Institutional Adherence to Current Mohs Surgery Appropriate Use Criteria With Reasons for Nonadherence and Recommendations for Future Versions.

BACKGROUND: The appropriate use criteria (AUC) were established to optimize the use of Mohs micrographic surgery (MMS) and confer the highest possible clinical benefit to the patient. OBJECTIVE: We documented our adherence to AUC and review reasons for nonadherence regarding lesions classified as inappropriate, in the hopes of informing future versions of the AUC. MATERIALS AND METHODS: A retrospective review of 1,000 consecutive patients who underwent MMS at a single institution. A total of 1,318 biopsy-proven nonmelanoma skin cancers were treated with MMS, and each skin cancer that underwent MMS was classified as appropriate, uncertain, or inappropriate based on the AUC. RESULTS: Data were collected on 1,318 lesions with 1,237 (93.9%) categorized as appropriate, 59 (4.5%) uncertain, and 22 (1.7%) not appropriate. The primary variables that determined appropriateness were type of cancer (p = .001), size (p < .001), and area of body (p < .001). CONCLUSION: Institutional adherence to AUC was high, with 93.9% of treated tumors classified as appropriate, 4.5% as uncertain and 1.7% as inappropriate. By far the most commonly reported reason for performing MMS on an inappropriate lesion in our review was the treatment of adjacent lesions in 1 session.

Assessing SPP1/Osteopontin (OPN) Splice Variants and Their Association to Nonmelanoma Skin Cancer by Absolute Quantification: Identification of OPN-5 Subvariants and Their Protein Coding Potential.

The study evaluated whether SPP1/osteopontin (OPN) splice variants are differentially expressed in nonmelanoma skin cancer compared to normal skin. The absolute number of mRNA molecules of OPN-a predominated in normal skin and nonmelanoma skin cancer compared to OPN-b, OPN-c, and OPN-5. However, mRNAs of OPN-a, OPN-b, and OPN-c were expressed in higher levels in cutaneous squamous cell carcinomas (cSCCs) and basal cell carcinomas relative to normal skin. Additionally, OPN-5 expression was higher than OPN-b and OPN-c, and OPN-c, in normal skin and nonmelanoma skin cancer, respectively. Furthermore, we identified four OPN-5 splice variants, which were cloned and analyzed for protein expression.

Sebaceous carcinoma: evidence-based clinical practice guidelines.

Sebaceous carcinoma usually occurs in adults older than 60 years, on the eyelid, head and neck, and trunk. In this Review, we present clinical care recommendations for sebaceous carcinoma, which were developed as a result of an expert panel evaluation of the findings of a systematic review. Key conclusions were drawn and recommendations made for diagnosis, first-line treatment, radiotherapy, and post-treatment care. For diagnosis, we concluded that deep biopsy is often required; furthermore, differential diagnoses that mimic the condition can be excluded with special histological stains. For treatment, the recommended first-line therapy is surgical removal, followed by margin assessment of the peripheral and deep tissue edges; conjunctival mapping biopsies can facilitate surgical planning. Radiotherapy can be considered for cases with nerve or lymph node involvement, and as the primary treatment in patients who are ineligible for surgery. Post-treatment clinical examination should occur every 6 months for at least 3 years. No specific systemic therapies for advanced disease can be recommended, but targeted therapies and immunotherapies are being developed.

Initial skin cancer screening for solid organ transplant recipients in the United States: Delphi method development of expert consensus guidelines.

Skin cancer is the most common malignancy affecting solid organ transplant recipients (SOTR), and SOTR experience increased skin cancer-associated morbidity and mortality. There are no formal multidisciplinary guidelines for skin cancer screening after transplant, and current practices are widely variable. We conducted three rounds of Delphi method surveys with a panel of 84 U.S. dermatologists and transplant physicians to establish skin cancer screening recommendations for SOTR. The transplant team should risk stratify SOTR for screening, and dermatologists should perform skin cancer screening by full-body skin examination. SOTR with a history of skin cancer should continue regular follow-up with dermatology for skin cancer surveillance. High-risk transplant patients include thoracic organ recipients, SOTR age 50 and above, and male SOTR. High-risk Caucasian patients should be screened within 2 years after transplant, all Caucasian, Asian, Hispanic, and high-risk African American patients should be screened within 5 years after transplant. No consensus was reached regarding screening for low-risk African American SOTR. We propose a standardized approach to skin cancer screening in SOTR based on multidisciplinary expert consensus. These guidelines prioritize and emphasize the need for screening for SOTR at greatest risk for skin cancer.

Evidence-Based Clinical Practice Guidelines for Microcystic Adnexal Carcinoma: Informed by a Systematic Review.

