How dermatologic surgeons decide to proceed with surgery for nonmelanoma skin cancer when site identification is initially uncertain: A nationwide, multicenter, prospective study.

BACKGROUND: Few studies show how dermatologic surgeons manage problems with site identification. OBJECTIVE: To estimate frequency and characterize management of skin cancer treated by surgery when the anatomic location of the tumor is in question. METHODS: Nationwide, prospective, multisite cohort study. RESULTS: Among 17,076 cases at 22 centers, 98 (0.60%) were lesions in question for which site identification was initially uncertain, with these more often in patients who were male, older, and biopsied more than 30 days ago. Surgeons employed on average 5.0 (95% CI: 4.61-5.39) additional techniques to confirm the site location, with common approaches including: re-checking available documentation (90 lesions, 92%); performing an expanded physical examination (89 lesions, 91%); and asking the patient to point using a mirror (61 lesions, 62%). In 15%, photographs were requested from the biopsying provider, and also in 15%, frozen section biopsies were obtained. In 10%, the referring physician was contacted. Eventually, surgeons succeeded in definitively identifying 82% (80 of 98) of initially uncertain sites, with the remaining 18% (18 of 98) postponed. Most postponed surgeries were at non-facial sites. LIMITATIONS: Sites were academic centers. CONCLUSIONS: When the anatomic location of the tumor is uncertain, dermatologic surgeons use multiple methods to identify the site, and sometimes cases are postponed.

A study of collagen refractility in dermatofibroma and dermatofibrosarcoma protuberans using diffractive microscopy.

BACKGROUND: Diffractive microscopy creates contrast within samples that are otherwise uniform under bright light. This technique can highlight subtle differences in refractive indices within birefringent samples containing varying amounts of mature collagen. Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) possess differences in their mature collagen content and, therefore, may be distinguishable using diffractive microscopy. METHODS: Two hundred forty-two DF and 85 DFSP hematoxylin-eosin (H&E)-stained specimens were analyzed using diffractive microscopy. Data regarding the distribution pattern and strength of refractility was recorded. RESULTS: DFSP was more frequently found to be focally, weakly, or non-refractile (82.9%; n = 68) under diffractive microscopy, while DF more often showed diffusely bright refractility (52.9%; n = 128). DFSP samples with diffuse refractility in portions of the lesion (17.1%; n = 14) also exhibited a unique checkerboard pattern distinct from that which was seen in DF samples. CONCLUSIONS: The absence of diffuse refractility was more closely associated with DFSP, as was the presence of a unique checkerboard diffraction pattern. Despite high sensitivity (Sn = 82.9%), absent refractility was not a specific test (Sp = 52.9%), with 47.1% (n = 114) of DF samples sharing this feature. The distinction between DF and DFSP is often diagnosed using H&E alone. In difficult cases, examination of collagen under diffractive microscopy may be useful in distinguishing DFSP from DF and provide an alternative cost-effective tool to immunohistochemical staining.

Comparative effectiveness of ice packs versus topical lidocaine-prilocaine mixture for pain control in laser hair removal of the axilla: A rater-blinded randomized controlled trial.

BACKGROUND: Laser hair removal is associated with moderate acute pain. OBJECTIVE: To compare effectiveness of ice pack to topical lidocaine-prilocaine for pain reduction during axillary laser hair removal. METHODS: Participants were randomly assigned to receive topical anesthetic to one axilla and ice packs to the other before each of 3, monthly 810 nm diode laser sessions. The primary endpoint was participant-reported pain on the visual analog scale (VAS) immediately following and 5 minutes after laser session. Posttreatment erythema, overall edema, and perifollicular edema were assessed by 2 blinded photoraters. Skin temperatures, patient preferences, and adverse events were recorded. RESULTS: Eighty-eight of 90 (98%) planned laser treatments were delivered and randomized. Participants reported higher VAS scores immediately after laser treatment with lidocaine-prilocaine compared to ice (P = .03). Five minutes after, participants reported higher VAS scores with ice (P = .03). After 53 of the 88 treatments (60.2%), participants reported preferring ice (P = .055). No serious adverse events were reported. LIMITATIONS: All participants were Caucasian or Asian with Fitzpatrick skin type I to III and coarse dark axillary hair, which may limit generalizability. CONCLUSIONS: While pain control with ice and topical anesthesia is associated with time after treatment, the 2 modalities do not differ in terms of degree of pain reduction associated with axillary laser hair removal.

