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PURPOSE To improve skin cancer screening among survivors of childhood cancer treated with radiotherapy where skin cancers make up 58% of all subsequent neoplasms. Less than 30% of survivors currently complete recommended skin cancer screening. PATIENTS AND METHODS This randomized controlled comparative effectiveness trial evaluated patient and provider activation (PAE + MD) and patient and provider activation with teledermoscopy (PAE + MD + TD) compared with patient activation alone (PAE), which included print materials, text messaging, and a website on skin cancer risk factors and screening behaviors. Seven hundred twenty-eight participants from the Childhood Cancer Survivor Study (median age at baseline 44 years), age > 18 years, treated with radiotherapy as children, and without previous history of skin cancer were randomly assigned (1:1:1). Primary outcomes included receiving a physician skin examination at 12 months and conducting a skin self-examination at 18 months after intervention. RESULTS Rates of physician skin examinations increased significantly from baseline to 12 months in all three intervention groups: PAE, 24%-39%, relative risk [RR], 1.65, 95% CI, 1.32 to 2.08; PAE + MD, 24% to 39%, RR, 1.56, 95% CI, 1.25 to 1.97; PAE + MD + TD, 24% to 46%, RR, 1.89, 95% CI, 1.51 to 2.37. The increase in rates did not differ between groups ( P = .49). Similarly, rates of skin self-examinations increased significantly from baseline to 18 months in all three groups: PAE, 29% to 50%, RR, 1.75, 95% CI, 1.42 to 2.16; PAE + MD, 31% to 58%, RR, 1.85, 95% CI, 1.52 to 2.26; PAE + MD + TD, 29% to 58%, RR, 1.95, 95% CI, 1.59 to 2.40, but the increase in rates did not differ between groups ( P = .43). CONCLUSION Although skin cancer screening rates increased more than 1.5-fold in each of the intervention groups, there were no differences between groups. Any of these interventions, if implemented, could improve skin cancer prevention behaviors among childhood cancer survivors.

Tertiary lymphoid structures (TLS) are specialized lymphoid formations that serve as local repertoire of T- and B-cells at sites of chronic inflammation, autoimmunity, and cancer. While presence of TLS has been associated with improved response to immune checkpoint blockade therapies and overall outcomes in several cancers, its prognostic value in basal cell carcinoma (BCC) has not been investigated. Herein, we determined the prognostic impact of TLS by relating its prevalence and maturation with outcome measures of anti-tumor immunity, namely tumor infiltrating lymphocytes (TILs) and tumor killing. In 30 distinct BCCs, we show the presence of TLS was significantly enriched in tumors harboring a nodular component and more mature primary TLS was associated with TIL counts. Moreover, assessment of the fibrillary matrix surrounding tumors showed discrete morphologies significantly associated with higher TIL counts, critically accounting for heterogeneity in TIL count distribution within TLS maturation stages. Specifically, increased length of fibers and lacunarity of the matrix with concomitant reduction in density and alignment of fibers were present surrounding tumors displaying high TIL counts. Given the interest in inducing TLS formation as a therapeutic intervention as well as its documented prognostic value, elucidating potential impediments to the ability of TLS in driving anti-tumor immunity within the tumor microenvironment warrants further investigation. These results begin to address and highlight the need to integrate stromal features which may present a hindrance to TLS formation and/or effective function as a mediator of immunotherapy response.

Response to immunotherapies can be variable and unpredictable. Pathology-based phenotyping of tumors into ‘hot’ and ‘cold’ is static, relying solely on T-cell infiltration in single-time single-site biopsies, resulting in suboptimal treatment response prediction. Dynamic vascular events (tumor angiogenesis, leukocyte trafficking) within tumor immune microenvironment (TiME) also influence anti-tumor immunity and treatment response. Here, we report dynamic cellular-level TiME phenotyping in vivo that combines inflammation profiles with vascular features through non-invasive reflectance confocal microscopic imaging. In skin cancer patients, we demonstrate three main TiME phenotypes that correlate with gene and protein expression, and response to toll-like receptor agonist immune-therapy. Notably, phenotypes with high inflammation associate with immunostimulatory signatures and those with high vasculature with angiogenic and endothelial anergy signatures. Moreover, phenotypes with high inflammation and low vasculature demonstrate the best treatment response. This non-invasive in vivo phenotyping approach integrating dynamic vasculature with inflammation serves as a reliable predictor of response to topical immune-therapy in patients.

