Analysis of hedgehog signaling in periocular sebaceous carcinoma

PURPOSE: Sebaceous carcinoma (SC) is a clinical masquerader of benign conditions resulting in significant eye morbidity, sometimes leading to extensive surgical treatment including exenteration, and even mortality. Little is known about the genetic or molecular basis of SC. This study identifies the involvement of Hedgehog (Hh) signaling in periocular SC. METHODS: Fifteen patients with periocular SC patients were compared to 15 patients with eyelid nodular basal cell carcinoma (nBCC; a known Hh tumor), alongside four normal individuals as a control for physiological Hh expression. Expression of Patched 1 (PTCH1), Smoothened (SMO), and glioma-associated zinc transcription factors (Gli1 and Gli2) were assessed in histological sections using immunohistochemistry and immunofluorescence (IF) techniques. Antibody specificity was verified using Western-blot analysis of a Gli1 over-expressed cancer cell line, LNCaP-Gli1. Semi-quantification compared tumors and control tissue using IF analysis by ImageJ software. RESULTS: Expression of the Hh pathway was observed in SC for all four major components of the pathway. PTCH1, SMO, and Gli2 were more significantly upregulated in SC (P < 0.01) compared to nBCC. Stromal expression of PTCH1 and Gli2 was observed in SC (P < 0.01). In contrast, stromal expression of these proteins in nBCC was similar or down-regulated compared to physiological Hh controls. CONCLUSIONS: The Hh signaling pathway is significantly more upregulated in periocular SC compared to nBCC, a known aberrant Hh pathway tumor. Furthermore, the stroma of the SC demonstrated Hh upregulation, in particular Gli2, compared to nBCC. Targeting of this pathway may be a potential treatment strategy for SC

Intraepithelial sebaceous carcinoma of the eyelid misdiagnosed as Bowen's disease

BackgroundSebaceous carcinoma (SC) is well known for its ability to masquerade clinically and histologically as a variety of periocular conditions resulting in a delayed diagnosis. We present a series of periocular SC cases and discuss the difficulties in histopathological diagnosis when this tumor presents with a Bowenoid pattern of intraepithelial spread.MethodsA retrospective case study of all patients with SC of the eyelid treated in our Hospital, from 1997 to 2004, was conducted.ResultsEight patients were identified (four females and four males). Seven cases involved the upper eyelid. Initial clinical diagnoses included blepharitis (three cases), blepharoconjunctivitis (one case), cicatrizing conjunctivitis (one case), and lid lesions (two cases). Histopathologically, 87.5% of cases were misdiagnosed as Bowen's disease (BD) on the initial biopsy. Six of these cases showed no invasive disease on the initial biopsy and were eventually found to be invasive SC on subsequent excisions. In one case, the tumor was wholly in situ. Delay in diagnosis ranged from 0 to 56 months.ConclusionsSC should always be considered in the histological differential diagnosis of any eyelid lesion which resembles BD, particularly if the upper eyelid is involved or if multivacuolated cytoplasmic clear cell changes are seen