Jet-injection assisted photodynamic therapy for superficial and nodular basal cell carcinoma: A pilot study.

BACKGROUND: Photodynamic therapy (PDT) with topical δ-Aminolevulinic acid (ALA) has efficacy in treating basal cell carcinoma (BCC) but is limited by incomplete penetration of ALA into the deeper dermis. This prospective open-label pilot trial investigated the safety and efficacy of photosensitizer jet injection for PDT (JI-PDT) for BCC treatment. It was performed with 15 patients (n = 15) with histologically confirmed, untreated, low-risk nodular BCCs at a single institution. METHODS: For the intervention, JI-PDT patients (n = 11) received two sessions of jet-injected ALA with PDT separated by four to 6 weeks. To further understand treatment technique, another group of patients (n = 4) received jet-injected ALA followed by tumor excision and fluorescence microscopy (JI-E). Treatment tolerability was assessed by local skin responses (LSR) score at five distinct time intervals. Fluorescence microscopy assessed protoporphyrin IX penetration depth and biodistribution within the tumor. At the primary endpoint, tumor clearance was evaluated via visual inspection, dermoscopy and reflectance confocal microscopy. Postinjection and postillumination pain levels, and patient satisfaction, were scored on a 0-10 scale. RESULTS: Fifteen participants with mean age of 58.3, who were 15/15 White, non-Hispanic enrolled. The median composite LSR score immediately after JI-PDT was 5 (interquartile range [IQR] = 3) which decreased to 0.5 (IQR = 1) at primary endpoint (p < 0.01). Immunofluorescence of excised BCC tumors with jet-injected ALA showed photosensitizer penetration into papillary and reticular dermis. Of the 13 JI-PDT tumors, 11 had tumor clearance confirmed, 1 recurred, and 1 was lost to follow-up. 1/11 patients experienced a serious adverse event of cellulitis. 70% of patients had local scarring at 3 months. Patients reported an average pain level of 5.6 (standard deviation [SD] = 2.3) during jet injection and 3.7 (SD = 1.8) during light illumination. CONCLUSIONS: Jet injection of ALA for PDT treatment of nodular low-risk BCC is tolerable and feasible and may represent a novel modality to improve PDT.

Lentigo maligna melanoma mapping using reflectance confocal microscopy correlates with staged excision: A prospective study.

BACKGROUND: Lentigo maligna/lentigo maligna melanoma (LM/LMM) can present with subclinical extension that may be difficult to define preoperatively and lead to incomplete excision and potential recurrence. Preliminarily studies have used reflectance confocal microscopy (RCM) to assess LM/LMM margins. OBJECTIVE: To evaluate the correlation of LM/LMM subclinical extension defined by RCM compared with the gold standard histopathology. METHODS: Prospective study of LM/LMM patients referred for dermatologic surgery. RCM was performed at the clinically defined initial surgical margin followed by margin-controlled staged excision with paraffin-embedded tissue, and histopathology was correlated with RCM results. RESULTS: Seventy-two patients were included. Mean age was 66.8 years (standard deviation, 11.1; range, 38-89); 69.4% were men. Seventy of 72 lesions (97.2%) were located on the head and neck with mean largest clinical diameter of 1.3 cm (range, 0.3-5). Diagnostic accuracy for detection of residual melanoma in the tumor debulk (after biopsy) had a sensitivity of 96.7% and a specificity of 66.7% when compared with histopathology. RCM margin assessment revealed an overall agreement with final histopathology of 85.9% (κ = 0.71; P < .001). LIMITATIONS: No RCM imaging beyond initial planned margins was performed. CONCLUSION: RCM showed moderate to excellent overall agreement between RCM imaging of LM/LMM and histopathology of staged excision margins.

Clinical size is a poor predictor of invasion in melanoma of the lentigo maligna type.

BACKGROUND: There are no well-defined clinical factors to predict the risk of occult invasion in melanoma of the lentigo maligna type (LM) before complete histopathologic analysis. OBJECTIVE: To evaluate whether clinical size was a predictor of invasion in LM and subclinical extension. METHODS: Consecutive cases of LM were recorded in a prospectively maintained database from 2006 to 2019. Patient and tumor data were recorded during initial evaluation. The LM clinical area was calculated in square millimeters (length × width). All patients were treated with staged excision. RESULTS: We included 600 patients. The mean age was 65.9 years (standard deviation, 12.3; range, 27-95 years); 62.8% (n = 377) were men. The mean LM clinical area was 128.32 mm2 for in situ lesions versus 200.14 mm for invasive lesions (P = .1). Based on quantile regression, the median margin required for complete removal increased with LM clinical area. LIMITATIONS: The study was performed in a tertiary cancer center with possible referral bias and more complex cases. CONCLUSIONS: LM can present with variable clinical size, which may correlate with subclinical extension; however, the presence of invasion is not well estimated by LM clinical area.

