Identification of Ocular Sebaceous Neoplasia with Evaluation for Mismatch Repair Proteins
Lynn Schoenfield, John Anthony, Risal Djohan, Irene Lalak, Mark Levine, Pamela Ng, Julian Perry, Arun Singh, Thomas Plesec. Cleveland Clinic, Cleveland, OH
Background: Recognizing sebaceous carcinoma is important because of its risk for metastasis and tumor death. Histopathology alone is often difficult because fresh tissue for oil red-O stain is not always available. Several immunohistochemical stains (IHC) have been evaluated but often the diagnosis is elusive. Furthermore, the diagnosis of a sebaceous adenoma or carcinoma raises the possibility of Lynch syndrome, a cancer predisposition syndrome. Mismatch repair protein(MMR) abnormalities are a feature of Lynch syndrome, and they can be detected with IHC for the MLH1, MSH2, PMS2, and MSH6 proteins.
Design: 14 sebaceous carcinomas and 3 adenomas from the eyelid (17 specimens) from 14 patients were evaluated for oil red-O when possible as well as IHC for AR, EMA, BER-EP4, CAM5.2 for diagnosis. MMR for MLH1, MSH2, PMS2, and MSH6 by IHC were evaluated as a possible screening panel for Lynch syndrome. Two patients already had other tissue tested by PCR for microsatellite instability (MSI) for Lynch syndrome.
Results: Oil red-O was done on 6 of 17 specimens and positive in 5 of the 6 (83%). AR was positive in 2 of 3 adenomas (67%) and 5 of 14 carcinomas (36%). EMA was positive in 2 of 3 adenomas (67%) and 11 of 14 carcinomas (79%). BER-EP4 was negative in all 3 adenomas and positive in 7 of 14 carcinomas (50%). CAM5.2 was positive in 1 of 3 adenomas (33%) and 8 of 14 carcinomas (57%). All 17 specimens(100%) showed positive nuclear staining for MLH1 and PMS2, indicative of normal protein expression. In 14 of 17 specimens from 12 patients, MSH2 and MSH6 were also normal. 3 specimens from 2 patients that had rare positive cells for MSH2 and MSH6. Both patients had previous colonic tumors tested for MSI and were found to be MSI-H, indicative of possible Lynch syndrome.
Conclusions: Diagnosing sebaceous carcinoma is important prognostically but sometimes challenging with routine histopathology. In our experience androgen receptor (AR) was found to be confirmatory in only 36% of cases and not dependent on the size of the tumor available. The other IHC stains were of marginal benefit and not specific. While none of the cases showed complete loss of expression of a MMR protein, there were 2 patients in with only rare positive cells who had known MSI-H tumors in the colon, suggestive of Lynch syndrome. Additional studies of these eyelid tumors may elucidate the possible role of using them for screening for Lynch syndrome.
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 218, Tuesday Morning