23 January 2025: Articles
Post-Transplant Lymphoproliferative Disorder at the Porta Hepatis Causing Hepatic Artery Stenosis and Cholestasis
Unusual clinical course, Challenging differential diagnosis, Unusual or unexpected effect of treatment, Diagnostic / therapeutic accidents
Badi Rawashdeh1AE*, Christina Papageorge2EF, Yazan Al-Adwan
DOI: 10.12659/AJCR.945837
Am J Case Rep 2025; 26:e945837
Abstract
BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) encompasses a group of disorders ranging from hyperplastic to malignant lymphoid proliferations in the post-transplant period owing to immunosuppression, often in the setting of EBV transformation. PTLD is a rare complication of immunosuppression that, like lymphomas, can have a variable presentation based on disease localization. We report a case of PTLD mass effect at the porta hepatis for the first time in the literature, resulting in hepatic artery stenosis (HAS) and common hepatic duct obstruction.
CASE REPORT: A 54-year-old woman presented with cholestasis 4 months after receiving a deceased donor liver transplant. MRCP revealed a mass at the porta hepatis causing biliary compression, which resolved with subsequent biliary stenting. The woman presented again 3 weeks later with a similar presentation. CT revealed that the mass had enlarged, causing HAS, which resolved with subsequent hepatic artery stenting. The biopsy revealed PTLD, and the patient was successfully managed with rituximab and a reduction of her immunosuppressive regimen.
CONCLUSIONS: This case report describes a rare occurrence of PTLD, which particularly impacting the porta hepatis, resulting in HAS and compression of the bile duct. PTLD should be considered in the differential diagnosis for obstructive jaundice and hepatic artery compression, even in the early post-transplant months, when these symptoms are often attributed to surgical factors.
Keywords: Liver Transplantation, Lymphoma, Bile Ducts, Hepatic Artery, Stents
Introduction
Post-transplant lymphoproliferative disorder (PTLD) is a rare and potentially life-threatening outcome of solid organ or hemopoietic stem cell transplantation, including liver transplantation [1–3]. PTLD represents a continuum of lymphoid proliferations ranging in severity from reactive polyclonal hyperplasia to malignant monoclonal lymphomas in the setting of post-transplantation immunosuppression status [1,4,5]. Reportedly, PTLD risk is highest among heart, lung, intestinal, and multi-organ transplant recipients in accordance with more intensive immunosuppressive regimens, reaching an absolute risk as high as 25%; among liver transplant recipients, PTLD risk ranges from 1–5% in adult and up to 15% in pediatric populations [4]. A strong association has been established between PTLD and Epstein-Barr virus (EBV), either acquired through primary infection from the organ donor or through latent infection of the host, resulting in lymphoid transformation and tumor growth secondary to EBV-positive lymphocyte proliferation; however, EBV-negative PTLD is reported in approximately 23% of cases [5,6].
Most cases of PTLD manifest within the first 2 years of transplantation [5,7]. Signs and symptoms of PTLD include fever, fatigue, anorexia, weight loss, and lymphadenopathy. Although the severity of symptoms depends upon the location and extent of organ involvement, mortality has been reported as high as 50% [6]. Extranodal PTLD is common and may involve many organs, including lung, skin, and bone marrow; 10–15% of cases present with central nervous system involvement [2,4]. The incidence of gastrointestinal (GI) tract involvement in liver transplant recipients is not well established, but is estimated to occur in approximately 25% of cases [2,6]. However, involvement of the porta hepatis is very rare and has been reported only sparsely in the literature through case reports with presentations of biliary compression secondary to mass effect [8].
Complications of the hepatic artery and bile duct are the most common causes of morbidity and mortality after liver transplantation, at times requiring re-transplantation. The incidence of post-transplant hepatic artery stenosis (HAS) has been reported in up to 5–10% of orthotopic liver transplants and, if left untreated, can result in hepatic artery thrombosis [9]. Most hepatic artery complications develop within 3 months of the initial transplant [9]. Biliary complications are divided into anastomotic leak or stricture associated with inadequate surgical technique versus non-anastomotic stricture associated with either external compression or ischemia of the donor bile duct [8–10].
To the best of our knowledge, this is the first published report of PTLD-related HAS. This report describes PTLD mass effect compressing the hepatic artery and common hepatic duct at the liver hilum after liver transplantation.