Pain of local anesthetic injection of lidocaine during subsequent stages of Mohs micrographic surgery: A multicenter prospective cohort study.

BACKGROUND: Patients awake during staged cutaneous surgery procedures may experience procedure-related pain. OBJECTIVE: To determine whether the level of pain associated with local anesthetic injections prior to each Mohs stage increases with subsequent Mohs stages. METHODS: Multicenter longitudinal cohort study. Patients rated pain (visual analog scale: 1-10) after anesthetic injection preceding each Mohs stage. RESULTS: Two hundred fifty-nine adult patients presenting for Mohs who required multiple Mohs stages at 2 academic medical centers were enrolled; 330 stages were excluded due to complete anesthesia from prior stages, and 511 stages were analyzed. Mean visual analog scale pain ratings were nominally but not significantly different for subsequent stages of Mohs surgery (stage 1: 2.5; stage 2: 2.5; stage 3: 2.7: stage 4:2.8: stage 5: 3.2; P = .770). Between 37% and 44% experienced moderate pain, and 9.5% and 12.5% severe pain, during first as versus subsequent stages (P > .05) LIMITATIONS: Both academic centers were in urban areas. Pain rating is inherently subjective. CONCLUSIONS: Patients did not report significantly increased anesthetic injection pain level during subsequent stages of Mohs.

Dermatopathologic features of cutaneous squamous cell carcinoma and actinic keratosis: Consensus criteria and proposed reporting guidelines.

BACKGROUND: There is considerable variation in the literature regarding the dermatopathologic diagnostic features of and reporting guidelines for actinic keratosis (AK) and cutaneous squamous cell carcinoma (cSCC). OBJECTIVE: To develop consensus recommendations regarding diagnostic criteria, nomenclature, and reporting of AK and cSCC. METHODS: Literature review and cross-sectional multiround Delphi process including an international group of expert dermatopathologists followed by a consensus meeting. RESULTS: Consensus was achieved regarding the key dermatopathologic features necessary for diagnosing cSCC, AK, and associated variants; grading of degree of cellular differentiation in cSCC; utility of immunohistochemistry for diagnosis of cSCC; and pathologic features that should be reported for cSCC and AK. LIMITATIONS: Consensus was not achieved on all questions considered. CONCLUSION: Despite the lack of clarity in the literature, there is consensus among expert dermatopathologists regarding diagnostic criteria and appropriate reporting of AK and cSCC. Widespread implementation of these consensus recommendations may improve communication between dermatopathologists and clinicians, facilitating appropriate treatment of AK and cSCC.

Cytologic atypia of benign inflammatory versus neoplastic cutaneous squamous lesions.

BACKGROUND: Cytologic atypia encompasses several features of abnormal cellular morphology. We sought to quantify these features in benign and premalignant/malignant squamous cell lesions to better characterize criteria for malignancy. METHODS: We conducted a rater-blinded observational study in which histopathology slides were evaluated under light microscopy, and the presence and relative quantity of 24 distinct cytological features were recorded, along with respective diagnoses. Each slide was evaluated, and the ratings were recorded and analyzed. RESULTS: The most helpful findings, whose presence in high numbers indicates an increased likelihood that the tissue sample is premalignant/malignant, were: (1) pleomorphic parakeratosis; (2) pleomorphic nuclei in the epithelium; (3) irregular nuclei; (4) thick refractile nuclear envelope; (5) presence of nuclear hyperchromasia (dark gray); (6) peripheral nucleoli; and (7) nucleolar stems. Higher values of round or oval nuclear shape and vesicular nuclei increase the likelihood that the tissue sample is benign. CONCLUSIONS: Certain nuclear features have a higher association with premalignancy/malignancy and may guide histologic evaluation of a given lesion. These findings can be used in combination with architectural features and clinical history to add to a complete diagnostic picture.

Dermatofibroma Versus Dermatofibrosarcoma Protuberans: A Nuclear Morphology Study.