Reflectance confocal microscopy terminology glossary for melanocytic skin lesions: A systematic review.

BACKGROUND: There is lack of uniformity in the reflectance confocal microscopy (RCM) terminology for melanocytic lesions. OBJECTIVE: To review published RCM terms for melanocytic lesions and identify redundant, synonymous terms. METHODS: A systematic review of original research articles adhering to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines was conducted until August 15, 2018. Two investigators gathered all published RCM terms used to describe melanoma and melanocytic nevi. Synonymous terms were grouped based on similarity in definition and in histopathologic correlation. RESULTS: Out of 156 full-text screened articles, 59 studies met the inclusion criteria. We identified 209 terms; 191 (91.4%) corresponding to high-magnification/cellular-level terms and 18 (8.6%) corresponding to low-magnification/architectural patterns terms. The overall average use frequency of RCM terms was 3.1 times (range, 1-31). By grouping of individual RCM terms based on likely synonymous definitions and by eliminating terms lacking clear definition, the total number of RCM terms could be potentially reduced from 209 to 40 terms (80.8% reduction). LIMITATIONS: Non-English and non-peer-reviewed articles were excluded. CONCLUSIONS: This systematic review of published RCM terms identified significant terminology redundancy. It provides the basis for subsequent terminology consensus on melanocytic neoplasms.

In vivo imaging characterization of basal cell carcinoma and cutaneous response to high-dose ionizing radiation therapy: A prospective study of reflectance confocal microscopy, dermoscopy, and ultrasonography.

BACKGROUND: Radiation therapy (RT) is a treatment option for select skin cancers. The histologic effects of RT on normal skin or skin cancers are not well characterized. Dermoscopy, high-frequency ultrasonography (HFUS), and reflectance confocal microscopy (RCM) are noninvasive imaging modalities that may help characterize RT response. OBJECTIVES: To describe changes in the tumor and surrounding skin of patients with basal cell carcinoma (BCC) treated with RT. METHODS: The study was conducted between 2014 and 2018. Patients with biopsy-proven BCCs were treated with 42 Gy in 6 fractions using a commercially available brachytherapy device. Dermoscopy, HFUS, and RCM were performed before treatment and at 6 weeks, 3 months, and 12 months after RT. RESULTS: A total of 137 imaging assessments (RCM + dermoscopy + HFUS) were performed in 12 patients. BCC-specific features were present in 81.8%, 91%, and 17% of patients imaged with dermoscopy, RCM, and HFUS at baseline, respectively, before treatment. After treatment, the resolution of these features was noted in 33.4%, 91.7%, and 100% of patients imaged with the respective modalities. No recurrences were seen after a mean of 31.7 months of follow-up. LIMITATIONS: Small sample size and no histopathologic correlation. CONCLUSION: Dermoscopy and HFUS were not as reliable as RCM at characterizing BCC RT response.

Angulated small nests and cords: Key diagnostic histopathologic features of infiltrative basal cell carcinoma can be identified using integrated reflectance confocal microscopy-optical coherence tomography.

BACKGROUND: Accurate basal cell carcinoma (BCC) subtyping is requisite for appropriate management, but non-representative sampling occurs in 18% to 25% of biopsies. By enabling non-invasive diagnosis and more comprehensive sampling, integrated reflectance confocal microscopy-optical coherence tomography (RCM-OCT) may improve the accuracy of BCC subtyping and subsequent management. We evaluated RCM-OCT images and histopathology slides for the presence of two key features, angulation and small nests and cords, and calculated (a) sensitivity and specificity of these features, combined and individually, for identifying an infiltrative BCC subtype and (b) agreement across modalities. METHODS: Thirty-three RCM-OCT-imaged, histopathologically-proven BCCs (17 superficial and/or nodular; 16 containing an infiltrative component) were evaluated. RESULTS: The presence of angulation or small nests and cords was sufficient to identify infiltrative BCC on RCM-OCT with 100% sensitivity and 82% specificity, similar to histopathology (100% sensitivity, 88% specificity, kappa = 0.82). When both features were present, the sensitivity for identifying infiltrative BCC was 100% using either modality and specificity was 88% on RCM-OCT vs 94% on histopathology, indicating near-perfect agreement between non-invasive and invasive diagnostic modalities (kappa = 0.94). CONCLUSIONS: RCM-OCT can non-invasively identify key histopathologic features of infiltrative BCC offering a possible alternative to traditional invasive biopsy.

