Exploring knowledge gaps in the understanding of peripheral and deep en face margin assessment.

In 2022, National Comprehensive Cancer Network updated the phrase of "complete circumferential peripheral and deep margin assessment (CCPDMA)" to "peripheral and deep en face margin assessment (PDEMA)," which was meant to create more consistency across all treatment modalities and provide clarity to the meaning of total margin evaluation. The aim of this project was to investigate the interpretation of PDEMA across pertinent specialties and to identify any existing knowledge gaps in hopes of improving clinical performance of institutional practice. An electronic survey was administered to medical professionals within the divisions of dermatology and otolaryngology retrieving demographic data and assessing respondents' knowledge on tissue processing techniques and PDEMA. Of the four knowledge-based assessment questions administered, dermatology respondents answered three questions with > 80% accuracy and one question with < 65% accuracy. Otolaryngology respondents answered one question with > 80% accuracy and three with < 65% accuracy. Both groups answered the knowledge-based question evaluating the concept of "what must be true for Mohs or PDEMA to have value" with under 65% accuracy. When comparing dermatology and otolaryngology respondents, only one question which evaluated the proper methods to "achieve processing of the epidermal edge and the base of the tumor along a single plane in the lab" significantly differed between groups, with a percentage correct of 96% for dermatologists compared to 54% for otolaryngologists (p < 0.001). Results were found to be similar when resident physicians were removed from analysis. The overall percent correct for knowledge-based questions was shifted higher for dermatologists compared to otolaryngologists (p = 0.014). This trend was also redemonstrated when analyzing the data excluding residents (p = 0.053).

Length-to-width ratio in Mohs defects: what is the golden rule?

A length-to-width ratio (LWR) of 3:1 for linear closures is often cited in the literature. However, there are limited studies evaluating this ratio in relation to various surgical sites. This study analyzes LWRs for 3318 patients undergoing Mohs micrographic surgery (MMS) and linear repair to identify the average LWRs stratified by patient age, anatomic location, gender, and surgeon. Average LWRs ranged between 2.89 and 3.82. The LWR for all anatomic sites averaged between 3:1 and 4:1, except for closures on the trunk. Locations with the highest LWR included the cheek, ear, and perioral sites.

Incidence of Second Primary Melanoma in Cutaneous Melanoma Survivors.

BACKGROUND: Cutaneous melanoma survivors are at increased risk of a second primary melanoma. Valid estimates facilitate counseling on recommended surveillance after a melanoma diagnosis. However, most estimates of 5- and 10-year incidences of second melanomas are from older cohorts and/or single institutions. This study aimed to determine the 5- and 10-year incidences of second primary cutaneous melanomas in survivors of cutaneous melanoma. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify cases of non-metastatic, first cutaneous melanoma diagnosed between 1998 and 2012 (follow-up through December 2017). Eligible survivors were 18 years old or older who underwent surgery as a treatment component. Kaplan-Meier survival analysis was used to estimate 5- and 10-year incidences of a second melanoma, excluding new diagnoses within 3 months after the initial diagnosis. Patients were censored at second melanoma diagnosis, death, or 10-years, whichever was first. Multivariable Cox regression analysis was used to identify factors associated with a second cutaneous melanoma diagnosis. RESULTS: The study cohort comprised 152,811 patients. The incidence of second primary melanoma was 3.9% at 5 years (95% confidence interval [CI], 3.8-4.0%) and 6.7% at 10 years (95% CI, 6.6-6.9%). Older age, male sex, and regional disease were associated with increased risk of a second primary melanoma diagnosis. CONCLUSION: Melanoma survivors are at risk of a second primary melanoma, making routine skin surveillance part of recommended follow-up evaluation. A higher incidence of second melanoma with older age and regional disease at presentation is possibly explained by increased health care use providing more diagnostic opportunities, whereas male sex may represent an inherent risk factor.

Contrasting recruitment of skin-associated adipose depots during cold challenge of mouse and human.

