Year : 2010 | Volume
: 53 | Issue : 3 | Page : 422--426
Pathology of pediatric liver tumors, a single center experience from south of Iran
Bita Geramizadeh1, Ali Bahador2, Hamid-Reza Foroutan3, Abbas Banani3, Saman Nikeghbalian4, Seyed-Ali Malek-Hosseini4,
1 Department of Pathology, Shiraz University of Medical Sciences, Shiraz, Iran
2 Department of Pediatric hepatobiliary surgery, Shiraz University of Medical Sciences, Shiraz, Iran
3 Department of Pediatric surgery, Shiraz University of Medical Sciences, Shiraz, Iran
4 Department of Hepatobiliary surgery, Shiraz University of Medical Sciences, Shiraz, Iran
Transplant Research Center, Department of Pathology, Shiraz University of Medical Sciences, Shiraz, PO Box: 71345-1864
Background: Pediatric hepatic malignancies are rare, accounting for 1-4% of all solid childhood tumors. The histopathology of childhood hepatic tumors guides the treatment and prognosis, and is the cornerstone for precise diagnosis. Until now, there has been no documented study on pediatric liver tumor cases from this center; in this report, we show our experience about the common types of childhood hepatic tumors during five years (2002-2007) and compare them with other studies. Materials and Methods: During five years (2002-2007), all the hepatic tumors of childhood (under 18 year-old) from the pathology file of Namazi Hospital of Shiraz University of Medical Sciences are recorded. This includes both resected specimens and biopsies. All the slides were reviewed and the pathologic diagnosis was confirmed. Results: We detected 53 liver tumor cases in children (below 18 years of age). Among these tumors, 36 (67.9%) were malignant. Male to female ratio was 1.5 to 1. Hepatoblastoma was the most common liver tumor in this age group accounting for 22 patients (41.5%). The second most common primary tumor was hepatocellular carcinoma (HCC), with five patients. Another malignant tumor was embryonal sarcoma. Benign tumors included adenoma, mesenchymal hamartoma, vascular tumors, focal nodular hyperplasia, and inflammatory pseudo tumor. There were also seven metastatic tumors during these five years. Conclusions: The spectrum of hepatic tumors in children is different from that found in the older age group (adults) and also different in different populations.
|How to cite this article:|
Geramizadeh B, Bahador A, Foroutan HR, Banani A, Nikeghbalian S, Malek-Hosseini SA. Pathology of pediatric liver tumors, a single center experience from south of Iran.Indian J Pathol Microbiol 2010;53:422-426
|How to cite this URL:|
Geramizadeh B, Bahador A, Foroutan HR, Banani A, Nikeghbalian S, Malek-Hosseini SA. Pathology of pediatric liver tumors, a single center experience from south of Iran. Indian J Pathol Microbiol [serial online] 2010 [cited 2021 Nov 27 ];53:422-426
Available from: https://www.ijpmonline.org/text.asp?2010/53/3/422/68258
Pediatric hepatic malignancies are rare, accounting for 1-4% of all solid childhood tumors. 
According to one of the largest series in the world, three-quarters of pediatric liver tumors are malignant, 85% of which are of hepatocellular origin. 
The histopathology of childhood hepatic tumors guides the treatment and prognosis, and is the cornerstone for their precise diagnosis.  Our center is the largest referral center for childhood hepatobiliary surgeries in South of Iran. Until now, there has been no documented study about the pediatric liver tumors from this center; hence this report we will show our experience about the common types of childhood hepatic tumors during five years (2002-2007) and compare them with other studies.
Materials and Methods
During five years (2002-2007), all cases of hepatic tumor of childhood (age - below 18 years) from the pathology file of Namazi Hospital of Shiraz University of Medical Sciences have been recorded. This includes both resected specimens and biopsies. All the slides were reviewed and the pathologic diagnosis was confirmed. Immunohistochemistry was done in some of the cases.
During five years, 53 liver tumors in children, under 18 years, were detected. Among these tumors, 36 (67.9%) were malignant. Male to female ratio was 1.5 to 1. Hepatoblastoma was the most common liver tumor in this age group accounting for 22 patients (41.5%). Histology of most of these cases (15 cases, 68%) was pure epithelial (14 cases of mixed fetal and embryonal as well as one fetal type). The others were mixed epithelial and mesenchymal (seven cases). None of our cases was of small cell undifferentiated type. The age distribution is shown in [Table 1].
