Drug Screening of Cutaneous Lesions of Squamous Cell Carcinoma

Inclusion Criteria: * Participants must have clinical diagnosis of cutaneous squamous cell carcinoma or metastatic squamous cell carcinoma with cutaneous involvement supported by histological evaluation of skin lesions based upon available clinical data including pathology reports from non-study institution (if applicable) * Participants must have visible cutaneous disease. Skin lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. * A single lesion is amenable to placement of one or multiple devices in terms of lesion size and location, as assessed by dermatologist (minimum lesion diameter of 1.0 cm). * Washout period from previous treatments is not necessary. * Age minimum of age 18. Because of limited incidence of cutaneous squamous cell carcinoma in the pediatric population, children are excluded from this study. * ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A). * Participants will undergo laboratory testing within 28 days prior to the procedure. Participants must have marrow function as defined below: absolute neutrophil count ≥500/mcL platelets ≥50,000/mcL * Human immunodeficiency virus (HIV)-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. * For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. * Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. * Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the efficacy assessment of the systemic regimen are eligible for this trial in the systemic treatment cohort (expansion cohort). * Participants must be evaluated by a dermatologist or medical oncologist who will determine the clinically appropriate treatment strategy based on clinical history and extent of disease. Systemic therapy will be mandatory for expansion/systemic treatment cohort. Systemic therapy may be initiated anytime within 4 weeks of MD removal. * Patients must be deemed medically stable to undergo percutaneous procedures by their treating cutaneous oncologist. * Ability to understand and the willingness to sign a written informed consent document. * Patients must be willing to undergo research-related genetic and transcriptomic sequencing (somatic and germline) and data management, including the deposition of de-identified genetic sequencing data in NIH central data repositories. * Patient is considered to have capacity to properly follow instructions at home for the care of device(s) (see Appendix B). Exclusion Criteria: * Positive serum pregnancy test at screening visit. Pregnant women are excluded from this study because the agents used for microdosing have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is enrolled in this study. * Uncorrectable bleeding or coagulation disorder known to cause increased risk with surgical or biopsy procedures. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in this study. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Patients who will receive standard of care systemic therapy in expansion cohort are not allowed to start any new skin directed therapy (e.g. topical 5-fluorouracil, imiquimod, etc.) concurrent with first systemic therapy initiated after device implantation and retrieval. Should a patient clinically progress on first systemic therapy and require a change in treatment, skin directed therapies may be introduced if desired.