.png){kind=icon}
.png){kind=icon}
Return
RUNX2 Rearrangement as a Recurrent Molecular Event and Diagnostic Marker in Salivary Gland Keratocystoma
.png){kind=icon}
OA
AI
M
J
N
R
Y
C
T
J
Z
J
L
R
DOI：10.1016/j.modpat.2026.101029.png)
.png){kind=icon}
.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Keratocystoma is considered a rare, benign salivary gland tumor predominantly occurring in the parotid gland. Due to its rarity, insufficiently recognized clinicopathological features, immunohistochemical phenotype, and molecular characteristics, keratocystoma remains diagnostically challenging. This study aimed to investigate the clinical, histological, and molecular features of keratocystoma to refine the histological diagnostic boundaries. Nineteen cases of keratocystoma were analyzed using fluorescence in situ hybridization (FISH), targeted RNA sequencing, and immunohistochemistry (IHC). Histological mimics, including 20 cases of squamous cell carcinoma, 21 cases of metaplastic Warthin tumor, 20 cases of pleomorphic adenoma, 19 cases of mucoepidermoid carcinoma, 19 cases of necrotizing sialometaplasia, 21 cases of branchial cleft cyst, and 21 cases of epidermoid cyst, were incorporated for IHC comparative analysis. All keratocystoma cases arose in the parotid gland. Of 19 cases, 13 were female and 6 were male. The age ranged from 5 to 74 years with a median age of 29 years. Histologically, the multiple cystic spaces were lined by parakeratinized and/or orthokeratinized stratified squamous epithelium. Interestingly, a distinct granular layer was observed in two cases, albeit only in focal areas. Multinucleated giant cell infiltration, cholesterol clefts and calcification were noted in 13 cases, 11 cases, and 5 cases, respectively. Involvement of salivary gland parenchyma by solid squamous cells nests was observed in 9 cases. Two cases showed areas where ductal epithelium appeared to undergo transition to keratocystoma components. Two cases presented with few mitoses in the solid squamous cell nests. One case demonstrated perineural invasion. All keratocystoma cases showed RUNX2 rearrangements. RNA sequencing identified a recurrent IRF2BP2::RUNX2 fusion in all successfully tested cases. It revealed significantly higher rate of RUNX2 protein expression in keratocystoma compared to squamous cell carcinoma, epidermoid cyst and branchial cleft cyst. Two cases experienced recurrence. These findings confirmed that RUNX2 rearrangement and IRF2BP2::RUNX2 fusion were specific molecular features of keratocystoma. While molecular testing for RUNX2 gene rearrangement or fusion is diagnostically helpful, the RUNX2 IHC is not significantly helpful. Although keratocystoma is benign, recurrence may occur occasionally, warranting close postoperative follow-up.
Keywords:
keratocystoma
RUNX2
RNA sequencing
immunohistochemistry
IRF2BP2
AI Summary
Key information extracted from the uploaded paper, including a brief overview, abstract, background, key highlights, visual analysis, and future outlook.
Journal
IF:
5.5
Papers:
5.2K
Citations:
1.8W
Organization
Cited Papers