Undifferentiated Embryonal Sarcoma of the Liver: Report of Two Cases and Literature Review

Abstract

Undifferentiated embryonal sarcoma of the liver is a rare tumor of mesenchymal origin, representing about 9 to 15% of pediatric hepatic tumors. Usually diagnosed in children between 6 and 10 years of age, it has no specific clinical or laboratory features. Its diagnosis is usually delayed due to nonspecific symptoms, leading to poorer outcomes. Early diagnosis is key to increasing the chances of long-term survival. We report two cases of undifferentiated embryonal sarcoma in children presenting with hemoperitoneum from spontaneous rupture of the tumor.

Keywords

UESL - liver tumor - sarcoma - hepatectomy

Undifferentiated embryonal sarcoma of the liver (UESL) is a rare malignant tumor of mesenchymal origin representing 9 to 15% of pediatric hepatic tumors, usually diagnosed between 6 and 10 years of age, with equal distribution between sexes. First described by Stocker in 1978, UESL is considered the third most common hepatic malignancy in children after hepatoblastoma and hepatocellular carcinoma. The presentation is nonspecific, with abdominal pain, fever, and a palpable mass being the most frequent symptoms. Laboratory findings are also nonspecific; alpha-fetoprotein (AFP) is usually normal, which helps differentiate it from hepatoblastoma. Imaging typically reveals a large, well-circumscribed, heterogeneous mass, but features are not specific enough to allow diagnosis without histology. Treatment consists of complete surgical resection combined with chemotherapy, which has significantly improved survival rates in recent decades, with 5-year survival now exceeding 80% in some series.

Case 1

An 8-year-old previously healthy girl was admitted for 2 weeks' history of abdominal pain associated with decreased per os intake and weight loss. On physical examination, she was found to have a palpable firm mass detected in the epigastric region associated with right upper quadrant tenderness and mild abdominal distension.

Laboratory studies revealed a hemoglobin of 5 g/dL. An enhanced computed tomography (CT) scan of the abdomen and pelvis showed a well-defined lobulated 11-cm heterogeneous intra-abdominal mass that seems to be taking origin from the left hepatic lobe, showing spontaneous heterogenous density suggesting intratumoral bleed, causing mass effect on the surrounding structures demonstrating partial rupture with active bleeding from the left hepatic artery ([Fig. 1]).

Fig. 1 Enhanced CT scan of the abdomen and pelvis showing 11 cm left hepatic lobe mass with heterogeneous density suggesting intratumoral bleed (yellow arrow). (A) Transversal view. (B) Coronal view. (C) Sagittal view. CT, computed tomography.

The patient received multiples transfusion for stabilization and an urgent embolization of the left liver mass was performed.

Serology for hepatitis B surface antigen and hepatitis C were negative. Serum AFP and carcinoembryonic antigen levels are also normal.

Follow-up CT scan the first day following embolization showed a large predominantly hypodense heterogeneous mass arising in segments 2, 3, and 4 of the liver with multiple hypodense areas most consistent with recent intraparenchymal hemorrhage. The mass expands and extends inferiorly into the abdominal cavity abutting the lesser curvature of the stomach, which appears to be laterally displaced. There was no evidence of active bleeding.

Two days later, we underwent left partial hepatectomy with complete excision of the left liver mass ([Fig. 2]). Intraoperative frozen section was suggestive of vascular neoplasm. The postoperative course was uneventful.

Fig. 2 Left partial hepatectomy + including the exophytic tumor.

Gross observation showed a well encapsulated partial hepatectomy specimen weighing 160 g and measuring 10 × 10 × 3 cm. Margins of resection are uninvolved. Histopathological examination revealed a well-circumscribed lesion with cystic parts filled with clotted blood and solid areas composed of spindle cells with ill-defined borders exhibiting marked pleomorphism with focal bizarre-shaped nuclei. Focal eosinophilic periodic acid-Schiff diastase (PASD)-resistant granules are seen intracytoplasmic and extracellular. Numerous mitotic figures as well as abundant hemorrhage and necrosis are present. Immunohistochemistry showed tumor cells positive for vimentin, CD-56 and focally for desmin. Cytokeratin AE 1/AE 3 is also focally expressed. Tumor cells are negative for CD-31, CD-34, epithelial membrane antigen, beta-catenin, and inhibin. Ki67 proliferating index is more than 80%. The histological and immunohistochemical staining patterns were consistent with undifferentiated embryonal sarcoma.

