Background
The Ewing sarcoma family of tumors (EFTs) is a rare entity that includes extraosseous Ewing sarcoma (ES), primitive neuroectodermal tumor (PNET), Askin tumor, and atypical ES. ES represents the second most common primary bone malignancy of children and young adults [
1] and most often arises in the long bones of the extremities and the pelvic bones [
2]. ES rarely occurs in soft tissues without bone involvement. Common primary sites of extraosseous ES are the deep soft tissues of the extremities, retroperitoneum, and chest wall. Extraosseous ES has also been reported to arise in the kidney [
3], uterus [
4], gastrointestinal tract [
5], and other visceral organs. To our knowledge, only three published case reports discuss ES arising in the liver [
6‐
8]. We report a case of a 27-year-old female with ES arising in the liver and we review the literature on extraosseous ES [
9].
Discussion
Approximately 80% of EFTs in the pediatric population arise in bone and < 20% occur in soft tissues, while > 50% of adult EFTs occur in soft tissues, including the trunk (14%), retroperitoneum or intra-abdominal tissues (14%), viscera (8%), and other sites (21%) [
10]. Visceral ES is reported to occur in the kidney [
3], uterus [
4], and gastrointestinal tract [
5]. Patient characteristics of extraosseous ES are similar to those of other EFTs, and approximately 80% of patients are younger than 20 years [
11].
To our knowledge, only three published case reports discuss ES arising in the liver [
6‐
8] and because of the rarity of this entity, little information on the imaging features is available. Two previous case reports described very large solid tumors without cystic lesions on CT [
6,
7], and a third case report described an enlarged liver without mass lesion on CT scan [
8]; CT scan in our case showed a multilocular cystic lesion. These findings indicate that CT scans in patients with ES arising in the liver can reveal a polycystic tumor, solid tumor, or an enlarged liver without mass lesion.
Cystic liver lesions generally represent a heterogeneous group of diseases. Simple solitary cyst, polycystic disease, parasitic cyst, neoplastic (primary or metastatic) disease, duct related disease, false cyst, and ciliated foregut cysts are classified as hepatic cysts [
12]. Although most liver cysts are found incidentally and tend to be benign, some are associated with malignant disease and thick or irregular cyst walls and/or multilocular cyst space on imaging studies are suspicious for malignancy. In our case, the multilocular cystic liver mass consisted of thickened, irregular septa and nodal walls and these findings were highly suspicious for a malignant neoplasm. The preoperative clinical diagnosis in our case was mucinous cystadenoma, which is a rare cystic tumor that occurs within the liver parenchyma or in the extrahepatic bile ducts. Differential diagnoses for neoplastic liver cysts are mucinous cystadenoma, mucinous cystadenocarcinoma, hepatocellular carcinoma, and metastasis from other malignant disease [
13]. ES is an uncommon differential diagnosis for cystic liver disease.
ES is described histologically as small, blue, round cells with hyperchromatic nuclei and scant cytoplasm. The morphological appearance of ES is similar to that of other small, blue, round cell tumors, including lymphoma, mesenchymal chondrosarcoma, medulloblastoma, desmoplastic small round cell tumors, and rhabdomyosarcoma. PAS stain is usually positive for ES because of the presence of abundant glycogen [
14] and the vast majority of ES express strong cell surface glycoprotein CD99. Our case was also positive for PAS, CD99, vimentin, and NKX2.2 [
15]. However, immunohistochemical findings are not sufficient for diagnosis because these findings are not specific for ES. Chromosomal translocation such as t(11;22)(q24;q12) is positive in > 85% of ES cases and also for PNET [
16]. Approximately 10% of ES cases have other analogous translocations such as t(21;22)(q22;q12) and t(7;22)(q22;q12) [
17,
18]; therefore, cytogenetic and molecular techniques are useful to distinguish ES/PNET from other tumors.
The standard treatment for extraosseous ES is not established because of its rarity; therefore, we used the same strategy as for osseous ES [
19]. Modern treatment guidelines recommend primary treatment with multi-agent chemotherapy followed by local treatment and additional chemotherapy [
20]. ES is highly sensitive to chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide (VDC/IE). In our case, preoperative biopsy was not diagnostic and surgical resection was performed as an initial treatment with six cycles of VDC/IE chemotherapy planned after complete resection. Current guidelines recommend physical examination, imaging of the primary site and chest, complete blood count, and other laboratory studies every 2–3 months for 24 months, with increasing testing intervals after 24 months and annually after five years [
20].
Competing interests
The authors declare that they have no competing interests.
Authors’contributions
YO and YM wrote the paper. TF reviewed the pathological findings. KT assessed the imaging studies. All authors read and approved the final manuscript.