KEY POINTS: Several distinct strategies produce and conserve heat to maintain the body temperature of mammals, each associated with unique physiologies, with consequences for wellness and disease susceptibility Highly regulated properties of skin offset the total requirement for heat production  We hypothesize that the adipose component of skin is primarily responsible for modulating heat flux; here we evaluate the relative regulation of adipose depots in mouse and human, to test their recruitment to heat production and conservation We found that insulating mouse dermal white adipose tissue accumulates in response to environmentally and genetically induced cool stress; this layer is one of two adipose depots closely apposed to mouse skin, where the subcutaneous mammary gland fat pads are actively recruited to heat production In contrast, the body-wide adipose depot associated with human skin produces heat directly, potentially creating an alternative to the centrally regulated brown adipose tissue ABSTRACT: Mammalian skin impacts metabolic efficiency system-wide, controlling the rate of heat loss and consequent heat production. Here we compare the unique fat depots associated with mouse and human skin, to determine whether they have corresponding functions and regulation. For humans, we assay a skin-associated fat (SAF) body-wide depot to distinguish it from the subcutaneous fat pads characteristic of the abdomen and upper limbs. We show that the thickness of SAF is not related to general adiposity; it is much thicker (1.6-fold) in women than men, and highly subject-specific. We used molecular and cellular assays of ß-adrenergic-induced lipolysis and found that dermal white adipose tissue (dWAT) in mice is resistant to lipolysis; in contrast, the body-wide human SAF depot becomes lipolytic, generating heat in response to ß-adrenergic stimulation. In mice challenged to make more heat to maintain body temperature (either environmentally or genetically), there is a compensatory increase in thickness of dWAT: a corresponding ß-adrenergic stimulation of human skin adipose (in vivo or in explant) depletes adipocyte lipid content. We summarize the regulation of skin-associated adipocytes by age, sex and adiposity, for both species. We conclude that the body-wide dWAT depot of mice shows unique regulation that enables it to be deployed for heat preservation; combined with the actively lipolytic subcutaneous mammary fat pads they enable thermal defence. The adipose tissue that covers human subjects produces heat directly, providing an alternative to the brown adipose tissues.

Lack of documentation of lymph node examination in patients with squamous cell carcinoma of the lower lip.

Cutaneous squamous cell carcinoma is the second most common cutaneous malignancy with a 5-year disease-specific survival rate of approximately 90%, which decreases dramatically to 50% in the presence of regional lymph node metastases. We sought to examine clinicians' documentation of pertinent neurological symptoms/signs and lymph node palpation at the time of initial biopsy and treatment using lower lip SCC patients as a cohort. Subsequently, we investigated the correlation between clinical and pathologic SCC features and the aforementioned documentation. A single center, retrospective study of all squamous cell carcinomas of the lower lip biopsied over 10 years was conducted, and univariate models were implemented to correlate the variables. A total of 66 squamous cell carcinomas of the lip in 63 patients were identified. Neurological signs and symptoms were not documented and only three of the tumors were palpated, therefore statistical analysis was not performed. A lymph node exam was documented in 14 of the 63 patients (22%), and statistical analysis showed that among all variables (age, gender, tumor size, tumor stages, tobacco or alcohol use, or history of skin cancer), only the size of the tumor correlated positively with a lymph node examination (RRE 1.15 [95% CI 1.06-1.25], p < 0.001). Our study illustrates a possible practice gap and quality improvement potential in tumor, neurologic, and lymph node examination and documentation in patients with cutaneous squamous cell carcinoma.

NCCN Guidelines® Insights: Squamous Cell Skin Cancer, Version 1.2022.

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.

Number of skin biopsies needed per malignancy: Comparing the use of skin biopsies among dermatologists and nondermatologist clinicians.

BACKGROUND: There are too few board-certified dermatologists to treat all patients with skin disease. Primary care physicians often serve at the frontline of skin cancer screening. OBJECTIVE: To compare biopsy use among dermatologist physicians, dermatology advanced practice professionals (APPs), primary care physicians (PCPs), and other nondermatology clinicians. METHODS: Pathology reports, requisition forms, and clinical notes of skin biopsies submitted to our institution during the study period were reviewed. Skin biopsies for inflammatory conditions, cosmetic or functional purposes, and re-excisions were excluded. The number needed to biopsy (NNB) was calculated as the number of biopsied lesions divided by histologically proven skin cancers. RESULTS: The NNB by clinician type was 2.82 for dermatology physicians, 4.69 for APPs, 4.55 for nondermatology PCPs, and 6.55 for other nondermatology clinicians (P < .001). The NNB was significant between clinician groups for nonmelanoma skin cancer (dermatology physicians, 2.00; APPs, 2.71; PCPs, 2.36; and other nondermatology clinicians, 3.47; P < .001) but not for melanoma (dermatology clinicians, 14.33; APPs, 20.78; PCPs, 27.80; and other nondermatology clinicians, 53.56; P = .061). LIMITATIONS: The NNB represents a measure of use but gives no insight into the number of malignant lesions that go unbiopsied and, therefore, undiagnosed. The prevalence of skin cancer varies among dermatology and nondermatology practices. The results are not generalizable to all practice settings. CONCLUSIONS: Dermatology physicians had the lowest NNB of all clinician groups. PCPs performed similarly to dermatology APPs.

Muir-Torre Syndrome: The Importance of a Detailed Family History.

Muir-Torre syndrome, a variant of Lynch syndrome or hereditary nonpolyposis colorectal cancer, is an autosomal dominant disease characterized by skin neoplasms (sebaceous or keratoacanthomas) and visceral malignancies. Due to the rarity of the syndrome there are no firm guidelines on how and when to test patients with its typical skin lesions. We describe a case that highlights the importance of a detailed family history.

Outcomes of malignant melanoma in kidney transplant recipients
.

