Track

Clinical Studies

Abstract

Basal cell carcinoma (BCC) is the most common type of skin cancer in the United States and is comprised of basaloid islands with peripheral palisading and a fibromyxoid stroma. Numerous BCC variants have been described, including a clear cell variant (CC-BCC). Clear change in CC-BCC ranges from focal to diffuse, with the latter creating diagnostic uncertainty. Depending on the degree of clear cell change in CC-BCC, the histologic differential diagnosis may include trichilemmoma, trichilemmal carcinoma, clear cell squamous cell carcinoma, and sebaceous carcinoma. Ber-EP4 staining commonly serves as a confirmatory test in diagnosing BCC, but its staining pattern in CC-BCC is not well-characterized.  Scant literature has captured both positive and negative results. After seeing a CC-BCC with negative Ber-EP4 staining, we assessed the staining pattern of Ber-EP4 in a cohort of CC-BCC to determine its limitations in this BCC variant. We performed immunohistochemical staining of 16 CC-BCC cases with Ber-EP4. Grading of Ber-EP4 was as follows: 1, no significant staining; 2, dim positivity; and 3, strong staining. In total, 5 (31.25%) cases were graded 1, 4 (25%) were graded 2, and 7 (43.75%) cases were graded 3. Additionally, to determine if keratinocyte glycogenation underlies the clear cell change in CC-BCC, we stained 5 cases with periodic acid-Schiff stain (PAS.) In 4 (80%) cases, PAS was strongly positive; 1 case demonstrated moderate positivity. These findings highlight a pitfall of relying on Ber-EBP4 alone to rule out CC-BCC and confirms that the clear cell change represents aberrant glycogenation in the neoplastic keratinocytes.