ABSTRACT

Although sialoblastoma (SBL) is defined as a low-grade malignant salivary gland anlage neoplasm in the 2022 World Health Organization (WHO) Classification of Head and Neck Tumors, its histology, genetics, and behavior remain controversial due to the rarity of the tumor. Here, we performed the first comprehensive clinical, histologic, and molecular analyses of 8 SBLs to better understand their pathogenesis and prognosis. This cohort consisted of 5 boys and 3 girls, with ages ranging from birth to 9 years at diagnosis. Tumors occurred in the parotid (4), cheek (3), and submandibular glands (1). Histologically, 5 tumors primarily presented as a solid pattern consisting of primitive basaloid epithelial cells, often with necrosis. Three tumors exhibited a non-solid pattern, with 1 tumor mainly showing epithelial-myoepithelial carcinoma (EMC)-like histology, whereas the other 2 tumors exhibited basal cell adenoma (BCA)-like histology. All 5 solid SBLs harbored FGFR2 mutations, and 1 also harbored mutations in PALB2, AR, and MAP2K1. In contrast, non-solid pattern tumors were characterized by HRAS mutations or significant β-catenin nuclear positivity. All 5 solid tumors recurred, 3 of them developed distant metastases, and 2 died 40 and 44 months after diagnosis. Three non-solid tumors showed no evidence of disease recurrence at 49, 144, and 132 months, suggesting a relatively favorable prognosis. Overall, SBLs can be stratified into solid and non-solid patterns, with solid pattern tumors usually having FGFR2 mutations, increasing the risk of recurrence and metastasis. This stratification underscores the importance of genetic and morphologic profiling for predicting the prognosis of SBLs.