NCCN Guidelines® Insights: Melanoma: Cutaneous, Version 2.2024.

The NCCN Guidelines for Cutaneous Melanoma (termed Melanoma: Cutaneous) provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients. These NCCN Guidelines Insights focus on the update to neoadjuvant systemic therapy options and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Cutaneous Melanoma.

Localized calcium oxalate crystals in primary cutaneous aspergillosis.

Select Aspergillus species can produce oxalate as a fermentation byproduct, which may react with calcium ions to produce insoluble calcium oxalate crystals in tissues. These crystals are frequently associated with pulmonary Aspergillus infections, yet are rarely described in primary cutaneous aspergillosis. Herein, we report the presence of calcium oxalate crystals detected on cutaneous specimens from primary cutaneous Aspergillus niger and Aspergillus fumigatus infections in an immunocompromised, premature infant. No metabolic sources of oxalosis were found.

Comparison of S100A8 and PRAME as biomarkers for distinguishing melanoma from melanocytic naevus: a case-control analysis.

BACKGROUND: S100A8 is a melanoma biomarker expressed in the melanoma-associated epidermal keratinocytes, but its diagnostic utility has not been compared with other biomarkers, including PRAME. OBJECTIVES: To compare the utility of S100A8 and PRAME immunohistochemistry (IHC) in the differential diagnosis of melanoma and naevi in a case-control study. METHODS: A previously described cohort of 209 melanomas (case samples) and naevi (control samples) dual-immunostained for S100A8 and PRAME were included. For S100A8, previously reported scores indicating the proportion of tumour-associated epidermis stained (0 = indeterminate; 1 = 0-4%; 2 = 5-25%; 3 = 26-50%; 4 = 51-75%; 5 = > 75%) were utilized. PRAME IHC was reviewed by at least two reviewers and a consensus score assigned, with score indicating the proportion of tumour stained (0 = indeterminate; 1 = 0%; 2 = 1-50%; 3 = > 50%). A positive test was defined as > 50% staining. RESULTS: The area under the receiver operating characteristic curves for S100A8 (0.833) and PRAME (0.874) were not significantly different from each other (P = 0.22). The diagnostic sensitivity and specificity were 42.4% [95% confidence interval (CI) 32.6-52.8%] and 98.2% (95% CI 93.6-99.8%) for S100A8, and 79.8% (95% CI 70.5-87.2%) and 87.3% (95% CI 79.6-92.9%) for PRAME, respectively. A combined test requiring both S100A8 and PRAME IHC positivity had a sensitivity of 39.4% (95% CI 29.7-49.7%) and specificity of 99.1% (95% CI 95.0-100.0%). CONCLUSIONS: S100A8 and PRAME have utility in the diagnostic workup of melanoma, with S100A8 being more specific and PRAME being more sensitive when using this threshold. Our findings suggest that these two immunohistochemical markers may favourably complement one another to improve the detection of melanoma.

Infliximab-induced amicrobial pustulosis of the folds in a patient with Crohn disease.

Tumor necrosis factor (TNF) inhibitors may paradoxically induce pustular eruptions, most of which are classified as pustular psoriasis. Amicrobial pustulosis of the folds (APF) is a much rarer entity that was recently recognized to occur in the setting of chronic anti-TNF therapy and inflammatory bowel disease, with 12 existing cases in the literature. Amicrobial pustulosis of the folds is a neutrophilic dermatosis characterized by aseptic pustules involving the major and minor skin folds, genital regions, and scalp. Herein, we report an additional case of paradoxical APF induced by chronic infliximab therapy in a patient with Crohn disease.

SCALP syndrome with a germline heterozygous DOCK6 mutation and somatic mosaic NRAS Q61R mutation.

We present a case of SCALP syndrome, which was diagnosed in a male infant with the characteristic findings of sebaceous nevi, central nervous system malformations, aplasia cutis congenita, limbal dermoid, and giant congenital melanocytic nevi, or pigmented nevi. We identified a germline compound heterozygous DOCK6 mutation and a somatic mosaic NRAS Q61R mutation in the giant congenital melanocytic nevus. This report will increase clinician awareness of SCALP syndrome and augment the literature in characterizing this rare syndrome, including its genetic background.

