The Role of GLI1-ISH in the Diagnostically Challenging Basal Cell Carcinoma

Summary: Basal cell carcinoma (BCC) and basaloid squamous cell carcinoma (basaloid SCC) are morphologically similar, often presenting diagnostic challenges. In situ hybridization (ISH) for glioma-associated oncogene homolog 1 (GLI1) is a helpful diagnostic tool for these cases. GLI1 expression is specific to BCC and is typically absent or minimally expressed in basaloid SCC. Our aim is to validate the use of GLI1-ISH in distinguishing BCC from basaloid SCC by analyzing four diagnostically challenging and unusual cases. A 58-year-old female with a history of high-grade serous ovarian cancer presented with a new lesion on the left vulva. A biopsy revealed BCC. A 64-year-old male was found to have a perianal lesion at the time of colonoscopy. A biopsy and subsequent wide excision revealed BCC. A 70-year-old male with a history of prostate adenocarcinoma was found to have perianal BCC. A 72-year-old male with a history of melanoma who underwent a wide local excision and axillary lymph node dissection was found to have metastatic BCC. GLI1 demonstrated strong nuclear expression in all cases, helping to confirm the diagnosis of BCC. These findings underscore GLI1-ISH as a valuable adjunct in the differential diagnosis of BCC.