Acta Dermato-Venereologica issue 50:1 98-1CompleteContent | Page 19

70 CLINICAL REPORT Epidemiology and Outcome of Squamous Cell Carcinoma in Epider­ molysis Bullosa in Australia and New Zealand* Minhee KIM 1,4 , Minmin LI 1,4 , Lizbeth R.A. INTONG-WHEELER 1 , Kim TRAN 2,4 , Damian MARUCCI 3,4 and Dedee F. MURRELL 1,4 Department of Dermatology, St. George Hospital, 2 Department of Anatomical Pathology, SEALS, 3 Department of Plastic Surgery, St George Hospital, and 4 University of New South Wales, Sydney, NSW, Australia 1 We investigate the epidemiology and outcomes of squamous cell carcinoma (SCC) in recessive dystrophic epidermolysis bullosa (RDEB) from the Australasian EB registry cohort. Seventeen out of 49 (34.6%) RDEB patients developed at least one SCC. Data detailing SCC was obtainable from 16/17 RDEB-SCC patients. A total number of 161 primary SCCs occurred in 16 RDEB-SCC patients with a mean of 10 SCCs per person. The ear- liest age of first SCC development was 16 years. Eleven out of 16 RDEB-SCC patients eventually developed me- tastatic SCCs. The majority of the tumours were well and moderately differentiated. The cumulative risk of SCC development by age 35 was 76.1% for RDEB-Ge- neralized Severe (RDEB-GS) and 10% for RDEB-Gene- ralized Intermediate (RDEB-GI). Amongst those who developed SCCs, their median time to death after first SCC was 5 years for RDEB-GI and 4 years for RDEB- GS. This is the first retrospective study of RDEB-SCC in Australasia. Key words: recessive dystrophic epidermolysis bullosa; squa- mous cell carcinoma; epidemiology; prognosis. Accepted Aug 29, 2017; Epub ahead of print Aug 30, 2017 Acta Derm Venereol 2018; 98: 70–76. Corr: Prof. Dedee F. Murrell, MA, BM, FAAD, MD, FACD FRCP (Edin), Head, Department of Dermatology, St George Hospital, Gray St, Kogarah, Syd- ney, NSW 2217, Australia. E-mail: [email protected] E pidermolysis bullosa (EB), first described in 1886 (1), is a group of rare heterogeneous genodermatoses defined by mechanical fragility, blistering of mucocuta- neous membranes, and compromised wound healing (2, 3). The prevalence of EB in Australia according to the Australasian EB registry (AEBR) is approximately 10.3 per million (4). Depending on the skin cleavage plain, EB is classified into 4 major types, i.e. EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler syndrome. DEB is broadly divided into dominant DEB (DDEB) and recessive DEB (RDEB) (2). Genetic mu- tations of the COL7A1 gene in DEB result in reduced or absent expression of type VII collagen, which is the main anchoring fibril that attaches the basement membrane of the epidermis to the dermis. RDEB can be further sub- divided into generalized severe (RDEB-GS), generalized intermediate (RDEB-GI). Rare variants of RDEB include * The study’s findings were presented at the Skin Research conference in Singapore, April 2016 and the Society for Investigative Dermatology (SID) Annual Meeting in Scottsdale, USA, May 2016. doi: 10.2340/00015555-2781 Acta Derm Venereol 2018; 98: 70–76 RDEB inversa (RDEB-I), RDEB localized (RDEB-loc), RDEB pretibial (RDEB-pt), RDEB pruriginosa (RDEB- pr), RDEB centripetalis (RDEB-ce) and RDEB bullous dermolysis of the newborn (RDEB-BDN) (2). Squamous cell carcinoma (SCC) is the most dreaded complication of EB. Detailed knowledge of its under- lying pathogenesis is still unknown (5). Traditionally, the repetitive cycle of tissue damage and repair was thought to cause deterioration of cellular differentiation and buildup of carcinogenic mutations (6, 7). Some have proposed reduced activity of natural killer cells, up- regulation of basic fibroblast growth factor, and p53 gene mutations as potential contributors to the pathogenesis (8–10). The latest research showed that RDEB fibroblas t gene expression is distinct from that of a non-RDEB fibroblasts, potentiating SCC adhesion, invasion, and growth (11). The role of collagen VII in EB tumorigene- sis was also explored. In a mouse-model study of RDEB, no tumours were detected in mice without collagen VII expression whereas those expressing the amino-terminal non-collagenous NC1 domain of collagen VII were tumorigenic (12). The study demonstrated that collagen VII is a pre-requisite for epidermal tumourigenesis and NC1 domain of collagen VII promoted tumour cell inva- sion. However, another similar study by Pourreyron and colleagues (13) found that two out of 11 RDEB patients developed SCC without detectable levels of collagen VII collagen. The study concluded that individuals with RDEB can develop SCC regardless of type VII collagen expression. Recent studies have suggested that wound colonization with flagellated bacteria is a promotor for SCC in RDEB (14). Unlike the pathogenesis, the epidemiology of EB is better understood with multiple case reports and case series on SCC development in EB (15–21). However, the data is limited to certain regions or states, rather than capturing all the cases within nations. The largest epidemiological study on the prevalence of SCC in EB is from the National EB Registry (NEBR) of the United States, amassing 3,280 patients with different EB sub- types (22). This study enhanced our understanding of SCC characteristics in EB including the common SCC occurrence sites, risk of SCC development, cumulative risk of death from metastatic disease, and therapeutic interventions for SCCs. A recent systematic review gathering 117 EB-SCC cases highlighted that the most frequently published cases of SCC were from RDEB This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2018 Acta Dermato-Venereologica.