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Importance: Germline SUFU pathogenic variants (PVs) have previously been associated with basal cell nevus syndrome (BCNS) and multiple infundibulocystic basal cell carcinoma syndrome; however, a broader spectrum of cutaneous findings in patients with SUFU PVs has not been well delineated., Objective: To define the clinical and histopathologic spectrum of cutaneous findings in patients with germline SUFU PVs., Design, Setting, and Participants: This case series was conducted in multiple US academic dermatology, medical genetics, and medical oncology clinics between July 2014 and July 2022. The study included patients with confirmed germline SUFU PVs who were evaluated by a dermatologist. The analysis took place from March to September 2023., Main Outcomes and Measures: Histopathologic evaluation of skin biopsies with or without immunohistochemical staining, and targeted next-generation sequencing (NGS) on tumor specimens., Results: All 5 patients were women. The mean (range) age at presentation was 50.2 (31-68) years, with skin manifestations initially appearing in the fourth to sixth decades of life. None had keratocystic odontogenic tumors. A total of 29 skin pathology specimens from the 5 patients were reviewed; of these, 3 (10.3%) were diagnosed as basaloid follicular hamartomas (BFHs), 10 (34.5%) classified as infundibulocystic basal cell carcinomas (iBCCs), 6 (20.7%) classified as nodular basal cell carcinomas (nBCCs), and 1 (3.4%) as infiltrative basal cell carcinoma (BCC). Targeted NGS studies on tumor specimens suggest that an increased number of UV-signature variants is associated with basal cell carcinomas compared with more indolent basaloid follicular hamartomas., Conclusions and Relevance: Patients with germline SUFU PVs may present with multiple indolent basaloid neoplasms in addition to conventional basal cell carcinomas, typically appearing in the fourth to sixth decades of life. Although there are overlapping clinical manifestations, these findings help to differentiate the clinical syndrome associated with SUFU PVs from PTCH1 BCNS. Awareness of the clinicopathologic spectrum of SUFU-associated basaloid neoplasms is important for dermatologists and dermatopathologists because many (although not all) of these lesions are indolent and do not require aggressive surgical treatment. Importantly, because SUFU lies downstream of the protein smoothened, vismodegib and other smoothened inhibitors are unlikely to be effective therapies in this subset of patients.

Importance: Patient preferences for pain medications after Mohs micrographic surgery are important to understand and have not been fully studied., Objective: To evaluate patient preferences for pain management with only over-the-counter medications (OTCs) or OTCs plus opioids after Mohs micrographic surgery given varying levels of theoretical pain and opioid addiction risk., Design, Setting, and Participants: This prospective discrete choice experiment was conducted in a single academic medical center from August 2021 to April 2022 among patients undergoing Mohs surgery and their accompanying support persons (≥18 years). A prospective survey was administered to all participants using the Conjointly platform. Data were analyzed from May 2022 to February 2023., Main Outcome and Measure: The primary outcome was the pain level at which half of the respondents chose OTCs plus opioids equally to only OTCs for pain management. This pain threshold was determined for varying opioid addiction risk profiles (low, 0%; low-moderate, 2%; moderate-high, 6%; high, 12%) and measured via a discrete choice experiment and linear interpolation of associated parameters (pain levels and risk of addiction)., Results: Of the 295 respondents (mean [SD] age, 64.6 [13.1] years; 174 [59%] were female; race and ethnicity were not considered) who completed the discrete choice experiment, 101 (34%) stated that they would never consider opioids for pain management regardless of the pain level experienced, and 147 (50%) expressed concern regarding possible opioid addiction. Across all scenarios, 224 respondents (76%) preferred only OTCs vs OTCs plus opioids after Mohs surgery for pain control. When the theoretical risk of addiction was low (0%), half of the respondents expressed a preference for OTCs plus opioids given pain levels of 6.5 on a 10-point scale (90% CI, 5.7-7.5). At higher opioid addiction risk profiles (2%, 6%, 12%), an equal preference for OTCs plus opioids and only OTCs was not achieved. In these scenarios, patients favored only OTCs despite experiencing high levels of pain., Conclusion and Relevance: The findings of this prospective discrete choice experiment indicate that the perceived risk of opioid addiction affects the patient's choice of pain medications after Mohs surgery. It is important to engage patients undergoing Mohs surgery in shared decision-making discussions to determine the optimal pain control plan for each individual. These findings may encourage future research on the risks associated with long-term opioid use after Mohs surgery.