IMPORTANCE: Microcystic adnexal carcinoma (MAC) occurs primarily in older adults of white race/ethnicity on sun-exposed skin of the head and neck. There are no formal guiding principles based on expert review of the evidence to assist clinicians in providing the highest-quality care for patients. OBJECTIVE: To develop recommendations for the care of adults with MAC. EVIDENCE REVIEW: A systematic review of the literature (1990 to June 2018) was performed using MEDLINE, Embase, Web of Science, and the Cochrane Library. The keywords searched were microcystic adnexal carcinoma, sclerosing sweat gland carcinoma, sclerosing sweat duct carcinoma, syringomatous carcinoma, malignant syringoma, sweat gland carcinoma with syringomatous features, locally aggressive adnexal carcinoma, and combined adnexal tumor. A multidisciplinary expert committee critically evaluated the literature to create recommendations for clinical practice. Statistical analysis was used to estimate optimal surgical margins. FINDINGS: In total, 55 studies met our inclusion criteria. The mean age of 1968 patients across the studies was 61.8 years; 54.1% were women. Recommendations were generated for diagnosis, treatment, and follow-up of MAC. There are 5 key findings of the expert committee based on the available evidence: (1) A suspect skin lesion requires a deep biopsy that includes subcutis. (2) MAC confined to the skin is best treated by surgery that examines the surrounding and deep edges of the tissue removed (Mohs micrographic surgery or complete circumferential peripheral and deep margin assessment). (3) Radiotherapy can be considered as an adjuvant for MAC at high risk for recurrence, surgically unresectable tumors, or patients who cannot have surgery for medical reasons. (4) Patients should be seen by a physician familiar with MAC every 6 to 12 months for the first 5 years after treatment. Patient education on photoprotection, periodic skin self-examination, postoperative healing, and the possible normal changes in local sensation (eg, initial hyperalgesia) should be considered. (5) There is limited evidence to guide the treatment of metastasis in MAC due to its rarity. Limitations of our findings are that the medical literature on MAC comprises only retrospective reviews and descriptions of individual patients and there are no controlled studies to guide management. CONCLUSIONS AND RELEVANCE: The presented clinical practice guidelines provide an outline for the diagnosis and management of MAC. Future efforts using multi-institutional registries may improve our understanding of the natural history of the disease in patients with lymph node or nerve involvement, the role of radiotherapy, and the treatment of metastatic MAC with drug therapy.

Randomized controlled pilot study of the preoperative use of brimonidine 0.33% topical gel for hemostasis in Mohs micrographic surgery.

BACKGROUND: Brimonidine topical gel may be useful in cutaneous surgical procedures because of its vasoconstricting properties. OBJECTIVE: Assess the hemostatic effect of topically applied brimonidine in patients being treated with anticoagulants and undergoing Mohs micrographic surgery (MMS). METHODS: Subjects undergoing MMS were randomly assigned to the control (n = 10) or study arm (n = 14). Controls received standard-of-care MMS, whereas the study arm received the same and preoperative application of brimonidine. Evaluations included rate of blood flow, percentage of wound bed surface area needing electrocautery, and changes in skin colorimeter readings. RESULTS: The treatment arm had 68% less blood loss over 30 seconds versus the control arm (P < .05). No patient in the brimonidine arm had more than 50% of the wound bed cauterized versus 80% in the controls. Erythema in the treatment arm was decreased by 3.89 times (P < .01) versus in the control arm. LIMITATIONS: Limitations were small sample size; sites limited to the face; the fact that measurement of bleeding did not account for anesthetic mixed with blood; visual estimation of percentage of wound surface area requiring cauterization; and no measurement of volume of anesthesia, wound depth, or postoperative complications. CONCLUSION: Preoperative application of brimonidine 0.33% gel may help decrease blood loss and the need for electrocautery during MMS for patients taking anticoagulants.

Observation of Dog-Ear Regression by Anatomical Location.

BACKGROUND: When an excision is performed by a method other than elliptical excision, direct primary wound closure can result in standing cones or "dog-ears." In 2008, Lee and colleagues noted that dog-ears of <8 mm in height have a statistically greater tendency to resolve without further surgical correction than larger dog-ears. OBJECTIVE: To stratify dog-ears by anatomic location and inform on the need for correction at the time of surgery. MATERIALS AND METHODS: After tumor extirpation, patients were counseled that primary closure of the surgical wound would result in dog-ears at the wound apices. Dog-ears were left uncorrected in participating patients. At 6 months, patients were assessed for resolution of the dog-ears and asked to rate the appearance of the scar. RESULTS: A total of 140 dog-ears were observed in the study period. Anatomical locations included the hand/foot, trunk, limb, and head/neck. Among these dog-ears, 114/140 (81%) showed complete resolution. Patient satisfaction with the scar appearance correlated well with the dog-ear resolution, with most patients rating the appearance of the scar as good to excellent. CONCLUSION: This study suggests that dog-ears on the hand and dog-ears ≤4 mm on the trunk may be observed without any final cosmetic penalty.