Kidney transplant recipients (KTRs) have an increased risk of skin cancer. We analyzed the outcomes of KTRs transplanted at our center between January 1, 1994, and December 31, 2015, who reported pretransplant melanoma or had post-transplant de novo melanoma. Of 6,522 kidney or kidney with pancreas transplant recipients, 37 had pretransplant melanoma. After adjustment of multiple variables, pretransplant melanoma was associated with overall increased risk of death (HR: 1.75, 95% CI 1.02 - 3.03, p = 0.04) but not for death-censored graft failure (DCGF). A total of 46 patients developed post-transplant de novo melanoma. After adjustment of multiple variables, post-transplant de novo melanoma was associated with significant risk for death within the first year of the diagnosis of melanoma (HR: 4.40, 95% CI 2.21 - 8.74, p < 0.001), and DCGF after the first year (HR: 1.93, 95% CI 1.13 - 3.64, p = 0.04). Similarly, among all pretransplant candidates (including those with history of melanoma) in Cox regression multivariate analysis, older age (HR: 1.32, 95% CI 0.31 - 1.14, p = 0.04) and a history of pretransplant melanoma (HR: 9.27, 95% CI 2.81 - 30.53, p < 0.001) were significantly associated with the risk for development of post-transplant melanoma. Proper risk stratification and early diagnosis may improve patient and graft survival.

Nodal staging of high-risk cutaneous squamous cell carcinoma.

BACKGROUND: While progress has been made in defining the clinical and histopathologic features of high-risk cutaneous squamous cell carcinoma (HRcSCC), optimal staging guidelines remain elusive. OBJECTIVE: We seek to guide clinical practice regarding nodal staging options for patients with HRcSCC via review of evolving definitions of HRcSCC, nodal staging options, and how nodal staging may impact treatment and affect outcomes. METHODS: This was a retrospective review of the published peer-reviewed literature regarding risk stratification, nodal staging, and treatment and outcomes for patients with HRcSCC via PubMed. RESULTS: For patients without clinical lymphadenopathy, based on literature from head and neck SCC, preoperative nodal staging with ultrasonography may be more useful than computed tomography or magnetic resonance imaging. Early nodal disease is usually curable, and therefore obtaining a sentinel lymph node biopsy specimen may be considered in those with negative imaging while we await studies of nodal staging outcomes. LIMITATIONS: More data are needed to validate the relationships between primary tumor stage and sentinel lymph node biopsy status and to determine if early detection of nodal disease impacts survival for patients with HRcSCC. CONCLUSION: It is reasonable to consider nodal staging for patients with HRcSCC (Brigham and Women's Hospital stage T2b and T3) in the absence of clinically palpable lymphadenopathy via radiographic imaging and, if negative, sentinel lymph node biopsy.

Merkel Cell Carcinoma, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Merkel Cell Carcinoma (MCC) focuses on areas impacted by recently emerging data, including sections describing MCC risk factors, diagnosis, workup, follow-up, and management of advanced disease with radiation and systemic therapy. Included in these sections are discussion of the new recommendations for use of Merkel cell polyomavirus as a biomarker and new recommendations for use of checkpoint immunotherapies to treat metastatic or unresectable disease. The next update of the complete version of the NCCN Guidelines for MCC will include more detailed information about elements of pathology and addresses additional aspects of management of MCC, including surgical management of the primary tumor and draining nodal basin, radiation therapy as primary treatment, and management of recurrence.

Targeting insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in metastatic melanoma to increase efficacy of BRAFV600E inhibitors.

Melanoma is one of the deadliest forms of skin cancer. Although BRAF inhibitors significantly enhance survival of metastatic melanoma patients, most patients relapse after less than a year of treatment. We previously reported that mRNA binding protein Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is overexpressed in metastatic melanoma and that expression of IGF2BP1 confers resistance to chemotherapeutic agents. Here we demonstrate that IGF2BP1 plays an important role in the sensitivity of melanoma to targeted therapy. Inhibition of IGF2BP1 enhances the effects of BRAF-inhibitor and BRAF-MEK inhibitors in BRAFV600E melanoma. Also, knockdown of IGF2BP1 alone is sufficient to reduce tumorigenic characteristics in vemurafenib-resistant melanoma. These findings suggest that IGF2BP1 can be a novel therapeutic target for melanoma.

Acute, Temporary, Unilateral Facial Nerve Palsy After Dermatologic Surgery: A Report of 3 Cases.

Facial nerve dysfunction can be functionally and cosmetically debilitating and is commonly associated with high anxiety for patients. We report 3 cases of temporary, unilateral facial nerve palsy following dermatologic surgery under local anaesthesia over the preauricular cheek and mandibular angle, which, to our knowledge, has not been reported in the literature. Given its frightening presentation mimicking a stroke, it is essential for dermatologists to become aware of this complication to inform their patients more thoroughly. Thus, when performing facial surgery over these regions, we recommend that dermatologists include this rare complication and its good prognosis in the consenting process to minimise anxiety for those who experience it intra- or postoperatively.