Importance: There are limited reports on the risks of multiple primary skin cancers in organ transplant recipients (OTRs)., Objective: To determine the risks over time and risk factors for OTRs developing (1) any skin cancer posttransplant, (2) a subsequent skin cancer after the first posttransplant skin cancer in the data sets used in the study, and (3) 10 or more skin cancers., Design, Setting, and Participants: This retrospective cohort study used data from Optum deidentified electronic health record data set (7.7 million patients) and Truven Health MarketScan insurance claims data set (161 million patients) from 2007 to 2017. Skin cancers were identified using diagnosis plus treatment codes for basal cell carcinoma, squamous cell carcinoma, and melanoma; OTRs were identified using 4 or more diagnosis codes for organ transplant. Data analysis took place from January 1, 2007, to December 31, 2017., Main Outcomes and Measures: Cumulative risks of (1) any skin cancer treatment posttransplant, (2) a subsequent skin cancer treatment after the first posttransplant skin cancer treatment in our data, and (3) 10 or more skin cancer treatments in OTRs. A Wei-Lin-Weissfeld marginal model was used to evaluate risk factors for any skin cancer., Results: A total of 7390 OTRs in Optum and 133 651 in MarketScan were identified, 4.5% and 13.3% of which had had at least 1 skin cancer treatment, respectively. At 2 years after the initial posttransplant skin cancer in the data sets, OTRs had a 44.0% to 57.0% risk of a subsequent skin cancer treatment and a 3.7% to 6.6% risk of having 10 or more skin cancer treatments. Statistically significant risk factors for any skin cancer included age, history of skin cancer, and history of actinic keratosis in both data sets, and male sex and thoracic transplant in MarketScan., Conclusions and Relevance: In this retrospective cohort study, approximately half of the OTRs who developed at least 1 posttransplant skin cancer developed a subsequent skin cancer within 2 years, and approximately 1 in 20 developed 10 or more skin cancers. Identifying OTRs at highest risk for multiple primary skin cancers may help target strategies for prevention and early detection.

Importance: To curtail the opioid epidemic, physicians have been advised to limit opioid prescriptions., Objective: To characterize the frequency and changes over time (2009-2020) of opioid prescriptions following Mohs micrographic surgery., Design, Setting, and Participants: This cross-sectional study using Optum Clinformatics DataMart (Optum CDM), a nationally representative insurance claims database, included patients aged 18 years and older who had Mohs micrographic surgery insurance claims in the Optum CDM database from 2009 to 2020. Data were analyzed from November 11, 2020, to March 30, 2021., Exposures: Opioid prescription following Mohs surgery., Main Outcomes and Measures: The primary outcome was the proportion of patients who underwent Mohs surgery and obtained an opioid prescription within 2 days of surgery. Secondary outcomes included type and opioid quantity prescribed., Results: Among 358 012 patients with Mohs micrographic surgery claims (mean [SD] age, 69 [13] years; 205 609 [57.4%] were men), the proportion of patients obtaining an opioid prescription after Mohs micrographic surgery increased from 2009 (34.6%) to 2011 (39.6%). This proportion then declined each year, reaching a low of 11.7% in 2020 (27.9% absolute decrease from 2011 to 2020). Hydrocodone, codeine, oxycodone, and tramadol were the 4 most commonly prescribed opioids. By 2020, hydrocodone was obtained less (2009: 47.5%; 2011: 67.1%; 2020: 45.4%; 21.7% absolute decrease from 2011 to 2020) and tramadol was obtained more (2009: 1.6%; 2020: 27.9%; 26.3% absolute increase from 2009 to 2020)., Conclusions and Relevance: In this cross-sectional study of Mohs micrographic surgery claims, patients obtained fewer postsurgery opioid prescriptions over the study period, suggesting responsiveness of patients and dermatologic surgeons to public health concerns regarding the opioid epidemic. During this decline, prescriptions for hydrocodone decreased and tramadol increased.

