Extensive Perineural Invasion vs Nerve Caliber to Assess Cutaneous Squamous Cell Carcinoma Prognosis.

Importance: Perineural invasion (PNI) is an adverse risk feature in cutaneous squamous cell carcinoma (CSCC) that affects patient prognosis and disease management. However, research comparing different PNI patterns on patient outcomes is limited. Objective: To compare 4 assessments of PNI in CSCC, their associations with poor outcomes, and implications for their inclusion in the Brigham and Women's Hospital (BWH) staging system. Design, Setting, and Participants: This retrospective cohort study was performed at a single tertiary care institution and compared 4 PNI assessments: nerve caliber, number of involved nerves per section, PNI maximal depth, and PNI location with respect to tumor. Patients with primary, localized, invasive CSCC with PNI diagnosed between January 1, 2000, and December 31, 2017, were identified via an electronic in-house database. Available pathology slides were secondarily reviewed by study authors. Relevant patient and tumor characteristics and outcomes were abstracted from the medical record. Data analysis was performed between September 6 and October 20, 2022. Main Outcomes and Measures: Risks of recurrence, disease-specific death, and a composite end point (any poor outcome) were calculated via multivariable stepwise Fine and Gray competing-risks regression. Considered revisions to the BWH staging system were assessed via receiver operating characteristic curves and test characteristics. Results: This study included 140 patients with CSCC, with a mean (SD) age of 75.1 (11.2) years. More than half of the patients were men (93 [66.4%]), and most identified as White (132 [94.3%]). Of the 4 PNI assessments studied, only involvement of multiple nerves was associated with poor outcomes. Perineural invasion of 5 or more distinct nerves (extensive PNI [ePNI]) was independently associated with local recurrence (subhazard ratio [SHR], 13.83 [95% CI, 3.50-54.62]; P < .001), disease-specific death (SHR, 6.20 [95% CI, 1.59-24.21]; P = .009), and any poor outcome (SHR, 10.21 [95% CI, 2.88-36.15]; P < .001). A revised BWH staging system with substitution of ePNI for large-caliber PNI resulted in improved area under the curve and test characteristics compared with current BWH staging criteria that use nerve caliber as the measure of PNI. Conclusions and Relevance: The findings of this cohort study suggest that ePNI is the best prognostic measure of PNI. Because ePNI obviated the need for a micrometer and had superior prognostic capacity to nerve caliber in this cohort, ePNI should be considered for inclusion in CSCC tumor staging. Inclusion of ePNI as a high-risk factor in CSCC staging systems may optimize patient selection for primary treatment and adjuvant interventions.

Factors associated with suspected nonmelanoma skin cancers, dysplastic nevus, and cutaneous melanoma among first-time SpotMe screening program participants during 2009-2010.

BACKGROUND: There have been no studies of the American Academy of Dermatology's SpotMe skin cancer screening program to collectively analyze and determine the factors associated with suspected basal cell carcinoma (BCC), squamous cell carcinoma (SCC), dysplastic nevus (DN), and cutaneous melanoma (CM) diagnoses. OBJECTIVE: Describe the demographics, risk factors, and access to care profiles associated with suspected diagnoses of BCC, SCC, DN, and CM among first-time SpotMe screenees during 2009-2010. METHODS: We conducted a cross-sectional analysis of data from the SpotMe skin cancer screenings conducted in 2009 and 2010. We performed multivariable logistic regression analysis for each diagnosis, incorporating standard demographic, access to care, and risk factor variables in the models. RESULTS: Men, those without a regular dermatologist, persons reporting recently changing moles, and those with a personal history of melanoma were at increased risk for each of the suspected diagnoses analyzed. Uninsured persons were at increased risk for suspected malignancies (BCC, SCC, and CM). LIMITATIONS: Lack of histologic confirmation for diagnoses and cross-sectional design. CONCLUSION: Among first-time SpotMe participants, suspected diagnoses of BCC, SCC, DN, and CM shared several associated factors, which may be considered when planning outreach and screening for populations at risk for skin cancer.

Impact of skin biopsy on the management of acute graft-versus-host disease in a pediatric population.

