The HTN3-MSANTD3 Fusion Gene Defines a Subset of Acinic Cell Carcinoma of the Salivary Gland

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  • Simon Andreasen
  • Sushama Varma
  • Nicholas Barasch
  • Lester D R Thompson
  • Markku Miettinen
  • Lisa Rooper
  • Edward B Stelow
  • Tina K Agander
  • Raja R Seethala
  • Simion I Chiosea
  • Homøe, Preben
  • Wessel, Irene
  • Stine R Larsen
  • Daiva Erentaite
  • Justin A Bishop
  • Benedicte P Ulhøi
  • Katalin Kiss
  • Linea C Melchior
  • Jonathan R Pollack
  • Robert B West

The spectrum of tumors arising in the salivary glands is wide and has recently been shown to harbor a network of tumor-specific fusion genes. Acinic cell carcinoma (AciCC) is one of the more frequently encountered types of salivary gland carcinoma, but it has remained a genetic orphan until recently when a fusion between the HTN3 and MSANTD3 genes was described in one case. Neither of these 2 genes is known to be implicated in any other malignancy. This study was undertaken to investigate whether the HTN3-MSANTD3 fusion is a recurrent genetic event in AciCC and whether it is a characteristic of one of its histological variants. Of the 273 AciCCs screened, 9 cases showed rearrangement of MSANTD3 by break-apart fluorescence in situ hybridization, 2 had 1 to 2 extra signals, and 1 had gain, giving a total of 4.4% with MSANTD3 aberrations. In 6 of 7 available cases with MSANTD3 rearrangement, the HTN3-MSANTD3 fusion transcript was demonstrated with real-time polymerase chain reaction . Histologically, all fusion-positive cases were predominantly composed of serous tumor cells growing in solid sheets, with serous tumor cells expressing DOG-1 and the intercalated duct-like cell component being CK7 positive and S-100 positive in 6/9 cases. All but one case arose in the parotid gland, and none of the patients experienced a recurrence during follow-up. In contrast, the case with MSANTD3 gain metastasized to the cervical lymph nodes and lungs. In conclusion, we find the HTN3-MSANTD3 gene fusion to be a recurrent event in AciCC with prominent serous differentiation and an indolent clinical course.

Original languageEnglish
JournalAmerican Journal of Surgical Pathology
Issue number4
Pages (from-to)489–496
Number of pages8
Publication statusPublished - 2019

ID: 209634416