Dermatologic toxicity from novel therapy using antimicrobial peptide LL-37 in melanoma: A detailed examination of the clinicopathologic features

Autor:	Michael T. Tetzlaff, Jonathan L. Curry, Phyu P. Aung, Rodabe N. Amaria, Doina Ivan, Priyadharsini Nagarajan, Tsetan Dolkar, Carlos A. Torres-Cabala, Victor G. Prieto, Celestine M Trinidad, Kelly C. Nelson
Rok vydání:	2018
Předmět:	Seborrheic keratosis Pathology medicine.medical_specialty Skin Neoplasms Histology Dacarbazine Dermatology Pathology and Forensic Medicine Lesion 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine Cathelicidins medicine Atypia Humans Melanoma business.industry Combination chemotherapy Middle Aged medicine.disease 030220 oncology & carcinogenesis Female Drug Eruptions Nivolumab medicine.symptom business Antimicrobial Cationic Peptides Spongiosis medicine.drug
Zdroj:	Journal of Cutaneous Pathology. 45:539-544
ISSN:	0303-6987
DOI:	10.1111/cup.13262
Popis:	LL-37 is a naturally occurring 37-amino-acid peptide that is part of the innate immune system in human skin. Preclinical studies have showed that intra-tumoral injections of LL-37 stimulate the innate immune system by activation of plasmacytoid dendritic cells, which mediate tumor destruction. LL-37 intra-tumoral injections have been utilized in a phase 1 clinical trial for melanoma patients with cutaneous metastases. We report dermatologic toxicity in a 63-year-old woman with stage IIIC melanoma of the right calf and inguinal lymph nodes. She was previously treated with nivolumab and combination chemotherapy (cisplatin, vinblastine and dacarbazine) and subsequently treated with LL-37 injections upon progression of both prior regimens. She received a total of 8 weekly LL-37 injections, with interval clinical shrinkage of injected lesions. However, approximately 45 days after initiation of this therapy, she presented with multiple verrucous papules and a vesiculo-bullous lesion on the trunk and extremities. Clinically, most of these lesions were thought to be either squamous cell carcinoma or inflamed seborrheic keratosis. Histologically, 11 of the total 12 skin biopsies showed similar histopathologic features, with a prominent lichenoid inflammatory infiltrate admixed with eosinophils and an overlying atypical squamous epithelial proliferation with verrucous and keratoacanthoma-like features and varying degrees of keratinocytic atypia. Interestingly, a majority of the lesions did not show spongiosis (11/12). All lesions resolved within 2 months of cessation of LL-37 injection therapy. This case highlights adverse dermatological manifestations of LL-37 therapy, similar to the consequences of other novel therapies.
Databáze:	OpenAIRE
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