BACKGROUND/OBJECTIVES: Acute graft-versus-host disease (GVHD) of the skin is a common complication of hematopoietic stem cell transplantation (HSCT) but often represents a diagnostic challenge. The adult literature suggests that histopathology rarely dictates management decisions, but the clinical utility of skin biopsies in pediatric patients with suspected acute GVHD is unknown. The objective of this study was to determine the frequency with which skin biopsy leads to a definitive diagnosis of acute GVHD and changes the management of acute GVHD in the pediatric population. METHODS: We conducted a retrospective analysis of histopathology results and the associated impact on clinical management based on chart review of pediatric patients who underwent skin biopsy for cutaneous eruptions suspicious for acute GVHD from 1995 to 2016. RESULTS: Among 27 pediatric HSCT patients, skin biopsy yielded definitive diagnoses (GVHD or otherwise) in only 15% (4/27) of cases. Overall, dermatology consultation was associated with clinical management changes in 78% (21/27) of cases. A change in management was definitively based on skin biopsy results in only 7.4% (2/27) of cases. The mean duration of time between dermatology consultation and return of biopsy results was 4.8 days (range 1-17). CONCLUSIONS: Our results suggest that skin biopsy of pediatric HSCT patients with findings concerning for acute skin GVHD rarely yields a definitive diagnosis or change in management.

A pink enlarging plaque on the plantar foot: amelanotic acral lentiginous melanoma.

Acral lentiginous melanomas account for less than 5% of all melanomas, whereas amelanotic melanomas account for around 2-8% of all melanomas. Amelanotic acral lentiginous melanomas are even less common and can often be mistaken for other clinical entities, including pyogenic granulomas, non-melanoma skin cancers, and warts. We describe a man in his 50s with a twenty-year history of a skin-colored plaque on the right plantar foot; after enlargement and failure of wart treatment, a shave biopsy revealed an amelanotic melanoma. A subsequent wide local excision and sentinel lymph node biopsy revealed melanoma in 4 lymph nodes and the patient underwent an abbreviated course of interferon-alpha therapy. The patient remained stable until 2 ? years after diagnosis, at which time he presented with in-transit metastases on the foot and right thigh; he has since been stable on nivolumab. This case represents the challenge of diagnosing amelanotic melanomas on acral surfaces and highlights the importance of considering a skin biopsy for diagnosis of any changing, atypical amelanotic lesions on the feet or hands.

The effect of scalp cooling on CIA-related quality of life in breast cancer patients: a systematic review.

PURPOSE: Chemotherapy-induced alopecia (CIA) remains a distressing adverse event of cancer treatment but may be prevented by scalp cooling. The effectiveness of scalp cooling, however, is dependent on the chemotherapy regimen with successful hair preservation (i.e., < 50% hair loss) in 41-59% of women on taxane-based therapies in comparison to 16-36% on anthracycline-based therapies. Despite the potential utility, use of scalp cooling has shown a more equivocal impact on quality of life (QoL). In this review, we aim to evaluate the use of scalp cooling for CIA and quantitative QoL measures. METHODS: A systematic review of PubMed, Embase, Web of Science, and Cochrane databases for clinical studies on scalp cooling to prevent CIA published before October 29, 2018 was performed. Clinical studies with 5 or more patients that reported on a quantitative QoL measure were included and graded according to a modified five-point scale from the Oxford Centre for Evidence-Based Medicine. RESULTS: Studies meeting inclusion criteria included 4 randomized clinical trials (RCT), 8 cohort studies, and 1 cross-sectional study with 1282 unique patients. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30: 46%) and Breast Cancer Module (QLQ-BR23: 46%) represented the most commonly used QoL assessments. Overall, 4 (31%) of the 13 studies concluded that scalp cooling was associated with significant improvements in QoL measures; 8 (62%) determined that there was either non-significant or no improvements; and 1 (7.7%) provided a mixed conclusion. Although 2 (50%) RCT demonstrated that scalp cooling can effectively prevent CIA depending on the chemotherapy regimen, these studies did not show that successful hair preservation was associated with improved QoL measures. CONCLUSIONS: This review demonstrates that scalp cooling is not consistently associated with significant QoL improvements as assessed by EORTC QLQ-C30 and -BR23. Representing a critical limitation, more than one-third of the studies did not subcategorize QoL outcomes for successfully or unsuccessfully scalp-cooled patients but rather reported on QoL measures for all scalp-cooled patients in general. Failure to prevent hair loss in patients undergoing an expensive and potentially uncomfortable treatment likely contributes to decreased well-being, impacting the overall distribution of QoL measures in scalp cooling patients compared to controls. Future studies should incorporate validated QoL instruments specific to hair disease and classify QoL outcomes for scalp-cooled patients based on the degree of hair preservation.

