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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 to 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 (SD 11.1; 38 – 89 years); 69.4% were males. 70/72 (97.2%) lesions were located on the head neck with mean largest clinical diameter of 1.3cm (0.3 – 5 cm). 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 to the histopathology. RCM margin assessment revealed an overall agreement with final histopathology of 85.9% (kappa 0.71; p 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.

Endocrine mucin-producing sweat gland carcinoma is a low-grade eyelid tumor. Small biopsies and insensitive immunohistochemistry predispose to misdiagnosis. We aimed to identify clarifying immunohistochemical markers, molecular markers, or both. Clinicopathologic data (22 cases) were reviewed. Immunohistochemistry (insulinoma-associated protein 1, BCL-2, mucin 2 [MUC2], mucin 4, androgen receptor, β-catenin, and Merkel cell polyomavirus) and next-generation sequencing (Memorial Sloan Kettering integrated mutation profiling of actionable cancer targets, 468 genes) were performed (3 cases). Female patients (n = 15) and male patients (n = 7) (mean age 71.8 years; range 53–88 years) had eyelid or periorbital tumors (>90%) with mucin-containing solid or cystic neuroendocrine pathology. Immunohistochemistry (insulinoma-associated protein 1, BCL2, androgen receptor, retinoblastoma-associated protein 1, and β-catenin) was diffusely positive (5/5), MUC2 partial, mucin 4 focal, and Merkel cell polyomavirus negative. Memorial Sloan Kettering integrated mutation profiling of actionable cancer targets identified 12 single-nucleotide variants and 1 in-frame deletion in 3 cases, each with DNA damage response or repair (BRD4, PPP4R2, and RTEL1) and tumor-suppressor pathway (BRD4, TP53, TSC1, and LATS2) mutations. Microsatellite instability, copy number alterations, and structural alterations were absent. Insulinoma-associated protein 1 and MUC2 are positive in endocrine mucin-producing sweat gland carcinoma. MUC2 positivity suggests conjunctival origin. Multistep pathogenesis involving DNA damage repair and tumor-suppressor pathways may be implicated.

BACKGROUND: Nasal scarring can compromise aesthetics and function given its complex three-dimensional structure and central location. This study aimed to measure patients' satisfaction after reconstruction for nasal defects following Mohs micrographic surgery.METHODS: Patients presenting with nasal nonmelanoma skin cancer at Memorial Sloan Kettering Cancer Center New York, USA and Catharina Hospital Eindhoven, Netherlands from April 2017 to November 2019 were asked to participate. Reconstruction type, complications, and patients satisfaction were assessed. Patients completed the FACE-Q Skin Cancer - Satisfaction with Facial Appearance scale (preoperative and 1-year postoperative) and the Appraisal of Scars scale (1-year postoperative).RESULTS: A total of 128 patients completed the preand postoperative scales. There were 35 (27%) surgical defects repaired with primary closures, 71 (55.5%) with flaps, and 22 (17.2%) with full-thickness skin grafts (FTSG). Patients that underwent a flap or FTSG reconstruction had higher scar satisfaction scores than primary closures (p = 0.03). A trend was seen with patients following flap reconstructions scoring 7.8 points higher than primary closures and patients with upper nose defects scoring 6.4 points higher than lower nose defects. Males were significantly more satisfied than females. No significant difference was observed in the preoperative and postoperative facial appearance scores between the three groups (p = 0.39).CONCLUSION: Patients are more satisfied in the long term with their scars after flap reconstructions compared to primary closures. Therefore, nasal skin reconstruction may not follow the traditional reconstructive ladder and more complex approaches may lead to higher long-term scar satisfaction.

The NCCN Guidelines for Squamous Cell Skin Cancer provide recommendations for diagnostic workup, clinical stage, and treatment options for patients with cutaneous squamous cell carcinoma. The NCCN panel meets annually to discuss updates to the guidelines based on comments from panel members and the Institutional Review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new surgical recommendation terminology (peripheral and deep en face margin assessment), as well as recent updates on topical prophylaxis, immunotherapy for regional and metastatic disease, and radiation therapy.

