Periocular Pigmented Basal Cell Carcinomas: Clinicopathologic Features and Mutational Profile

Area of Science:

• Oncology
• Dermatology
• Genetics

Background:

• Pigmented basal cell carcinoma (PBCC) is an uncommon variant of basal cell carcinoma (BCC) affecting the periocular region.
• Limited literature exists on the specific clinicopathological profile and genetic landscape of periocular PBCC.

Purpose of the Study:

• To investigate the clinicopathological features of periocular PBCC.
• To identify and analyze somatic mutations within periocular PBCC.
• To compare these findings with non-PBCC of the periocular region and other BCC locations.

Main Methods:

• Clinicopathological data from 31 patients with periocular PBCC were collected.
• Next-generation sequencing panel analysis was performed on excised tumor samples.
• Data were compared with existing literature on periocular non-PBCC.

Main Results:

• PBCC was more prevalent in females and commonly presented as a solitary mass on the lower eyelid.
• Nodular or mixed subtypes were most frequent, with a low recurrence rate (3.5%).
• Somatic mutations were detected in 25/31 tumors, with common variants in PTCH1, TERT, and SMO. Novel drivers like POLE, FANCD2, and CREBBP were identified. SMO and TERT mutations showed associations with specific demographics and subtypes.

Conclusions:

• Periocular PBCC exhibits similar clinicopathological features and tumor behavior to periocular non-PBCC.
• The somatic mutation profile of PBCC aligns with nonperiocular cutaneous BCC, including the discovery of novel drivers.
• Identified actionable mutations offer potential targets for molecular therapy in PBCC.