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J Clinic Care Skill 2024, 5(2): 81-84 |
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Received: 2023/05/31 | Accepted: 2024/05/28 | Published: 2024/06/30
Received: 2023/05/31 | Accepted: 2024/05/28 | Published: 2024/06/30
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Ashayeri N, Zarei E, Shamspour M, Tagrian Isfahani M. Fetal Type Hepatoblastoma in an 11-Year-Old Boy; A Case Report. J Clinic Care Skill 2024; 5 (2) :81-84
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1- “Hazrat Ali Asghar Children Hospital” and “Department of Pediatric Hematology & Oncology, School of Medicine”, Iran University of Medical Sciences, Tehran, Iran
2- “Hazrat Ali Asghar Children Hospital” and “Department of Pediatric Radiology, School of Medicine”, Iran University of Medical Sciences, Tehran, Iran
2- “Hazrat Ali Asghar Children Hospital” and “Department of Pediatric Radiology, School of Medicine”, Iran University of Medical Sciences, Tehran, Iran
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Introduction
Although hepatoblastoma has been identified as a rare tumor regardless of age, it is one of the most frequent types of embryonal primary liver tumors in children in the age groups of 6 months to 3 years with an overall prevalence of less than all childhood malignancies [1]. From a histopathological point of view, this tumor is classified as epithelial, mixed epithelial, and mesenchymal subtypes [2]. Pathologically, upregulation in the Wnt/β-catenin pathway is powerfully linked to hepatoblastoma [3]. The most common manifestations and thus diagnostic arms of hepatoblastoma include detecting abdominal mass followed by tracking raised serum alpha-fetoprotein [4]. However, for a definitive diagnosis of this tumor, a histomorphological assessment is essential. In the study by Zhong et al., a rare case of hepatoblastoma occured with pure epithelial differentiation in a 10-year-old boy. Based on these findings, the case was diagnosed as hepatoblastoma with pure fetal epithelial differentiation [5]. In the study by Spyridakis et al. they present a case of a five-month-old girl with embryonal/fetal subtype hepatoblastoma and the clinical presentation was an asymptomatic abdominal mass [6]. We presented a case of hepatoblastoma fetal type and described our experience with its clinical management.
Patient and Method
The case described was an 11-year-old boy with complaints of pain in the right upper quadrant of the abdomen from the previous week following the ball hitting the abdomen. He has not had any nausea, vomiting, loss of appetite or any other symptoms.
Findings
In a physical examination, a mass in the right upper quadrant of the abdomen was identified. Also, moderate tenderness was detected in that part during palpation. Due to persistent abdominal pain and detection of the mass in physical examination, an abdominal ultrasound was done (Table 1) that revealed a solid abdominal mass with dimensions of 91×86×84 mm3 originating in the right lobe of the liver with a compressive effect on the renal cortex. There was no evidence of calcification or paraaortic lymphadenopathy. The spleen and kidney appeared normal. In further evaluation using CT scans evidence of a relatively well-defined heterogeneous solid mass was found in the right liver lobe (segments IV and V) containing faint calcification foci (Figure 1). In the laboratory hematological assessment, no abnormal findings were reported. WBC, ESR, and CRP were normal and fever was not detected in history taking or physical examination. Consequently, abscess formation and infectious causes were ruled out. In the next step and to achieve a definitive diagnosis, pathological studies were scheduled that found a typical hepatoblastic tumor with fetal type morphology, an area with ballooned cells, cytoplasmic hyaline globules, and foci of calcification which matched the diagnosis of hepatoblastoma fetal type. Mitotic features were quite infrequent. The resection margin was free of tumor. The assessment of serum biomarkers revealed the normal level of βHCG tumor markers, but with the raised alpha-fetoprotein level complies with the diagnosis of hepatoblastoma fetal type. In this regard, the patient was planned afor a surgical approach. Following preb and drep and general anesthesia induction, an abdomen incision was performed, indicating a liver round mass in segments V and VI. Therefore, hepatic ligaments were released using a ligator. The liver mass was resected with a margin of one centimeter, and the ducts and arteries were exposed. The resection surface was closed. The subcutaneous was anesthetized with dilute marcaine. Then, the subcutaneous and skin tissues were repaired with a 3-0 monocryl suture. Chemotherapy was then scheduled for the patient with cisplatin and doxorubicin, and he was evaluated after six courses of treatment. In this regard, abdominal and pelvic ultrasonography showed no evidence of tumor residue after surgery. At present, three months have passed since the completion of the patient's treatment, and he has no problems and is under monthly follow-up.
