The Cellular and Molecular Landscape of Synchronous Pediatric Sialoblastoma and Hepatoblastoma

Abstract

Sialoblastoma (SBL) is an infrequent embryonal malignant tumor originating from the salivary gland, resembling primitive salivary gland anlage, whereas hepatoblastoma (HB) is the most common pediatric liver malignancy. The simultaneous occurrence of both tumors is extremely rare. Here we reported a case of a 6-month-old infant diagnosed with synchronous SBL and HB. The patient received neoadjuvant chemotherapy followed by surgical resection. Fresh tissues of both tumors were collected before and after chemotherapy, which were further profiled by whole exome sequencing (WES) and single-cell RNA sequencing (scRNA-seq). WES analysis revealed potential somatic driver mutation PIK3CA p.Glu454Lys for SBL and canonical mutation CTNNB1 p.Ser45Pro for HB. No shared somatic variants or common copy number alterations were found between SBL and HB primary tumor samples. Though scRNA-seq, single-cell atlases were constructed for both tumors. SBL may recapitulate a pre-acinar stage in the development of salivary gland, including basaloid, duct-like, myoepithelial-like, and cycling phenotypes. In the meantime, HB was composed of tumor cells resembling different stages of the liver, including hepatocyte-like, hepatic progenitor-like, and hepatoblast-like cells. After chemotherapy, both tumors were induced into a more mature phenotype. In terms of transcriptional signatures, SBL and HB showed enhanced expression of epithelial markers KRT8, KRT18, and essential embryo development genes SDC1, MDK, indicating the disruption of normal embryo epithelium development. Finally, heterozygous deleterious germline mutation BLM and FANCI were identified which could predispose the patient to higher cancer risk. It partially explained the reason for the co-occurrence of SBL and HB. Taken together, we provided valuable resources for deciphering cellular heterogeneity and adaptive change of tumor cells after chemotherapy for synchronous SBL and HB, providing insights into the mechanisms leading to synchronous pediatric tumors.

Clinicopathological study and survival outcomes of sialoblastoma: A systematic review

“…In the screening phase, 103 articles were selected for full‐text evaluation. Of these, 51 selected studies 3,5,7–10,13–57 met the eligibility criteria. Additionally, 1 article 58 was added from a manual search of the reference lists of included studies, resulting in the inclusion of 52 articles in the qualitative synthesis.…”

“…In one case the sex was not reported. 50 Anatomical location was reported in all included cases. Most of the lesions affected the parotid gland (n = 28; 45.2%), followed by the submandibular gland (n = 18; 29.0%) (Figure 2).…”

“…36 There are four reports in the literature demonstrating the synchronic association of sialoblastoma and hepatoblastoma, which is an extremely uncommon event. 20,34,50,52 Such occurrence can be explained due to the common embryonic origin of the parotid gland and the liver. As a result, the abnormality would affect the cells of both organs, leading to the appearance of two synchronous tumor producers of alpha-fetoprotein (AFP) in different sites in the same patient.…”

Infant with Parotid Sialoblastoma and Nevus Sebaceous, Treated with Surgery and Adjuvant Chemotherapy

“…There have been at least eight reported cases of synchronous sialoblastoma and hepatoblastoma. The analysis of one such case conducted by Yang et al [ 26 ] revealed that certain germline mutations might be associated with the development of such a bizarre combination. Since few cases of sialoblastoma have been reported to date, the combination of sialoblastoma cases with co-existing hepatoblastoma is significant, and every patient with sialoblastoma should be carefully assessed for a possible abdominal tumor with proper abdominal imaging and AFP level measurement (sialoblastoma itself can also generate elevated AFP levels) [ 27 ].…”

Primary immature teratoma in the liver with growing teratoma syndrome and gliomatosis peritonei: a rare case report

“…Unlike immature teratoma, both carcinosarcoma and undifferentiated carcinoma of liver do not contain mature epithelial or mesenchymal components such as squamous epithelium, mature cartilage or adipose tissue [ 26 ]. Hepatoblastoma occurs mainly in children but rarely in adults, consisting of variable combinations of epithelial and mesenchymal elements, which are absent in this case [ 27 ].…”