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Betapapillomavirus in multiple non‐melanoma skin cancers of Netherton syndrome: Case report and published work review
Author(s) -
Guerra Liliana,
Fortugno Paola,
Sinistro Anna,
Proto Vittoria,
Zambruno Giovanna,
Didona Biagio,
Castiglia Daniele
Publication year - 2015
Publication title -
the journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.9
H-Index - 65
eISSN - 1346-8138
pISSN - 0385-2407
DOI - 10.1111/1346-8138.12913
Subject(s) - filaggrin , medicine , pathology , hpv infection , cancer , basal cell carcinoma , skin cancer , dermatology , cancer research , cervical cancer , atopic dermatitis , basal cell
Abstract Netherton syndrome ( NS ) is a rare genetic disease presenting with ichthyosiform erythroderma, hair alterations and atopy. NS is due to SPINK 5 gene mutations, which cause absent or decreased expression of the encoded protein lymphoepithelial Kazal‐type‐related inhibitor ( LEKTI ) in all stratified epithelia. We report a 43‐year‐old man affected with NS , who developed several squamous and basal cell carcinomas on the face, ears and scalp and papillomatous lesions of hips, groin and genitoanal area. Molecular analysis of the SPINK 5 gene revealed homozygosity for the recurrent mutation c.238dupG. Human papillomavirus ( HPV ) DNA detection and genotyping on patient skin carcinomas and hyperplastic lesions found betapapillomavirus DNA in 10 of 12 (83%) carcinomas and in a hip papilloma, with multiple betapapillomavirus types being identified. Immunohistochemistry showed upregulated expression of p16 INK4a protein in nine of 12 (75%) patient carcinomas, in line with findings reported in HPV ‐related cancers. LEKTI and filaggrin immunostaining was strongly decreased in patient skin. A published work search for NS cases with skin cancers and HPV infection identified 15 NS patients, five of them showing mucosal or cutaneous HPV infection. Overall, our results confirm the increased susceptibility to skin carcinomas of some NS patients and provide further evidence of an association between HPV and non‐melanoma skin cancers in NS . The highly impaired skin barrier function, hallmark of NS , could facilitate HPV infection, in turn increasing the risk for cancer development.