Case Report
A 54-year-old White woman was admitted 4 months after receiving a deceased donor liver transplant secondary to non-alcoholic steatohepatitis with symptoms including dark urine and yellow discoloration of her eyes. She had a past medical history of hypertension. Her perioperative course and recovery have been uncomplicated to date. On admission, her total bilirubin was elevated to 10.1 mg/dl; ALT and AST were elevated to 205 U/L and 133 U/L, respectively; and alkaline phosphatase was elevated to 821. Her immunosuppressive induction regimen had been with basiliximab, and her maintenance regimen was with cyclosporine and mycophenolic acid; notably, tacrolimus had been discontinued due to adverse effects of tremor and paresthesia.
Upon workup, MRCP revealed a 3.4×3.1 cm mass located in the porta hepatis at the hilum of the liver, causing intrahepatic dilatation of the biliary system (Figure 1). CMV viral load was negative, whereas EBV viral load was positive at 26 200 copies/mL. Fine-needle aspiration did not yield a sufficient sample to determine pathology. Subsequently, ERCP revealed bile duct stenosis, and stents were successfully deployed (Figure 2). Within 4 days, liver function test results were down-trending, and the patient showed clinical improvement.
Three weeks following discharge, the patient presented with severe epigastric pain, anorexia, nausea, and vomiting with concomitant elevations in total bilirubin to 8.2 mg/dl, liver enzymes ALT and AST to 200 U/L and 121 U/L, respectively, and alkaline phosphatase to 715. Liver US revealed decreased flow velocity through the left hepatic artery, concerning for an occlusion. Abdominal and pelvic CT revealed that the previously identified mass had grown to 5.8×5.5×5.8 cm and was now encompassing the hepatic artery and portal vein. EBV viral load had also increased to 262 000 copies/mL. Biopsy was obtained, revealing necrotic tissue with atypical large B cells consistent with PTLD, which falls under the monomorphic PTLD category according to the WHO classification.
The patient’s immunosuppressive treatment was subsequently lowered, including a drop in cyclosporin dose and the discontinuation of mycophenolic acid. In an effort to reduce the tumor burden, rituximab was combined with immunotherapy directed against PTLD. Due to persistent abdominal pain, repeat MRCP and liver US were performed, which demonstrated enhancing fluid in the left hepatic lobe, consistent with a biloma. The biloma was subsequently drained, resulting in clinical improvement of the abdominal pain. To address the ongoing HAS, multiple bare metal stents were successfully deployed in the hepatic artery (Figure 3).
Five months later, the patient presented with fever and chills. Workup revealed an abscess. MRI at this time demonstrated that the PTLD tumor was stable in size. The abscess was deemed too small for drainage, and the patient started on an 8-week course of antibiotics. Following these complications, the patient had a full recovery and has not suffered any further sequela attributable to PTLD.
Discussion
Bile duct compression by hilar lymph nodes has been reported in the setting of primary lymphoma [11,12]. However, PTLD localized to the porta hepatis following liver transplant is rare and has only been documented at the case series level. Since PTLD can develop in either a local or disseminated fashion, the symptomatic manifestations of PTLD are accordingly variable. In cases where PTLD progresses quickly, featuring rapid tumor growth, compressive symptoms often present at the site of tumor burden secondary to mass effect [4,5]. A recent review by Jain et al reported that 31% of patients with PTLD present with frank lymph node involvement, 25% experience GI symptoms, and 16% present with involvement of the liver and/or spleen [2]. Among patients with GI symptoms, abdominal pain is the most prevalent, followed by chronic diarrhea and bleeding [5]. Further studies have identified GI obstruction and perforation as additional complications of PTLD [5,8,11].
PTLD can be classified as either early or late. Early PTLD is frequently associated with EBV seropositivity and occurs within the first year after transplantation. Late PTLD is frequently EBV-negative and typically manifests years later [3,4]. Early PTLD presented diagnostic challenges in this case, as symptoms such as HAS or biliary compression are frequently attributed to surgical factors. PET/CT imaging tools are indispensable for the diagnosis and staging of PTLD, as they facilitate evaluation of tumor burden and monitoring of disease progression [3,9].
The reduction of immunosuppression is a critical component of management of EBV-positive PTLD. The immunosuppressive regimen was modified for this patient by discontinuing mycophenolate and decreasing the dosage of cyclosporine. Notably, the regimen did not include tacrolimus, a calcineurin inhibitor (CNI). CNIs have been linked to the promotion of EBV-infected cell survival, which can contribute to the development of PTLD. In contrast, mTOR inhibitors (mTORi), including sirolimus, are believed to limit EBV-driven tumor growth and may serve as alternative agents for the treatment of PTLD, particularly in the context of long-term immunosuppression [4,10,13,14].
