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Giant mesenchymal hamartoma in pediatric patients: A new indication for liver transplantation


Abstract

Mesenchymal hamartoma is the second most frequent benign liver tumor in young children and usually occurs in the first two years of life. Currently, the gold standard for treatment is a complete surgical resection. We report a 17-month old patient with a giant mesenchymal hamartoma who, due to the impossibility of resection and the risk of malignant transformation, received liver transplantation from a living donor with a satisfactory outcome in the first year post-transplant. In this report, we show that liver transplantation is a viable therapeutic alternative for this pathology, in patients who have no possibility of receiving another type of treatment due to their clinical characteristics

Introduction

Mesenchymal hamartoma is the second most frequent benign liver tumor in young children and constitutes approximately 8% of all tumors in this population, with 80% of these tumors presenting within the first two years of life. The clinical picture includes gastrointestinal symptoms, weight loss, and anorexia. The physical examination of affected individuals includes a palpable homogeneous abdominal mass, malnutrition, and in advanced cases respiratory distress. Elevated alpha-fetoprotein levels mandate a differential diagnosis with hepatoblastoma, using radiological and pathology tests. Some authors consider the mesenchymal hamartoma to be a pre-malignant tumor, due to the possibility of its recurrence as an undifferentiated embryonic sarcoma and recommend a radical resection of the tumor. Currently, the gold standard for the treatment of this pathology is a complete surgical resection. Liver transplantation is controversial for benign tumors in pediatric patients and is not recommended in clinical practice guidelines. Yet in unresectable giant mesenchymal hamartoma, liver transplantation should be considered as a therapeutic alternative.
In this report, we present a pediatric patient with a diagnosis of a unresectable giant mesenchymal hamartoma of the liver who received a living donor liver transplantation.

 Presentation of the case

 A 17-month old female patient, product of a normal birth, with a 8-month history of noticeable weight loss, abdominal distention, and progressive deterioration was referred to the Fundacion Valle del Lili. Upon physical examination the patient was found to be cachectic with a distended abdomen, collateral circulation and hepatomegaly reaching the right flank and crossing the middle line. The initial blood tests were as follow: total bilirubin 0.32 mg/dL; direct bilirubin 0.27 mg/dL; alanine transaminase 24.5 U/L; aspartate transaminase 45.5 U/L, alkaline phosphatase 239 U/L; serum alpha-fetoprotein 4376 IU/ml. Initial differential diagnosis of hepatoblastoma and hydatidosis was made with the addition of an abdominal ultrasound and MRI, as shown in Fig. 1, that showed hepatomegaly with multiple images of a complex cyst. To clarify the diagnosis, a liver biopsy was performed. The microscopic examination revealed the presence of fibro-connective tissue with arterial vessels, venous capillaries, lymph nodes and the presence of stratified columnar epithelium arranged in a branched form. Nests of mature hepatocytes were observed and there was no malignancy in the sample examined. Immunohistochemistry wasfound to be positive, as expected for a mature tissue. The Pathology Department diagnosed mesenchymal hamartoma. Despite being a benign pathology, due to the condition of the patient and the impossibility of surgical resection, it was decided that a living donor liver transplantation from the patient's father was the best surgical option for the patient. The liver explant weighed 2 kg, and the only intraoperative complication was a 3000 cc hemoperitoneum. Twenty-four hours after the transplant, the patient was revised by the surgical team and discovered active bleeding from the arterial anastomosis. As a result, the patient received a transfusion of red blood cells and cryoprecipitate. The pathology report of the liver explant reported the macroscopical presence, between segments VIII and IV, of two cystic cavities of 7 6.8 3 cm and 5 4 2 cm; the remainder of the parenchyma presented a mottled hemorrhagic appearance. Microscopic examination revealed the presence of fibro-connective tissue with multiple arterial, venous and lymphatic vessels, nests of mature hepatocytes and cystic fibro-connective cavities lined with epithelium (Fig. 2). These observations confirmed the diagnosis of mesenchymal hamartoma. Ten months after the liver transplantation, the patient continues with an adequate clinical and laboratory evolution, with an immunosuppressive management with tacrolimus 3 mg/day, mycophenolate mofetil 450 mg per day and prednisolone 5 mg per day.

Discussion

Mesenchymal hamartoma of the liver was described in a definitive manner in 1956 by Edmonson. This pathology usually presents in pediatric patients with a median time of appearance of ten months. Histologically, the condition shows a stroma of fibromyxoid tissue with wavy cells and cystic spaces in the middle of biliary ducts and normal hepatocytes. Differential diagnosis includes other liver masses and infectious cystic lesions. Laboratory tests are usually normal, yet in some cases elevated alphafetoprotein levels are associated with poorly organized hepatocytes in liver biopsies. This can be a source of confusion at the time of diagnosis, suspecting malignant liver masses such as hepatoblastoma, as was the case for this patient. In the past, non-radical resection of the tumor had been proposed as an acceptable management, yet it is now clear that mesenchymal hamartomas share a common genetic finding with undifferentiated embryonal sarcoma of the liver. More over, recent reports propose, if feasible, a radical surgical resection of the tumor since recurrence and malignant transformation have been documented. Currently, the gold standard for the treatment of mesenchymal hamartoma is a complete surgical resection of the tumor to avoid local recurrences and long-term malignant transformation. However, cases of complex surgical management have been reported when dealing with multiple and giant tumors. In a series of 17 cases, Karpelowsky et al. mention intraoperative problems ranging from one intraoperative death, one bile duct injury and an accelerated recurrence after an incomplete tumor resection who also died in surgery. Liver transplantation is controversial in this pathology but in giant unresectable tumors, it is a viable therapeutic option. So far, three pediatric liver transplants have been reported for unresectable giant mesenchymal hamartoma following an incomplete resection, and Tepetes et al. reported two cases in adult patients, with progressive liver failure and previous partial hepatectomies, who experienced a satisfactory outcome. Our article describes the case of a pediatric patient with a giant unresectable mesenchymal hamartoma who received a living donor liver transplantation as surgical management. At 10 months post-transplant, the patient has experienced a satisfactory evolution, with alpha-fetoprotein and liver enzymes levels within normal ranges. This surgical approach was possible due to the characteristics of the tumor, the condition of the patient and the availability of a living donor. To our knowledge, this is the first case of Liver Transplantation as surgical management for a giant mesenchymal hamartoma in Latin America. We believe that liver transplantation is a safe surgical option for pediatric patients with unresectable giant mesenchymal hamartoma, who generally have no other therapeutic alternative.

Clinical Research Center, Fundacion Valle del Lili, Center for Research in Advanced Surgery and Transplants (CICAT), ICESI University, Cali, Colombia, 2017 Published by Elsevier Inc.