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Hepatoblastoma is the most common malignant hepatic tumor in children. About 50% of the cases occur before the age of 18 months and almost all before the age of 2 years. We present an extremely rare case of hepatoblastoma in an 11-year-old girl, which was pathologically verified and treated twice with transcatheter arterial infusion combined with radical resection. To date she has been followed-up for 15 years and has shown normal development after the operation. She has received no chemotherapy or radiation and has displayed no evidence of metastatic or recurrent disease.
Case Report
An 11-year-old girl, healthy up until 6 days prior to admission, sought medical attention complaining of right upper abdominal quadrant megalgia with vomiting after meals. Family and past history were not contributory. The patient denied any history of abdominal trauma, anorexia, jaundice, weight loss, hematochezia, diarrhea, alcohol intake, blood transfusion, previous liver disease, or exposure to known hepatotoxins. Cardiopulmonary examination was normal except that breath sounds were diminished in the right lower lung field. Abdominal examination revealed an underdeveloped girl with a symmetric abdomen; the liver span was palpably hard, smooth and 3 cm below the right costal margin. There was right upper quadrant tenderness, but no rebound and ascites. The chest x-ray showed pleural effusion in the right lower lung field. With abdominal ultrasound a well-defined, 12.6x7.4 cm (transverse diameter) mass was detected in the anterior segment of the right lobe of the liver, with heterogeneous echoic texture of uncertain topographic origin, but apparently compressing the liver and gall bladder. Computerized tomography (CT) of the abdomen after bolus intravenous injection of contrast medium, confirmed the presence of a centrally cystic, 15 cm (largest dimension), heterogeneous hepatic mass, with several necrotic areas. There was no evidence of adenopathy or retroperitoneal masses in any other location. The pancreas was normal but splenomegaly was detected. An exhaustive work-up excluded a metastatic lesion to the liver.
Routine laboratory results were within normal limits with the exception of an increased leukocyte count (13.0×109 cells/L). The prothrombin time and fibrinogen were normal. Total serum protein, bilirubin, transaminases, electrolytes, creatinine, glucose, alkaline phosphatase, and lactate dehydrogenase were within normal limits. Test results for a-fetoprotein (AFP), carcinoembryonic antigen (CEA), 50-1 carbohydrate antigenic determinant (CA50-1), and hepatic viral markers were all negative except for serum ferroprotein (SF) which was 315 μg/mL (normal less than 300 μg/mL).
The patient underwent a thin needle CT-directed biopsy with the result being interpreted as a sarcoma of hepatic origin. With digital subtractive angiography (DSA), anatomic variants of the hepatic arteries were seen. The anterior segmental artery of the liver was from the common hepatic artery (CHA), however, the replaced posterior segmental artery was from the superior mesenteric artery (SMA). The selective hepatic arteriogram revealed a large relatively hypovascular mass showing a faint tumor staining. The mass was hypovascular due to the necrotic nature of the tumor.
Then in our institute we treated the patient with transcatheter arterial infusion (TAI). DSA was performed and a therapeutic strategy for further TAI, the transcatheter hepatic arterial chemoembolization (TACE) or surgical therapy was individualized in terms of the change of the tumor appearance and the newly formed arterial supply. In the meantime, the patient underwent two sessions of TAI within 2 months at 1-month intervals in order to control the tumor progression and preserve her liver function. With each TAI, Cisplatin (CDDP, 50 mg/m2), Adriamycin (ADM, 30 mg/m2) and Mitomycin C (MMC, 5 mg/m2) were infused into the main arterial supply of the tumor.
The patient was reexamined once a month. A month after the second TAI, the patient’s cardiopulmonary examination was unremarkable and no mass was detected on physical examination. The ultrasonographic examination of the abdomen identified a well circumscribed, predominantly echo-poor, 6.0x6.2 cm (transverse diameter) mass in the anterior segment of the right lobe of the liver, with heterogeneous echoic texture. An extended right anterior hepatectomy and cholecystectomy were subsequently performed. The surrounding hepatic tissue was reddish brown and was not cirrhotic. The rest of the intraabdominal examination was unremarkable. At surgery the firm neoplasm involved the anterior segment of the right lobe and partial lateral segments of the right lobe of the liver. The capsule was ruptured previously and showed a huge exophytic mass.
Sectioning of the liver specimen revealed a partially encapsulated well-defined tumor (8.0x 0.5x 3.0 cm), which had a variegated appearance consisting of red-brown, gelatinous tissues and was irregularly mottled with central hemorrhage and necrosis. On microscopic examination, the tumor was mainly composed of coagulation necrotic components Fig.1. in which the necrotic tumor cells of inequality of size can be indistinctly seen. The “surviving tumor tissue" was very limited and difficult to produce a differential diagnosis. It was entirely composed of uniform fetal epithelial cells and intermingled with small undifferentiated cells and a cluster of hematopoietic cells Fig.2. The tumor also contained scattered lipidie foamy cytoplasm as well as bile pigment Fig.3. The pathological diagnosis was that of primary hepatoblastoma, consistent with a pure fetal type.