Ultraviolet Radiation-Induced Downregulation of SERCA2 Mediates Activation of NLRP3 Inflammasome in Basal Cell Carcinoma.

Basal cell carcinomas (BCCs) account for majority of skin malignancies in the United States. The incidence of BCCs is strongly associated with exposure of ultraviolet (UV) radiation. Nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3 (NLRP3) inflammasome plays an important role in innate immune responses. Different stimuli such as toxins, microorganisms and particles released from injured cells activate the NLRP3 inflammasome. Activated NLRP3 results in activation of caspase-1, which cleaves pro-IL-1ß to active IL-1ß. In this study, we have shown that NLRP3 is expressed in human basal cell carcinomas. The proximal steps in activation of NLRP3 inflammasome are not well understood. Here, we have attempted to elucidate a critical role for Ca2+ mobilization in activation of the NLRP3 inflammasome by UVB exposure using HaCaT keratinocytes. We have demonstrated that UVB exposure blocks Ca2+ mobilization by downregulating the expression of sarco/endoplasmic reticulum Ca2+ -ATPase (SERCA2), a component of store-operated Ca2+ entry that leads to activation of the NLRP3 inflammasome.

Incidence of and Risk Factors for Skin Cancer in Organ Transplant Recipients in the United States.

Importance: Skin cancer is the most common malignancy occurring after organ transplantation. Although previous research has reported an increased risk of skin cancer in solid organ transplant recipients (OTRs), no study has estimated the posttransplant population-based incidence in the United States. Objective: To determine the incidence and evaluate the risk factors for posttransplant skin cancer, including squamous cell carcinoma (SCC), melanoma (MM), and Merkel cell carcinoma (MCC) in a cohort of US OTRs receiving a primary organ transplant in 2003 or 2008. Design, Setting, and Participants: This multicenter retrospective cohort study examined 10 649 adult recipients of a primary transplant performed at 26 centers across the United States in the Transplant Skin Cancer Network during 1 of 2 calendar years (either 2003 or 2008) identified through the Organ Procurement and Transplantation Network (OPTN) database. Recipients of all organs except intestine were included, and the follow-up periods were 5 and 10 years. Main Outcomes and Measures: Incident skin cancer was determined through detailed medical record review. Data on predictors were obtained from the OPTN database. The incidence rates for posttransplant skin cancer overall and for SCC, MM, and MCC were calculated per 100 000 person-years. Potential risk factors for posttransplant skin cancer were tested using multivariate Cox regression analysis to yield adjusted hazard ratios (HR). Results: Overall, 10 649 organ transplant recipients (mean [SD] age, 51 [12] years; 3873 women [36%] and 6776 men [64%]) contributed 59 923 years of follow-up. The incidence rates for posttransplant skin cancer was 1437 per 100 000 person-years. Specific subtype rates for SCC, MM, and MCC were 812, 75, and 2 per 100 000 person-years, respectively. Statistically significant risk factors for posttransplant skin cancer included pretransplant skin cancer (HR, 4.69; 95% CI, 3.26-6.73), male sex (HR, 1.56; 95% CI, 1.34-1.81), white race (HR, 9.04; 95% CI, 6.20-13.18), age at transplant 50 years or older (HR, 2.77; 95% CI, 2.20-3.48), and being transplanted in 2008 vs 2003 (HR, 1.53; 95% CI, 1.22-1.94). Conclusions and Relevance: Posttransplant skin cancer is common, with elevated risk imparted by increased age, white race, male sex, and thoracic organ transplantation. A temporal cohort effect was present. Understanding the risk factors and trends in posttransplant skin cancer is fundamental to targeted screening and prevention in this population.

On the horizon: Optical imaging for cutaneous squamous cell carcinoma.

BACKGROUND: Surgical resection with negative margins remains the standard of care for high-risk cutaneous squamous cell carcinoma (SCC). However, surgical management is often limited by poor intraoperative tumor visualization and inability to detect occult nodal metastasis. The inability to intraoperatively detect microscopic disease can lead to additional surgery, tumor recurrence, and decreased survival. METHODS: A comprehensive literature review was conducted to identify studies incorporating optical imaging technology in the management of cutaneous SCC (January 1, 2000-December 1, 2014). RESULTS: Several innovative optical imaging techniques, Raman spectroscopy, confocal microscopy, and fluorescence imaging, have been developed for intraoperative surgical guidance. Fifty-seven studies review the ability of these techniques to improve cutaneous SCC localization at the gross and microscopic level. CONCLUSION: Significant advances have been achieved with real-time optical imaging strategies for intraoperative cutaneous SCC margin assessment and tumor detection. Optical imaging holds promise in improving the percentage of negative surgical margins and in the early detection of micrometastatic disease. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2204-E2213, 2016.