Clinicopathologic, misdiagnosis, and survival differences between clinically amelanotic melanomas and pigmented melanomas.

BACKGROUND: Amelanotic malignant melanoma (AMM) is challenging to diagnose. Clinical risk factors for AMM are not well defined. OBJECTIVE: To investigate clinicopathologic, misdiagnosis, and survival differences between patients with AMM and those with pigmented malignant melanoma (PMM). METHODS: A cross-sectional retrospective medical record review at a tertiary academic medical center. RESULTS: A total of 933 patients with melanoma with known presenting tumor color were identified (342 with AMM vs 591 with PMM). AMM was associated with older age, history of nonmelanoma skin cancer, and red hair, whereas AMM was inversely associated with a family history of melanoma, more than 50 nevi, and a history of dysplastic nevi. Compared with PMM, AMM was more likely to be located on the head and/or neck, had more aggressive pathologic features (greater Breslow depth and/or mitoses, ulceration, nodular subtype), and was less likely to be associated with a precursor nevus or regression. Finally, patients with AMM were more likely to be misdiagnosed than were patients with PMM (25% vs 12% clinically and 12% vs 7% pathologically), and they had poorer melanoma-specific survival (5-year overall survival rate, 0.77 [95% confidence interval, 0.72-0.82] vs 0.84 [95% confidence interval, 0.80-0.87]). LIMITATIONS: Retrospective study design, single-institutional study. CONCLUSION: Greater clinician awareness, lower biopsy thresholds, and increased patient education may be useful to enhance AMM detection in patients with certain characteristics.

Preclinical Studies Support Combined Inhibition of BET Family Proteins and Histone Deacetylases as Epigenetic Therapy for Cutaneous T-Cell Lymphoma.

Advanced-stage cutaneous T-cell lymphoma (CTCL) is usually a fatal malignancy despite optimal use of currently available treatments. In this preclinical study of novel CTCL therapy, we performed in vitro and ex vivo experiments to determine the efficacy of combination treatment with a panel of BET bromodomain inhibitors (BETi) (JQ1, OTX015, CPI-0610, I-BET762) and HDAC inhibitors (HDACi) (SAHA/Vorinostat, Romidepsin). BETi/HDACi combinations were synergistic (combination index <1) against cell viability and induced G0/G1 cell cycle arrest. Apoptosis was uniformly enhanced. From a mechanistic standpoint, proliferative drivers c-Myc, Cyclin D1, NFkB, and IL-15Rα were reduced. Inhibitory CDKN1A was increased. CDKN1B, IL-7R, IL-17Rα, STAT3, and STAT5 alterations varied. There were significant increases in extrinsic apoptotic pathway death receptors and ligands (FasL, DR4, DR5, TRAIL, and TNFR1). At clinically tolerable levels of single agents, Romidepsin (1 nM) + OTX015 (125 nM) induced the greatest apoptosis (60%_80%) at 96 hours. Ex vivo studies of leukemic CTCL cells obtained from patients with Sezary syndrome also showed higher levels of apoptosis (about 60%-90%) in response to combination treatments relative to single agents. In contrast, combination treatment of normal CD4+ T cells induced only minimal apoptosis (<10%). Our findings show that the mechanism of action of BETi/HDACi therapy in CTCL involves induction of both cell cycle arrest and apoptosis with reduced proliferative drivers and enhanced expression of apoptotic extrinsic pathway death receptors and ligands. Relative to single agents, the superior anti-CTCL effects of BETi/HDACi combinations in vitro and ex vivo provide a rationale for clinical trials exploring their efficacy as therapy for CTCL.

Photodynamic therapy for Bowen's Disease (squamous cell carcinoma in situ) current review and update.

The aim of this review is to provide clinicians with an overview of outcomes in the current literature concerning the use of Photodynamic Therapy to treat Bowen's Disease, also known as Squamous Cell Carcinoma in situ. The review discusses clinical response, recurrence rates, cosmetic outcomes, and adverse effects. Strong evidence shows that PDT is an effective therapy for SCCis with acceptable clinical response rates and lower recurrence rates in comparison to conventional therapies such as cryotherapy and 5-fluorouracil. Furthermore, PDT is associated with superior cosmetic outcomes and is generally well tolerated by patients, with minimal side effects. PDT is especially useful in patients with multiple lesions and those whom are considered to be non-surgical candidates.

The first 30 years of the American Academy of Dermatology skin cancer screening program: 1985-2014.

