Koo Selene C, Ma Jingqun, Tran Quynh T, Alaggio Rita, Stracuzzi Alessandra, Chou Pauline M, Wilkins Benjamin J, Orr Brent A, Malik Faizan
Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Pathology and Oncology Unit, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy.
Head Neck Pathol. 2025 Sep 4;19(1):107. doi: 10.1007/s12105-025-01838-3.
Sialoblastoma is an extremely rare low-grade malignant salivary gland neoplasm that presents at birth or early infancy and has heterogeneous clinical behavior. Due to its rarity, the molecular landscape remains incompletely characterized. We aimed to expand the current understanding of the genetic alterations in sialoblastoma through comprehensive molecular analysis.
Five sialoblastoma cases were retrieved from four institutional archives. Clinical and pathologic review was performed, and targeted next-generation sequencing was conducted using clinically validated panels. Copy number analysis was performed on four cases.
The cohort included five patients with tumors located in parotid gland (n = 2), minor salivary glands (n = 2), and submandibular gland (n = 1). Four patients were diagnosed before 6 months of age. Histologically, all tumors showed solid organoid nests with primitive basaloid cells, dense fibrous stroma, and mitotic activity ranging from 8 to 25 per 10 high-power fields. Recurrent FGFR2 p.C382R variants were identified in 80% (4/5) of cases. Additional alterations were seen in FGFR2 p.C382R mutated tumors, including PIK3CA hotspot mutations in two cases (p.R88Q, p.R38H) and a truncating FGFR2 variant (p.L776Rfs) in one. The single tumor that lacked FGFR2 mutations harbored a CTNNB1 p.I35T variant and showed more favorable histologic features. Copy number analysis revealed recurrent whole-chromosome gains of chromosomes 8, 10, and 11.
A distinct subset of sialoblastoma has FGFR2 p.C382R hotspot mutation as the predominant driver mutation. Tumors with this mutation tend to have solid growth pattern, aggressive histologic features, and clinical behavior. The identification of concurrent genomic alterations expands the molecular landscape of this rare tumor. The detection of alternative drivers, such as CTNNB1 hotspot mutations typical of basal cell adenoma, also suggests that a subset of sialoblastoma may represent other salivary gland tumors presenting in infancy.
涎母细胞瘤是一种极其罕见的低级别恶性涎腺肿瘤，在出生时或婴儿早期出现，具有异质性临床行为。由于其罕见性，分子特征仍不完全清楚。我们旨在通过全面的分子分析来扩展目前对涎母细胞瘤基因改变的认识。
从四个机构档案中检索出5例涎母细胞瘤病例。进行了临床和病理评估，并使用经过临床验证的检测板进行了靶向二代测序。对4例病例进行了拷贝数分析。
该队列包括5例患者，肿瘤分别位于腮腺（n = 2）、小涎腺（n = 2）和下颌下腺（n = 1）。4例患者在6个月龄前被诊断。组织学上，所有肿瘤均显示实性类器官巢，伴有原始基底样细胞、致密纤维性间质，每10个高倍视野有丝分裂活性为8至25个。80%（4/5）的病例中鉴定出复发性FGFR2 p.C382R变异。在FGFR2 p.C382R突变的肿瘤中还发现了其他改变，包括2例PIK3CA热点突变（p.R88Q、p.R38H）和1例截短型FGFR2变异（p.L776Rfs）。唯一缺乏FGFR2突变的肿瘤含有CTNNB1 p.I35T变异，并且显示出更有利的组织学特征。拷贝数分析显示8号、10号和11号染色体反复出现全染色体增加。
涎母细胞瘤的一个独特亚组以FGFR2 p.C382R热点突变为主要驱动突变。具有这种突变的肿瘤往往具有实性生长模式、侵袭性组织学特征和临床行为。同时发生的基因组改变的鉴定扩展了这种罕见肿瘤的分子特征。检测到替代驱动因素，如基底细胞腺瘤典型的CTNNB1热点突变，也表明一部分涎母细胞瘤可能代表婴儿期出现 的其他涎腺肿瘤。
