The Diagnostic Utility of Novel Sebocyte Maturation Markers ABHD5, PGRMC-1 and Perilipin in Differentiating Sebaceous Carcinoma from Basal Cell Carcinoma with Clear Cell Features
Wei-Shen Chen, Pei-Ling Chen, Jianping Li, Anne C Lind, Dongsi Lu. Washington University School of Medicine, St Louis
Background: Sebaceous carcinoma (SebCA) is an uncommon adnexal tumor that occurs predominantly in the ocular and head/neck regions. Distal metastases affect up to 25% of patients, and the overall 5 year mortality is ∼20%. Histologically, sebaceous carcinoma consists of sebocytes at varying stages of differentiation, with more differentiated sebocytes at the center of tumor nests. Depending on the degree of sebaceous differentiation, it can be difficult to distinguish SebCA from basal cell carcinoma (BCC). Ancillary markers that separate SebCA from its mimickers are limited. In this study, we sought to identify novel and reliable immunohistochemical markers of SebCA. Specifically, we sought to test if antibodies against ABHD5, PGRMC-1 and Perilipin, proteins involved in either lipogenesis or regulation of lipid synthesis, can be utilized for this purpose.
Design: Archival surgical pathology specimens were retrieved, including 25 cases with diagnosis of SebCA, 17 BCC with clear cell features (BCC-CC) or sebaceous differentiation. Immunostains were performed on FFPE sections using anti-ABHD5, PGRMC-1 and Perilipin antibodies.
Results: First, we demonstrated the distinct localization pattern of ABHD5, PGRMC-1 and Perilipin within normal sebaceous lobules. Second, we showed that ABHD5, PGRMC-1 and Perilipin can reliably differentiate SebCA from its mimickers, namely, BCC-CC. In SebCA, PGRMC-1 showed patchy/organoid distribution and highlighted early differentiating sebocytes; ABHD5 expression was markedly diminished and reduced to a dot-like pattern; and anti-Perilipin diffusely highlighted the majority of intracytoplasmic lipid storage vacuoles in SebCA. In BCC-CC, PGRMC-1, ABHD5 and Perilipin were not expressed. In tumors with sebaceous differentiation, the antibodies highlighted only the areas of sebaceous differentiation in a pattern similar to normal sebaceous lobules (Table 1).