Keratinocyte carcinomas are amenable to many treatments, including radiotherapy (RT). Electronic skin surface brachytherapy (ESSB) enables the precise delivery of radiation without radioisotopes.In this prospective multicenter clinical trial, we characterized early outcomes of ESSB prospectively through both patient- and clinician-reported measures. To corroborate the cosmesis observations, we also assessed patient-reported quality of life (QoL) and adverse events.Patients ≥60 years old with stage TCosmesis and QoL were collected at 97% (99/102) of possible follow-up patient-time points. By 12 weeks post-treatment, 93.9% (31/33) of patient-reported and 96.9% (31/32) of clinician-reported cosmesis outcomes were "good." Compared to baseline, total Skindex-16 score significantly deteriorated at 2 weeks post-treatment (10.5 vs 24.5, p0.001), but significantly improved at 6 weeks (10.5 vs 4.7, p=.014) and 12 weeks (10.5 vs 2.1, p=.001) post-treatment. Total SCI score significantly improved from baseline to 6 weeks (78.4 vs 89.0, p=.001) post-treatment. The most frequent adverse events were radiation dermatitis, skin pain, and pruritus. All adverse events resolved to Grade ≤1 by 12 weeks post-treatment.This prospective, multicenter study demonstrated that ESSB is associated with a high rate of "good" early patient-reported cosmesis and increasing QoL and satisfaction with time. Validated assessments demonstrated a significant improvement in quality of life and resolution of moderate early adverse events by 6-12 weeks after treatment and corroborate the observation of favorable cosmesis.

BACKGROUND: There are multiple modalities for patient education ranging from written to audiovisual formats. However, little is known regarding which modality is optimal.OBJECTIVE: To assess patient preference for educational materials about scar care following surgery for facial skin cancer using the FACE-Q Skin Cancer patient reported outcome measure.MATERIALS AND METHODS: On the day of Mohs surgery, patients were given a written handout or viewed a 3-minute animation video regarding best practices in scar improvement. Afterward, patients received the FACE-Q Skin Cancer-Satisfaction with Information: Appearance scale. Three months later, patients were called and given the same scale and additional questions regarding scar care.RESULTS: A total of 75 patients were enrolled. There was no difference between the 2 groups' preoperative information scores (p = .85) and the three-month postoperative scores (p = .37). The change in preoperative and postoperative score showed no significant difference between the 2 groups (p = .21); but there was a trend of higher satisfaction in the video group on the day of Mohs surgery. After the 3-month timepoint, there was a higher satisfaction trend observed with the written handout group.CONCLUSION: Patient preferences in information delivery and accessibility will contribute to greater information retention and satisfaction.

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.

While telemedicine has been utilized with more frequency over the past two decades, there remained significant barriers to its broad implementation. The COVID-19 global pandemic served as a stimulus for rapid expansion and implementation of telemedicine services across medical institutions worldwide in order to maximize patient care delivery, minimize exposure risk among healthcare providers and patients alike, and avoid overcrowding of patient care facilities. In this experience report, we highlight the teledermatology initiatives executed by the Dermatology Service at Memorial Sloan Kettering Cancer Center in New York City, with particular emphasis on image ingestion and potential for future automation and improvement.

BACKGROUND: 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. OBJECTIVES: We sought to evaluate the rate of upstaging in nail unit SCCIS after Mohs micrographic surgery (MMS). METHODS: 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. RESULTS: Thirty-one cases met the inclusion criteria and were analyzed. Twenty-four patients were male (77.4%). Mean age was 55 years (SD 17.26, range 27–84). 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. CONCLUSION: 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.

INTRODUCTION: Recently, a combined reflectance confocal microscopy (RCM)-optical coherence tomography (OCT) has been tested for the diagnosis of basal cell carcinoma (BCC). Evaluating the role of RCM-OCT in management of complex BCCs has not been studied. The objective of the study was to investigate the utility of a new combined RCM-OCT device in the evaluation and management of complex BCCs in a descriptive study. METHODS: Prospective study of consecutive cases (July 2018- June 2019) of biopsy proven ‘complex’ BCC defined as BCC in the head and neck area with multiple high risk criteria such as large size in the mask area, multiple recurrences, and infiltrative subtype. All cases were evaluated with a combined RCM-OCT device that provided simultaneous image viewing on a screen. Lesions were evaluated bedside with RCM-OCT according to previously described criteria. RESULTS: Ten patients with complex head and neck BCCs had mean age of 73.1±13.0 years. Six (60%) patients were males. Mean BCC clinical size was 1.9±1.2 cm (range 0.6–4.0 cm). RCM detected residual BCC in 8 out of 10 cases (80%) and OCT detected residual BCC in all 10 cases (100%). Six BCCs (60%) had a depth estimate of >1000 μm under OCT. In 5 cases, (50%) RCM-OCT imaging results led to a change/modification in BCC management. CONCLUSION: The use of a combined RCM-OCT device may help in the evaluation of complex head and neck BCCs by guiding treatment selection and defining the extent of surgery.

Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and axillary skin. Extramammary Paget disease can precede or occur along with internal malignant neoplasms.To develop recommendations for the care of adults with EMPD.A systematic review of the literature on EMPD from January 1990 to September 18, 2019, was conducted using MEDLINE, Embase, Web of Science Core Collection, and Cochrane Libraries. Analysis included 483 studies. A multidisciplinary expert panel evaluation of the findings led to the development of clinical care recommendations for EMPD.The key findings were as follows: (1) Multiple skin biopsies, including those of any nodular areas, are critical for diagnosis. (2) Malignant neoplasm screening appropriate for age and anatomical site should be performed at baseline to distinguish between primary and secondary EMPD. (3) Routine use of sentinel lymph node biopsy or lymph node dissection is not recommended. (4) For intraepidermal EMPD, surgical and nonsurgical treatments may be used depending on patient and tumor characteristics, although cure rates may be superior with surgical approaches. For invasive EMPD, surgical resection with curative intent is preferred. (5) Patients with unresectable intraepidermal EMPD or patients who are medically unable to undergo surgery may receive nonsurgical treatments, including radiotherapy, imiquimod, photodynamic therapy, carbon dioxide laser therapy, or other modalities. (6) Distant metastatic disease may be treated with chemotherapy or individualized targeted approaches. (7) Close follow-up to monitor for recurrence is recommended for at least the first 5 years.Clinical practice guidelines for EMPD provide guidance regarding recommended diagnostic approaches, differentiation between invasive and noninvasive disease, and use of surgical vs nonsurgical treatments. Prospective registries may further improve our understanding of the natural history of the disease in primary vs secondary EMPD, clarify features of high-risk tumors, and identify superior management approaches.

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.

Ex vivo confocal microscopy (EVCM) generates digitally colored purple-pink images similar to HE without time-consuming tissue processing. It can be used during Mohs surgery for rapid detection of basal cell carcinoma (BCC); however, reading EVCM images requires specialized training. An automated approach using a deep learning algorithm for BCC detection in EVCM images can aid in diagnosis. A total of 40 BCCs and 28 negative (not-BCC) samples were collected at Memorial Sloan Kettering Cancer Center to create three training datasets: (i) EVCM image dataset (663 images), (ii) HE image dataset (516 images), and (iii) a combination of the two datasets. A total of seven BCCs and four negative samples were collected to create an EVCM test dataset (107 images). The model trained with the EVCM dataset achieved 92% diagnostic accuracy, similar to the HE model (93%). The area under the receiver operator characteristic curve was 0.94, 0.95, and 0.94 for EVCM-, HE-, and combination-trained models, respectively. We developed an algorithm for automatic BCC detection in EVCM images (comparable accuracy to dermatologists). This approach could be used to assist with BCC detection during Mohs surgery. Furthermore, we found that a model trained with only HE images (which are more available than EVCM images) can accurately detect BCC in EVCM images.

BACKGROUND The rate of occult invasive disease within biopsy-proven squamous cell carcinoma in situ (SCCIS) is not well defined. OBJECTIVE To examine the rate of occult invasion in SCCIS. METHODS An institutional-wide pathology database was retrospectively searched for "squamous cell carcinoma in situ" over a 6-year period, and the treatment modality and final pathology results were analyzed for evidence of invasion. In addition, consecutive tumor blocks from Mohs micrographic surgery (MMS) cases of SCCIS were prospectively analyzed for invasion. RESULTS The rate of occult invasion for biopsy-proven SCCIS treated with excision was 4.0% (N = 49) and for the MMS margins was 3.5% (N = 310). For the prospective MMS tumor block analysis, the rate of occult invasion was 10.1% (N = 69). No clinical factors (age, sex, location, or size) correlated with increased risk of invasion. All invasive SCCs detected were superficial and well differentiated. CONCLUSION The rate of occult invasion for biopsy-proven SCCIS ranged from 3.5% to 10.1%. The detected rate of invasion varies based on the method of excision and pathology processing of specimens. The rate of invasion should be considered when managing SSCIS.

