Familial seborrhoeic keratosis associated with multiple ‘pure reticulated acanthomas’ and infundibulocystic basal cell carcinomas

• Published in: British journal of dermatology (1951) Vol. 177; no. 6; pp. 1654 - 1663
• Main Authors: Agustí Martínez, J., Bella‐Navarro, R., García‐García, A.B., Bueno, E., González‐Sarmiento, R., Navarro, L., Sanchez‐Sendra, B., Revert, A., Jordá, E., Monteagudo, C.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.12.2017
• Subjects: Acanthoma - genetics; Acanthoma - pathology; Aged; Basal cell carcinoma; Biopsy; Carcinoma; Carcinoma, Basal Cell - genetics; Carcinoma, Basal Cell - pathology; Dermoscopy; Female; Fibroblast growth factor receptors; Germ-Line Mutation - genetics; Humans; Keratosis; Keratosis, Seborrheic - genetics; Keratosis, Seborrheic - pathology; Male; Middle Aged; Mutation; Patched-1 Receptor - genetics; Pedigree; Polymorphism, Genetic - genetics; Receptor, Fibroblast Growth Factor, Type 3 - genetics; Skin; Skin cancer; Skin Neoplasms - genetics; Skin Neoplasms - pathology; Tumors
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/bjd.15736

Summary Background A variety of genodermatoses with multiple cutaneous tumours and germline genetic alterations, such as PTCH1 mutations, have been described. Other cutaneous syndromes have been associated with somatic gene mutations, such as FGFR3 in familial seborrhoeic keratosis. Objectives To describe the clinical, dermoscopic and histopathological features of multiple cutaneous lesions, mostly infundibulocystic basal cell carcinomas (ICBCCs) and pure reticulated acanthomas, present in a family affected by familial seborrhoeic keratosis. In addition, we tested for possible germline alterations in FGFR3 and PTCH1. Methods Ten members of one family were clinically examined and 92 skin biopsy specimens were evaluated. Blood samples from six individuals were analysed for FGFR3 and PTCH1 germline alterations. We reviewed the literature concerning genetic FGFR3 alterations in seborrhoeic keratosis. Results Individuals of all generations affected by familial seborrhoeic keratosis also presented other skin tumours that corresponded histologically to reticulated acanthomas without apocrine or sebaceous differentiation, as well as ICBCCs. In addition, two novel germline variants, p.Pro449Ser (c.1345C>T) in FGFR3 and p.Pro725Ser (c.2173C>T) in exon 14 of PTCH1 were identified in five participants. Conclusions We characterize for the first time the clinical, dermoscopic and histopathological features of multiple reticulated acanthomas without apocrine or sebaceous differentiation, for which we propose the term ‘pure reticulated acanthoma’, and ICBCCs associated with familial seborrhoeic keratosis. We identified FGFR3 and PTCH1 germline polymorphisms whose influence in the development of reticulated acanthomas is unknown. What's already known about this topic? Rare cases of familial seborrhoeic keratosis have been reported in the literature, including presentation of high numbers of seborrhoeic keratosis at a young age, supporting a hereditary background. Somatic activating mutations of FGFR3 have been identified in human seborrhoeic keratosis. To date, no germline FGFR3 alterations have been found related to familial seborrhoeic keratosis in patients without skeletal dysplasias. What does this study add? This is the first report of multiple reticulated acanthomas without apocrine or sebaceous differentiation, for which we propose the term ‘pure reticulated acanthomas’ in a family with familial seborrhoeic keratosis. Germline FGFR3 or PTCH1 variants were identified in five members of the same family. What is the translational message? Recognizing multiple pure reticulated acanthomas would avoid an unnecessary excisional approach. FGFR3 and PTCH1 germline polymorphisms may potentially be involved in an undetermined, complex pathway influencing the development of multiple pure reticulated acanthomas, seborrhoeic keratoses and infundibulocystic basal cell carcinomas. Plain language summary available online