UESL is a rare primary mesenchymal tumor in children but there have been a few reports in adults as well [7, 8]. The oldest reported patient was an 86-year-old woman described by Ellis and Cotton in 1983 [9]. Because of the low incidence of UESL, especially among adults, most of the literature comprises case reports, with a limited number of small case series. These reports often present as masses with solid and cystic components. Due to the rarity of UESL in adult patients, these patients are often misdiagnosed as hepatic abscess, hemorrhage cystic tumor, or hydatic cyst, as in the current case [2]. The diagnosis of UESL is difficult because it has no specific clinical characteristics, as shown in this case. Some patients may present with various non-specific gastrointestinal symptoms, such as nausea, vomiting, abdominal pain, diarrhea, and jaundice. A large liver mass along with persistent weight loss is apparent in most adult cases. UESL is not associated with cirrhosis or chronic liver disease; thus, liver functions and tumor markers such as AFP, CEA, and CA 19-9 are normal in most cases, such as in the present case.
Macroscopically, UESL is a large, well-circumscribed mass with areas of cystic degeneration, necrosis, hemorrhage, and an occasional gelatinous appearance, and the tumor is surrounded by a fibrous pseudocapsule with direct invasion of the adjacent parenchyma, consistent with our findings. The cellular component is composed of medium-to-large spindled or stellate cells with marked nuclear pleomorphism [10, 11]. Although its pathological origin is unclear, studies have shown histiocytic, lipoblastic, myoblastic, myofibroblastic, rhabdomyoblastic, and leiomyoblastic differentiation [12]. UESLs are usually diffusely positive for vimentin and a1-antitrypsin and focally positive for cytokeratin, desmin, α-SMA, muscle-specific actin, CD68, myoglobin, neuron-specific enolase, S100, and CD34, suggesting that an embryonal sarcoma is undifferentiated [13]. PAS-positive and diastase-resistant intra- and extracytoplasmic globules may be observed in UESL [14], as was seen in our case. Histology sometimes showed sloughed-off biliary epithelial cells of preexisting bile ducts trapped between the degenerated masses and fibrous septae of the tumor.
The standard treatment of UESL includes complete resection of the tumor and combined adjuvant chemotherapy [15]. Liver transplantation may also be an option for patients with unresectable tumors [6]. Radical resection is also recommended for recurrent cases [16]. Lenze et al. reviewed reports from 1955 to 2007 and reported that the combination of surgical resection and adjuvant chemotherapy may improve prognosis compared with resection alone [17]. Although there are no standard regimens for adjuvant chemotherapy, sarcoma-directed chemotherapy such as combination of vincristine, actinomycin, ifosfamide, and doxorubicin or combination of carboplatin and etoposide has been used [18]. Drug selection for adjuvant chemotherapy was based on past reports rather than on genomic results. In this genomic results, there were no ready-to-use actionable drugs for UESL. To our knowledge, there are reports that only 6 of 16 adult patients over the age of 18 years (37.5%) who survived for more than 48 months had no recurrence after the primary surgery [17, 19]. Of the 10 patients who relapsed, eight patients (80%) presented with recurrence in the remnant liver [19]. The current patient has been disease-free for 1 year after surgery, but careful follow up is still necessary.
To date, there have been no reports of genomic comprehensive analyses of UESL cases. There have been a few studies of TP53 mutations in some UESL cases, as well as overexpression of p53 in tumoral cells, suggesting that the p53 pathway may be involved in the carcinogenesis of UESL, similar to a number of other tumors [20, 21]. Hu et al. emphasized the inactivation of TP53 through the loss of heterozygosity and a pathogenic mutation of the remaining allele [21]. Restoration of TP53 function could be of interest for therapeutic strategies for UESL [21].
We considered that UESL was not the recurrence of osteosarcoma because histological types were completely different. There are three possible relationships between the present UESL and past osteosarcoma in this case: completely unrelated, secondary carcinogenesis due to chemotherapy, and genetic factors. Although the possibility of secondary carcinogenesis due to the chemotherapy for osteosarcoma could not be denied, there has been no reports that UESL occurred as a secondary cancer due to chemotherapy or radiation therapy. Taking into account that the present UESL had TP53 mutation, the Li–Fraumeni syndrome might be possible in this case. However, we could not investigate TP53 mutations in this case’s germline or past osteosarcoma because informed consent had not been obtained from the patient.
In the present case, genomic analysis revealed 11 somatic mutations. We identified a STK11 mutation that has never been reported in UESL thus far. There is a report that the therapeutic effect of programmed death-(ligand) 1 (PD-1/PD-L1) inhibition was diminished in STK11- and KEAP1-mutant lung adenocarcinoma [22]. This suggests that our findings might shed new light on the clinical diagnosis and add strong evidence of a potential targeted treatment through comprehensive genome analysis and companion diagnostics.