GI involvement of PTLD (GI-PTLD) requiring surgical intervention is extremely rare. Cruz et al conducted a retrospective single-center cohort study of 5677 adult liver transplant recipients, wherein they identified 36 cases (0.63%) of GI-PTLD. Only 16 cases (0.28%) of GI-PTLD presented with complications requiring emergency surgical intervention, most often involving the small bowel or ascending colon. Of these cases requiring surgical intervention, 7 (44%) were due to small bowel obstruction, 6 (38%) due to perforation, and 3 (18%) due to GI bleeding. Furthermore, most of these cases requiring surgical intervention were monoclonal lymphomas involving the lower GI tract, presenting late after transplantation [2,5,6].
Complications of the hepatic artery and bile duct are the most common causes of morbidity and mortality after liver transplantation, but to the best of our knowledge, this report presents the first case of HAS caused directly by the mass effect of PTLD tumor burden localized to the porta hepatis. This case also offers a relatively rare, though previously documented, initial presentation of PTLD in the form of obstructive jaundice secondary to bile duct compression by mass effect. This case invites discussion regarding the management of atypical sequelae of PTLD.
Compression of the bile duct by hilar lymph nodes has been reported previously in cases of primary lymphomas presenting in the non-transplant population [11,12]. However, PTLD localized to the porta hepatis after liver transplantation is extremely rare.
Previous case reports have identified bile duct compression secondary to the mass effect of PTLD, as well as diffuse intrinsic bile duct infiltration of PTLD [8,15]. For example, Baron et al documented 2 cases of EBV-positive B cell lymphoma in the porta hepatis following liver transplantation [8]. Both patients developed jaundice, vomiting, and anorexia. One case presented total hepatic duct obstruction, which was managed by Roux-en-Y hepaticojejunostomy. The second showed significant bile duct stricture, which was managed by stepwise dilation and stenting. The study identified 12 cases of biliary strictures associated with PTLD, with treatments including retransplantation, bypass surgery, reduction of immunosuppressive therapy, chemotherapy, and radiotherapy [8].
Morard et al reported 2 cases of diffuse intrinsic bile duct infiltration by PTLD that mimicked an anastomotic biliary stricture [15]. Both patients presented with obstructive jaundice following liver transplantation. The first case was successfully managed by biliary-enteric bypass, while the second case required laparotomy and a new anastomosis. EBV-positive polymorphic PTLD was confirmed in both cases by pathology. In both patients, immunosuppressive therapy was modified, which involved the reduction of cyclosporine and the inclusion of rituximab. After 6 and 5 years of follow-up, respectively, neither patient demonstrated any signs of PTLD recurrence [15].
HAS is an ominous complication of liver transplantation, with a reported incidence of 4–10% [16]. It is most commonly localized to the anastomosis between the donor and recipient hepatic arteries; if left untreated, stenosis can result in hepatic artery thrombosis, which can ultimately result in biliary stricture, graft dysfunction, and patient demise. The most common etiologies of HAS are associated with the operative technique, microvascular injury, vessel kinking, clamp injury, anastomotic ischemia, and acute graft rejection [16].
HAS caused by mass tumor effect at the porta hepatis has never been reported in the literature until now.
With the advancement of endovascular techniques, the management of HAS has evolved dramatically within the past 2 decades. Percutaneous transluminal angioplasty (PTA) with or without stenting has emerged as the primary management of hepatic arterial complications, including HAS. In patients with HAS, PTA ensures sufficient arterial patency, improving graft function and patient survival while decreasing rates of retransplantation [17,18].
The present case report demonstrates successful short-term management of obstructive jaundice and HAS due to a large PTLD tumor burden localized to the porta hepatis. The mass effect of the PTLD tumor burden caused external compression and stenosis of both the common bile duct and hepatic artery. Additionally, we report successful stenting of the common bile duct and hepatic artery over the same 5-month period.
Complications included the development of a biloma requiring drainage, as well as a small abscess managed conservatively with antibiotics. Stent durability, prevention of tumor recurrence, and presentation of future complications, including infection, will continue to be assessed as we monitor this patient over a longer time course. As prior authors have noted, it is worthwhile to consider PTLD in liver transplant recipients who present with new-onset signs and symptoms of obstructive jaundice and to perform appropriate diagnostic work-up to identify tumor burden and resultant compression of structures within the porta hepatis, including the hepatic artery, as we have presented herein.
Conclusions
This case report describes a rare occurrence of PTLD particularly affecting the porta hepatis, resulting in HAS and compression of the bile duct. The liver transplant recipient was successfully treated using endovascular and ERCP stenting, in addition to immunotherapy modifications involving rituximab. This case highlights the importance of considering PTLD when liver transplant recipients exhibit hepatic artery compression and obstructive jaundice. The effective utilization of endovascular techniques underscores their significance in the management of such complications.
Figures
References:
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