To Treat or Not to Treat: PD-L1 Inhibitor-induced Keratoacanthoma and Squamous Cell Carcinoma

Overview

Journal Arch Dermatol Res

Specialty Dermatology

Date 2022 Nov 17

PMID 36394634

Authors

Mackenzie Poole

Robert A Schwartz

W Clark Lambert

Albert Alhatem

Affiliations

Soon will be listed here.

Abstract

Keratoacanthoma (KA) and squamous cell carcinoma (SCC) are rare side effects of programmed cell death ligand-1 (PD-L1) inhibitors that can disrupt therapy. There is no consensus on optimal treatment. We investigated the management strategy and factors influencing pathophysiology. An institutional cancer registry and literature search were used for this retrospective study. Only PD-L1-induced KA and SCC cases were included. Pathology specimens were stained with immune markers and management strategies were analyzed. Four cases were identified at our institution. Immunohistochemistry of atypical keratinocytes revealed PD-1/PD-L1 positivity, high p53, and low bcl-2 for all cases with differential expression of CD44 and beta-catenin for KA versus SCC. Nivolumab was continued or temporarily held with complete resolution. In addition, a literature search identified 30 additional cases of KA/SCC after PDL-1 inhibitor use. The most common treatment was excision/destruction followed by topical and/or intralesional corticosteroids. Therapy was definitely withheld in 22% of KA patients and in 9% of SCC cases. The expression of PD-L1 by atypical keratinocytes helps to explain the effects of nivolumab on the development of cutaneous neoplasms. The expression of immune markers provides mechanistic insights into pathophysiology. Management may be achieved with conservative therapy and without treatment interruption.

Citing Articles

Defining D-irAEs: consensus-based disease definitions for the diagnosis of dermatologic adverse events from immune checkpoint inhibitor therapy.

Chen S, Semenov Y, Alloo A, Bach D, Betof Warner A, Bougrine A J Immunother Cancer. 2024; 12(4).

PMID: 38599660 PMC: 11015215. DOI: 10.1136/jitc-2023-007675.

References

Freites-Martinez A, Kwong B, Rieger K, Coit D, Colevas A, Lacouture M . Eruptive Keratoacanthomas Associated With Pembrolizumab Therapy. JAMA Dermatol. 2017; 153(7):694-697. PMC: 5523926. DOI: 10.1001/jamadermatol.2017.0989. View

Apalla Z, Nikolaou V, Fattore D, Fabbrocini G, Freites-Martinez A, Sollena P . European recommendations for management of immune checkpoint inhibitors-derived dermatologic adverse events. The EADV task force 'Dermatology for cancer patients' position statement. J Eur Acad Dermatol Venereol. 2021; 36(3):332-350. DOI: 10.1111/jdv.17855. View

Schneider B, Naidoo J, Santomasso B, Lacchetti C, Adkins S, Anadkat M . Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline Update. J Clin Oncol. 2021; 39(36):4073-4126. DOI: 10.1200/JCO.21.01440. View

Antonov N, Nair K, Halasz C . Transient eruptive keratoacanthomas associated with nivolumab. JAAD Case Rep. 2019; 5(4):342-345. PMC: 6476889. DOI: 10.1016/j.jdcr.2019.01.025. View

Bandino J, Perry D, Clarke C, Marchell R, Elston D . Two cases of anti-programmed cell death 1-associated bullous pemphigoid-like disease and eruptive keratoacanthomas featuring combined histopathology. J Eur Acad Dermatol Venereol. 2017; 31(8):e378-e380. DOI: 10.1111/jdv.14179. View

Bednarek R, Marks K, Lin G . Eruptive keratoacanthomas secondary to nivolumab immunotherapy. Int J Dermatol. 2018; 57(3):e28-e29. DOI: 10.1111/ijd.13893. View

Chaudhari S, Leon A, Levin E, Neuhaus I, Liao W . Case Report of Multiple Keratoacanthomas and Squamous Cell Carcinomas in a Patient Receiving Pembrolizumab. J Drugs Dermatol. 2017; 16(5):513-515. View

