A case report of disappearing pigmented skin lesions associated with pembrolizumab treatment for metastatic melanoma

Abstract

Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death (PD)-1 receptor. Common cutaneous adverse side-effects of PD-1 inhibitors include maculopapular rash, pruritus, vitiligo and lichenoid skin and mucosal reactions. Here we describe a man in his sixties with metastatic melanoma treated with pembrolizumab who subsequently developed fading or disappearance of pigmented skin lesions, lightening of the skin, and poliosis of the eyebrows, eyelashes and scalp and body hair. Compared with baseline high-resolution three-dimensional total-body photography, we observed fading or disappearance of solar lentigines, seborrhoeic keratoses and melanocytic naevi, suggesting that PD-1 inhibitors may affect the evolution of these benign skin lesions. With dermatoscopic follow-up, altered lesions showed either blue-grey peppering/granularity or fading in colour without other identifiable features. No halo lesions or lesions with surrounding inflammation were identified. One changed pigmented lesion that showed blue-grey peppering/granularity on dermoscopy was biopsied and interpreted as a macular seborrhoeic keratosis with melanophages. Further studies are required to elucidate the effects of PD-1 inhibition on benign skin lesions.

Figure 1

Clinical images of the anterior trunk, posterior trunk, and dorsal hand before (A, C, E) and 13-months after (B, D, F) initiating pembrolizumab therapy. Most pigmented lesions have faded or disappeared. Note: Panels A, C, and E were acquired with three-dimensional whole-body stereophotogrammetry imaging. Irregularities in anatomic outline are secondary to the computer rendering process.

Figure 2

Dermatoscopic images of representative skin lesions taken prior to (left panels) and 13-months after (right panels) initiating pembrolizumab therapy. Naevi (A-F) faded with (D) and without (B,F) peppering. Seborrheic keratosis (G) undergoing regression with peppering (H). A dermatofibroma on the lower extremity exhibited no visible changes (I-J).

Figure 3

Clinical (A) image of a pigmented macule on the chest that was noted to change in colour 3-months after initiating pembrolizumab. Dermatoscopic image (B) shows blue-grey peppering/granularity. (C) Haematoxylin and Eosin, 400x original magnification photomicrograph; a sparse lichenoid infiltrate extends to the dermo-epidermal junction where there is subtle interface alteration and numerous superficial dermal melanophages. Epidermis shows acanthosis and basketweave hyperkeratosis consistent with a macular seborrheic keratosis. (D) PD-L1 immunohistochemical stain, 400x original magnification photomicrograph; positive staining is seen in elongated dendritic cells amidst melanin-bearing melanophages of the superficial papillary dermis.