Table 1. Abdominal ultrasound and laboratory before and after surgery
Figure 1. A relatively well-defined hypodense solid mass with small punctuate foci of calcification approximately measuring 96*90 mm (anteroposterior *transverse diameter) involving segments V and VI of right liver lobe (pretext II)
Discussion
Hepatoblastoma is a rare embryonic tumor and represents about 1% of all pediatric tumors.
The most common epithelial malignant neoplasm of the liver is that it occurs primarily in young children, which accounts for 80% of all liver malignancies under the age of 3 years [1] and 91% of liver tumors under the age of 5 years, the majority of hepatoblastomas are sporadic and with a predominance in boys [2, 3], with an increase in incidence from 0.8 per million (1975-83) to 1.6 per million (2002-09) in age less than 19 years [1]. Hepatoblastoma is classified into two broad categories: Epithelial type and mixed epithelial, mesenchymal type, the majority of this tumor is epithelial type [4]. The pure fetal pattern is a subtype of epithelial-type hepatoblastoma and its onset is rare above the age of 5 years [5]. The study by Zhong et al. presents a rare case of hepatoblastoma with pure epithelial differentiation in a 10-year-old boy. The case is diagnosed as hepatoblastoma with pure fetal epithelial differentiation [5]. In the study by Spyridakis et al., they present a case of a five-month-old girl with embryonal/fetal subtype hepatoblastoma and the clinical presentation is an asymptomatic abdominal mass [6]. Alkhamisy et al. have presented a rare case of non-treated fetal-type hepatoblastoma in an 18-month-old baby male with an asymptomatic abdominal mass [7].
Overall, liver cancers in infancy and childhood represent only 1-2% of all solid tumors [8]. Hepatoblastoma may be completely asymptomatic and may be discovered quite incidentally, however, the disease may be manifested by general symptoms such as fatigue, mild fever, weight loss and anorexia. Other severe findings of jaundice or tumor rupture are very rare [9]. Of laboratory markers beneficial for disease detection, alpha-fetoprotein has a special place that is raised in more than 90% of patients; However, it has also showed that low alpha-fetoprotein levels can also be an important indicator for poor disease prognosis [10]. Along with genetic predisposition to the disease (polymorphisms on chromosomes 2q 13-22, 2q 36-37 and deletions of 2p and 4q), some other determinants have also been discovered to be linked to childhood hepatoblastoma, such as premature birth and very low birth weight, radiation, total parenteral nutrition, the use of furosemide, and even oxygen therapy [11]. Moreover, the association of some congenital syndromes with this disease is also worth considering, which can be referred to as trisomy 2, 8, 20, familial adenomatous polyposis, Beckwith-Wiedemann syndrome, and Edward’s syndrome [10]. Early suspicion of the tumor can be raised by observing a liver mass with an increased alpha-fetoprotein level, followed by liver ultrasonography and CT scanning, especially to detect lung metastasis. However, ultimate diagnostic confirmation is usually achieved by a histological approach. Therapeutically, a complete surgical resection remains the mainstay of hepatoblastoma treatment. In addition, pre-surgical chemotherapy followed by tumoral excision and then a short period of post-surgery chemotherapy is also recommended [11]. However, it should be noted that for nonexcisable tumors or after tumor relapse, liver transplantation can be indicated. In total, monitoring alpha-fetoprotein levels can be very valuable to assess the response to the treatment regimen, which can be normalized after 4-6 weeks [12, 13]. In this regard, ultrasound monitoring is also compulsory [14].
As pointed out above, the lowering alpha-fetoprotein level may be a serious indicator of the poorer outcome of childhood hepatoblastoma. This point has also been indicated in some previous reports. As described in a case report by Chattopadhyay et al. [15], poor hepatoblastoma might be associated with negative alpha-fetoprotein. As indicated in their report, a hepatic mass in infants and a children with low serum AFP level indicates the presence of either well-differentiated or immature hepatoblastoma, or fibrolamellar hepatocellular carcinoma. In another case reported by Ismail et al. [16], liver transplantation might be indicated for those children suffering hepatoblastoma with a lowered alpha-fetoprotein level. Thus, this marker, along with the evidence of invasion or metastasis (mostly to the pulmonary system), can be considered a valuable indicator for the poor prognosis of the tumor.