The second most common primary tumor was hepatocellular carcinoma (HCC), with five patients (9.4%). All patients were above 10 years of age and just one of them was female. HCC tumors in our series were neither related to cirrhosis, hepatitis B nor any underlying metabolic disease. Two of our cases were fibro lamellar HCC [Figure 1],[Figure 2] and the other three were well differentiated HCC.
We had two patients with the pathologic diagnosis of embryonal sarcoma [Figure 3], both of which were male and under one year of age.
Vascular tumors were also diagnosed in eight patients. Four of these vascular tumors were hemangioendothelioma, three of which were infantile type [Figure 4] and the other one was adult type epithelioid hemangioendothelioma [Figure 5],[Figure 6]. Three infantile hemangioendothelioma cases were in children below one year of age (M / F= 1 / 2). Adult type hemangioendothelioma was diagnosed incidentally in the hepatectomy specimen of a five-year-old patient who underwent liver transplantation with underlying progressive familial intrahepatic cholestasis.
There were four cases with the diagnosis of cavernous hemangioma, all of which were above five years of age (F/M=2/2). In addition to hemangioma, there were nine other benign hepatic tumors in children, composed of adenoma (two cases), mesenchymal hamartoma (four cases) [Figure 7],[Figure 8], focal nodular hyperplasia (one patient) [Figure 9],[Figure 10], and inflammatory pseudo tumor (two cases) [Figure 11],[Figure 12]. Both the adenomas were detected in hepatectomy specimens of the patients after liver transplantation, due to tyrosinemia in the age group of 1-5 years.
Secondary or metatstatic liver tumors were detected in seven children, including , Wilm's tumor (two cases), lymphoma (one case), metastatic ovarian germ cell tumor (one case), primitive neuroectodermal tumor (PNET) (one case), desmoplastic small round cell tumor (DSRCT) (one case) and neuroblastoma (one case).
The spectrum of hepatic tumors in children is different from that found in older age groups (adults). Hepatic tumor types are also unique in the pediatric age group, with the exception of HCC. 
Based on previous reports, primary hepatic malignancies make up 1- 4% of all malignant neoplasm cases among children less than 18 years of age.  The two more common malignant tumors of children are hepatoblastoma and HCC. Hepatoblastoma is seen mostly in younger children, whereas HCC occurs in older children. 
Hepatoblastoma accounts for 79% of all liver tumors in children below 18 years and more than 90% manifest by the fourth birthday. , Histologic appearances of most of these tumors are epithelial.  These findings were relatively similar to our finding, i.e. 61% of all hepatic malignancies, 68% of which were pure epithelial. HCC is the most common hepatic malignancy in adolescence.  Reports from South East Asia and Africa show accompanying hepatitis B related cirrhosis, , however, other reports, mostly from the West, indicate less frequent cases of cirrhosis in HCC of children compared to adults.  Eighteen per cent of hepatic malignancies in our center were HCC. None of our cases were associated with hepatitis B. It seems that universal vaccination of newborns was the reason of this finding.
Embryonic sarcoma (undifferentiated sarcoma) has been recognized as a unique entity after Stocker and Ishak published a series of 31 cases in 1978.  Histologic, histochemical (periodic acid schiff staining for periodic acid schiff positive globules) and immunohistochemical (IHC) studies (negative markers for all the differentiated sarcomas) are mandatory to distinguish it from other hepatic malignancies especially of mesenchymal origin. ,
In these five years, we had two cases of embryonal undifferentiated sarcoma of the liver in Two, four and five year-old boys, which were diagnosed by PAS and IHC for mesenchymal markers. According to vascular tumors, our case with the histology of adult type epithelioid hemangioendothelioma is the first incidental case after liver transplantation in a child. It was confirmed by IHC (reactive for CD31).
Four cases with the diagnosis of mesenchymal hamartoma were diagnosed by typical histologic findings, i.e. combination of bile ducts and hepatocytes admixed with bland mesenchymal cells in a myxoid background, but IHC is recommended to exclude other more common tumors. 