Treatment of Extramammary Paget Disease and the Role of Reflectance Confocal Microscopy: A Prospective Study.

BACKGROUND: Extramammary Paget disease (EMPD) poses treatment challenges. Invasive and noninvasive treatment modalities exist with variable success reported. Reflectance confocal microscopy (RCM) is emerging as an adjuvant diagnostic tool. OBJECTIVE: To evaluate the treatment of EMPD patients and the role of RCM. METHODS: Prospective study. Demographic and tumor characteristics were recorded. Handheld-RCM was performed and correlated with histology. Treatment, clearance, pathology, and follow-up were all recorded. RESULTS: Thirty-six EMPD lesions in 33 patients were included. Mean age was 71.7 years, and 23 were men. Mean number of surgical stages needed to clear margins was 1.9 (SD, 0.9; 1.0-3.0 stages), and mean margin needed to clear was 1.8 cm. Reflectance confocal microscopy correlated well with scouting punch biopsies (kappa, 0.93; p < .001). Disruption of the dermoepidermal junction was associated with invasive EMPD versus in situ (83.3% vs 25.9%) on histology (p = .01). LIMITATIONS: Relatively small sample size. CONCLUSION: Extramammary Paget disease is challenging, and lesion demarcation is of the utmost importance. Using a staged surgical excision approach, the mean margins needed were 1.8 cm, less than previously reported. Nonsurgical modalities, including radiation therapy, imiquimod, or photodynamic therapy can be considered if surgery is not pursued. Reflectance confocal microscopy is a valuable noninvasive imaging modality for the management of EMPD.

Presurgical evaluation of basal cell carcinoma using combined reflectance confocal microscopy-optical coherence tomography: A prospective study.

BACKGROUND: Initial biopsy of basal cell carcinoma (BCC) may fail to show aggressive histologic subtypes. Additionality, the clinical evaluation of BCC before surgery can miss subclinical extension. Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) are emerging tools that can help in the presurgical evaluation of BCCs. OBJECTIVE: To assess the feasibility of a combined RCM-OCT imaging modality for presurgical evaluation of biopsy-proven BCCs for residual tumor, margin status, and depth. METHODS: Thirty-eight BCCs in 35 patients referred to a tertiary cancer center for Mohs micrographic surgery (MMS) were imaged with combined RCM-OCT. Images were correlated to MMS frozen sections. RESULTS: Thirty-eight BCCs were analyzed. The mean age of patients was 67.34 years (range, 36-84 years), and 20 patients were female (57.14%). Twenty four BCCs were located on the head (63.16%) , and the mean size was 8.58 mm (range, 3-30 mm). RCM-OCT showed an overall agreement of 91.1% with MMS frozen sections. A sensitivity of 82.6% (95% confidence interval [CI], 69%-92%), specificity of 93.8% (95% CI, 88%-97%), and receiver operating characteristic curve of 0.88 (95% CI, 0.82-0.94) was found. OCT depth was highly correlated with MMS depth (r2 = 0.9). LIMITATIONS: Small sample size and difficulty evaluating certain challenging anatomic sites. CONCLUSIONS: Combined RCM-OCT may emerge as a useful tool for presurgical evaluation of BCCs.

Reflectance confocal microscopy-guided carbon dioxide laser ablation of low-risk basal cell carcinomas: A prospective study.

BACKGROUND: Basal cell carcinoma (BCC) treatment modalities can be stratified by tumor subtype and recurrence risk. The main limitation of nonsurgical treatment modalities is the lack of histopathologic confirmation. Reflectance confocal microscopy (RCM) is a noninvasive imaging device that provides quasihistologic images. OBJECTIVE: To evaluate the feasibility and efficacy of RCM-guided carbon dioxide (CO2) laser ablation of low-risk BCCs. METHODS: Prospective study with biopsy specimen-proven low-risk BCCs imaged with RCM. RCM was performed on these sites before and after ablation. If residual tumor was found, a new series of laser passes were performed. The patients were then monitored for recurrence clinically and with RCM. RESULTS: Twenty-two tumor sites in 9 patients (5 men, 4 women) were imaged and treated. Median age was 59 ± 12.9 years (range, 30-74 years). Mean tumor size was 7.7 mm (range, 5-10 mm). Residual tumor was identified in 5 of 22 cases (22.7%) under RCM on immediate first-pass postablation sites, prompting additional laser passes. Median follow-up was 28.5 months (range, 22-32 months) with no recurrences found. CONCLUSIONS: Addition of RCM to laser ablation workflow can detect subclinical persistent tumor after initial ablation and may serve as an aid to increase the efficacy of laser ablation.

