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Training Level

Resident PGY4


Henry Ford Hospital


A case of metastatic squamous cell carcinoma in a patient with recessive dystrophic epidermolysis bullosa that was responsive to pembrolizumab, a programmed cell death protein 1 inhibitor.

Purpose: Cutaneous squamous cell carcinomas (SCCs) are the leading cause of death in patients with recessive dystrophic epidermolysis bullosa (RDEB). Management of SCCs in these patients is challenging with higher rates of recurrence and lymph nodes metastases. Although surgery is the first-line treatment in the majority of cases, certain clinical situations, such as local recurrence, or regional or distant metastasis, may call for nonsurgical treatment such as chemotherapy. We report the complex management of SCCs in a young female patient with RDEB whose nodal disease responded successfully to programmed cell death protein 1 (PD-1) inhibitor, pembrolizumab.

Design: Patient is a 29-year-old female with a long-standing history of RDEB that has been complicated by multifocal and recurrent SCC of the skin. She initially presented in 2015, at the age of 24, for SCC of the skin that was treated with a combination of Mohs micrographic surgery (MMS), wide local excision, and laser-assisted topical delivery of aminolevulinic acid. Over the following 6 months she developed several additional invasive SCCs. Surgical resection was again attempted, however, pathology revealed positive deep and lateral margins at 2 excision sites. Computed tomography (CT) scan at this time revealed bilateral pulmonary nodules and axillary nodes concerning for early metastatic disease. Left axillary node biopsy performed however, was negative for metastatic disease and these were thought to be consistent with a reactive process. Oncology recommended off-label palliative use of cetuximab given her multifocal disease and higher risk of metastasis in RDEB patients. She completed 4 cycles of cetuximab complicated by sepsis due to group G streptococcus, likely from a cutaneous source, as well as a grade 2 EGFR-associated acneiform eruption. After 4 cycles, her CT remained stable and there was no evidence of cutaneous recurrence, so the decision was made to discontinue cetuximab at this time. However, two years following the cessation of cetuximab she developed multiple cutaneous recurrences and a surveillance CT scan showed enlargement of her left axillary lymph nodes to a mass of 3.7 x 4.0 cm in size. Nodal biopsy revealed metastatic SCC and molecular testing performed showed that 100% of tumor cells (tumor proportion score) were positive for PD-L1 staining. The decision was made to start pembrolizumab as off label therapy with plans to pursue axillary node excision after she completed treatment. At the completion of 4 cycles of pembrolizumab, a repeat CT scan showed improvement in the enlarged nodes with reduction to 2.2 x 1.4 cm in size and regional lymph node resection was successfully performed.

Summary: Pembrolizumab was the first PD-1 inhibitor approved by the FDA for metastatic melanoma. Recently in clinical trials, a new PD-1 inhibitor cemiplimab showed a 50% response rate in the treatment of cutaneous SCC and became the first systemic drug in it’s class to be approved for the treatment of locally advanced or metastatic cutaneous SCC. We report the first case of metastatic SCC in a RDEB patient that responded to treatment with PD-1 inhibitor, pembrolizumab.

Conclusion: Immunotherapy with PD-1 inhibitors, such as pembrolizumab may be an alternative treatment modality for SCC in RDEB patients with late stage or metastatic disease. Further larger scale studies are warranted to determine the utility of PD-1 inhibitors in the multimodal management of these high-risk patients.

Presentation Date


Metastatic squamous cell carcinoma in a RDEB patient treated with pembrolizumab