NCCN Guidelines® Insights: Merkel Cell Carcinoma, Version 1.2024.

The NCCN Guidelines for Merkel Cell Carcinoma (MCC) provide recommendations for diagnostic workup, clinical stage, and treatment options for patients. The panel meets annually to discuss updates to the guidelines based on comments from expert review from panel members, institutional review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new page for locally advanced disease in the setting of clinical node negative status, entitled "Clinical N0 Disease, Locally Advanced MCC." This new algorithm page addresses locally advanced disease, and the panel clarifies the meaning behind the term "nonsurgical" by further defining locally advanced disease. In addition, the guideline includes the management of in-transit disease and updates to the systemic therapy options.

Role of Wnt signaling in dermatofibroma induction phenomenon.

BACKGROUND: Dermatofibroma (DF) is a common benign skin neoplasm. Induction above DF lesions, including follicular unit induction, is a frequently observed phenomenon. Wnt signaling is known to be critical in hair follicle morphogenesis. Our study assesses the role of Wnt signaling in DF induction by evaluating intracellular localization of ß-catenin in various types of DF induction. METHODS: Archived tissue collected between 1 October 1980 and 1 October 2013 was stained per protocol using hematoxylin and eosin and anti-ß-catenin monoclonal antibody. Specimens were grouped into categories based on the presence or absence and type of induction. All specimens were scored for nuclear ß-catenin localization. RESULTS: Of 62 specimens, 42 (68%) showed induction while 20 (32%) showed none. Nuclear ß-catenin staining was detected in 23 (55%) of the induction and in none of the no-induction specimens (P-value < 0.001). Types of induction included: 15 (24%) follicular induction, 31 (50%) acanthosis, and 4 (6%) sebaceous induction. For follicular induction, 13 (87%) showed positive nuclear ß-catenin staining compared to 11 (35%) for acanthosis and 1 (25%) for sebaceous induction (P-value = 0.002). CONCLUSION: Our findings support the hypothesis that DFs promote an ectopic activation of Wnt pathway signaling in follicular induction phenomenon.

Sebaceous carcinoma: evidence-based clinical practice guidelines.

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

Acrochordon With Histological Features of Lichen Sclerosus.

Lichen sclerosus (LS) is a chronic inflammatory dermatosis that classically presents as sclerotic, atrophic plaques in the genital region. We present a case of acrochordon with histological features of LS, clinically mimicking intradermal nevus, in a 53-year-old man with no prior history of LS. Our case highlights an unusual morphologic variant of acrochordon and illustrates the role of chronic pressure and occlusion in the development of secondary features of LS.

Quantification of noninvasive fat reduction: A systematic review.

BACKGROUND AND OBJECTIVE: Noninvasive fat reduction appears effective, but there are various methods for quantifying changes. The objective of this review is to assess comparative utility measures of subcutaneous fat. STUDY DESIGN/MATERIALS AND METHODS: Articles describing noninvasive fat reduction were searched using MEDLINE, EMBASE, CINAHL and Scopus electronic databases on two dates (January 28, 2014 and February 16, 2016). Titles of studies and abstracts were screened for eligibility. Manual review was performed by two investigators to detect those that: (1) included original data; (2) were randomized controlled trials, or prospective or retrospective cohort studies; (3) quantified fat outcomes; and (4) enrolled at least 10 subjects. RESULTS: Of 1,057 retrieved articles, 36 met criteria. Most reported four or more measurement techniques. Circumference measurements were most commonly cited. Other objective techniques, like caliper thickness, ultrasound, magnetic resonance imaging (MRI), and three-dimensional (3D) photography, were also used. Common subjective methods were evaluation of standardized photographs by blinded raters and patient satisfaction surveys. CONCLUSIONS: For quantifying noninvasive fat reduction, all available methods had significant limitations: photographic comparisons were subjective; circumference or caliper measurements were confounded; ultrasound was operator dependent; MRI was expensive; computed models and simulations were in early development. As new technologies are developed, the need for reliable, accurate and practical measures of subcutaneous fat will increase. Lasers Surg. Med. 50:96-110, 2018. © 2017 Wiley Periodicals, Inc.