BACKGROUND: Over two million facial skin cancers occur globally each year. Facial skin cancer surgery can leave scars that may alter appearance and impact psychosocial functioning. OBJECTIVE: To assess patient-reported appearance-related psychosocial distress following facial skin cancer surgery, and to identify independent predictors of psychosocial impairment. METHODS: This was a single-center, cross-sectional study at a tertiary care cancer center including patients who underwent dermatologic surgery on the face from March 1, 2016 to March 31, 2018. Patients completed the FACE-Q Skin Cancer Appearance-Related Psychosocial Distress scale postoperatively between May 21, 2018 and October 1, 2018. Patient responses were rated on a 4-point Likert scale and converted on a scale from 0 to 100. RESULTS: In total, 359 patients completed the questionnaire (34.2% response rate). Overall, patients reported a low level of psychosocial distress. Patients most frequently reported items of self-consciousness, unhappiness, and insecurity

Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in the United States. Outcomes are generally favorable, but a subset of cSCC is biologically distinct and requires a different approach because of its higher risk of local recurrence, metastasis, and death. This article focuses on the recent literature regarding identification of this high-risk subset, efforts to validate and improve the prognostic ability of staging systems, and updates in management.

Background There is little evidence to guide surgical management of biopsies yielding the histologic descriptor atypical intraepidermal melanocytic proliferation (AIMP). Objective Determine frequency of and factors associated with melanoma and melanoma in-situ (MIS) diagnoses after excision of AIMP and evaluate margins used to completely excise AIMP. Methods Retrospective, cross-sectional study of 1127 biopsies reported as AIMP and subsequently excised within one academic institution. Results Melanoma (in situ, stage 1A) was diagnosed after excision in 8.2% (92/1127) of AIMP samples. Characteristics associated with melanoma/MIS diagnosis included age 60-79 years (odds ratio [OR] 8.1, 95% confidence interval [CI] 2.5-26.2), age ≥80 years (OR 7.2, 95% CI 1.7-31.5), head/neck location (OR 4.9, 95% CI 3.1-7.7), clinical lesion partially biopsied (OR 11.0, 95% CI 6.7-18.1), and lesion extending to deep biopsy margin (OR 15.1, 95% CI 1.7-136.0). Average ± standard deviation surgical margin used to excise AIMP lesions was 4.5 ± 1.8 mm. Limitations Single-site, retrospective, observational study; interobserver variability across dermatopathologists. Conclusion Dermatologists and pathologists can endeavor to avoid ambiguous melanocytic designations whenever possible through excisional biopsy technique, interdisciplinary communication, and ancillary studies. In the event of AIMP biopsy, physicians should consider the term a histologic description rather than a diagnosis, and, during surgical planning, use clinicopathologic correlation while bearing in mind factors that might predict true melanoma/MIS.

As the most common human cancer worldwide and continuing to increase in incidence, basal cell carcinoma is associated with significant morbidity and cost. Continued advances in research have refined both our insight and approach to this seemingly ubiquitous disease. This 2-part continuing medical education article will provide a comprehensive and contemporary review of basal cell carcinoma. The first article in this series describes our current understanding of this disease regarding epidemiology, cost, clinical and histopathologic presentations, carcinogenesis, natural history, and disease associations.

As the most common human cancer worldwide and continuing to increase in incidence, basal cell carcinoma is associated with significant morbidity and cost. Continued advances in research have refined both our insight and approach to this seemingly ubiquitous disease. This 2-part continuing medical education series provides a comprehensive and contemporary review of basal cell carcinoma. The second article in this series will present both the current standard of care and newly developed approaches to diagnosis, treatment, and prevention of this disease.

