A biopsy from a pearly, telangiectatic nodule on the nasal ala of a 65-year-old shows islands of basaloid cells with peripheral palisading, retraction artifact (mucin), and surrounding stroma. The molecular pathway predominantly mutated is:

• A Hedgehog (PTCH1/SMO) signalling pathway ✓
• B RAS-RAF-MEK pathway
• C VEGFR-2 signalling
• D EGF receptor pathway

Explanation

Basal cell carcinoma (BCC) pathogenesis is dominated by Hedgehog pathway mutations. Most sporadic BCCs have somatic loss-of-function mutations in PTCH1 (Gorlin syndrome is germline PTCH1 mutation) or gain-of-function SMO mutations, leading to constitutive activation of GLI transcription factors. Vismodegib (SMO inhibitor) and sonidegib target this pathway for advanced/metastatic BCC. The histological retraction artifact (clefting between tumor islands and stroma) is pathognomonic. BRAF mutations are more characteristic of melanoma.

Reference: Neena Khanna Illustrated Synopsis of Dermatology & STD, 6th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.