ABSTRACT: The locally invasive soft-tissue sarcoma, dermatofibrosarcoma protuberans (DFSPs), shares certain histologic features of the much more common and benign dermatofibroma (DF). While immunohistochemical stains, specifically cluster of differentiation 34 and Factor XIIIa, can be used to distinguish the 2 entities using microscopy, these markers are not entirely sensitive nor specific. Three-dimensionally, DFSP nuclei resemble a "puck" or "coin"-like shape. As hematoxylin/eosin-stained slides are prepared, these "puck" nuclei are fixed in an infinite number of orientations depending on their current position in rotation about their axes within the tumor cells. Under histological examination, this random nuclear positioning produces the appearance of 2 predominate morphologies: an ovoid "disk" shape (en face) and a narrow spindled shape (side view), which distribute in a roughly 50:50 ratio throughout the tumor sample slide. Nuclear morphology was analyzed in 324 DFSP and DF samples at high magnification (×400) to determine the presence or absence of a predominant morphology in which nuclei appear to alternate between an ovoid (en face) and spindled (side view) throughout most of the tumor sample. An alternating ovoid-spindled nuclear morphology was the predominant cytology in 98% of DFSP and was not predominant in 100% of DF samples (P < 0.001). This morphology was found to be highly specific (Sp = 1) and sensitive (Sn = 0.98) for DFSP. This unique nuclear morphology may be a more sensitive and specific diagnostic tool in identifying DFSP from DF in comparison with costly immunohistochemical stains.

Treatment of Surgical Scars With Combination Pulsed Dye and Fractional Nonablative Laser: A Randomized Controlled Trial.

OBJECTIVE: To assess the effectiveness and safety of combined pulsed-dye laser (PDL) and NAFL for treatment of surgical scars. SUMMARY BACKGROUND DATA: PDL and NAFL have not been compared to healing by time alone. METHODS: Randomized controlled, single-blinded clinical trial at an urban, university hospital. Healthy adults' status post skin surgery with primary closure were randomized to either 3 sessions of combination PDL and NAFL every 2 to 8 weeks, or control of no treatment. At baseline and 36-week follow-up, Patient and observer Scar Assessment Scale and Scar Cosmesis Assessment and Rating were completed by participants and blinded physicians. The primary outcome was scar improvement, as measured by the score difference over time. RESULTS: Of 76 participants, 52 completed the study (July 2017 to June 2019). No severe adverse events were reported. Patient and observer Scar Assessment Scale assessments demonstrated improvement in total score in the laser group compared to controls, as reported by patients [mean difference (standard deviation), laser: 12.86 (6.91) vs control: 7.25 (6.34); P = 0.004] and blinded physicians [18.32 (8.69) vs 13.08 (9.63); P = 0.044]. Patients observed a greater improvement in scar thickness [3.68 (2.04) vs 1.88 (1.85); P = 0.002] and stiffness [3.57 (2.78) vs 1.50 (2.11); P = 0.004] with lasers, and physicians reported greater improvement in vascularity [3.71 (1.98) vs 1.71 (1.52); P = 0.0002]. The live Scar Cosmesis Assessment and Rating subscore for erythema improved significantly with lasers [1.04 (0.79) vs 0.42 (0.50); P = 0.001]. CONCLUSIONS AND RELEVANCE: Combined PDL and NAFL resulted in scar improvement. Scar thickness, stiffness, and erythema were improved. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03057964).

Development of a core outcome set for basal cell carcinoma.

BACKGROUND: There is variation in the outcomes reported in clinical studies of basal cell carcinoma. This can prevent effective meta-analyses from answering important clinical questions. OBJECTIVE: To identify a recommended minimum set of core outcomes for basal cell carcinoma clinical trials. METHODS: Patient and professional Delphi process to cull a long list, culminating in a consensus meeting. To be provisionally accepted, outcomes needed to be deemed important (score, 7-9, with 9 being the maximum) by 70% of each stakeholder group. RESULTS: Two hundred thirty-five candidate outcomes identified via a systematic literature review and survey of key stakeholders were reduced to 74 that were rated by 100 health care professionals and patients in 2 Delphi rounds. Twenty-seven outcomes were provisionally accepted. The final core set of 5 agreed-upon outcomes after the consensus meeting included complete response; persistent or serious adverse events; recurrence-free survival; quality of life; and patient satisfaction, including cosmetic outcome. LIMITATIONS: English-speaking patients and professionals rated outcomes extracted from English language studies. CONCLUSION: A core outcome set for basal cell carcinoma has been developed. The use of relevant measures may improve the utility of clinical research and the quality of therapeutic guidance available to clinicians.

