MART-1-labeled melanocyte density and distribution in actinic keratosis and squamous cell cancer in situ: Pagetoid melanocytes are a potential source of misdiagnosis as melanoma in situ.

Abstract

Actinic keratosis (AK) and squamous cell carcinoma in-situ (SCCIS) within or near melanoma in situ (MIS) can complicate diagnosis due to overlapping clinical and microscopic features. This study aimed to describe basilar melanocyte density and pagetoid spread in AK and SCCIS for improved diagnostic accuracy. A total of 22 AK and 22 SCCIS biopsies containing a margin of uninvolved epidermis were immunostained with MART-1 (melanoma antigen recognized by T-cells 1). The basilar melanocyte:keratinocyte ratio and the number and distribution of pagetoid melanocytes were compared in AK, SCCIS, and uninvolved epidermis. An in-vitro human skin model was created to assess the impact of keratinocyte atypia on melanocyte distribution. The median basilar melanocyte:keratinocyte ratio in SCCIS (1:11.49) was lower than in uninvolved epidermis (1:5.59, P = 0.0011), and the ratio in AK (1:6.94) was similar to uninvolved epidermis (P = 0.987). Pagetoid melanocytes were absent in perilesional skin but common in AK (21/22, P < 0.0001) and SCCIS (22/22, P < 0.0001). Pagetoid melanocytes at or above the mid-spinous layer were more common in SCCIS (21/22) vs AK (7/22, P < 0.0001). Pagetoid melanocytes were present in the in-vitro skin model made with neoplastic but not normal keratinocytes. Pagetoid melanocytes in AK and SCCIS should be interpreted with caution to avoid overdiagnosis of MIS.