After surgery and histopathological result, the patient was referred to an oncologist for further management. Positron emission tomography (PET) scan 1 month postoperatively showed no evidence of hepatic, lymphatic, or distant metastases. The patient was then started on vincristine, etoposide, and actinomycin.

Case 2

A 14-year-old previously healthy male patient presented for right upper quadrant pain posttrauma and one episode of fever reaching 39°C self-resolved.

Abdomen and pelvis CT scan showed 5 × 4.5 × 5 cm well-limited and rounded shaped lesion in the subcapsular aspect of the segment IV of the liver. This lesion shows hyperdense foci with a mean density of 30 HU most probably related to hemorrhage and hypodense foci most probably related to liquefied areas. These findings were suggestive of hematoma ([Fig. 3]).

Fig. 3 Enhanced CT scan of the abdomen and pelvis showing 5 × 4.5 × cm well-limited and rounded shaped lesion in the subcapsular aspect of the segment IV of the liver. CT, computed tomography.

Repeat CT scan after 2 days showed 30% resorption of the lesion, measuring at present 3.5 × 2.5 × 3.5 cm. Based on the CT scan findings, and the fact that the patient was stable the working diagnosis was hematoma, and the patient was discharged home with close follow-up imaging.

A repeat imaging in 1 week showed further resorption of the mass by 10%. One month later, the patient experienced the same pain. An ultrasound showed that the mass had enlarged in size reaching 10.6 cm.

The patient was scheduled for hepatectomy. Upon entry into the abdomen, a massive hemoperitoneum was identified. A large ruptured abdominal tumor arising from the edge of segment IV of the liver extending toward the pelvis was seen. Enucleation of the lesion from the liver was done with grossly negative margins. Tissue debris from the abdominal cavity were removed with no grossly residual tumor left and lavage performed. Intraoperative frozen pathology was in favor of benign hemangioma with hemorrhage.

The final pathology confirmed the diagnosis of hemangioendothelioma. The hepatectomy specimen measured 24 × 14 × 1.5 cm and weighed 408 g. Numerous sections showed a mixture of large numbers of small vascular channels and few large irregular shaped spaces with a cavernous appearance, embedded sometimes in a fibromyxomatous stroma. Mitosis was numerous within the stroma and hemorrhage was extensive. Spindle-cell fascicles were absent. Immunohistochemistry showed cells lining the vascular channels positive for CD34/CD31.

Six months later, on follow-up CT scan, the patient was found to have an extensive hemoperitoneum. An urgent laparotomy revealed a large hemorrhagic tumor adherent to the omentum and extending downward toward the pelvis, occupying all the abdominal cavity. A total of 3 L of blood were suctioned from the abdomen. The perforated tumor was removed and all macroscopic tissue debris retrieved from the pelvis and paracolic gutters along with omentectomy performed. No residual tumor seen at the end of the surgery.

The final pathology showed a neoplastic proliferation involving all the tissue fragments. In many areas, the tumor was very cellular, exhibiting spindled tumor cells admixed with round to oval cells, with nuclear atypia, hyperchromasia, and pleomorphism and an abundant clear acidophilic cytoplasm. Scattered multinucleated bizarre giant tumor cells are associated. In the round or stellate spindle cells, the cytoplasm contained hyaline globules PASD positive. There was a brisk mitotic activity with 1 mitotic figure in certain HPFs. There were numerous abnormal tripolar or quadripolar mitotic figures. The immunostaining revealed cytokeratin cocktail positive focally. Strong diffuse positivity was found of all tumor cells for vimentin, negative desmin, negative myogenin, and negative S100. The majority of the tumor cells were positive for smooth muscle actin. Few cells positive for BCL2. Tumor cells negative but endothelial lining of the blood vessels positive for CD31 and CD34. Histopathological result in favor of UESL.

The patient was referred to an oncologist for further management and received chemotherapy and radiotherapy ([Table 1]).