A pruritic pedunculated pink nodule on the leg.

Herein, we present a patient with a lipidized fibrous histiocytoma, an underrecognized variant of dermatofibroma (cutaneous fibrous histiocytoma). Our patient presented with a nodule on the ankle that showed foamy histiocytes and hyalinized collagen bundles on histology. This case highlights a classic presentation and features of lipidized fibrous histiocytoma, raising further awareness of this distinctive variant of dermatofibroma that should be distinguished from xanthoma and xanthogranuloma.

The seventh international RASopathies symposium: Pathways to a cure-expanding knowledge, enhancing research, and therapeutic discovery.

RASopathies are a group of genetic disorders that are caused by genes that affect the canonical Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Despite tremendous progress in understanding the molecular consequences of these genetic anomalies, little movement has been made in translating these findings to the clinic. This year, the seventh International RASopathies Symposium focused on expanding the research knowledge that we have gained over the years to enhance new discoveries in the field, ones that we hope can lead to effective therapeutic treatments. Indeed, for the first time, research efforts are finally being translated to the clinic, with compassionate use of Ras/MAPK pathway inhibitors for the treatment of RASopathies. This biannual meeting, organized by the RASopathies Network, brought together basic scientists, clinicians, clinician scientists, patients, advocates, and their families, as well as representatives from pharmaceutical companies and the National Institutes of Health. A history of RASopathy gene discovery, identification of new disease genes, and the latest research, both at the bench and in the clinic, were discussed.

Treatment of pediatric alopecia areata: A systematic review.

BACKGROUND: Alopecia areata (AA) is an autoimmune, nonscarring hair loss disorder with slightly greater prevalence in children than adults. Various treatment modalities exist; however, their evidence in pediatric AA patients is lacking. OBJECTIVE: To evaluate the evidence of current treatment modalities for pediatric AA. METHODS: We conducted a systematic review on the PubMed database in October 2019 for all published articles involving patients <18 years old. Articles discussing AA treatment in pediatric patients were included, as were articles discussing both pediatric and adult patients, if data on individual pediatric patients were available. RESULTS: Inclusion criteria were met by 122 total reports discussing 1032 patients. Reports consisted of 2 randomized controlled trials, 4 prospective comparative cohorts, 83 case series, 2 case-control studies, and 31 case reports. Included articles assessed the use of aloe, apremilast, anthralin, anti-interferon gamma antibodies, botulinum toxin, corticosteroids, contact immunotherapies, cryotherapy, hydroxychloroquine, hypnotherapy, imiquimod, Janus kinase inhibitors, laser and light therapy, methotrexate, minoxidil, phototherapy, psychotherapy, prostaglandin analogs, sulfasalazine, topical calcineurin inhibitors, topical nitrogen mustard, and ustekinumab. LIMITATIONS: English-only articles with full texts were used. Manuscripts with adult and pediatric data were only incorporated if individual-level data for pediatric patients were provided. No meta-analysis was performed. CONCLUSION: Topical corticosteroids are the preferred first-line treatment for pediatric AA, as they hold the highest level of evidence, followed by contact immunotherapy. More clinical trials and comparative studies are needed to further guide management of pediatric AA and to promote the potential use of pre-existing, low-cost, and novel therapies, including Janus kinase inhibitors.

Pilot study of fluorescence imitating brightfield imaging for rapid, slide-free dermatopathology.

