Cutaneous Eruptions in Patients Receiving Immune Checkpoint Blockade

Abstract

Cutaneous eruptions are among the most common immune-related adverse events (irAEs) associated with anti-PD-1/PD-L1 therapy, and are often clinically and histologically characterized as lichenoid. Non-lichenoid patterns may also occur and are likely to be encountered by surgical pathologists, given the increasing clinical use of these agents. The purpose of this study is to describe the histopathologic features of non-lichenoid cutaneous irAEs from patients receiving anti-PD-1/PD-L1 therapies for a variety of underlying advanced malignancies. Sixteen patients with 17 biopsied eruptions were included from two academic institutions with extensive experience administering and monitoring responses to immune checkpoint blockade as well as treating the potential side effects. Eruptions occurred a median of 10 days (range 1 day to 11.4 months) after treatment initiation. Nearly half of specimens demonstrated either a psoriasiform/spongiotic or an urticarial-type reaction pattern on histologic review. Patterns consistent with Grover’s disease, bullous pemphigoid, and granulomatous dermatitis were also observed. Nearly two-thirds of patients required systemic corticosteroids for treatment of the cutaneous irAE, and 19% of patients discontinued immunotherapy due to their skin eruptions. 75% of patients showed an objective antitumor response. The diverse array of non-lichenoid cutaneous irAE presented here should reflect and inform the scope of histologic patterns encountered by the practicing surgical pathologist. Such eruptions are seen in patients with a variety of underlying tumor types, many of whom ultimately demonstrate a favorable response to immune checkpoint blockade.

Characterization of dermatitis after PD-1/PD-L1 inhibitor therapy and association with multiple oncologic outcomes: A retrospective case-control study

“…Although previous reports have demonstrated lichenoid and other types of histologic patterns as being associated with PD-1/PD-L1 inhibition, 17–19 our study links the lichenoid and spongiotic types with multiple favorable oncologic outcomes, including favorable ORR, PFS, and OS. This information is useful when dermatologists counsel patients with this drug-related dermatitis.…”

Implications of the tumor immune microenvironment for staging and therapeutics

“…Histopathological descriptions of many of these reactions have now been reported. 161–165 The need for pathologists to maintain awareness of the histological manifestations of these drug-related events is critical for patient management, as is the importance of clear communication of clinical history by the treating physicians.…”

Toxic Side Effects of Targeted Therapies and Immunotherapies Affecting the Skin, Oral Mucosa, Hair, and Nails

“…2 ), with a frequency ranging from 14 to 40% depending on the drug and whether it is used in combination or alone [ 33 ]. Subsets of patients also present eczema-like or psoriatic lesions [ 34 ] while others develop lichenoid dermatitis [ 35 , 36 ] in response to PD-1 and PD-L1 inhibitors. Lichenoid rash in patients treated with ICIs is very similar to idiopathic lichen planus, except for a slightly increased abundance of CD163-positive cells indicating a macrophage–monocyte lineage [ 36 ].…”