# Cutaneous Squamous Cell Carcinoma in Epidermolysis Bullosa: A Review of Pathogenesis, Diagnosis and Management

## TL;DR

This review discusses how epidermolysis bullosa increases the risk of aggressive skin cancer and explores diagnosis and treatment strategies to improve patient outcomes.

## Contribution

The paper provides a comprehensive review of the pathogenesis, diagnosis, and management of cSCC in EB patients, emphasizing the need for early detection and improved therapies.

## Key findings

- EB, particularly RDEB, significantly increases the risk of aggressive and metastatic cSCC.
- Current treatments for EB-associated cSCC include surgical excision, immunotherapy, and anti-EGFR therapy.
- Early screening and education are critical for improving survival and quality of life in EB patients.

## Abstract

Epidermolysis bullosa (EB) and its subtypes represent debilitating, genetic skin conditions characterized by fragility, blistering, and wounds. Its pathology causes patients to be at an increased susceptibility for developing cutaneous squamous cell carcinoma (cSCC). cSCC in EB has proven to dramatically decrease the life expectancy of such patients since they are often undiagnosed and more susceptible to metastasis. This review aims to discuss the various subtypes of EB through their pathogenesis and clinical presentation, as well as that of cSCC in normal skin and in EB. We also discuss current methods of diagnosis and treatment, including surgical excision, immunotherapy, and anti-epidermal growth factor receptor (anti-EGFR) therapy. The review concludes with a discussion on future directions and additional research needed to decrease mortality in EB-associated cSCC.

Epidermolysis bullosa (EB) is a group of debilitating, genetic skin disorders characterized by excessive skin fragility, blistering, and ulcerations that cause a cyclical wound healing process. EB presents itself in various subtypes, such as EB simplex (EBS), junctional EB (JEB), dystrophic (DEB), and Kindler Syndrome (KS), which all differ in their genetic cause, severity, and harbor different causes of mortality. Of these variants, JEB and DEB are the most severe, with EBS being the mildest form of the disease and KS presenting in extremely rare cases. The JEB variant tends to cause mortality early on in children less than two years of age due to failure to thrive, sepsis from wound infections, and airway obstruction. In the recessive form of DEB (RDEB), cutaneous squamous cell carcinoma (cSCC) is the major cause of death in patients, with one study reporting a mere 4-year survival after the first EB-cSCC diagnosis. Cutaneous SCCs in the setting of RDEB are particularly concerning because they are often more aggressive and show greater metastatic potential, as compared to ultraviolet-induced SCCs. This review aims to explore the pathophysiology of these EB variants as well as their implications for developing cSCCs. It will also discuss elements of the clinical presentation of such lesions in EB patients and the challenges associated with making a definitive diagnosis. Additionally, we will illuminate various diagnostic techniques, current and future management and treatment strategies for both cSCC and EB, and the importance of early screening and education for patients with EB to maximize patient lifespan and quality of life.