Table 1 Comparison of the two cases

Feature	Case 1	Case 2
Age/sex	8-year-old female	14-year-old male
Presenting symptoms	2-wk abdominal pain, decreased oral intake, weight loss, mild abdominal distension	Right upper quadrant pain posttrauma, transient fever (39°C)
Physical exam	Palpable firm mass in epigastrium, RUQ tenderness	Stable on initial exam
Hemoglobin at presentation	5 g/dL	Not specified
Initial imaging	CT: 11 cm heterogeneous left hepatic lobe mass (segments 2–4) with intratumoral bleed, partial rupture, active bleeding	CT: 5 × 4.5 × 5 cm well-limited segment IV subcapsular lesion with hemorrhage, interpreted as hematoma
AFP/CEA	Normal	Normal
Initial management	Blood transfusions, urgent embolization of left hepatic artery	Conservative management for presumed hematoma, later repeat imaging showing growth
Surgical procedure	Left partial hepatectomy (segments 2–4)	Initial enucleation for presumed hemangioma; 6 mo later urgent resection of large hemorrhagic tumor + omentectomy
Histopathology (initial)	Suggestive of vascular neoplasm on frozen section; final: UESL	Initial: hemangioendothelioma; recurrence final: UESL
Immunohistochemistry	Positive: vimentin, CD56, focal desmin, focal cytokeratin AE1/AE3; negative: CD31, CD34, EMA, beta-catenin, inhibin	Positive: vimentin, cytokeratin, smooth muscle actin, BCL2; negative: desmin, myogenin, S100; endothelial lining positive for CD31/CD34
Ki-67 index	>80%	Not specified
Postoperative management	Vincristine, etoposide, actinomycin	Chemotherapy and radiotherapy
Follow-up	PET scan 1 month postop: no metastasis	Recurrence at 6 mo with hemoperitoneum, large tumor resected

Abbreviations: AFP, alpha-fetoprotein; CEA, carcinoembryonic antigen; CT, computed tomography; EMA, epithelial membrane antigen; PET, positron emission tomography; postop, postoperative; RUQ, right upper quadrant; UESL, undifferentiated embryonal sarcoma of the liver.

Discussion

UESL is a rare mesenchymal tumor that accounts for 9 to 13% of pediatric tumors, and it is the third most common primary liver malignancy in children after hepatoblastoma and hepatocellular carcinoma.[1] [2] [3]

The precise etiology of UESL is unclear. It is often considered a malignant evolution of mesenchymal hamartoma, which is a benign tumor noted in the pediatric population. Additionally, multiple cytogenetic studies have shown overexpression of p53 in more than 80% of these tumor cells, thus suggesting a role of the p53 pathway in the pathogenesis of this tumor.[4]

The clinical presentations of these tumors are diverse, but the typical clinical presentation includes abdominal pain in the right upper quadrant and epigastric area, associated with a mass that is at risk of bleeding or rupture.[5] Other complaints, including fever, nausea, headache, anorexia, diarrhea, malaise, or jaundice, have also been reported. In both of our cases, abdominal pain was a prevalent presenting symptom accompanied by hemorrhage, which was also a common finding. Additionally, the second case exhibited symptoms of fever. Typically, fever arises as a result of hemorrhage and tissue death.[6]

Laboratory studies are nonspecific. They usually show no abnormalities in liver function, complete blood count, urinalysis, or AFP levels.[6] Radiologic findings of UESL are likewise nonspecific. Ultrasonography usually shows a large mass with mixed solid and cystic components. It is often mistaken for a benign hepatic lesion. The right lobe of the liver is more commonly involved, although the tumor can arise from the right, left, or both lobes simultaneously. CT scan often reveals a large hypodense mass with multiple septations. On MRI, UESL can be well characterized on T1-weighted and T2-weighted images, as well as postcontrast delayed T1 sequences, in addition to visualizing a large mixed solid and multicystic mass with frequently associated central necrosis.[5] The preferred imaging modality was CT scan in both of our patients. Both revealed a tumor affecting the left lobe of the liver. In addition, both cases exhibited heterogeneous densities, indicating bleeding within the tumor.