BACKGROUND: Fluorescence imitating brightfield imaging (FIBI) is a novel alternative microscopy method that can image freshly excised, non-sectioned tissue. We examine its potential utility in dermatopathology by examining readily available specimens embedded in paraffin blocks. METHODS: Nine skin samples embedded in paraffin blocks were superficially deparaffinized using xylene and ethanol and stained with H&E. FIBI captured tissue surface histopathology images using simple microscope optics and a color camera. We then applied deep-learning-based models to improve resemblance to standard H&E coloration and contrast. FIBI images were compared with corresponding standard H&E slides and concordance was assessed by two dermatopathologists who numerically scored epidermal and dermal structure appearance and overall diagnostic utility. RESULTS: Dermatopathologist scores indicate that FIBI images are at least equivalent to standard H&E slides for visualizing structures such as epidermal layers, sweat glands, and nerves. CONCLUSION: Images acquired with FIBI are comparable to traditional H&E-stained slides, suggesting that this rapid, inexpensive, and non-destructive microscopy technique is a conceivable alternative to standard histopathology processes especially for time-sensitive procedures and in settings with limited histopathology resources.

CDKN2A exon 1B deletion predisposing to melanoma and neural system tumour syndrome.

CDKN2A at chromosome positon 9p21 is a tumour suppressor gene encoding the cell cycle regulators p16 and p14ARF. While melanoma is associated with variants affecting both transcripts, families with mutations involving the p14ARF-specific exon 1B may be predisposed to central nervous system tumours. We describe a family with a deletion of exon 1B in CDKN2A, who had multiple cutaneous melanomas, neural tumours and various malignancies.

Pruritic papules after induction chemotherapy with daunorubicin and cytarabine.

We present a 65-year-old woman who developed a diffuse pruritic papular eruption after receiving induction chemotherapy with daunorubicin and cytarabine for newly diagnosed acute myelomonocytic leukemia. The rash improved clinically with triamcinolone treatment and chemotherapy was allowed to continue. This case adds to the growing literature of transient acantholytic dermatosis development in the setting of anti-cancer therapy and emphasizes the importance of clinicopathologic correlation in cutaneous eruptions in cancer patients.

Characteristics of patients with juvenile dermatomyositis from 2001-2021 at a tertiary care center.

BACKGROUND: Juvenile dermatomyositis (JDM) is the most common inflammatory myopathy in the pediatric population and can represent a medical emergency. However, many features of JDM remain poorly understood, disease presentation is highly variable, and predictors of disease course have yet to be identified. METHODS: This retrospective chart review included 47 JDM patients seen at a tertiary care center over a 20-year period. Characteristics such as demographics, clinical signs and symptoms, antibody positivity, dermatopathology features, and treatments were recorded. RESULTS: All patients had evidence of cutaneous involvement, whereas 88.4% experienced muscle weakness. Constitutional symptoms and dysphagia were commonly present. The most frequent cutaneous findings were Gottron papules, heliotrope rash, and nailfold changes. Anti-TIF1? was the most prevalent myositis-specific autoantibody. Management involved systemic corticosteroids in nearly all cases. Strikingly, the dermatology department was only involved in the care of four in every ten (19/47) patients. CONCLUSIONS: Prompt recognition of the strikingly reproducible skin findings present in JDM can improve disease outcomes in this population. This study highlights the need for increased education of such pathognomonic findings as well as more multidisciplinary care. In particular, a dermatologist should be involved in the care of patients presenting with muscle weakness and skin changes.

Psychosocial and psychiatric comorbidities and health-related quality of life in alopecia areata: A systematic review.

BACKGROUND: Alopecia areata (AA) is an immune-mediated disease resulting in nonscarring hair loss. Systematic reviews on the psychosocial and psychiatric comorbidities, health-related quality of life, and interventions targeting psychosocial well-being are limited. OBJECTIVE: To conduct a systematic review of the psychosocial comorbidities, health-related quality of life, and treatment options targeting psychosocial well-being in adult and pediatric AA patients. METHODS: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines within the PubMed database. Specific search terms included, but were not limited to, alopecia areata, psychosocial, psychiatry, and quality of life. Studies were then evaluated for their design and categorized into corresponding levels of evidence according to the guidelines adapted from the Oxford Center for Evidence Based Medicine. FINDINGS: Seventy-three reports met inclusion criteria, involving approximately 414,319 unique participants. AA patients were found to have psychiatric comorbidities, particularly anxiety and depression. Health-related quality of life is reduced in AA patients, but data on pediatric AA quality of life are limited. Psychotherapy is often recommended as adjuvant treatment. CONCLUSION: AA has substantial psychosocial impact on patients and results in reduced health-related quality of life. Addressing this should be an active part of treatment.

