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
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.
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.
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.