Utility of high-resolution ultrasound in measuring subcutaneous fat thickness.

OBJECTIVE: Previous studies conclude that high-resolution ultrasound (HRUS) enables noninvasive and accurate measurements of subcutaneous fat thickness. The primary objective of this cross-sectional study was to better characterize subcutaneous fat thickness measurements in a diverse patient population using HRUS. Secondarily, we sought to correlate these measurements with patients' body image. METHODS: A cross-sectional study to measure subcutaneous fat measurements at seven distinct anatomic sites, including upper and lower extremities, submental, and torso regions, in 40 men and women of different ages and races using HRUS. Independent t-tests and analysis of variance were performed to analyze findings. RESULTS: In our patient population, on average, women had thicker subcutaneous fat than men at all anatomic sites. Asian patients had significantly reduced fat thickness at peripheral anatomic sites, such as arms when compared to patients who identified as Black and Other (p = 0.05 and p = 0.008, respectively). Lastly, women reported decreased total body satisfaction at all anatomic sites when compared to men. CONCLUSION: The information obtained and methods developed in this study may be utilized clinically during patient selection for fat reduction procedures, including for estimating the degree of likely benefit; for managing pathologies involving subcutaneous fat thickness alteration; and to monitor the progression of lipodystrophy secondary to disease or drugs.

Dermatology Match Preference Signaling Tokens: Impact and Implications.

BACKGROUND: The dermatology residency application process implemented a new system of preference signaling tokens (PSTs) in the 2021-2022 cycle to allow applicants to express a higher level of interest in specific programs. Limited data are available on the utilization and impact of these tokens. OBJECTIVE: To determine the impact of PSTs on the application process and where in the process PSTs had the greatest influence. MATERIALS AND METHODS: A 14-question survey was sent to 62 ACGME-accredited dermatology residency programs. Primary outcomes were PST impact on 2021-2022 applications. Variables were evaluated using open-ended questions, yes/no responses, and importance ratings from 0 to 100. RESULTS: An average of 7.1% of applicants were offered interviews, but 21.1% of applicants that submitted PSTs were interviewed versus 3.7% of nonsubmitters. 22.5% of ranked applicants and 19% of matched applicants submitted a PST to that program. LIMITATIONS: Not all programs responded, and PST submission restrictions could not be assessed. CONCLUSION: The greatest PST impact was on the interview decision but had minimal subsequent impact. Given PSTs cannot be submitted to home programs or in-person away rotations, the actual impact was probably greater than found. Programs will continue to implement PSTs in future cycles.

Subcision with and without suction for acne scars: a split-faced, rater-blinded randomized control trial.

Therapeutic options for acne scars include subcision and suction with microdermabrasion, but these treatment modalities have not been studied in conjunction. To compare effectiveness of subcision alone versus subcision with suction for the treatment of facial acne scars. Randomized, split-faced, evaluator-blinded control trial. Participants underwent one subcision treatment on both sides of the face followed by 10 sessions of suction to one side. Photographs at baseline, 1-month, and 4-months were assessed. Primary outcome measures were the validated Acne Scar Severity Scale (ASSS) (0 = no acne scarring, 4 = severe), Acne Scar Improvement Grading Scale (ASIGS) (-100 to 100%), and modified Quantitative Global Scarring Grades (QGSG) (point-based questionnaire instrument), as well as subject preference. Twenty-eight treatment areas and 154 treatments were analyzed. Dermatologist raters found no differences between subcision alone and subcision-suction at 1-month or 4-months. Mean subject-assessed percent improvement for subcision-suction was higher than that for subcision alone at 1-month (37% versus 24%, p = 0.04) but not at 4-months (p = 0.37). Subjects preferred combination therapy to monotherapy at 1-month (50% vs. 21%) and 4-months (43% vs. 21%). While blinded raters did not detect significant differences, subjects perceived combination treatment as working more quickly than monotherapy, and preferred combination treatment at all time points.Clinical trial registration NCT01696513 on Clinicaltrials.gov.