Introduction: Among the various widely recognized basal cell carcinoma (BCC) clinical patterns, linear basal cell carcinoma (LBCC) is an uncommon morphologic variant of BCC. Objective: Describe the clinical and dermoscopic characteristics of LBCC. Methods: Retrospective study including LBCC cases from 5 dermatology centers in North and South America. Biopsy-proven primary BCCs, that presented with at least 3:1 length:width ratio on physical examination, irrespective of tumor subtype or location, were included. Clinical and dermoscopic analysis were performed by 2 experts in dermoscopy. Results: Eighteen cases of LBCC met our inclusion criteria and were included in the study. Median age at diagnosis was 86.0 years, 10 patients (58.8%) were males. Regarding anatomic location, 11/18 (61.1%) were located on the head and neck, 5/18 (27.7%) cases were found on the trunk, and 2 on lower extremities (11.1%). Under dermoscopy, 15/18 (83.3%) of LBCC were pigmented. All tumors displayed at least one of the BCC-specific dermoscopic criteria the most common being blue-grey globules (72.2%). Conclusions: Dermoscopy might be useful in the differentiation of LBCC from other diagnoses presenting as linear lesions such as scars, scratches/erosions, and tattoos, among others. Some of these lesions might be confused by naked eye examination alone.

Introduction: A wide range of descriptive terms have been used for dermoscopic findings in intraepidermal carcinoma (IEC) and the clinical diagnostic accuracy of IEC can be challenging. Furthermore, dermoscopic findings in IEC have only rarely been evaluated in fair-skinned populations. Objectives: To measure the interobserver agreement between dermatologists for dermoscopic findings in IEC. Furthermore, to describe the frequency of these findings in a predominantly fair-skinned population. Methods: One hundred dermoscopic images of histopathologically verified IECs were collected. The 11 most common dermoscopic findings described in previous studies were re-defined in a new terminology in a pre-study consensus meeting. Images were assessed by eight experienced international dermoscopists. The frequency of findings and the interobserver agreement was analyzed. Results: Scales (83%), dotted/glomerular vessels (77%), pinkish-white areas (73%) and hemorrhage (46%) were the most commonly present dermoscopic findings. Pigmented structures were found in 32% and shiny white structures (follicular or stromal) in 54% of the IEC. Vascular structures (vessels and/or hemorrhage) could be seen in 89% of the lesions. Overall, the interobserver agreement for the respective dermoscopic findings was poor to moderate, with the highest kappa values noted for scales (0.55) and hemorrhage (0.54) and the lowest for pinkish-white areas (0.015). Conclusion: Our results confirm those of previous studies on dermoscopy in IEC, including the frequency of pigmented structures despite the fair-skinned population. The interobserver agreement was relatively low. The proposed new terminology and our findings can hopefully serve as a guideline for researchers, teachers and students on how to identify IEC.

