ENTPD1 (CD39) Expression Inhibits UVR-Induced DNA Damage Repair through Purinergic Signaling and Is Associated with Metastasis in Human Cutaneous Squamous Cell Carcinoma.

UVR and immunosuppression are major risk factors for cutaneous squamous cell carcinoma (cSCC). Regulatory T cells promote cSCC carcinogenesis, and in other solid tumors, infiltrating regulatory T cells and CD8+ T cells express ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1) (also known as CD39), an ectoenzyme that catalyzes the rate-limiting step in converting extracellular adenosine triphosphate (ATP) to extracellular adenosine (ADO). We previously showed that extracellular purine nucleotides influence DNA damage repair. In this study, we investigate whether DNA damage repair is modulated through purinergic signaling in cSCC. We found increased ENTPD1 expression on T cells within cSCCs when compared with the expression on T cells from blood or nonlesional skin, and accordingly, concentrations of derivative extracellular adenosine diphosphate (ADP), adenosine monophosphate (AMP), and ADO are increased in tumors compared with those in normal skin. Importantly, ENTPD1 expression is significantly higher in human cSCCs that metastasize than in those that are nonmetastatic. We also identify in a mouse model that ENTPD1 expression is induced by UVR in an IL-27-dependent manner. Finally, increased extracellular ADO is shown to downregulate the expression of NAP1L2, a nucleosome assembly protein we show to be important for DNA damage repair secondary to UVR. Together, these data suggest a role for ENTPD1 expression on skin-resident T cells to regulate DNA damage repair through purinergic signaling to promote skin carcinogenesis and metastasis.

Infection rates of wound repairs during Mohs micrographic surgery using sterile versus nonsterile gloves: a prospective randomized pilot study.

BACKGROUND: Mohs micrographic surgery (MMS) is a multistep outpatient procedure that has become the treatment of choice for the removal of many cutaneous malignancies. The surgeon initially removes the tumor with nonsterile gloves in MMS. Sterile or nonsterile gloves are then used during the final repairs. OBJECTIVE: This prospective patient-blinded single-institution pilot study was performed to evaluate whether there is a difference in infection rate when using clean, nonsterile gloves versus sterile gloves during tumor removal and the wound repair phases of MMS. MATERIALS AND METHODS: This study randomized 60 patients undergoing MMS. Data on age, sex, anatomic location, number of Mohs stages, closure type, size of final defect, operative time, number of pairs of gloves used, and type of glove used were recorded and evaluated. RESULTS: Three infections were identified. Two infections occurred in the sterile glove arm and one in the clean glove arm. Overall, there was no greater infection rate when using clean, nonsterile gloves than sterile gloves (p=.99). CONCLUSIONS: Our study supports the use of clean, nonsterile gloves as a safe alternative to sterile gloves during all steps of MMS, at a significant cost savings. A larger confirmatory study comparing the equivalence in infection rates between clean and sterile gloves is warranted.

Perineural spread of squamous cell carcinoma involving the spinal accessory nerve in an immunocompromised organ transplant recipient.

BACKGROUND: Squamous cell carcinoma is the second most common cutaneous malignancy in humans, affecting approximately 200,000 people in the United States each year. In immunocompromised patients, squamous cell carcinoma is the most common skin cancer, and it also tends to behave more aggressively than in immunocompetent patients. OBJECTIVE: We describe an immunocompromised patient, previously treated for a squamous cell carcinoma of the left posterior shoulder, who subsequently developed a cord-like, intraneural metastasis of the spinal accessory nerve. RESULTS: The patient presented with a 3-month history of lancinating pain of the left neck and shoulder. He had been treated previously for a squamous cell carcinoma of the left posterior shoulder, which subsequently recurred twice. On examination, a cord-like mass was palpable along the path of the spinal accessory nerve. Given the aggressive nature of this patient's squamous cell carcinoma, surgical exploration was performed. Frozen-section analysis of the spinal accessory nerve and of the multiple supraclavicular nerves revealed perineural and intraneural squamous cell carcinoma. CONCLUSION: To our knowledge, this is the first reported case of a primary cutaneous squamous cell carcinoma of the trunk or extremity metastasizing to a cranial nerve.

Squamous cell carcinoma of the skin.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Identify the subtypes of squamous cell carcinoma of the skin. 2. Identify factors that affect recurrence and/or metastasis. 3. Develop a surgical management plan for treating high-risk squamous cell carcinoma of the skin. In treating squamous cell carcinoma of the skin, a key concept in proper management is understanding why certain tumors are more prone to both recurrence and metastasis. When developing a surgical management plan, an understanding of "high risk" is essential. This article concentrates on identifying those tumor subtypes and factors that may serve as predictors of high-risk status as well as on providing management suggestions.