Reflectance confocal microscopy (RCM) with endogenous backscattered contrast can noninvasively image basal cell carcinomas (BCCs) in skin. However, BCCs present with high nuclear density, and the relatively weak backscattering from nuclei imposes a fundamental limit on contrast, detectability, and diagnostic accuracy. We investigated PARPi-FL, an exogenous nuclear poly(adenosine diphosphate ribose) polymerase (PARP1)–targeted fluorescent contrast agent, and fluorescence confocal microscopy toward improving BCC diagnosis. Methods: We tested PARP1 expression in 95 BCC tissues using immunohistochemistry, followed by PARPi-FL staining in 32 fresh surgical BCC specimens. The diagnostic accuracy of PARPi-FL contrast was evaluated in 83 surgical specimens. The optimal parameters for permeability of PARPi-FL through intact skin was tested ex vivo on 5 human skin specimens and in vivo in 3 adult Yorkshire pigs. Results: We found significantly higher PARP1 expression and PARPi-FL binding in BCCs than in normal skin structures. Blinded reading of RCM–and–fluorescence confocal microscopy images by 2 experts demonstrated a higher diagnostic accuracy for BCCs with combined fluorescence and reflectance contrast than for RCM alone. Optimal parameters (time and concentration) for PARPi-FL transepidermal permeation through intact skin were successfully determined. Conclusion: Combined fluorescence and reflectance contrast may improve noninvasive BCC diagnosis with confocal microscopy.

Background Novel solutions are needed for expediting margin assessment to guide BCC surgeries. Ex-vivo fluorescence confocal microscopy (FCM) is starting to be used in freshly-excised surgical specimens to examine BCC margins in real-time. Training and educational process are needed for this novel technology to be implemented into clinic. Objective To test a training and reading process, and measure diagnostic accuracy of clinicians with varying expertise level in reading ex-vivo FCM images. Methods An international 3-center study was designed for training and reading to assess BCC surgical margins and residual subtypes. Each center included a lead dermatologic/Mohs surgeon (clinical developer of FCM), and 3 additional readers (dermatologist, dermatopathologist, dermatologic/Mohs surgeon), who use confocal in clinical practice. Testing was conducted on 30 samples. Results Overall, the readers achieved 90% average sensitivity, 78% average specificity in detecting residual BCC margins, showing high and consistent diagnostic reading accuracy. Those with expertise in dermatologic surgery and dermatopathology showed the strongest potential for learning to assess FCM images. Limitations Small dataset, variability in mosaic quality between centers. Conclusion Suggested process is feasible and effective. This process is proposed for wider implementation, to facilitate wider adoption of FCM to potentially expedite BCC margin assessment to guide surgery in real-time. This article is protected by copyright. All rights reserved.

Towards improving non-invasive BCC diagnosis, we demonstrate successful PARPi-FL (PARP1-targeted nuclear contrast) labeling in tumors, permeability through stratum corneum, and high diagnostic accuracy with combined PARPi-FL and reflectance contrast.

The expanding role of social media in medical care has resulted in dermatology patients seeking support online regarding personal experience with diagnosis and treatment of skin cancer. Owing to increased privacy settings in closed Facebook groups, the current study analyzed themes of keratinocyte carcinoma patients' posts within a relatively private social media network. Although the majority of messages included sharing personal experience and provided psychosocial support (50%), there were a significant number of posts offering medical advice (35%), with the majority of such replies being unsupported by evidence-based medicine (87%). The level of medical misinformation and potential harm to patients seeking advice online is important for medical practitioners treating skin cancer and provides impetus for possible further research into online support and education groups that are moderated for misinformation.

One of the major challenges faced when treating high-risk keratinocyte carcinoma (KC) is the unpredictable subclinical extension. Yaroslavsky et al. (2020) evaluated dual-wavelength optical polarization imaging (OPI) for the detection for KC margins before Mohs surgery with promising results. OPI might be useful as a screening tool to limit unnecessary surgery.

The expanding role of social media in medical care has resulted in dermatology patients seeking support online regarding personal experience with diagnosis and treatment of skin cancer. Owing to increased privacy settings in closed Facebook groups, the current study analyzed themes of keratinocyte carcinoma patients' posts within a relatively private social media network. Although the majority of messages included sharing personal experience and provided psychosocial support (50%), there were a significant number of posts offering medical advice (35%), with the majority of such replies being unsupported by evidence-based medicine (87%). The level of medical misinformation and potential harm to patients seeking advice online is important for medical practitioners treating skin cancer and provides impetus for possible further research into online support and education groups that are moderated for misinformation.