The diagnosis of UESL before histopathologic evaluation is very difficult because the clinical features are various and nonspecific. It usually presents as a single and well-circumscribed lesion grossly. The well-demarcated appearance is created by a fibrous pseudocapsule, which is formed by compressed liver parenchyma. As a primitive mesenchymal phenotype tumor, the tumor size often exceeds 10 cm and can be as large as 30 cm.[7] Immunohistochemically, UESL is generally positive for vimentin, desmin, CD68, B-cell lymphoma 2, and alpha-1 antitrypsin but is negative for hepatocyte paraffin 1, myogenin, CD34, C-kit (CD117), surfactant, anaplastic lymphoma kinase, and S100. Individual markers are often not helpful in differentiating UESL from other liver tumors. Therefore, multiple immunostains are usually performed to help with the diagnosis. In practice, the negative markers are valuable to rule out the differential diagnoses. Namely, hepatoblastoma and hepatocellular carcinoma are commonly positive for hepatocyte paraffin 1 antibody. Myogenin is usually positive in embryonal rhabdomyosarcoma. CD34 positivity is seen in solitary fibrous tumor and vascular neoplasms. Gastrointestinal stromal tumor is positive for both C-kit and CD34.[6] In the first case, the diagnosis was confirmed as UESL with positive markers for CD56, vimentin, desmin, and cytokeratin. The second case was initially mistaken for hemangioendothelioma, showing CD31 and CD34 positivity, and later was found to be UESL with positive markers for cytokeratin, vimentin, SMA, and BCL2.

The differential diagnosis for UESL in the pediatric population includes mesenchymal hamartoma, hepatoblastoma, and embryonal rhabdomyosarcoma of the biliary tree. Hepatocellular carcinoma, gastrointestinal stromal tumor, angiolipoma, leiomyosarcoma, liposarcoma, angiosarcoma, epithelioid hemangioendothelioma, and malignant melanoma are more commonly seen in adults.[7]

Although it used to be considered a highly malignant neoplasm with poor prognosis in the pediatric population, recent evidence has revealed that modern surgical procedures, along with neoadjuvant or adjuvant chemotherapy, have led to an increase in survival rate. As the tumors are usually large, preoperative chemotherapy may result in tumor shrinkage, thus enabling complete resection.[8] Recent evidence has shown that with modern surgical procedures and chemotherapy, there has been an increase in the 5-year overall survival rate, ranging from 50 to 100%, compared with 33 to 37% in the past.[2] Metastatic disease is present in 13 to 15% of the patients at diagnosis, with most cases involving the lungs (8%), followed by the diaphragm, heart, and peritoneum. Presence of metastasis at the time of diagnosis is associated with worse survival. Hence, early diagnosis and therapy are required.[8]

There is no established standard chemotherapy for children with UESL. Similar to standard treatment for nonrhabdomyosarcoma soft tissue sarcomas, chemotherapy combining alkylating agents with anthracyclines has been used in the majority of reported series, and more recently, ifosfamide and doxorubicin have gained widespread use. Radiotherapy, on the other hand, has been used rarely.[2] Both of the cases presented were managed through surgical intervention involving the resection of the affected liver lobes. Notably, both cases exhibited involvement of the left liver. When coupled with systemic therapy, this approach ensured that these patients received suitable treatment.

On another note, orthotopic liver transplantation has been reported as a successful management option for patients with recurrent and refractory disease, and PET scan has been useful in evaluating the response after chemotherapy.[9]

The recurrence rate of UESL is higher during the first 2 years after surgery, and the risk is higher with positive resection margins and in cases with spontaneous or iatrogenic rupture of the hepatic lesion. In cases of recurrence, radical excision, if feasible, is recommended.[4]

Conclusion

The diagnosis of UESL before acquiring histopathologic evaluation is rather challenging. We describe here two rare cases of UESL, both cases described in depth; the immunohistochemical findings add credibility.

UESL should be included in the differential diagnosis when dealing with masses of the liver, especially with well-defined heterogeneous imaging findings and normal AFP levels.

While it can be an aggressive tumor, the diagnosis and treatment should be carried out promptly, as UESL is a potentially treatable tumor.

Conflict of Interest

None declared.

Acknowledgments

We would like to acknowledge the efforts of the General Surgery Department at the Saint George hospital University Medical Center and the encouragement of the Faculty of Balamand for the completion of this work.

Ethical Approval

Case report approved for publishing by the Ethical Committee at Saint George hospital University Medical Center, and Head of General Surgery Division.

• References

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Publication History

Received: 29 July 2025

Accepted: 09 October 2025

Article published online:
06 November 2025