Reflectance confocal microscopy confirms residual basal cell carcinoma on clinically negative biopsy sites before Mohs micrographic surgery: A prospective study.

BACKGROUND: Biopsy specimens from patients with basal cell carcinoma (BCC) can present to surgery with no clinically residual tumor, complicating treatment decisions. OBJECTIVE: To evaluate reflectance confocal microscopy (RCM) for the assessment of residual BCC following biopsy. METHODS: Consecutive patients with biopsy-proven BCC and no clinical evidence of residual tumor who had been referred for Mohs micrographic surgery were included. Biopsy sites were imaged with a handheld RCM device. On the basis of RCM evaluation, cases were labeled RCM positive or RCM negative. Mohs micrographic surgery was performed in all cases; margins and 15-µm serial vertical sectioning were evaluated. RESULTS: A total of 61 patients were included (mean age, 61.7 years [standard deviation, 12.2 years]; range, 37-87 years); 60.7% were women. The mean lesion size was 5.1 mm (range, 3-12 mm); 73.8% of patients were positive on RCM, and 68.9% had residual BCC on histopathologic examination. The rates of RCM sensitivity, specificity, positive predictive value, and negative predictive value were 92.8%, 68.4%, 86.6%, and 81.2%, respectively. Three cases of BCC (high-risk, infiltrative, and basosquamous) were missed with use of RCM. When high-risk subtypes were excluded (n = 5), sensitivity and negative predictive value were both 100%. LIMITATIONS: RCM can miss deep-seated residual tumor. CONCLUSION: RCM is a valuable tool for the evaluation of residual BCC following biopsy, with the potential to reduce unnecessary surgical procedures.

A randomized, prospective, sham-controlled study of localized narrow-band UVB phototherapy in the treatment of plaque psoriasis.

IMPORTANCE: UV phototherapy remains a useful and frequently employed treatment for chronic plaque psoriasis. In those patients with plaque body surface area less than 10%, targeted treatment is the safest and most effective modality. OBJECTIVE: We aimed to evaluate the efficacy of the Levia® localized NB-UVB phototherapy machine in the treatment of patients with symmetrical psoriatic lesions. DESIGN: We performed a prospective, double-blinded, sham-treatment controlled study of this device beginning March 2012 through April 2014. SETTING: a comprehensive dermatology clinic in the northeastern United States. PARTICIPANTS: 21 subjects with chronic plaque psoriasis. INTERVENTIONS: Each patient had one lesion randomized to receive the Levia treatment and one lesion (the control) treated with visible light. Treatment was administered three times a week for twelve weeks. Target lesion score (TLS), a rating of 0-4 each of erythema, scaling, and thickness, was measured biweekly by a blinded assessor, and visual analogue scale of pruritus was recorded by subjects. MAIN OUTCOMES AND MEASURES: The primary outcome, formulated prior to study initiation, was the percentage of lesions achieving clear or almost clear TLS after 12 weeks of treatment. Secondary endpoints included changes in target lesion pruritus VAS, percentage improvement in TLS, and the percentage of subjects achieving 50% improvement in TLS (TLS-50). RESULTS: The primary endpoint, TLS of three or less, was not achieved (P=0.118), but the secondary endpoints of percentage improvement in TLS (P=0.043) and TLS-50 (P=0.0195) were significantly superior in treated compared to sham-treated lesions. Percentage improvement in pruritus VAS was not significant (P=0.0565). CONCLUSIONS AND RELEVANCE: This device was found to be efficacious, though not necessarily to the point of clearance, in the treatment of psoriasis over a 12-week period. TRIAL REGISTRATION: www.clinicaltrials.gov, identifier: NCT02107482, http://clinicaltrials.gov/show/NCT02107482

The Extent of Misconceptions, Negative Prejudices, and Discriminatory Behaviors Toward Psoriasis Patients: A Cross-Sectional Survey Study Among the Population of Jeddah, Saudi Arabia.