Importance: There is a paucity of evidence to guide physicians regarding prevention strategies for cutaneous squamous cell carcinoma (CSCC) in solid organ transplant recipients (SOTRs)., Objective: To examine the development and results of a Delphi process initiated to identify consensus-based medical management recommendations for prevention of CSCC in SOTRs., Evidence Review: Dermatologists with more than 5 years' experience treating SOTRs were invited to participate. A novel actinic damage and skin cancer index (AD-SCI), consisting of 6 ordinal stages corresponding to an increasing burden of actinic damage and CSCC, was used to guide survey design. Three sequential web-based surveys were administered from January 1, 2019, to December 31, 2020. Pursuant to Delphi principles, respondents thoroughly reviewed all peer responses between rounds. Supplemental questions were also asked to better understand panelists' rationale for their responses., Findings: The Delphi panel comprised 48 dermatologists. Respondents represented 13 countries, with 27 (56%) from the US. Twenty-nine respondents (60%) were Mohs surgeons. Consensus was reached with 80% or higher concordance among respondents when presented with a statement, question, or management strategy pertaining to prevention of CSCC in SOTRs. A near-consensus category of 70% to less than 80% concordance was also defined. The AD-SCI stage-based recommendations were established if consensus or near-consensus was achieved. The panel was able to make recommendations for 5 of 6 AD-SCI stages. Key recommendations include the following: cryotherapy for scattered actinic keratosis (AK); field therapy for AK when grouped in 1 anatomical area, unless AKs are thick in which case field therapy and cryotherapy were recommended; combination lesion directed and field therapy with fluorouracil for field cancerized skin; and initiation of acitretin therapy and discussion of immunosuppression reduction or modification for patients who develop multiple skin cancers at a high rate (10 CSCCs per year) or develop high-risk CSCC (defined by a tumor with approximately ≥20% risk of nodal metastasis). No consensus recommendation was achieved for SOTRs with a first low risk CSCC., Conclusions and Relevance: Physicians may consider implementation of panel recommendations for prevention of CSCC in SOTRs while awaiting high-level-of-evidence data. Additional clinical trials are needed in areas where consensus was not reached.

Importance: Single-center studies have shown that patients report better skin cancer-specific quality of life (QOL) after Mohs micrographic surgery (MMS), but it is unclear whether this improved QOL applies to patients after MMS and complex reconstruction in cosmetically sensitive areas., Objective: To evaluate patient QOL after MMS and interpolation flap reconstruction for patients with nasal skin cancers., Design, Setting and Participants: This multicenter prospective survey study used the Skin Cancer Index (SCI), a validated, 15-question QOL questionnaire administered at 4 time points: before MMS, 1 week after flap placement, 4 weeks after flap takedown, and 16 weeks after flap takedown. Patients age 18 years or older with a nasal skin cancer who presented for MMS and were anticipated to undergo 2-stage interpolated flap repair by a Mohs surgeon were recruited from August 9, 2018, to February 2, 2020, at 8 outpatient MMS locations across the United States, including both academic centers and private practices., Main Outcomes and Measures: Mean difference in overall SCI score before MMS vs 16 weeks after flap takedown., Results: A total of 169 patients (92 men [54.4%]; mean [SD] age, 67.7 [11.4] years) were enrolled, with 147 patients (75 men [51.0%]; mean [SD] age, 67.8 [11.7] years) completing SCI surveys both before MMS and 16 weeks after flap takedown. Total SCI scores improved significantly 16 weeks after flap takedown compared with pre-MMS scores, increasing by a mean of 13% (increase of 7.11 points; 95% CI, 5.48-8.76; P < .001). All 3 SCI subscale scores (emotion, appearance, and social) improved significantly (emotion subscale, increase of 3.27 points; 95% CI, 2.35-4.18; P < .001; appearance subscale, increase of 1.65 points; 95% CI, 1.12-2.18; P < .001; and social subscale, increase of 2.10 points; 95% CI, 1.55-2.84; P < .001) 16 weeks after flap takedown compared with pre-MMS., Conclusions and Relevance: Removal of a nasal skin cancer and repair of the resulting defect can be distressing for patients. However, this cohort study suggests that physicians referring patients for MMS can be reassured that their patient's QOL will improve on average after surgery, even when a complex reconstruction is required.