Histologic Status of Squamous Cell Carcinoma In Situ After Diagnostic Biopsy in Immunocompetent and Immunosuppressed Patients.

BACKGROUND: The histologic status of squamous cell carcinoma in situ (SCC-IS) after diagnostic biopsy has not been well described or compared between immunocompetent and immunosuppressed patients. Expression of immunohistochemical (IHC) markers of aggressive SCC has not been compared between SCC-IS that clears or becomes invasive after biopsy. OBJECTIVE: To determine the histologic status of SCC-IS after diagnostic biopsy in these populations. METHODS: Retrospective analysis of 129 patients with SCC-IS treated with excision and 55 patients treated with Mohs surgery. Histologic features of SCC in excised tissue after biopsy were recorded. Known SCC markers were evaluated using IHC. RESULTS: Invasive SCC was found in 3% to 16% of residual SCC-IS depending on surgical treatment modality. The history of skin cancer increased the odds of having invasive SCC in SCC-IS excisions (odds ratio 7.1, p < .05). Forty-seven percent of SCC-IS in immunosuppressed patients cleared after diagnostic biopsy compared with 70% in immunocompetent patients (p < .05). Inflammatory infiltrate and molecular markers of aggressive SCCs (Ki-67, matrix metalloproteinase [MMP]-9, MMP-7, transforming growth factor-beta (TGFß)-RI, TGFß-RII, and Sox-2) were not predictive of residual or invasive SCC at the time of treatment. CONCLUSION: Up to 16% of SCC-IS showed invasive SCC at the time of surgical treatment. Immunosuppressed patients are more likely to have residual disease after biopsy. IHC markers of invasive SCC may not predict invasion.

Regenerative Medicine and Stem Cells in Dermatology.

BACKGROUND: Clinically relevant regenerative medicine is still in its early stages of development. Difficulties in regenerating large-scale and complex structures, the lack of safety data, and the paucity of clinical trials have slowed the process of technological advance. OBJECTIVE: To familiarize the clinician with techniques available in the laboratory and experimental approaches being tested clinically. In addition, a layout is discussed for how dermatologists can lead the way in bringing regenerative medicine to clinical reality. METHODS: This article reviews the relevant literature on regenerative medicine for dermatological applications and discusses findings and techniques in a clinically relevant context. RESULTS: Multiple cell-free and cell-based approaches for regenerating dermatologic tissues have been reported in the basic science and clinical literature. These are reviewed in the order of complexity. CONCLUSION: Incremental steps are needed to apply the principles of regenerative medicine to simple medical problems first. Such a stepwise approach would commence, for example, with creation of single-function tissues that could fill soft-tissue defects and proceed to the development of fully functional skin grafts. Likewise, cell-free approaches can build the foundation for the more technically demanding cell-based strategies that are likely necessary for achieving the ultimate goal of regenerative dermatology.

ASDS Guidelines Task Force: Consensus Recommendations Regarding the Safety of Lasers, Dermabrasion, Chemical Peels, Energy Devices, and Skin Surgery During and After Isotretinoin Use.

BACKGROUND: Currently, the isotretinoin (13-cis-retinoic acid) package insert contains language advising the discontinuation of isotretinoin for 6 months before performing cosmetic procedures, including waxing, dermabrasion, chemical peels, laser procedures, or incisional and excisional cold-steel surgery. It is common practice to follow this standard because of concerns regarding reports of sporadic adverse events and increased risk of scarring. OBJECTIVE: To develop expert consensus regarding the safety of skin procedures, including resurfacing, energy device treatments, and incisional and excisional procedures, in the setting of concurrent or recent isotretinoin use. MATERIALS AND METHODS: The American Society for Dermatologic Surgery authorized a task force of content experts to review the evidence and provide guidance. First, data were extracted from the literature. This was followed by a clinical question review, a consensus Delphi process, and validation of the results by peer review. RESULTS: The task force concluded that there is insufficient evidence to justify delaying treatment with superficial chemical peels and nonablative lasers, including hair removal lasers and lights, vascular lasers, and nonablative fractional devices for patients currently or recently exposed to isotretinoin. Superficial and focal dermabrasion may also be safe when performed by a well-trained clinician.

Consensus statement regarding storage and reuse of previously reconstituted neuromodulators.

