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

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 biospy 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.https://scholarlycommons.henryford.com/merf2020caserpt/1131/thumbnail.jp

35224 Identifying a correlation between preceding trauma and development of dermatofibrosarcoma protuberans: A review of the literature

Background: Dermatofibrosarcoma protuberans (DFSP) is a malignant fibrohistiocytic neoplasm that is slow-growing, has low metastatic potential, and is locally infiltrative with a predisposition for recurrence. The development of DFSP can occur spontaneously, but anecdotal evidence suggests a correlation between preceding injury and tumor onset. Methods: A comprehensive literature search was performed using PubMed, Embase, and web of science for articles with unambiguous reporting of DFSP with a history of physical trauma. Of 139 identified articles, 23 (17%) met criteria and were analyzed. Results: In total, 52 patients were reported as having had some form of physical trauma prior to DFSP development, and of these, sex was reported for half (40% men; 60% women). The mean (standard deviation) age at time of diagnosis was 42 (14) years, and lesions ranged from 1 to 20 cm. Involved locations included the trunk (62%), lower extremities (19%), upper extremities (12%), and head/neck (8%). The median (range) time between injury and self-reported lesion was 10 (1-19) years, while the median (range) time between injury and DFSP diagnosis was 10 (2-41) years. Types of injuries reported included tattoos (most common), vaccinations/injections, burns, surgeries, radiation, insect bites, and various levels of minor to blunt force. Discussion: A subset of DFSP cases arise in the setting of prior cutaneous trauma, which may play a role in their pathogenesis. Recognition of this possibility is important to avoid misdiagnosis (i.e., hypertrophic scar or keloid) or delay in diagnosis

Metastatic squamous cell carcinoma in a RDEB patient treated with pembrolizumab

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.https://scholarlycommons.henryford.com/merf2020caserpt/1006/thumbnail.jp

ETS-related Gene (ERG) is Differentially Expressed in Dermatofibroma (Fibrous Histiocytoma) as Compared With Dermatofibrosarcoma Protuberans and Hypertrophic Scars: A Pilot Immunohistochemical Study

Immunohistochemical staining can be of great utility in differentiating various cutaneous spindle cell neoplasms, particularly when the histomorphologic appearance of the lesions is inconclusive. Nuclear staining for ETS-related gene (ERG), a highly sensitive endothelial cell marker, has seldom been studied in the context of cutaneous spindle cell neoplasms. Little is known about its specificity for vascular differentiation. In this pilot study, immunohistochemical analysis for ERG was performed on 15 dermatofibromas (DF), 10 keloids, and 9 dermatofibrosarcoma protuberans (DFSP) tumors. Consistent nuclear expression of ERG was found in DF [100% (15/15) of the lesions demonstrated \u3e50% labeling of tumor cells with moderate to strong intensity]. However, ERG expression was largely absent in DFSP [89% (8/9) of the lesions demonstrating \u3c50% labeling staining, generally of mild intensity] and hypertrophic scars-keloids [80% (8/10) without expression]. On the basis of the results of this pilot study, immunohistochemical staining for ERG may prove useful in helping to differentiate DF from DFSP and hypertrophic scars in the context of partial biopsy sampling. If replicated in a larger number of samples, this finding could mitigate the use of costly sequencing panels and potentially avoid unnecessary reexcisions in certain contexts

Research Techniques Made Simple: Use of Imaging Mass Cytometry for Dermatological Research and Clinical Applications

Traditional immunohistochemistry (IHC) is inherently limited by its ability to analyze only several markers within a histological tissue section at a given time, which hinders in-depth characterization and phenotyping of tissues. Imaging mass cytometry (IMC), which combines IHC using metal-labeled antibodies with laser ablation and detection using mass cytometry by time-of-flight, overcomes this limitation with the capability to simultaneously analyze up to 40 protein markers to generate high-dimensional images from a single tissue section. IMC analysis preserves tissue architecture and spatial cellular relationships that would otherwise be lost or significantly altered in applications requiring tissue dissociation, such as flow cytometry or single-cell RNA sequencing. Resulting high-dimensional histological images permit spatially conserved analysis to identify unique cell populations, cellular interactions and avoidances, and insight into activation and behavioral status based on tissue location. IMC can be performed on both frozen and formalin-fixed paraffin-embedded tissue, allowing for previously banked samples to be analyzed and correlated with known clinical outcomes. Expectedly, IMC will change the landscape of investigative pathology, particularly when used in coordination with multiomic platforms to combine transcriptomic and proteomic data at a single-cell resolution. Here, we aim to highlight the potential utility of IMC within dermatologic research and clinical applications

31064 The Detroit Keloid Scale: A validated tool for rating keloids

Background: No keloid-specific outcome measures exist. Objective: To develop and validate the Detroit Keloid Scale (DKS), a standardized method of keloid assessment to better compare treatments. Methods: Forty-seven physicians were polled to develop the DKS. The scale was validated in 52 patients with keloids against the Vancouver Scar Scale (VSS), Patient and Observer Scar Assessment Scale (POSAS), and Dermatology Life Quality Index (DLQI) by 3 physicians. Results: The interrater reliability was “substantial” for observer component of the DKS and only “moderate” for the VSS and observer POSAS (ICC were 0.80, 0.60, and 0.47, respectively). Pearson’s correlation indicated a “moderate” association between the observer component of DKS with observer component of POSAS (ρ = 0.56, P \u3c.001) and a “substantial” relationship between the observer component of DKS and VSS (ρ = 0.63, P \u3c.001). Pearson’s correlation indicated a “moderate” association between the patient portion of DKS and patient portion of POSAS and the patient portion of the DKS and DLQI (0.61 and 0.60, respectively, P \u3c.05). The DKS total score consistently showed “substantial” relationship with POSAS total score (ρ = 0.65, P \u3c.001). Limitations: Single center study, no intrarater reliability analysis. Conclusions: The substantial interrater reliability of the DKS will allow for improved standardization in future keloid research