging further identified several small subcapsular linear areas of irregular, nonenhancing hypodensities in segments VI, VII, and VIII of the graft, which were interpreted as being of inflammatory origin. Additionally, multiple discrete heterogeneous enhancing lymph nodes were observed in the periportal, celiac trunk, peripancreatic, aortocaval, retrocaval, left paraaortic, and bilateral iliac regions. The largest lymph node in the portocaval area (12p) measured 3.5 × 1.7 cm. Fine needle aspiration cytology was suggestive of KS. Core biopsy revealed lesion cells that were oval- to spindle-shaped, with minimal pleomorphism and mitotic activity of up to five to six per 10 high-power fields. These cells formed vascular channels, and marked nuclear pleomorphism was not observed. Immunohistochemistry (IHC) indicated that these spindle cells were diffusely positive for CD31, D2-40, and FLI-1, with focal patchy positivity for CD34. Tests for cytokeratin and leukocyte common antigen were negative. The spindle cells expressed HHV-8 on IHC. Based on these findings, a diagnosis of KS was established.

Serology was negative for all viruses tested, including HHV and CMV. The patient underwent the placement of two 8-French stents in the biliary ducts. Rapamycin was initiated as the primary immunosuppressive agent. The postoperative period was marked by a high fever reaching 38 °C, as well as chills. Chest X-ray revealed an increase in right-sided pleural effusion, prompting drainage for decompression along with fluid cultures and sensitivity testing. Bacteriological analysis revealed the presence of Klebsiella pneumoniae, which was sensitive to polymyxin. In the third week after stenting, the patient developed acute respiratory failure and required intubation. Analysis of bronchoalveolar lavage fluid identified infections with human rhinovirus and enterovirus. Treatment for these infections was administered in accordance with current guidelines, and the patient was subsequently extubated. Her condition gradually stabilized, and she was discharged with normal LFTs and without the need for oxygen support. Her immunosuppressive regimen included rapamycin, tacrolimus, and prednisolone.

Three months following the establishment of the Kaposi tumor and the initiation of rapamycin therapy, a slight increase in LFTs was observed. CT revealed the persistence of focal lesions in the graft (Fig. 1). Due to the limited response of the tumor to treatment, oral tacrolimus and prednisolone were discontinued, and rapamycin monotherapy was initiated as the preferred treatment approach. Repeat CT indicated a partial tumor response, along with changes in the structure and location of the lesions (Fig. 2). Given this response, rapamycin monotherapy was maintained as the immunosuppressive regimen. The patient’s general condition gradually improved.

Five months after initiating rapamycin, CT imaging showed a good tumor response (Fig. 3). Sixteen months following the detection of KS, a CT scan revealed a nearly complete tumor response (Fig. 4). By the 33rd month, a complete response was achieved, with no focal lesions observed. Throughout the follow-up period, the patient underwent two episodes of biliary stent replacement, both of which were unremarkable.

Forty-two months after discharge, in compliance with local healthcare regulations [5], the patient was transitioned from rapamycin to a combined regimen of everolimus and tacrolimus. The dynamics of her LFTs are detailed in Table 1. At the time of publication of this case report, the follow-up period has reached 64 months since liver transplantation. The patient’s condition remains satisfactory, with LFT values consistently within normal limits. Routine ultrasound examinations of the liver graft are currently performed every 6 months.

According to the European consensus-based interdisciplinary guidelines, KS is characterized as a multifocal neoplasm originating from lymphatic endothelium-derived cells infected with HHV-8. Numerous authors have emphasized the importance of immunodeficiency contexts, such as those induced by human immunodeficiency virus infection or immunosuppressive therapy, in the development of KS. Presently, four main subtypes of KS have been identified, each with distinct clinical and immunohistochemical characteristics [6–8].

The management of KS varies based on the subtype of the lesion. In the posttransplant setting, treatment options include tapering immunosuppressive therapy and switching to mTOR inhibitors [7,9]. Although established agents are available for the treatment of posttransplant KS, prognostic factors have not been well-studied, and detailed treatment recommendations are scarce [7]. Furthermore, the literature on KS in liver transplant recipients is limited, with only a few case studies, and follow-up periods in these studies seldom extend beyond several weeks.

Visceral KS is a rare malignancy that may arise de novo in patients after liver transplantation [10]. As previously mentioned, very few published studies have described this form of posttransplant lymphoproliferative disorder affecting liver grafts. Due to the rarity of KS, its morphological variability, and the unique characteristics of the recipient’s immune system, our understanding of KS in solid organ transplant recipients is primarily based on isolated case reports.

Several studies have demonstrated the involvement of HHV-8 in the pathogenesis of KS [7,11]. HHV-8 is known to encode proteins homologous to human oncoproteins, which increases the risk of malignant proliferation. Thus, it is crucial to detect HHV-8 in solid organ transplant recipients to assess their risk of developing KS. However, current guidelines do not endorse routine HHV-8 blood testing, and not all patients with KS test positive for HHV-8, even after the disease has developed. For instance, a multicenter European retrospective study conducted by Delyon et al. [12] across six countries reported prior primary HHV-8 infection in only two out of 145 posttransplant patients. Furthermore, management strategies for these patients are not standardized and often rely on empirical approaches. Balancing disease control with the preservation of graft function poses a significant therapeutic challenge [12].

Stallone et al. [13] were among the first to describe the treatment response of KS to mTOR inhibitors in solid organ transplant recipients. The authors reported on 15 kidney transplant recipients who developed de novo skin KS following transplantation and were successfully treated with an mTOR inhibitor (sirolimus), along with the complete withdrawal of a calcineurin inhibitor [13]. Although the study reported a 100% efficacy rate, no definitive treatment regimen for posttransplant KS has been established. Therapeutic options have varied and include surgical excision, radiation therapy, intralesional injection of chemotherapeutic agents, reduction of immunosuppressive therapy, and systemic chemotherapy [14,15]. Over time, transitioning to mTOR inhibitors has become a component of the standard management strategy for posttransplant KS. Research has shown that sirolimus possesses antitumor properties, mediated by the inhibition of mTOR, as well as antiangiogenic effects through disruption of the production of vascular endothelial growth factor [16]. The current therapeutic armamentarium for posttransplant KS is founded on three main strategies: reducing immunosuppression, converting to mTOR inhibitors, and administering chemotherapy [9,12]. However, additional research is needed to better understand and treat this rare complication.

During the 64-month follow-up period described in this report, we administered only low doses of calcineurin inhibitors, with blood tacrolimus levels ranging from 0.7 to 1.1 ng/dL. Nevertheless, we observed only two mild episodes of alanine aminotransferase and aspartate aminotransferase elevation, which were effectively managed by temporarily supplementing the treatment regimen with mycophenolate mofetil at a dose of 250 mg. Such immunosuppressive protocols are specifically designed to reduce KS lesions in the transplanted liver while maintaining graft integrity. However, they are not suitable for patients with a standard posttransplant course due to the increased risk of acute rejection. In our assessment, the benign biliary stricture developed independently of KS and was addressed according to the standard protocol. The patient underwent endoscopic retrograde cholangiopancreatography for stent placement in the common bile duct, which successfully resolved the stricture. During the follow-up period, no recurrence of stricture was observed. In conclusion, we believe that the case presented here contributes valuable insights into the progression and treatment of KS in solid organ transplant recipients.