Overall, most patients with childhood hepatoblastoma should be surgically treated (more than 95% of patients) with and without chemotherapy; however, others may be candidates for only palliative treatment [17]. The survival of children with hepatoblastoma treated with liver resection has been estimated to be 71% to 80% [18]. In total, a favorable therapeutic outcome can be predicted by the epithelial-fetal subtype, no evidence of teratoid features, and a proper response to chemotherapy, in contrast, a poorer prognosis can be expected by small cells that are undifferentiated, α-fetoprotein levels above 1,000,000IU/mL and below 100IU/mL, and pulmonary metastasis [18]. Due to the epithelial nature of the tumor in our case elevated alpha-fetoprotein and no evidence of metastasis led to a favorable treatment outcome.
There was limited information about the prevalence of hepatoblastoma in the Iranian population. Moreover, due to the absence of the patient for follow-up, there was no more information. Therefore, due to the rarity of this tumor, both in terms of its prevalence at this age and its asymptomatic nature, it is suggested to report these cases to find a method for screening and early diagnosis. Annual health examinations may therefore be helpful in detecting these rare tumors and improving patient outcomes.
Conclusion
This tumor was diagnosed as embryonal hepatoblastoma in an 11-year-old patient. Hepatoblastoma is rare in patients, but our case shows that fetal-type hepatoblastoma can also occur in children. We know that surgical intervention is possible if diagnosed, followed by chemotherapy after surgery, which remains its mainstay hepatoblastoma treatment.
Acknowledgments: I would like to thank all those who helped in grossing and writing this article.
Ethical Permissions: Patients have given written informed consent for the publication of the data and medical diagnostic imaging. The patient has undergone all stages of diagnosis and therapy in accordance with the standard protocol.
Conflicts of Interests: The authors declare that they have no known competing financial interests that could have appeared to influence the work reported in this paper.
Authors’ Contribution: Ashayeri N (First Author), Introduction Writer/Methodologist/Main Researcher/Discussion Writer/Statistical Analyst (35%); Zarei E (Second Author), Methodologist/Assistant Researcher/Statistical Analyst (20%); Shamspour M (Third Author), Methodologist/Assistant Researcher (10%); Tagrian Isfahani M (Fourth Author), Introduction Writer/Methodologist/Main Researcher/Discussion Writer/Statistical Analyst (35%)
Funding/Support: The present study received no support or funding.
Although hepatoblastoma has been identified as a rare tumor regardless of age, it is one of the most frequent types of embryonal primary liver tumors in children in the age groups of 6 months to 3 years with an overall prevalence of less than all childhood malignancies [1]. From a histopathological point of view, this tumor is classified as epithelial, mixed epithelial, and mesenchymal subtypes [2]. Pathologically, upregulation in the Wnt/β-catenin pathway is powerfully linked to hepatoblastoma [3]. The most common manifestations and thus diagnostic arms of hepatoblastoma include detecting abdominal mass followed by tracking raised serum alpha-fetoprotein [4]. However, for a definitive diagnosis of this tumor, a histomorphological assessment is essential. In the study by Zhong et al., a rare case of hepatoblastoma occured with pure epithelial differentiation in a 10-year-old boy. Based on these findings, the case was diagnosed as hepatoblastoma with pure fetal epithelial differentiation [5]. In the study by Spyridakis et al. they present a case of a five-month-old girl with embryonal/fetal subtype hepatoblastoma and the clinical presentation was an asymptomatic abdominal mass [6]. We presented a case of hepatoblastoma fetal type and described our experience with its clinical management.
Patient and Method
The case described was an 11-year-old boy with complaints of pain in the right upper quadrant of the abdomen from the previous week following the ball hitting the abdomen. He has not had any nausea, vomiting, loss of appetite or any other symptoms.
