Clinical and Immunohistochemical Features of Sebaceous Carcinoma: Focusing on the p53 Tumor Suppressor

Abstract

Purpose: Considerable focus has recently revealed the importance of p53 in sebaceous carcinoma (SC). This study investigates the utility of p53 as an immunohistochemistry (IHC) marker for differentiating benign and malignant sebaceous tissues and reports the clinical characteristics of patients diagnosed with SC at Mount Sinai Hospital (MSH). Methods:A retrospective chart analysis of 102 patients with SC was performed in addition to a histopathological examination of benign and malignant sebaceous tissues. Immunohistochemistry was performed in 30 cases of SC, 4 cases of sebaceous hyperplasia, 4 cases of sebaceous epitheliomas, and 3 cases of sebaceous adenoma. A separate outpatient cohort was used to compare the clinical and histologic features of eyelid lesions. This included 31 available cases with histologic descriptions of SC. The clinical features of 20 SC cases, 25 BCC cases, and 21 chalazia cases were available and compared from this outpatient cohort. Data collected included age, gender, lesion anatomical location, histopathologic descriptions, and percentage of p53 positive sebocytes. Results:Of the 102 SC cases at MSH, the mean age was 69 years, males composed 58%, and 59% were periorbital or orbital. Positive p53 staining without atypia was reproducibly observed at cell membranes in all cases of sebaceous hyperplasia. Using a standardized p53 grading system used at MSH, the average p53 staining grade for SC and epithelioma was calculated to be 2.3 ± 0.7 and 1 ± 0.7, respectively (p=0.002). An outpatient cohort revealed that 65% of SC was found on the lower eyelid and 84% of BCC was on the upper eyelid. The most common histologic features seen in SC were nuclear atypia (61%) and cytoplasmic vacuoles (55%). Conclusions:This study provides the first comprehensive staining profile of p53 in benign and malignant sebaceous tissues. We also report for the first time that membrane p53 staining was helpful and appeared to be highly specific for identifying sebaceous hyperplasia. p53 staining was also helpful for identifying SC and intraepithelial spreading tumor cells. The clinical and histologic characteristics of specific eyelid lesions in an outpatient setting are also shared. Lastly, this work incorporates the latest research to synthesize IHC recommendations for improving SC detection.

NGS Analysis Confirms Common TP53 and RB1 Mutations, and Suggests MYC Amplification in Ocular Adnexal Sebaceous Carcinomas

“…The low incidence of 0.16/100,000 person-years for sebaceous carcinoma in the US, as well as the small size of many biopsy specimens, means that it is difficult for a single institution to accumulate large cohorts with excess tissue for molecular analysis. [9] However, several studies have identified mutations in tumor suppressor genes, including TP53 and RB1, and p16 expression has been implicated as a robust immunohistochemical marker for these tumors [10][11][12][13][14][15][16][17][18][19]. High-risk human papillomavirus (HPV), whose oncogenes encode well-characterized inhibitors of p53 and Rb, has been detected in up to 18% of OA sebaceous carcinomas without concurrent tumor suppressor mutations, and additional studies have demonstrated overexpression of miRNAs that influence the p53 suppressor complex [6,11,[20][21][22].…”