Importance: Defining which populations are affected by basal cell carcinoma (BCC) vs cutaneous squamous cell carcinoma (cSCC) may inform targeted public health strategies. Incidence of BCC and cSCC is not reported to national cancer registries, but claims data for the treatment of BCC and cSCC provide insights into the epidemiology of keratinocyte carcinoma., Objective: To define differences in the ratio of BCC to cSCC in adults (age, ≥18 years) in a large database of patients with commercial insurance and Medicare Advantage coverage., Design, Setting, and Participants: This cross-sectional analysis used deidentified data derived from the Optum Clinformatics Data Mart to perform a retrospective evaluation of a large commercially insured cohort based on treatment claims from January 1, 2012, to December 31, 2016. Patients with a diagnosed and treated BCC or cSCC as determined by codes from the International Classification of Diseases, Ninth Revision, International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, and Current Procedural Terminology were included. Data were analyzed from November 30, 2019, to March 20, 2020., Exposure: Diagnosis and treatment of BCC or cSCC., Main Outcomes and Measures: The ratio of BCC to cSCC based on age, sex, race, and geographic location. Multivariable logistic regression was used to assess how demographics were associated with the odds of a treated keratinocyte carcinoma being a BCC., Results: Among the 985 317 claims for patients included in the analysis (61.59% for men; mean [SD] age, 69.82 [12.58] years), BCCs were 1.69 (95% CI, 1.6899-1.6901) times more likely than cSCCs to be treated in the United States from 2012 to 2016. Basal cell carcinomas were significantly more prevalent than cSCCs in younger patients (18-39 years, 9.63 [95% CI, 9.6088-9.6574] BCCs per cSCC; 40-64 years, 2.92 [95% CI, 2.9171-2.9187] BCCs per cSCC; and ≥65 years, 1.33 [95% CI, 1.3289-1.3291] BCCs per cSCC; P < .001). Basal cell carcinomas were significantly more prevalent than cSCCs in women vs men, except in adults 65 years or older (odds ratios [ORs], 0.98 [95% CI, 0.97-0.99] vs 1.67 [95% CI, 1.47-1.88] for those aged 18-39 and 1.15 [95% CI, 1.12-1.19] for those aged 40-64 years; P < .001). The difference in BCC:cSCC ratios between men and women diminished with increasing age (OR, 1.67 for 18-39 years, 1.15 for 40-64 years, and 0.98 for 65 years or older). Basal cell carcinoma was more prevalent than cSCC in all races, including Black patients (BCC:SCC ratios, 1.60 for Asian patients, 1.45 for Black patients, 2.00 for Hispanic patients, and 1.69 for White patients of all ages). The BCC:cSCC ratio varied based on geography, with the highest ratio in the West North Central census division (2.12) and the lowest ratio in the South Atlantic census division (1.35)., Conclusions and Relevance: In the absence of a national registry, claims data can improve our understanding of the epidemiology of keratinocyte carcinomas. In this cross-sectional study, basal cell carcinomas were more common than cSCCs for all demographics, including in Black patients. In populations younger than 40 years, BCCs were 12.6 times more likely for women and 7.2 times more likely for men. These demographic groups may benefit from public health education focused on the presentation and management of BCCs.

Importance: National Comprehensive Cancer Network guidelines for melanoma have consistently recommended wide local excision as the standard of care since their inception. Although surgery with more comprehensive margin assessment (eg, Mohs surgery) has been advocated for certain subsets of melanoma, how often these techniques are used in clinical practice is uncertain., Objective: To examine trends in the use of comprehensive margin assessment surgery for melanoma by tracking claims data for Mohs surgery., Design, Setting, and Participants: This national cross-sectional analysis examined claims data from the Optum Clinformatics Data Mart, a nationally representative database. The study cohort consisted of 79 108 patients undergoing surgical excision for melanoma from January 1, 2001, through December 31, 2016. Data were analyzed from January 1, 2001, through December 31, 2016., Main Outcomes and Measures: The primary outcome was the likelihood of a melanoma being treated with Mohs surgery over time, evaluated by multivariable logistic regression and expressed as the odds of treatment per additional calendar year., Results: Among 79 108 patients with melanoma (median age, 63 years [interquartile range {IQR}, 51-73]; 47 407 men [59.9%]), 75 047 were treated with conventional excision (median age, 62 years [IQR, 50-73 years]; 44 786 men [59.7%]) and 4061 with Mohs surgery (median age, 67 years [IQR, 56-76 years]; 2621 men [64.5%]). Mohs surgery was used in 5.1% of all surgical cases, with the rate of Mohs surgery increasing 304% from 2.6% in 2001 to 7.9% in 2016. Odds of receiving Mohs surgery for melanoma increased significantly in more recent calendar years (odds ratio [OR], 1.02 per calendar year; 95% CI, 1.01-1.03; P < .001). Immunohistochemistry (IHC) use was only coded with Mohs surgery in 1087 cases (26.8%), and the odds of receiving Mohs surgery with IHC increased in more recent calendar years (OR, 1.13 per calendar year; 95% CI, 1.10-1.15; P < .001). Use of Mohs surgery and Mohs surgery with IHC for melanoma differed widely across geographic census divisions with greater than 3-fold variation between the regions with highest and lowest use in every period (eg, for 2013 through 2016, the East South Central region used Mohs surgery in 8.8% of melanoma excisions compared with 2.6 in the New England region)., Conclusions and Relevance: Despite stable guidelines for melanoma surgery, the results of this study suggest that surgical practices for melanoma are evolving. Wide variations in surgical practice patterns for melanoma are present in the United States. This study's findings suggest that the effect of variations in surgical techniques on outcomes requires scrutiny and further study.

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.