Crow L, Perkins I, Twigg A, Fassett M, LeBoit P, Berger T . Treatment of PD-1/PD-L1 Inhibitor-Induced Dermatitis Resolves Concomitant Eruptive Keratoacanthomas. JAMA Dermatol. 2020; 156(5):598-600. DOI: 10.1001/jamadermatol.2020.0176. View

Feldstein S, Patel F, Larsen L, Kim E, Hwang S, Fung M . Eruptive keratoacanthomas arising in the setting of lichenoid toxicity after programmed cell death 1 inhibition with nivolumab. J Eur Acad Dermatol Venereol. 2017; 32(2):e58-e59. DOI: 10.1111/jdv.14503. View

10.

Fradet M, Sibaud V, Tournier E, Lamant L, Boulinguez S, Brun A . Multiple Keratoacanthoma-like Lesions in a Patient Treated with Pembrolizumab. Acta Derm Venereol. 2019; 99(13):1301-1302. DOI: 10.2340/00015555-3301. View

11.

Fujimura T, Lyu C, Tsukada A, Sato Y, Kambayashi Y, Aiba S . Eruptive keratoacanthoma with spontaneous regression arising from a cervical squamous cell carcinoma patient treated with nivolumab. J Dermatol. 2018; 46(5):e177-e178. DOI: 10.1111/1346-8138.14684. View

12.

Haraszti S, Polly S, Ezaldein H, Rothbaum R, Delost G, Beveridge M . Eruptive squamous cell carcinomas in metastatic melanoma: An unintended consequence of immunotherapy. JAAD Case Rep. 2019; 5(6):514-517. PMC: 6558268. DOI: 10.1016/j.jdcr.2019.03.014. View

13.

Hwang S, Carlos G, Wakade D, Byth K, Kong B, Chou S . Cutaneous adverse events (AEs) of anti-programmed cell death (PD)-1 therapy in patients with metastatic melanoma: A single-institution cohort. J Am Acad Dermatol. 2016; 74(3):455-61.e1. DOI: 10.1016/j.jaad.2015.10.029. View

14.

Kanekura T, Arimura A, Kirishima M, Tanimoto A . Eruptive squamous cell carcinoma in a patient treated with concomitant pembrolizumab and imiquimod. J Dermatol. 2019; 46(12):1202-1204. DOI: 10.1111/1346-8138.15101. View

15.

Lee J, Guffey D, Noland M, Russell M . Eruptive squamous cell carcinomas associated with programmed cell death protein-1 inhibitor therapy. Indian J Dermatol Venereol Leprol. 2018; 85(1):97-100. DOI: 10.4103/ijdvl.IJDVL_147_18. View

16.

Marsh R, Kolodney J, Iyengar S, Yousaf A, Louden B, Al-Bouri A . Formation of eruptive cutaneous squamous cell carcinomas after programmed cell death protein-1 blockade. JAAD Case Rep. 2020; 6(5):390-393. PMC: 7200186. DOI: 10.1016/j.jdcr.2020.02.024. View

17.

Park J, Yoon D, Lee J, Oh S, Kim H, Lee J . Clinical profile of cutaneous adverse events of immune checkpoint inhibitors in a single tertiary center. J Dermatol. 2021; 48(7):979-988. DOI: 10.1111/1346-8138.15824. View

18.

Preti B, Pencz A, Cowger J, Vincent M, Breadner D . Skin Deep: A Fascinating Case Report of Immunotherapy-Triggered, Treatment-Refractory Autoimmune Lichen Planus and Keratoacanthoma. Case Rep Oncol. 2021; 14(2):1189-1193. PMC: 8460940. DOI: 10.1159/000518313. View

19.

BADELL A, Marcoval J, Gallego I, Moreno A, PEYRI J . Keratoacanthoma arising in hypertrophic lichen planus. Br J Dermatol. 2000; 142(2):380-2. DOI: 10.1046/j.1365-2133.2000.03319.x. View

20.

Giesecke L, Reid C, James C, Huilgol S . Giant keratoacanthoma arising in hypertrophic lichen planus. Australas J Dermatol. 2003; 44(4):267-9. DOI: 10.1046/j.1440-0960.2003.00006.x. View