Background Psoriasis is a chronic inflammatory disease that affects around 2% of the population. The lives of psoriasis patients are greatly impacted by stigma and social exclusion, regardless of the severity of the condition. This is the first study of its kind to be conducted in Saudi Arabia. This study aimed to assess peoples' psoriasis-related misconceptions, negative prejudice, and discriminatory behaviors. Methodology A self-administered Google Forms survey was distributed between January and February 2023. The survey was conducted among residents of Jeddah, Saudi Arabia who were enrolled randomly via social media. We aimed to investigate their perception and awareness related to psoriasis, as well as how varying educational levels, age groups, and genders affected these variables. Results In total, 803 individuals participated in the survey. Results showed that 19.9% of the participants did not know about psoriasis. Only 5.1% of respondents stated that they were well knowledgeable about psoriasis. Moreover, psoriasis was more frequently perceived as a communicable disease by people in the age group of 18-29 years (p = 0.000). Surprisingly, only 43.5% of the participants reported that they would shake hands with someone with psoriasis without hesitation. Additionally, 40.7% of the participants were aware that psoriasis requires lifelong treatment. Moreover, the belief that psoriasis does not require lifelong therapy was more prevalent among university graduates (p = 0.000). Conclusions This study found that the residents of Jeddah need further education on skin disorders, in general, and psoriasis, in particular. Future studies should be conducted utilizing various approaches, with a greater emphasis on certain groups of people who engage physically with psoriasis patients.

Assessing the Ability of Non-dermatology Physicians to Recognize Urgent Skin Diseases.

Introduction Many patients present to the emergency department with skin conditions that are not true dermatologic emergencies. Urgent skin conditions are uncommon. Because these conditions are rare, they can be sometimes challenging to diagnose. Few works of literature discussed the accuracy of non-dermatologists' initial judgment on dermatologic conditions concluding that non-dermatologists misdiagnose many common and uncommon skin conditions. Because the study was never done in our region, we aim to conduct an online assessment using a questionnaire assessing the ability of non-dermatologists to recognize urgent skin diseases at King Abdulaziz University Hospital (KAUH) in Jeddah, Saudi Arabia. Methods A cross-sectional study was conducted. Non-dermatologist physicians were contacted through their verified emails, provided by the secretaries of each department and the academic affairs unit. The questionnaire consisted of two main sections, the first section covered demographics, specialty, and academic level. The second part had eight questions, each containing a brief case scenario about an urgent dermatological condition with a picture of the condition attached. Participants were required to answer the questions and assess on a scale from one to 10 how confident they were about their answers. The responses were collected and analyzed. Results Out of all 161 responses, this study included 93 male physicians (57.8%) and 68 female physicians (42.2%). The mean age in the study was approximately 45 ± 3 years. This study showed that the percentage of accuracy by non-dermatologists in diagnosing urgent skin diseases given the typical presentation of the condition was (61.33%); nevertheless, the percentage decreased when it was recalculated in relation to the full level of confidence to (25.3%). Herpes zoster appeared to be the most recognizable urgent skin disease, and Pemphigus vulgaris was the least recognizable one. Conclusion This study shows that it is difficult for physicians to recognize some urgent skin diseases, which affects offering the optimum health care for the patients. Moreover, more dermatology-focused courses are needed to strengthen the knowledge about dermatological diseases.

Squamous cell carcinoma in situ upstaging is not frequent in the nail unit: a tertiary cancer center experience.

Squamous cell carcinoma in situ (SCCIS) of the nail unit is a complex malignancy; with little understanding of rate of upstaging or occult invasion in these patients. We sought to evaluate the rate of upstaging in nail unit SCCIS after Mohs micrographic surgery (MMS). Retrospective review of 346 patients who referred for and underwent MMS for biopsy proven SCCIS on the hands and feet between January 1, 2000 and December 30, 2019. Only cases in the nail unit were included. Clinical, surgical details, histopathological features, HPV status, and rate of upstaging were recorded. Thirty-one cases met the inclusion criteria and were analyzed. Twenty-four patients were males (77.4%). The mean age was 55 years (SD 17.26, range 27-84). The mean clinical size was 9.9 mm; 19 cases tested for HPV, 15/19 were positive (78.9%), and 8/19 (42.1%) were associated with high-risk HPV. Three patients (9.7%) were upstaged to invasive on either MMS margins or tumor debulking. Limitations included a relatively small sample size and retrospective in nature. The rate of upstaging of SCCIS in the nail unit is not frequent, and when upstaging occurred it was focal, superficial, and with no PNI or bone invasion.