One month after the second TAI, the tumor showed complete necrosis (H&E, x 200).
A cluster of hematopoietic cells is present at the center (H&E, * 200).
The tumor was composed of uniform fetal epithelial cells and intermingled with small undifferentiated cells and scattered lipidie foamy cytoplasm and bile pigment was occasionally found (H&E, × 200).
The uninvolved hepatic parenchyma was unremarkable, and free of hepatitis and cirrhosis. The avidin-biotin peroxidase complex (ABC) method was applied to the formaldehyde-fixed, paraffin-embedded tumor tissue. A panel of immunohistochemical stains was selected to differentiate the tumor from a carcinoma and to investigate the tumor differentiation of the sarcoma. Most of the tumor cells were strongly alpha-fetoprotein positive Fig.4, but were negative for CD68, CD34, vascular endothelial growth factor (VEGF), S-100 protein and myoglobin. The patient’s postoperation course was uneventful, and to date she is alive without any sign of recurrence with normal development 15 years after the operation. No chemotherapy or radiation has been performed.
Immunoreactivity for alpha-fetoprotein is present in most tumor cells(lmmunoperoxidase stain, x 200).
DISCUSSION
Hepatoblastoma is definited as a malignant embryonal tumor with divergent patterns of differentiation, ranging from cells resembling fetal epithelial hepatocytes, to embryonal cells, and some differentiated tissues. Hepatoblastoma in children is the most common malignant hepatic tumor.[1] Four percent of hepatoblastomas are present at birth and about 50% of the cases occur before the age of 18 months and almost all before the age of 2 years. Adolescents or young adults are seldom affected. In this report we present an extremely rare case of hepatoblastoma in an 11-year-old girl, who was treated twice with transcatheter arterial infusion combined with radical resection. The therapy produced an excellent outcome.
For a long time, surgical treatment in the form of resection with or without liver transplantation was considered to be the only option for complete cure and long-term survival; however, 50% of the cases are un-resectable at the initial presentation. In this situation patients rarely survive more than 12 months.[2] Preoperative systemic combined chemotherapy plays a vital role in reducing the tumor size and controlling tumor spread to convert an unresectable tumor to a resectable one, thus improving prognosis.[3,4] However, the associated systemic adverse effects sometimes lead to delayed surgery and hence tumor recurrence and chemotherapy-related death.[5] Interventional therapy is an effective and useful preoperative therapeutic alternative for unresectable hepatoblastoma, and can improve the resectablity of the bulky tumor and the survival rate of a hepatoblastoma patient.[6]
As we all know, at a very early stage, liver tumors are not highly vascularized, receiving their blood supply from both the portal vein and the hepatic artery. However, when the neoplasm grows into a more advanced stage, the hepatic artery mostly provides the supply. Our patient had anatomic variants of the hepatic arteries; the posterior segmental artery was from the SMA. Therefore chemotherapeutic drugs were highly selectively injected into the arteries feeding the tumor. This approach has the advantages of maximum drug uptake by the tumor and minimal systemic exposure to the drug. Furthermore, it can be combined with arterial embolization to occlude the arterial supply and thus induce ischemic tumor necrosis and prolong the dwell-time of the anticancer drugs in the tumor vasculature which enhances its effect. Transcatheter arterial infusion (TAI) or transarterial chemoembolization (TACE) can effectively kill the tumor and control tumor growth; meanwhile, it can provide a chance for surgery for those children with unresectable hepatoblastoma and as a temporary measure while waiting for a liver donor.[7]
Our patient was a very young girl, with clinical findings and x-ray studies suggesting that her general state of health was poor and that there was pleural effusion in the right lower lung field. We employed TAl to control the tumor progression and reduce the tumor volume adequately within 2 months. Because of the marked response after TAI, the girl was judged as being surgically resectable. Microscopically, the tumor was completely composed of coagulation necrosis components, and we had to identify the histologic features from the very few “surviving tumor tissues" and the remnant of necrosis tumor cells so it was difficult to produce a differential diagnosis. It is absolutely rare that the girl had an excellent recovery and remained tumor-free for 15 years postoperatively up to now.
In conclusion, accompanied with gene therapy and the invention and application of targeted drugs, interventional therapy can play a very important role in the treatment of at least several primary malignant hepatic neoplasms, either as a single line of treatment to induce partial or complete tumor necrosis or in combination with other treatment modalities, such as radical resection and liver transplantation.
- Received June 2, 2006.
- Accepted July 4, 2006.
- Copyright © 2006 by Tianjin Medical University Cancer Institute & Hospital and Springer
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