Findings
In a physical examination, a mass in the right upper quadrant of the abdomen was identified. Also, moderate tenderness was detected in that part during palpation. Due to persistent abdominal pain and detection of the mass in physical examination, an abdominal ultrasound was done (Table 1) that revealed a solid abdominal mass with dimensions of 91×86×84 mm3 originating in the right lobe of the liver with a compressive effect on the renal cortex. There was no evidence of calcification or paraaortic lymphadenopathy. The spleen and kidney appeared normal. In further evaluation using CT scans evidence of a relatively well-defined heterogeneous solid mass was found in the right liver lobe (segments IV and V) containing faint calcification foci (Figure 1). In the laboratory hematological assessment, no abnormal findings were reported. WBC, ESR, and CRP were normal and fever was not detected in history taking or physical examination. Consequently, abscess formation and infectious causes were ruled out. In the next step and to achieve a definitive diagnosis, pathological studies were scheduled that found a typical hepatoblastic tumor with fetal type morphology, an area with ballooned cells, cytoplasmic hyaline globules, and foci of calcification which matched the diagnosis of hepatoblastoma fetal type. Mitotic features were quite infrequent. The resection margin was free of tumor. The assessment of serum biomarkers revealed the normal level of βHCG tumor markers, but with the raised alpha-fetoprotein level complies with the diagnosis of hepatoblastoma fetal type. In this regard, the patient was planned afor a surgical approach. Following preb and drep and general anesthesia induction, an abdomen incision was performed, indicating a liver round mass in segments V and VI. Therefore, hepatic ligaments were released using a ligator. The liver mass was resected with a margin of one centimeter, and the ducts and arteries were exposed. The resection surface was closed. The subcutaneous was anesthetized with dilute marcaine. Then, the subcutaneous and skin tissues were repaired with a 3-0 monocryl suture. Chemotherapy was then scheduled for the patient with cisplatin and doxorubicin, and he was evaluated after six courses of treatment. In this regard, abdominal and pelvic ultrasonography showed no evidence of tumor residue after surgery. At present, three months have passed since the completion of the patient's treatment, and he has no problems and is under monthly follow-up.
Table 1. Abdominal ultrasound and laboratory before and after surgery
Figure 1. A relatively well-defined hypodense solid mass with small punctuate foci of calcification approximately measuring 96*90 mm (anteroposterior *transverse diameter) involving segments V and VI of right liver lobe (pretext II)
Discussion
Hepatoblastoma is a rare embryonic tumor and represents about 1% of all pediatric tumors.
The most common epithelial malignant neoplasm of the liver is that it occurs primarily in young children, which accounts for 80% of all liver malignancies under the age of 3 years [1] and 91% of liver tumors under the age of 5 years, the majority of hepatoblastomas are sporadic and with a predominance in boys [2, 3], with an increase in incidence from 0.8 per million (1975-83) to 1.6 per million (2002-09) in age less than 19 years [1]. Hepatoblastoma is classified into two broad categories: Epithelial type and mixed epithelial, mesenchymal type, the majority of this tumor is epithelial type [4]. The pure fetal pattern is a subtype of epithelial-type hepatoblastoma and its onset is rare above the age of 5 years [5]. The study by Zhong et al. presents a rare case of hepatoblastoma with pure epithelial differentiation in a 10-year-old boy. The case is diagnosed as hepatoblastoma with pure fetal epithelial differentiation [5]. In the study by Spyridakis et al., they present a case of a five-month-old girl with embryonal/fetal subtype hepatoblastoma and the clinical presentation is an asymptomatic abdominal mass [6]. Alkhamisy et al. have presented a rare case of non-treated fetal-type hepatoblastoma in an 18-month-old baby male with an asymptomatic abdominal mass [7].