BACKGROUND: Legacy recommendations suggest that vials of botulinum toxin be used within 24 hours of reconstitution and in a single patient. Current standard of care is consistent with storage after reconstitution and use of a single vial for several patients. OBJECTIVE: To develop expert consensus regarding the effectiveness and safety of storage and reuse of botulinum toxin. MATERIALS AND METHODS: The American Society for Dermatologic Surgery authorized a task force of content experts to review the literature and provide guidance. Data extraction was followed by clinical question review, a consensus Delphi process, and validation of the results by peer review. RESULTS: After 2 rounds of Delphi process, the task force concluded by unanimous consensus and with the highest level of confidence that a vial of toxin reconstituted appropriately can, for facial muscle indications, be (1) refrigerated or refrozen for at least 4 weeks before injection without significant risk for contamination or decreased effectiveness and (2) used to treat multiple patients, assuming appropriate handling. CONCLUSION: The standard of care, which allows for use of botulinum toxin more than 24 hours after reconstitution and in more than 1 patient per vial, is appropriate and consistent with the safe and effective practice of medicine.

The comparative effectiveness of suction-curettage and onabotulinumtoxin-A injections for the treatment of primary focal axillary hyperhidrosis: a randomized control trial.

BACKGROUND: Botulinum toxin injections and suction-curettage have been separately shown to be effective in treating axillary hyperhidrosis but have not been compared in the same patients. OBJECTIVE: We sought to compare effectiveness of suction-curettage versus neurotoxin for the treatment of axillary hyperhidrosis. METHODS: Each of 20 patients was randomized to receive toxin injections to one axilla and suction-curettage to the contralateral axilla. The primary outcome measure was reduction of sweat rate measured by gravimetry, and the secondary measure was quality of life as measured by a patient-directed questionnaire. RESULTS: At 3 months posttreatment, toxin injections decreased baseline resting sweat production by 72.1% versus 60.4% (P = .29) for suction-curettage, and baseline exercise-induced sweat production by 73.8% versus 58.8% (P = .10). When patients were stratified into the categories of light and heavy sweaters, there was a difference among heavy sweaters, with exercise-induced sweat production lower by 10.48 mg/min or 34.3% (P = .0025) at toxin-treated sites. Compared with suction-curettage, toxin also resulted in greater improvements in quality of life by 0.80 points (P = .0002) and 0.90 points (P = .0017) at 3 and 6 months posttreatment, respectively, as measured by the patient questionnaire. LIMITATIONS: The follow-up period was limited to 6 months. CONCLUSIONS: By objective measures 3 months after treatment, neurotoxin injections are nominally more effective than suction-curettage in all cases, and markedly more effective in heavy sweaters. Patients have a very significant preference for neurotoxin injections at 3 months, and this is maintained at 6 months.

Targeted Therapy and Immunotherapy in Melanoma.

While metastatic melanoma still carries significant mortality rates, the introduction of targeted therapy with BRAF/MEK inhibition and immunotherapy with PD-1, PD-L1, and CTLA-4 inhibitors has led to significant strides in outcomes and prognosis.

Needs and Gaps in Resident Trainee Education, Clinical Patient Care, and Clinical Research in Cosmetic Dermatology: Position Statement of the Association of Academic Cosmetic Dermatology.

Cosmetic dermatology is a key subspecialty of academic dermatology. As such, academic centers are expected to demonstrate excellence in the teaching of cosmetic dermatology skills to trainees, the clinical delivery of cosmetic dermatology services to patients, and the performance of clinical research that advances knowledge and uncovers new therapies in cosmetic dermatology. The Association of Academic Cosmetic Dermatology (AACD), a newly formed medical professional society, includes as its principal aims the support of all of these areas. AACD is comprised of group of board-certified dermatologists who teach cosmetic and laser dermatology at US dermatology residency programs. An expert panel constituted by the AACD recently convened a workshop to review gaps pertaining to academic cosmetic dermatology. This panel considered needs and potential corrective initiatives in three domains: resident education, patient experience, and clinical research. The work of the panel was used to develop a roadmap, which was adopted by consensus, and which will serve to guide the AACD moving forward.

The Association of Academic Cosmetic Dermatology: improving cosmetic dermatology education through collaboration, research, and advocacy.