Background: Minimal knowledge exists regarding skin cancers in Black individuals, which may adversely affect patient care. Objectives: To describe clinical features and risk factors of skin cancers in Black individuals. Methods: Retrospective study of Black individuals diagnosed with skin cancer between January 2000 and January 2020 at our institution. Results: 38,589 patients were diagnosed with skin cancer, of which 165 were Black. One-hundred-thirteen of these Black individuals were diagnosed with melanoma, 35 with squamous cell carcinoma (SCC), and 17 with basal cell carcinoma (BCC). Most melanomas (80.0%, n=90) were of the acral subtype; 75% (6 of 8 cases with dermoscopic images) displayed a parallel ridge pattern (PRP). The surrounding uninvolved background skin was visible in 7 cases, all demonstrating a PRP. This disappeared adjacent to most of the melanoma lesions (n=4, 57.1%) – creating a peripheral hypopigmented “halo”. The nonmelanoma skin cancers were pigmented and had similar dermoscopic features as reported in predominantly white populations. Most SCCs (n=5, 71.4%) had a hypopigmented “halo” and most BCCs (n=10, 55.6%) had an accentuated reticular network adjacent to the lesions. Most (80.0%, n=28) SCC patients had a chronic inflammatory condition. Two BCC patients (16.7%) had Gorlin syndrome. Conclusions: Skin cancers are pigmented in Black individuals. In both ALMs and SCCs, we noted a peripheral rim of hypopigmentation between the lesions and the surrounding uninvolved background skin, while BCCs had accentuation of the background pigmentation adjacent to the lesions. Most acral melanomas displayed a PRP, which was also seen in surrounding uninvolved background skin.

Introduction: In patients with multiple nevi, sequential imaging using total body skin photography (TBSP) coupled with digital dermoscopy (DD) documentation reduces unnecessary excisions and improves the early detection of melanoma. Correct patient selection is essential for optimizing the efficacy of this diagnostic approach. Objectives: The purpose of the study was to identify, via expert consensus, the best indications for TBSP and DD follow-up. Methods: This study was performed on behalf of the International Dermoscopy Society (IDS). We attained consensus by using an e-Delphi methodology. The panel of participants included international experts in dermoscopy. In each Delphi round, experts were asked to select from a list of indications for TBSP and DD. Results: Expert consensus was attained after 3 rounds of Delphi. Participants considered a total nevus count of 60 or more nevi or the presence of a CDKN2A mutation sufficient to refer the patient for digital monitoring. Patients with more than 40 nevi were only considered an indication in case of personal history of melanoma or red hair and/or a MC1R mutation or history of organ transplantation. Conclusions: Our recommendations support clinicians in choosing appropriate follow-up regimens for patients with multiple nevi and in applying the time-consuming procedure of sequential imaging more efficiently. Further studies and real-life data are needed to confirm the usefulness of this list of indications in clinical practice.

Conventional tissue sampling used in disease and cancer diagnosis can lead to misdiagnoses and repeated biopsies, and the tissue processed for histopathology suffers from poor nucleic acid quality/quantity for molecular profiling. Targeted micro-sampling of tissue can ensure accurate diagnosis and molecular profiling in the presence of spatial heterogeneity and complexity, especially in tumors, and facilitate acquisition of fresh tissue for molecular analysis. In this study, we explored the feasibility of a 1-mm precision biopsy approach guided by high-resolution reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) imaging, and reflective metallic grids for accurate spatial targeting and sampling in 7 skin cancers lesions in 6 patients. Accurate sampling was confirmed by histopathology or successful molecular profiling using next generation sequencing (NGS) approaches. Imaging guided 1-mm biopsy enabled spatial targeting and sampling for in vivo diagnosis, feature correlation and predicted depth as confirmed on histopathology. High DNA quantity (680 ng) and quality (DIN: 8) were obtained from imaging-guided high melanoma cell density areas. Subsequent mutational profiling on a 505-gene panel revealed a missense BRAF V600E oncogenic mutations at 0.02 allelic frequency for guiding therapy. Our findings demonstrate accurate sampling of regions of interest that enables downstream diagnosis, molecular analysis and research in both in vivo and ex vivo settings with broad diagnostic, therapeutic and research potential in dermatological and mucosal settings currently accessible to RCM-OCT imaging.