Adenoma was another benign tumor in our series. Both our cases were discovered in the liver of patients with tyrosinemia in hepatectomy specimens after liver transplantation. Our finding in this tumor is completely different from previous reports. In some of the previous series, adenoma was reported with the history of oral contraceptive pill in adolescents, , and in some others adenoma in childhood has not been reported. 
Our single focal nodular hyperplasia (FNH) was in a 16-year-old adolescent who presented with unusual combination of fever of unknown origin (FUO) and liver mass. Excision of mass showed FNH. This tumor has been reported very rarely in younger age group in childhood. 
During these five years, two cases were diagnosed as inflammatory pseudo tumor (IPT); although this tumor is non-neoplastic and reactive to inflammatory processes, it is presented by liver mass. , Conventional histology by H and E is enough for the diagnosis of this tumor. Seven liver tumors in this study were secondary or metastatic tumors (13.2%).
Reports of metastatic liver tumors in children are scanty, but common reported tumors are Wilm's, neuroblastoma, desmoplastic small round cell tumor ( DSRCT), osteogenic sarcoma and lymphoma, , which is relatively similar to our finding, i.e. lymphoma, Primitive neuroectodermal tumors (PNET), DSRCT, Wilm's, germ cell tumor and neuroblastoma.
|1||Stocker JT. Hepatic tumors in children. Clin Liver Dis 2001;5:259-81.|
|2||Weinberg AG, Finegold MJ. Primary hepatic tumors in childhood. In: Finegold MJ, editor. Pathology of neoplasia in children and adolescents. 1st ed. Philadelphia: WB Saunders; 1986. p. 333.|
|3||Litten JB, Tomlinson GE. Liver tumors in children. Oncologist 2008;13:812-20.|
|4||Emre S, McKenna GJ. Liver tumors in children. Pediatr Transplant 2004;8:632-8.|
|5||Darbari A, Sabin KM, Shapiro CN, Schwarz KB. Epidemiology of primary hepatic malignancies in U.S. children. Hepatology 2003;38:560-6.|
|6||Meyers RL. Tumors of liver in children. Surg Oncol 2007;16:195-203.|
|7||Chen JC, Chang ML, Lin JN, Lai HS, Chen CC, Chen WJ, et al. Comparison of childhood hepatic malignancies in hepatitis B hyperendemic area. World J Gastroenterol 2005;11:5289-94.|
|8||Moore SW, Millar AJ, Hadley GP, Lonescu G, Kruger M, Poole J, et al. Hepatocellular carcinoma and liver tumors in South African children. Cancer 2004;101:642-8.|
|9||Chen WJ, Lee JC, Hung WT. Primary malignant tumor of liver in infants and children in Taiwan. J Pediatr Surg 1988;23:457-61.|
|10||Czauderna P. Adult type versus childhood hepatocellular carcinoma-are they the same or different lesions? Biology, natural history, prognosis and treatment. Med Pediatr Oncol 2002;39:519-23.|
|11||Stocker JT, Ishak KG. Undifferentiated (embryonal) sarcoma of the liver: Report of 31 cases. Cancer 1978;42:336-48.|
|12||Bi Songo G, Pilz T, Perilongo G, Ferrari A, Harms D, Ninfo V, et al. Undifferentiated sarcoma of liver in childhood: A curable disease. Cancer 2002;94:252-7.|
|13||Lack EE, Schloo BL, Azumi N, Travis WD, Grier HE, Kozakewich HP. Undifferentiated (embryonal sarcoma of liver): Clinical, pathologic study of 16 cases with emphasis on immunohistochemical features. Am J Surg Pathol 1991;15:1-16.|
|14||Siddiqui MA, McKenna BJ. Hepatic mesenchymal hamartoma: A short review. Arch Pathol Lab Med 2006;130:1567-9.|
|15||Geramizadeh B, Tahamtan MR, Bahador A, Sefidbakht S, Modjalal M, Nabai S, et al. Inflammatory pseudo tumor of the liver: Two case reports and review of literature. Indian J Pathol Microbiol 2009;52:211-3. |
|16||Su WT, Rutigliano DN, Gholizadeh M, Jarnagin WR, Blumgart DH, La Quaglia MP. Hepatic malignancies in children. Cancer 2007;109:3089-92.|
|17||Fabre M, Yilmaz F, Buendia MA. Hepatic tumors in childhood: Experience in 245 tumors and review of literature. Ann Pathol 2004;24:536-55.|