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Purpose <p>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.</p> Methods <p>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.</p> Results <p>The cohort included five patients with tumors located in parotid gland (<i>n</i> = 2), minor salivary glands (<i>n</i> = 2), and submandibular gland (<i>n</i> = 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 <i>FGFR2</i> p.C382R variants were identified in 80% (4/5) of cases. Additional alterations were seen in <i>FGFR2</i> p.C382R mutated tumors, including <i>PIK3CA</i> hotspot mutations in two cases (p.R88Q, p.R38H) and a truncating <i>FGFR2</i> variant (p.L776Rfs) in one. The single tumor that lacked <i>FGFR2</i> mutations harbored a <i>CTNNB1</i> p.I35T variant and showed more favorable histologic features. Copy number analysis revealed recurrent whole-chromosome gains of chromosomes 8, 10, and 11.</p> Conclusion <p>A distinct subset of sialoblastoma has <i>FGFR2</i> 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 <i>CTNNB1</i> hotspot mutations typical of basal cell adenoma, also suggests that a subset of sialoblastoma may represent other salivary gland tumors presenting in infancy.</p>

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Recurrent FGFR2 and PIK3CA Mutations in Sialoblastoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月4日

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  • Selene C. Koo,
  • Jingqun Ma,
  • Quynh T. Tran,
  • Rita Alaggio,
  • Alessandra Stracuzzi,
  • Pauline M. Chou,
  • Benjamin J. Wilkins,
  • Brent A. Orr,
  • Faizan Malik

摘要

Purpose

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.

Methods

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.

Results

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.

Conclusion

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.