OBJECTIVE: We hypothesize that patients with neurocutaneous melanocytosis-associated melanoma and ventriculoperitoneal shunts are at risk of developing intraperitoneal spread of melanoma. BACKGROUND: Neurocutaneous melanocytosis, a rare condition characterized by excessive proliferation and deposition of melanocytes in the leptomeninges and brain parenchyma, typically occurs in children with large congenital melanocytic nevi and multiple smaller congenital nevi. These patients are at heightened risk for developing NRAS+ melanomas in the central nervous system, which in turn may lead to symptomatic hydrocephalus requiring cerebrospinal fluid diversion for symptom relief. METHODS: Retrospective single-institution study of patients with histologically or radiographically confirmed NCM evaluated at Memorial Sloan Kettering Cancer Center (MSKCC) from 2001-2022. RESULTS: Of the 47 patients with a diagnosis of NCM, 44 patients had symptomatic neurological complications. Eleven patients developed hydrocephalus, 10 had CNS melanoma, and required ventriculoperitoneal shunt placement. Nine of the 10 patients ultimately died of their disease. Three patients were diagnosed with intraperitoneal melanoma, though data are unavailable for the remaining eight. CONCLUSIONS: All (n=11) patients with NCM-associated CNS melanoma required VP shunts for symptomatic relief. Ten of these patients died within 4.3 years of VP shunt placement, with a range of 1 month to 13.5 years prior to succumbing to their disease. While the intraperitoneal pathology remains unknown for 7 of the cases, 3 had confirmed intraperitoneal melanoma, suggesting that VP shunts provided the conduit to CNS melanoma seeding of the peritoneum. Obtaining baseline abdominal imaging studies prior to VP shunt placement may be helpful in the follow-up of these patients.

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The number needed to excise (NNE) is a metric used to convey the efficiency of dermatological practice by serving as a gauge for the diagnostic accuracy of melanoma. Rather than an NNE for melanoma alone, we assert that the NNE should measure all skin cancer types and we present data on NNE from two clinical sites demonstrating the utility and trends in NNE over time.

Neurocutaneous melanocytosis is a rare neurocutaneous syndrome defined by the presence of large and/or multiple congenital cutaneous nevi and melanocytic deposits in the central nervous system. We sought to define the spectrum of central nervous system abnormalities in children with neurocutaneous melanocytosis.We retrospectively reviewed cases of neurocutaneous melanocytosis referred to the pediatric neuro-oncology service at our center from 2003 to 2010.Of 14 patients (11 males, 3 females) identified, eight were living. Median age of survivors was 31 months (range 12mo-6y 10mo) while median age of death was 81 months (19mo-28y). Of the six patients who died, all had diffuse leptomeningeal melanocytic deposits and four had leptomeningeal melanoma. All patients had neuroimaging: six had findings suggestive of diffuse leptomeningeal melanocytosis; seven had multifocal melanocytic deposits; and one patient had normal neuroimaging but focal seizures. Spinal abnormalities were common: three patients had extensive dorsal spinal arachnoid cysts and one had a benign cervical spindle cell tumor. Seven patients had epilepsy. Three patients had profound developmental delay; the other 11 patients had no or mild delay.Children with neurocutaneous melanocytosis exhibit a wide range of intracranial and intraspinal abnormalities and variable clinical outcomes.

Mohs micrographic surgery is often considered the treatment of choice for a variety of skin malignancies. In recent years, the application of immunostaining techniques has facilitated the successful removal of a number of common and less common cutaneous malignancies, including basal cell carcinoma, squamous cell carcinoma, malignant melanoma, dermatofibrosarcoma protuberans, microcystic adnexal carcinoma, sebaceous carcinoma, atypical fibroxanthoma, extramammary Paget's disease, and even sarcomas. Immunostains highlight the tumor cells and allow the Mohs surgeons to pinpoint and eliminate the residual tumor at the surgical margin. It is especially helpful when a tumor presents with subtle or nonspecific histologic features or when a tumor is masked in a pocket of dense inflammation. However, the cost, the labor, and the time consumption are of concern to many of our peers, as are the diversity of antigens, which may overwhelm some. This article serves as a review of the literature on current uses of immunostaining in Mohs micrographic surgery and as a summary of their realistic applications in the dermatologic surgeon's practice. We conclude that immunohistochemical technique has played an important role in Mohs surgery advancement. With greater use and more cost-effective staining methods, we believe that the use of immunostains in a Mohs practice will become routine.