Dermatologic toxicities to immune checkpoint inhibitor therapy: A review of histopathologic features.

Antineoplastic agents that use the immune system have revolutionized cancer treatment. Specifically, implementation of immune checkpoint inhibitors, monoclonal antibodies that block cytotoxic T-lymphocyte-associated antigen-4, programmed cell death protein 1, or programmed cell death ligand 1 show improved and sustained responses in patients with cancer. However, these agents are associated with a plethora of adverse events, many manifesting in the skin. As the clinical application of cancer immunotherapies expands, understanding the clinical and histopathologic features of associated cutaneous toxicities becomes increasingly important to dermatologists, oncologists, and pathologists to ensure timely diagnosis and appropriate care. This review discusses cutaneous reactions to immune checkpoint inhibitors, focusing on histopathologic features.

Germline mutations predisposing to melanoma.

Nearly 15% of melanomas occur in patients with a family history and a subset of these patients have a germline mutation in a melanoma predisposing gene. CDKN2A mutations are responsible for the majority of hereditary melanoma, but many other susceptibility genes have been discovered in recent years, including CDK4, TERT, ACD, TERF2IP, POT1, MITF, MC1R, and BAP1. Additionally, melanoma risk is increased in mixed cancer syndromes caused by mutations in PTEN, BRCA2, BRCA1, RB1, and TP53. While early onset, multiple tumors, and family cancer history remain the most valuable clinical clues for hereditary melanoma, characteristic epithelioid cytology of melanocytic tumors may suggest an underlying BAP1 mutation. Herein, we review the clinical and histopathologic characteristics of melanocytic tumors associated with these germline mutations and discuss the role of genetic counseling.

A patient with anti-NXP2-positive dermatomyositis and syphilis.

Dermatomyositis is an auto-immune inflammatory myopathy that primarily affects the skin and muscle and can be triggered by exposure to various environmental factors. We present a patient with active syphilis infection who developed dermatomyositis and discuss the significance of anti-NXP2 autoantibody positivity.

Nummular dermatitis on guselkumab for palmoplantar psoriasis.

A 40-year-old man with chronic history of refractory palmoplantar psoriasis presented with new onset of well-demarcated oval erythematous asteatotic plaques on bilateral shins after starting guselkumab therapy. Histopathology revealed chronic spongiotic dermatitis consistent with a diagnosis of nummular dermatitis. This case highlights a previously unreported adverse event to guselkumab therapy.

Eosinophilic fasciitis presenting as a unilateral, solitary plaque.

Eosinophilic fasciitis is a rare connective tissue disorder characterized by inflammation of the fascia that leads to painful, indurated skin. Because of its variable clinical presentation and overlap with conditions, such as morphea, the diagnosis of eosinophilic fasciitis can be challenging and relies on clinical presentation, histopathologic and laboratory analysis, and response to therapy. Herein, we present an unusual, solitary, isolated plaque with pathologic features and response to therapy most consistent with eosinophilic fasciitis.

Pink verrucous plaque in a man with systemic mastocytosis.

Porokeratosis ptychotropica is a rare and commonly misdiagnosed subtype of porokeratosis involving the body folds. We present a 53-year-old man with systemic mastocytosis who presented with a pruritic, verrucous plaque in the gluteal fold that showed multiple cornoid lamellae on histopathologic evaluation, diagnostic of porokeratosis ptychotropica. Various treatments have been reported, including topical corticosteroids, retinoids, vitamin D analogs, calcineurin inhibitors, imiquimod, phototherapy, cryotherapy, or ablative laser therapy, but recurrences are common.