Epidermolysis bullosa complicated by squamous cell carcinoma: report of 10 cases

Abstract

Epidermolysis bullosa (EB) refers to a group of hereditary mechano-bullous conditions, many of which are associated with chronic scarring. Several forms of the disease have been reported in association with cutaneous malignancy. We present a series of 10 EB patients (eight generalised recessive dystrophic EB, one dominant dystrophic EB, one non-lethal junctional EB) aged 24-55 years with a total of 29 squamous cell carcinomas (SCC). Three patients died from metastatic disease associated with invasive, poorly differentiated SCC. Six cases had multiple primary SCC, including three patients with simultaneous multifocal disease. Twenty-eight of the 29 SCC arose on the limbs. Histology revealed that most of the SCC were well or moderately differentiated (22/29). Unusual histological findings included two verrucous SCC, as well as a spindle cell (angiosarcoma-like) SCC. Most of the SCC developed in areas of chronic non-healing ulceration (10/29) or longstanding hyperkeratotic crusting (14/29). The dermis around or beneath the carcinomas was densely scarred, more so than in non-malignant areas. In some cases it was difficult to distinguish the clinical appearances of certain areas of chronic ulceration, scarring, and crusting typical of dystrophic EB from many of the SCC. This study underlines the need for constant vigilance for the development of carcinomas in this group of patients, the occasional diagnostic difficulty, and the potential for metastasis.

Generation of keratinocytes from normal and recessive dystrophic epidermolysis bullosa-induced pluripotent stem cells

“…Occasionally, the blisters and erosions become infected, resulting in sepsis and multiple organ failure. The development of multiple aggressive metastatic squamous cell carcinomas is considered the most common cause of death in patients with RDEB (9).…”

Serpin Peptidase Inhibitor Clade A Member 1 (SerpinA1) Is a Novel Biomarker for Progression of Cutaneous Squamous Cell Carcinoma

“…[1][2][3] An example of the latter is individuals with recessive dystrophic epidermolysis bullosa (RDEB), who often develop rapidly progressing cutaneous SCCs at sites of chronic ulceration and scarring. 5,6 At present, no specific molecular markers for progression of cutaneous SCC are available. Such biomarkers would be valuable in clinical practice for early detection of individual cutaneous SCCs with a high risk of progression and metastasis.…”

Genetic Predisposition to Cutaneous Squamous Cell Carcinoma

“…In addition, blistering can extend to the oral cavity, gastro-intestinal tract and eyes in RDEB patients, leading to soft tissue scarring, microstomia, ankyloglossia and dental caries (Fine et al, 2008;Fine and Mellerio, 2009). Importantly and unlike RDEB, no evidence for an increased incidence of cSCC was reported in a large study of 442 DDEB patients although case reports do exist in the literature (Song and Dicksheet, 1985;McGrath et al, 1992b;Christiano et al, 1999). RDEB is further sub-divided on the basis of clinical features into: RDEB severe generalized, RDEB generalized other and RDEB inversa (Fine, 1999;.…”

“…Such clinical, genetic and immunohistological data could shed further light on the relationships between the loss of type VII collagen, formation of anchoring fibrils, severity of blistering and the risk of developing cSCC. Perplexingly, although most cSCCs in RDEB patients are histo-pathologically moderately differentiated (McGrath et al, 1992b), these cSCCs are biologically aggressive and have the propensity to recur or metastasize to distant sites, eventually causing the death of the patient. In fact, most RDEB patients will develop multiple cSCCs (median number per RDEB patient = 3-3.5) and die from metastatic disease despite surgical excision .…”