Cosmetic and laser procedures are increasingly popular among patients and are skills in which dermatologists are regarded as well trained. Most dermatology residents intend to incorporate cosmetic procedures into their practice and prefer to learn such procedures during residency through direct patient care. However, there are notable challenges in optimizing how residents are trained in cosmetic and laser dermatology. To address these barriers and elevate the practice of cosmetic dermatology in academic medicine, the Association of Academic Cosmetic Dermatology (AACD) was founded in 2021 as the lead professional society for dermatologists who direct the education of resident trainees in cosmetic and laser dermatology. The AACD, a group of board-certified dermatologists who teach cosmetic and laser dermatology to residents, aims to improve cosmetic dermatology education through collaboration, research, and advocacy.

Nonmelanoma Skin Cancer in Patients Older Than Age 85 Years Presenting for Mohs Surgery: A Prospective, Multicenter Cohort Study.

Importance: It has been suggested that Mohs surgery for skin cancer among individuals with limited life expectancy may be associated with needless risk and discomfort, along with increased health care costs. Objective: To investigate patient- and tumor-specific indications considered by clinicians for treatment of nonmelanoma skin cancer in older individuals. Design, Setting, and Participants: This multicenter, prospective cohort study was conducted using data from US private practice and academic centers. Included patients were those older than age 85 years presenting for skin cancer surgery and referred for Mohs surgery, with reference groups of those younger than age 85 years receiving Mohs surgery and those older than age 85 years not receiving Mohs surgery. Data were analyzed from November 2018 through January 2019. Exposures: Mohs surgery for nonmelanoma skin cancer. Main Outcomes and Measures: Reason for treatment selection. Results: Among 1181 patients older than age 85 years referred for Mohs surgery (724 [61.9%] men among 1169 patients with sex data; 681 individuals aged >85 to 88 years [57.9%] among 1176 patients with age data) treated at 22 sites, 1078 patients (91.3%) were treated by Mohs surgery, and 103 patients (8.7%) received alternate treatment. Patients receiving Mohs surgery were more likely to have tumors on the face (738 patients [68.5%] vs 26 patients [25.2%]; P < .001) and nearly 4-fold more likely to have high functional status (614 patients [57.0%] vs 16 patients [15.5%]; P < .001). Of 15 distinct reasons provided by surgeons for opting to proceed with Mohs surgery, the most common were patient desire for treatment with a high cure rate (712 patients [66.0%]), good or excellent patient functional status for age (614 patients [57.0%]), and high risk associated with the tumor based on histology (433 patients [40.2%]). Conclusions and Relevance: This study found that older patients who received Mohs surgery often had high functional status, high-risk tumors, and tumors located on the face. These findings suggest that timely surgical treatment may be appropriate in older patients given that their tumors may be aggressive, painful, disfiguring, and anxiety provoking.

Evidence-Based Clinical Practice Guidelines for Extramammary Paget Disease.

IMPORTANCE: 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. OBJECTIVE: To develop recommendations for the care of adults with EMPD. EVIDENCE REVIEW: 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. FINDINGS: 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. CONCLUSIONS AND RELEVANCE: 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.

AP-2alpha: a regulator of EGF receptor signaling and proliferation in skin epidermis.

AP-2 transcription factors have been implicated in epidermal biology, but their functional significance has remained elusive. Using conditional knockout technology, we show that AP-2alpha is essential for governing the balance between growth and differentiation in epidermis. In vivo, epidermis lacking AP-2alpha exhibits elevated expression of the epidermal growth factor receptor (EGFR) in the differentiating layers, resulting in hyperproliferation when the receptors are activated. Chromatin immunoprecipitation and promoter activity assays identify EGFR as a direct target gene for AP-2alpha repression, and, in the absence of AP-2alpha, this is manifested primarily in excessive EGF-dependent phosphoinositol-3 kinase/Akt activity. Together, our findings unveil a hitherto unrecognized repressive role for AP-2alpha in governing EGFR gene transcription as cells exit the basal layer and withdraw from the cell cycle. These results provide insights into why elevated AP-2alpha levels are often associated with terminal differentiation and why tumor cells often display reduced AP-2alpha and elevated EGFR proteins.