De novo solid tumors rarely occur in a graft after liver transplantation, although some de novo hepatocellular carcinomas have been reported. To the best of our knowledge, there have been no reports of de novo inflammatory pseudotumors (IPTs) in a liver graft. Here we report the first case of a de novo IPT in a liver graft after living donor liver transplantation (LDLT).
The patient was a 54-year-old female with end-stage liver disease secondary to cryptogenic liver cirrhosis. She underwent LDLT with a left lobe graft donated by her 57-year-old husband. Her postoperative immunosuppression consisted of cyclosporine, mycophenolate mofetil, and steroids. This patient did not experience acute cellular rejection or biliary complications (eg, cholangitis, biliary leakage, or biliary strictures) after LDLT. One year after LDLT, routine abdominal ultrasound screening revealed an asymptomatic solid liver tumor in the transplanted graft that was adjacent to the umbilical portion. Enhanced computed tomography (CT) revealed a solid tumor in segment 3 and 4 of the graft with B2 (biliary duct in segment 2) dilatation (Fig. 1A,B). The levels of tumor markers were as follows: α-fetoprotein, 1.8 ng/mL (normal range < 6.2 ng/mL); des-γ-carboxyprothrombin, 49 mAU/mL (normal range < 40 mAU/mL); carcinoembryonic antigen, 1.2 ng/mL (normal range < 3.2 ng/mL); and carbohydrate antigen 19-9, 82 U/mL (normal range < 37 U/mL). Enhanced magnetic resonance imaging and CT angiography showed a hypovascular tumor consistent with cholangiocellular carcinoma. Endoscopic retrograde cholangiography revealed a B2 (biliary duct in segment 2) stricture that was caused by the tumor and distal dilation (Fig. 1C). 18F-fluorodeoxy glucose positron emission tomography demonstrated abnormal 18F-fluorodeoxy glucose uptake by the tumor (maximum standardized uptake value = 23.3; Fig. 1D). Therefore, we diagnosed de novo cholangiocellular carcinoma in the graft just above the umbilical portion.
Because the tumor location was very delicate, we planned to perform surgical tumor biopsy followed by partial hepatectomy. However, the biopsy sample indicated that the tumor was an IPT (Fig. 2). Therefore, we immediately suspended the procedure and treated the patient conservatively with antibiotics.
IPTs of the liver are rare benign tumors. Although the etiology and pathogenesis of IPTs are unclear, they were initially histologically characterized by dense hyalinized fibrosis and/or infiltrating inflammatory cells, including large numbers of foamy histiocytes, lymphocytes, and plasma cells. Typical radiological findings from enhanced CT include hypoattenuation of the mass with respect to the hepatic parenchyma with a variable degree of enhancement in the internal septa or periphery in the portal or equilibrium phase. Therefore, it is difficult to distinguish IPTs from malignant tumors and especially cholangiocellular carcinomas. Ahn et al. reported that 78.2% of their patients with IPTs had symptoms, including abdominal pain (54.5%), febrile sensation (22.7%), and malaise (4.5%), although some patients were asymptomatic. Interestingly, they also found that carbohydrate antigen 19-9 and α-fetoprotein levels were elevated in 22.7% and 4.5% of their patients, respectively.
IPTs can be treated conservatively with antibiotics with or without nonsteroidal anti-inflammatory drugs or with surgical resection. Surgical resection should be recommended for patients with poor responses to conservative therapy, tumor growth, increasing tumor marker levels, or an uncertain diagnosis.
Zen et al. suggested that hepatic IPTs could be classified as lymphoplasmacytic or fibrohistiocytic on the basis of the results of immunoglobulin G4 (IgG4) immunohistochemistry. They reported that lymphoplasmacytic IPTs were associated with IgG4-related diseases. In contrast, the pathogenesis of the fibrohistiocytic type remained speculative, but it could represent the end stage of a heterogeneous and destructive inflammatory process. The lymphoplasmacytic IPTs showed some similarities to hepatic malignant lymphoma, a posttransplant lymphoproliferative disorder. Notably, lymphoplasmacytic IPTs were more frequent in patients with Epstein-Barr virus mismatch, excess immunosuppression, and muromonab-CD3 exposure. Our patient had none of these risk factors, and the pathological analyses indicated that the IPT was the fibrohistiocytic type.
Here we have reported the first case of a de novo IPT occurring in a liver graft after LDLT. This case suggests that an IPT could be considered in the differential diagnosis of a de novo liver tumor after LDLT. The prognosis of an IPT is good with or without hepatectomy. Detailed clinical examinations, including biopsy, are important if the preoperative diagnosis is unclear.
Shohei Yoshiya, M.D.1
Toru Ikegami, M.D.1
Tomoharu Yoshizumi, M.D.1
Huanlin Wang, M.D.1,2
Noboru Harada, M.D.1
Yo-Ichi Yamashita, M.D.1
Akihiro Nishie, M.D.3
Ken Shirabe, M.D.1
Yoshinao Oda, M.D.2
Yoshihiko Maehara, M.D.1
Departments of 1Surgery and Science, 2Anatomic Pathology, and 3Clinical Radiology
Graduate School of Medical Sciences