Rearrangement of the EWSR1 Gene Is a Consistent Feature in Hyalinizing Clear Cell Carcinoma of Salivary Gland.
Cristina R Antonescu, Nora Katabi, Lei Zhang, Raja R Seethala, Richard C Jordan, Bayardo Perez-Ordonez, Iona T Leong, Grace Bradley, Hagen Klieb, Ilan Weinreb. Memorial Sloan-Kettering Cancer Center, New York, NY; University of Pittsburgh Medical Center, PA; UCSF, San Francisco, CA; University Health Network, Toronto, ON, Canada; University of Toronto, ON, Canada
Background: Hyalinizing clear cell carcinoma (HCCC) is a low grade salivary gland tumor with a characteristic nested and cordlike growth within hyalinized stroma. HCCC typically stains with squamous cell markers and shows occasional mucous cells making distinction from mucoepidermoid carcinoma (MEC) a challenge. We have observed that the characteristic clear cell nests of HCCC resemble those seen in soft tissue myoepithelial tumors (SMET). Up to 50% of MECs show a MAML2 gene rearrangement, while SMETs show EWSR1 rearrangement in 45% of cases. This has not been studied in HCCC to examine a possible link between these entities.
Design: 23 cases of HCCC with typical morphologic and immunohistochemical features were collected. FISH for EWSR1 and MAML2 were performed using custom BAC probes and 200 cells were scored per case. A case was called positive when ≥20% of cells had a break-apart signal.
Results: The 23 cases included 14 females & 9 males ranging from 25-87 yrs of age (avg. 59.4). Sites were 18 oral, 3 parotid, 1 nasal & 1 larynx. All cases showed nests and cords of clear cells in a hyalinized stroma. Follow up in 19 cases ranging from 2 to 195 mths (avg. 47.6) demonstrated 4 recurrences (21%). The remainder showed no evidence of disease (NED). There were no metastases or mortality in any case. Mucin was seen in 10 of 23 cases (44%) and varied from focal to diffuse. The tumors were positive for 34βE12 (16/17), p63 (19/20) and EMA (9/12). They were negative for S100, SMA and calponin. FISH showed a EWSR1 rearrangement in 18 of 22 cases (82%), while no MAML2 break-apart was detected in any of the cases (0/14), including all mucin containing tumors (0/7). No EWSR1 abnormality was present in any of the control cases tested, including 3 MEC with clear cells and 5 epithelial-myoepithelial carcinomas.
Conclusions: HCCC is a unique tumor entity that shares EWSR1 rearrangement with SMET, despite S100, SMA and calponin negativity. It is distinct from MEC, despite common mucinous differentiation. This critical distinction impacts on grading, since all mucin positive HCCC cases showed NED and would have been over graded (grade III) with conventional MEC grading schemes. FISH analysis for EWSR1 rearrangement can be used as a reliable tool when confronted with limited material or a challenging diagnosis.
Category: Head & Neck
Tuesday, March 1, 2011 11:00 AM
Platform Session: Section G, Tuesday Morning