Clear Cell Odontogenic Carcinomas Show EWSR1 Rearrangements: A Novel Finding & Biologic Link to Salivary Clear Cell Carcinomas
Elizabeth A Bilodeau, Ilan Weinreb, Sanja Dacic, Susan Muller, Bruce Barker, Raja R Seethala. University of Pittsburgh School of Dental Medicine, Pittsburgh, PA; University of Toronto, Toronto, ON, Canada; University of Pittsburgh, Pittsburgh, PA; Emory University, Atlanta, GA; University of Missouri-Kansas City, Kansas City, MO
Background: Clear cell odontogenic carcinomas (CCOC) and salivary clear cell carcinomas (CCC) have considerable morphologic and immunophenotypic overlap making distinction difficult. LEF-1 is a transcription factor that is a marker of odontogenic differentiation that may serve to separate these entities. Recently, CCC have been noted to harbor an EWSR1-ATF1 translocation, which may potentially serve as a discriminatory marker. We performed a comparative analysis of CCC and CCOC for EWSR1 rearrangements and LEF-1 expression.
Design: Fluorescensce in-situ hybridization (FISH) for EWSR1 dual color break-apart 22q12 probe (Abbott Molecular, Des Plaines, IL) was performed on paraffin sections from 12 CCOC, 14 CCC, and 1 sinonasal renal cell clear cell-like adenocarcinoma (SRCCA), 1 clear cell calcifying epithelial odontogenic tumor (CCCEOT), and 1 central squamous cell carcinoma with clear cell features (CCSCC). A case was considered FISH positive when ≥20% of the cells showed an EWSR1 rearrangement. Immunohistochemical staining for LEF-1 (sc-8591, 1:200 dilution; Santa Cruz Biotechnology, Santa Cruz, CA, USA) was also performed and considered positive if over half the lesional cells showed at least moderate positivity.
Results: FISH testing failed in 4 CCOCs and 1 CCC. EWSR1 was rearranged in 62.5% (5/8) CCOC and 92.3% (12/13) CCC. All translocation positive CCC and CCOC showed clear cell tumor nests embedded in a characteristic juxtaposition of hyaline and fibrocellular stroma. One EWSR1 intact CCC was of the parotid but was morphologically identical to the EWSR1 translocated CCC. Two of the 3 EWSR1 negative CCOC, however, had only sparse, compressed tumor islands embedded in a fibrocellular stroma. EWSR1 was intact in the SRCCA, CSCC, and CCCEOT. Immunohistochemistry for LEF-1 was only positive in 1/11 CCOC and 1/14 CCC.
Conclusions: Most cases designated as CCOC demonstrate EWSR1 rearrangements suggesting that they are related entities to salivary CCC. Furthermore, LEF-1 is unable to serve as a discriminatory marker between these entities.
Category: Head & Neck
Monday, March 19, 2012 1:15 PM
Platform Session: Section F, Monday Afternoon