Rosacea Core Domain Set for Clinical Trials and Practice: A Consensus Statement.

Importance: Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. Objective: To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. Evidence Review: A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. Findings: The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. Conclusions and Relevance: This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.

Electrical impedance spectroscopy significantly enhances correct biopsy choice for pigmented skin lesions beyond clinical evaluation and dermoscopy.

The purpose of this study was to investigate whether EIS technology can further improve correct biopsy choices beyond clinical and dermoscopic evaluation for melanoma (MM), severe dysplastic nevi (SDN) and benign PSLs. Images of 49 MMs, SDNs and benign PSLs were randomly selected from a prior study and were provided in a reader-type survey study to dermatologists to evaluate for biopsy. A total of 33,957 biopsy decisions were analyzed. Respondents significantly improved on the correct biopsy choice with the addition of dermoscopy versus clinical image alone for melanoma and severely dysplastic nevi. Respondents also showed a statistically significant improvement in correct biopsy choice beyond their dermoscopic evaluation when integrating the EIS score versus dermoscopy with clinical images for MM, SDN and benign lesions. Respondents also made fewer incorrect biopsy choices with the addition of the EIS score versus dermoscopy and clinical image for MM and benign lesions. Sub-analyses of biopsy choices were also conducted based on experience and practice type. The findings from this study demonstrate that the integration of EIS technology into PSL biopsy decisions has the potential to significantly improve the accuracy of lesion selection for biopsy beyond clinical and dermoscopic evaluation alone.

Treatment of actinic keratosis: a systematic review.

Treatment of actinic keratoses (AKs) can help lower the risk of eventual skin cancer and address field pre-cancerization. This review compares the different therapeutic options for actinic keratosis. Databases used include Medline, EMBASE, Web of Science and the Cochrane Library from inception to December 2019. Randomized control trials that were related to any approved or recognized treatment for actinic keratosis were included. 1186 studies were found, of which 80 with 6748 patients were included in the analysis. A network meta-analysis was not possible due to interstudy heterogeneity. The greatest degree of improvement was seen with photodynamic therapy (PDT) used adjunctively with other modalities, but this was not significantly different compared to other treatments. PDT, cryotherapy, imiquimod, ingenol mebutate (IMB), 5-fluorouracil (5-FU), trichloroacetic acid (TCA), and ablative fractional laser (AFXL), were all non-inferior to one another in terms of percent clearance of AKs, but the lowest rates of clearance were seen with diclofenac sodium. When results were substratified by body site, 5-FU, combination PDT and combination 5-FU with calcipotriol were the most beneficial for AKs on the head and neck, although they often caused the highest proportion of initial side effects. Absence of randomized control trials for surgical treatments and non-ablative laser limits comparison of these treatments to other modalities. Limitations include the lack of standardized outcome reporting limited the comparability of results across trials. The results of this analysis do not account for individual patient risk or cumulative risk for development of skin cancer. At present, PDT, cryotherapy, imiquimod, IMB, 5-FU, TCA, AFXL, and combination treatments are similarly efficacious in reducing AKs in immunocompetent patients.Registration: N/A.

Improvements and advances in core outcome set methodology: proceedings of the CS-COUSIN & COMFA Joint Meeting.

A COS is a systematically developed list of outcomes recommended for reporting all studies within a particular disease area. The Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN) and the Core Outcome Measures in Food Allergy (COMFA) Initiative Joint Meeting was held virtually on September 23 through 28, 2021. This meeting brought together core outcome set (COS) developers within the domains of dermatology and food allergy, respectively. The meeting assessed the state of COS methodology, provided a forward look, and facilitated the networking of members of individual COS groups. The meeting hosted several expert-led key addresses and focus sessions, in which work was critically discussed, new developments were shared, and groundwork was laid for future projects. The conference emphasized the importance of ongoing COS work to improve patient outcomes and limit research waste.