Overall, liver cancers in infancy and childhood represent only 1-2% of all solid tumors [8]. Hepatoblastoma may be completely asymptomatic and may be discovered quite incidentally, however, the disease may be manifested by general symptoms such as fatigue, mild fever, weight loss and anorexia. Other severe findings of jaundice or tumor rupture are very rare [9]. Of laboratory markers beneficial for disease detection, alpha-fetoprotein has a special place that is raised in more than 90% of patients; However, it has also showed that low alpha-fetoprotein levels can also be an important indicator for poor disease prognosis [10]. Along with genetic predisposition to the disease (polymorphisms on chromosomes 2q 13-22, 2q 36-37 and deletions of 2p and 4q), some other determinants have also been discovered to be linked to childhood hepatoblastoma, such as premature birth and very low birth weight, radiation, total parenteral nutrition, the use of furosemide, and even oxygen therapy [11]. Moreover, the association of some congenital syndromes with this disease is also worth considering, which can be referred to as trisomy 2, 8, 20, familial adenomatous polyposis, Beckwith-Wiedemann syndrome, and Edward’s syndrome [10]. Early suspicion of the tumor can be raised by observing a liver mass with an increased alpha-fetoprotein level, followed by liver ultrasonography and CT scanning, especially to detect lung metastasis. However, ultimate diagnostic confirmation is usually achieved by a histological approach. Therapeutically, a complete surgical resection remains the mainstay of hepatoblastoma treatment. In addition, pre-surgical chemotherapy followed by tumoral excision and then a short period of post-surgery chemotherapy is also recommended [11]. However, it should be noted that for nonexcisable tumors or after tumor relapse, liver transplantation can be indicated. In total, monitoring alpha-fetoprotein levels can be very valuable to assess the response to the treatment regimen, which can be normalized after 4-6 weeks [12, 13]. In this regard, ultrasound monitoring is also compulsory [14].
As pointed out above, the lowering alpha-fetoprotein level may be a serious indicator of the poorer outcome of childhood hepatoblastoma. This point has also been indicated in some previous reports. As described in a case report by Chattopadhyay et al. [15], poor hepatoblastoma might be associated with negative alpha-fetoprotein. As indicated in their report, a hepatic mass in infants and a children with low serum AFP level indicates the presence of either well-differentiated or immature hepatoblastoma, or fibrolamellar hepatocellular carcinoma. In another case reported by Ismail et al. [16], liver transplantation might be indicated for those children suffering hepatoblastoma with a lowered alpha-fetoprotein level. Thus, this marker, along with the evidence of invasion or metastasis (mostly to the pulmonary system), can be considered a valuable indicator for the poor prognosis of the tumor.
Overall, most patients with childhood hepatoblastoma should be surgically treated (more than 95% of patients) with and without chemotherapy; however, others may be candidates for only palliative treatment [17]. The survival of children with hepatoblastoma treated with liver resection has been estimated to be 71% to 80% [18]. In total, a favorable therapeutic outcome can be predicted by the epithelial-fetal subtype, no evidence of teratoid features, and a proper response to chemotherapy, in contrast, a poorer prognosis can be expected by small cells that are undifferentiated, α-fetoprotein levels above 1,000,000IU/mL and below 100IU/mL, and pulmonary metastasis [18]. Due to the epithelial nature of the tumor in our case elevated alpha-fetoprotein and no evidence of metastasis led to a favorable treatment outcome.
There was limited information about the prevalence of hepatoblastoma in the Iranian population. Moreover, due to the absence of the patient for follow-up, there was no more information. Therefore, due to the rarity of this tumor, both in terms of its prevalence at this age and its asymptomatic nature, it is suggested to report these cases to find a method for screening and early diagnosis. Annual health examinations may therefore be helpful in detecting these rare tumors and improving patient outcomes.
Conclusion
This tumor was diagnosed as embryonal hepatoblastoma in an 11-year-old patient. Hepatoblastoma is rare in patients, but our case shows that fetal-type hepatoblastoma can also occur in children. We know that surgical intervention is possible if diagnosed, followed by chemotherapy after surgery, which remains its mainstay hepatoblastoma treatment.
Acknowledgments: I would like to thank all those who helped in grossing and writing this article.
Ethical Permissions: Patients have given written informed consent for the publication of the data and medical diagnostic imaging. The patient has undergone all stages of diagnosis and therapy in accordance with the standard protocol.
Conflicts of Interests: The authors declare that they have no known competing financial interests that could have appeared to influence the work reported in this paper.
Authors’ Contribution: Ashayeri N (First Author), Introduction Writer/Methodologist/Main Researcher/Discussion Writer/Statistical Analyst (35%); Zarei E (Second Author), Methodologist/Assistant Researcher/Statistical Analyst (20%); Shamspour M (Third Author), Methodologist/Assistant Researcher (10%); Tagrian Isfahani M (Fourth Author), Introduction Writer/Methodologist/Main Researcher/Discussion Writer/Statistical Analyst (35%)
Funding/Support: The present study received no support or funding.
Keywords:
References
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