BACKGROUND: The incidence of melanoma is rising faster than that of any other preventable cancer in the United States. The American Academy of Dermatology has sponsored free skin cancer education and screenings conducted by volunteer dermatologists in the United States since 1985. OBJECTIVE: We aimed to assess the American Academy of Dermatology's national skin cancer screening program from 1986 to 2014 by analyzing the risk factor profile, access to dermatologic services, and examination results. METHODS: We conducted several detailed statistical analyses of the screening population. RESULTS: From 1986 to 2014, records were available for 2,046,531 screenings, 1,963,141 (96%) of which were subjected to detailed analysis. Men comprised 38% of all participants. The number of annual screenings reached approximately 100,000 in 1990 and remained relatively stable thereafter. From 1991 to 2014 (data for 1995, 1996 and 2000 were unavailable), clinical diagnoses were rendered for 20,628 melanomas, 156,087 dysplastic nevi, 32,893 squamous cell carcinomas, and 129,848 basal cell carcinomas. Only 21% of screenees had a regular dermatologist. Those with a clinical diagnosis of skin cancer were more likely than the general screening population to be uninsured. LIMITATIONS: Inability to verify clinical diagnoses histopathologically. CONCLUSION: Our findings suggest that the SPOTme program has detected thousands of skin cancers that may have gone undetected or experienced a delay in detection.

Skin cancer interventions across the cancer control continuum: Review of technology, environment, and theory.

The National Cancer Institute's Skin Cancer Intervention across the Cancer Control Continuum model was developed to summarize research and identify gaps concerning skin cancer interventions. We conducted a mapping review to characterize whether behavioral interventions addressing skin cancer prevention and control from 2000 to 2015 included (1) technology, (2) environmental manipulations (policy and/or built environment), and (3) a theoretical basis. We included 86 studies with a randomized controlled or quasi-experimental design that targeted behavioral intervention in skin cancer for children and/or adults; seven of these were dissemination or implementation studies. Of the interventions described in the remaining 79 articles, 57 promoted only prevention behaviors (e.g., ultraviolet radiation protection), five promoted only detection (e.g., skin examinations), 10 promoted both prevention and detection, and seven focused on survivorship. Of the 79 non-dissemination studies, two-thirds used some type of technology (n=52; 65.8%). Technology specific to skin cancer was infrequently used: UVR photography was used in 15.2% of studies (n=12), reflectance spectroscopy was used in 12.7% (n=10), and dermatoscopes (n=1) and dosimeters (n=2) were each used in less than 3%. Ten studies (12.7%) targeted the built environment. Fifty-two (65.8%) of the studies included theory-based interventions. The most common theories were Social Cognitive Theory (n=20; 25.3%), Health Belief Model (n=17; 21.5%), and the Theory of Planned Behavior/Reasoned Action (n=12; 15.2%). Results suggest that skin cancer specific technology and environmental manipulations are underutilized in skin cancer behavioral interventions. We discuss implications of these results for researchers developing skin cancer behavioral interventions.

Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network Consortium (PPACMAN) Survey: Benefits and Challenges of Combined Rheumatology-dermatology Clinics.

Optimal management of patients with both psoriasis and psoriatic arthritis (PsA) necessitates collaboration among dermatologists and rheumatologists. In this manuscript, we discuss challenges and opportunities for dual care models for patients with psoriasis and PsA and the results of a survey of combined clinics based in North America.

Polycystic Ovary Syndrome: Special Diagnostic and Therapeutic Considerations for Children.

Polycystic ovary syndrome (PCOS) is an endocrine syndrome with variable phenotypic expression and important systemic associations and sequelae, including obesity, insulin resistance, infertility, risk of endometrial cancer, and possible risk of cardiovascular events. PCOS is recognized as a condition influenced by genetic and environmental factors and distinct manifestations in all stages of life, including the prenatal period, childhood, adolescence, and adulthood. Identification of this disorder in childhood and adolescence has received growing attention, in part because of emerging evidence of the benefit of early intervention, but the diagnosis and management of PCOS in children and adolescents can be challenging. Diagnostic and therapeutic considerations of PCOS in children are reviewed to enhance identification and evaluation of patients suspected of having this disorder. When a diagnosis of PCOS is suspected in a child but cannot be confirmed, a provisional diagnosis is strongly recommended so as to prompt ongoing monitoring with an emphasis on important early interventions such as obesity reduction.