Case series have demonstrated that potentially lethal cutaneous squamous cell carcinomas
arise in patients with recessive dystrophic epidermolysis bullosa (RDEB), although
the magnitude of this risk is undefined.
Systematic case finding and data collection were performed throughout the continental
United States (1986-2002) by the National EB Registry on 3280 EB patients to determine
cumulative and conditional risks for squamous cell carcinoma (SCC), basal cell carcinoma
(BCC), and malignant melanoma (MM) within each major EB subtype, as well as the cumulative
risk of death from each tumor. Study design was cross-sectional, with a nested randomly
sampled longitudinal subcohort (N = 450).
SCCs arose primarily in RDEB, especially the Hallopeau-Siemens subtype (RDEB-HS),
first beginning in adolescence. Less frequently, SCCs occurred in junctional EB (JEB).
Cumulative risks rose steeply in RDEB-HS, from 7.5% by age 20 to 67.8%, 80.2%, and
90.1% by ages 35, 45, and 55, respectively. In Herlitz JEB, the risk was 18.2% by
age 25. SCC deaths occurred only in RDEB, with cumulative risks in RDEB-HS of 38.7%,
70.0%, and 78.7% by ages 35, 45, and 55, respectively. MM arose in RDEB-HS, with a
cumulative risk of 2.5% by age 12. BCCs arose almost exclusively in the most severe
EB simplex subtype (Dowling-Meara) (cumulative risk = 43.6% by age 55).
Mutational analyses were performed on only a minority of enrollees in the National
EB Registry, preventing evaluation of the possible influence of specific genotypes
on the risk of developing or dying from cutaneous SCCs.
SCC is the most serious complication of EB within adults, especially those with RDEB-HS.
By mid-adulthood, nearly all will have had at least one SCC, and nearly 80% will have
died of metastatic SCC despite aggressive surgical resection. When compared with SCCs
arising within the normal population, the remarkably high risk of occurrence of and
then death from SCCs among RDEB patients suggests likely differences in pathogenesis.
Additional studies of EB-derived tumors and SCC cell lines may not only provide new
insights into the mechanisms of carcinogenesis but also means whereby these particular
tumors may be prevented or more effectively treated.