Importance Limited therapies are available in patients with inoperable locally advanced cutaneous squamous cell carcinoma (cSCC). Objective To determine the efficacy of programmed cell death 1 receptor (PD-1) inhibitors in locally advanced cSCC. Design, Setting, and Participants A single patient with locally advanced cSCC who declined surgery and radiotherapy underwent treatment with pembrolizumab, an anti–PD-1 antibody, at an academic dermatologic surgery section and cancer center. The patient was followed up for clinical and radiologic regression of cSCC. With the use of NanoString to amplify potential biomarkers, immunohistochemistry, and immunofluorescence, the ex vivo expression of PD-1 and a ligand (PD-L2) was assessed in 38 cSCC biopsy specimens from 24 patients with cSCC. Expression of PD-L1 and PD-L2 in the cSCC microenvironment was defined. Intervention Pembrolizumab, 2 mg/kg every 3 weeks, for 4 cycles. Main Outcomes and Measures Expression of PD-L1 and PD-L2 in the cSCC microenvironment. Results In 1 patient with locally advanced cSCC who was treated with pembrolizumab, nearly complete tumor regression was observed after 4 cycles of therapy. The NanoString technology used in 38 cSCC biopsy specimens from 24 patients with cSCC (19 men and 5 women; mean [SD] age, 76.4 [12.2] years) detected increased PD-1 and PD-L2 expression in high-risk cSCC. Immunohistochemical analysis confirmed enhanced expression of PD-1 and its ligands in cSCC with perineural invasion (mean [SEM] expression, 5.06 [1.27];P = .05), superficial cSCC (mean [SEM] expression, 3.58 [1.50];P = .15), organ transplant–associated cSCC (mean [SEM] expression, 3.01 [0.54];P = .005), and infiltrative cSCC (mean [SD] expression, 2.01 [0.30];P = .006) compared with normal skin specimens. In double-label immunofluorescence staining, CD11c⁺, a marker of myeloid dendritic cells, colocalized with PD-L1 and PD-L2 in cSCC lesions. Conclusions and Relevance The favorable treatment response combined with significant involvement of PD-1 and PD ligands in cSCC lesions suggests that PD-1 blockade may be a viable therapeutic option for locally advanced cSCC and provides rationale for further investigation in future clinical trials.

Oral allergy syndrome (OAS) or pollen-food allergy syndrome (PFS) is a hypersensitivity reaction to plant-based foods, manifesting most commonly with pruritus of the lips, tongue, and mouth. Unlike simple food allergy, OAS requires prior sensitization to a cross-reacting inhalant allergen rather than direct sensitization to a specific food protein. In this review, we summarize the clinical features and pathophysiology of OAS and provide an overview of known pollen-food associations.

Cutaneous squamous cell carcinoma (cSCC) is the second most common malignant neoplasm in the US, with an estimated annual incidence of 1.1 million to 1.8 million per year.^1-4 Although cSCC usually carries an excellent prognosis, a subset of patients develops poor outcomes, including local recurrence (LR), nodal metastasis (NM), distant metastasis (DM), and disease-specific death (DSD). We performed a systematic review and meta-analysis of all electronically available studies of cSCC and reviewed the associations of risk factors and treatments with poor outcomes to identify those with higher risk.

Over 5 million cases of nonmelanoma skin cancer (NMSC) are diagnosed annually in the United States, with a 35% increase in incidence between 2006 and 2012.¹ The growing cost of NMSC to the health care system compels the refinement of current diagnostic and treatment techniques. Confocal microscopy, introduced to clinical dermatology in 1991, has the potential to provide more rapid bedside pathologic analysis by producing images with subcellular resolution without physical sectioning.^2-4 However, the clinical implementation of confocal microscopy is impeded in part by differences between traditional grayscale confocal images and histopathologic slides requiring physician retraining for accurate interpretation.^3,5-8

Perineural invasion in cutaneous squamous cell carcinoma (cSCC) is associated with an increased risk of local recurrence, nodal metastases, and disease-specific death. Adjuvant radiotherapy has been suggested to mitigate aggressive behavior of cSCC with perineural invasion.^1-3 To clarify the utility of adjuvant radiotherapy for cSCC with perineural invasion, we investigated the outcomes of local recurrence, nodal metastases, distant metastases, and disease-free survival of patients treated surgically with or without adjuvant radiotherapy.