Erythrasma.

This case report describes well-demarcated brown plaques with overlying fine scale in the bilateral axillae, inframammary folds, and inguinal folds and widespread coral-red fluorescence.

Dermatopathologic features of cutaneous squamous cell carcinoma and actinic keratosis: Consensus criteria and proposed reporting guidelines.

BACKGROUND: There is considerable variation in the literature regarding the dermatopathologic diagnostic features of and reporting guidelines for actinic keratosis (AK) and cutaneous squamous cell carcinoma (cSCC). OBJECTIVE: To develop consensus recommendations regarding diagnostic criteria, nomenclature, and reporting of AK and cSCC. METHODS: Literature review and cross-sectional multiround Delphi process including an international group of expert dermatopathologists followed by a consensus meeting. RESULTS: Consensus was achieved regarding the key dermatopathologic features necessary for diagnosing cSCC, AK, and associated variants; grading of degree of cellular differentiation in cSCC; utility of immunohistochemistry for diagnosis of cSCC; and pathologic features that should be reported for cSCC and AK. LIMITATIONS: Consensus was not achieved on all questions considered. CONCLUSION: Despite the lack of clarity in the literature, there is consensus among expert dermatopathologists regarding diagnostic criteria and appropriate reporting of AK and cSCC. Widespread implementation of these consensus recommendations may improve communication between dermatopathologists and clinicians, facilitating appropriate treatment of AK and cSCC.

Milestones 2.0: An advancement in competency-based assessment for dermatology.

In 2013, Next Accreditation System and Milestones became the competency-based assessment framework required for all specialties accredited by the Accreditation Council for Graduate Medical Education. Dermatology residency programs implemented Milestones 1.0 in the 2013-2014 academic year. The Accreditation Council for Graduate Medical Education committed to review and revise Milestones 1.0 within 3 to 5 years. Subsequently, feedback from key stakeholders influenced the goals for revision, including reducing complexity, enhancing community engagement, and providing additional resources for programs. In 2019, the Dermatology Milestones 2.0 work group streamlined the specialty-specific patient care and medical knowledge subcompetencies. The harmonized milestones allowed for greater uniformity across specialties in systems-based practice, practice-based learning and improvement, professionalism, and interpersonal communication and skills. The work group developed a supplemental guide with specialty-specific context to help program directors, clinical competency committee members, and other faculty understand individual milestones. Dermatology Milestones 2.0 reduces the number of subcompetencies from 28 to 21. Milestones 2.0 represents an advancement in competency-based assessment for dermatology. The first year of reporting for Dermatology Milestones 2.0 is 2021.

Pityriasis rosea-like rash after messenger RNA COVID-19 vaccination: A case report and review of the literature.

A spectrum of cutaneous reactions to SARs-CoV-2 (COVID-19) vaccines have been reported in the literature. We present a case of a pityriasis rosea-like rash occurring after Pfizer COVID-19 vaccination and review cases of pityriasis rosea (PR)/PR-like eruption (PR-LE) after mRNA COVID-19 vaccine published in the medical literature. Of the 30 cases found, none experienced severe adverse effects and the rash resolved in an average of 5.6 weeks. It is important for physicians to be aware of this self-limited reaction so they can reassure and appropriately counsel patients that it is safe to receive subsequent vaccine doses despite the cutaneous eruption. Additionally, differences in incidence of this reaction after Pfizer and Moderna vaccination may suggest a differing host immune response incited by these vaccines which warrants further investigation.

Cutaneous adverse events in 155 patients with metastatic melanoma consecutively treated with anti-CTLA4 and anti-PD1 combination immunotherapy: Incidence, management, and clinical benefit.

BACKGROUND: In response to the increased use of combination checkpoint inhibitors (CPIs) and the resulting increased cutaneous adverse events (CAEs), this study reviewed patients with melanoma treated with combination CPIs to characterize CAE features and their clinical impact, correlation to adverse events in other organs, and correlation to tumor response. METHODS: Patients from the authors' institutional database who received at least 1 dose of ipilimumab in combination with either nivolumab or pembrolizumab between January 1, 2012, and December 31, 2017, for stage IV or unresectable stage III melanoma were identified. The time to next treatment (TTNT) was calculated from the start of CPI therapy to the start of the next treatment or death, and the development of CAEs was tested in a time-dependent Cox regression to identify associations with TTNT. RESULTS: Eighty-one patients (52.3%) experienced a total of 92 CAEs, including eczematous dermatitis (25.0%), morbilliform eruption (22.8%), vitiligo (12.0%), and pruritus without rash (8.7%). The median times to the onset and resolution of CAEs were 21 days (range, 0-341 days) and 50 days (range, 1-352 days), respectively. Most CAEs resolved after patients entered the CPI maintenance phase and treatment with oral antihistamines with or without topical steroids. CPI discontinuation occurred in 4 patients (2.6%) because of CAEs, in 49 (31.6%) because of other immune-related adverse events, and in 20 (12.9%) because of melanoma progression or death. For patients definitively treated with CPIs (n = 134; 86.5%), TTNT was significantly longer with CAEs than without CAEs (hazard ratio, 0.567; 95% CI, 0.331-0.972; P = .039). CONCLUSIONS: CAEs were mostly reversible and rarely required therapy discontinuation. The development of CAEs was associated with a longer TTNT, and this suggested a possible clinical benefit.

What's Eating You? Caterpillars.

Caterpillar envenomation is a worldwide problem, with manifestations ranging from dermatitis to iridocyclitis and a fatal hemorrhagic diathesis. This article focuses on the diagnosis and management of dermatoses related to caterpillars.

Concomitant Cutaneous Langerhans Cell Hystiocytosis and Leukemia Cutis.

Leukemia cutis develops in <4% of all acute leukemias. Concurrent acute myeloid leukemia (AML) and Langerhans cell histiocytosis (LCH) is rare, with most cases involving lymph nodes or spleen, and no cutaneous involvement. We report the case of a 59-year-old man who presented with fever, malaise, and fatigue. The CBC showed leukocytosis (30.4 × 10/L, 9% blasts), anemia, and thrombocytopenia. Bone marrow biopsy was diagnosed with AML, not otherwise specified, with mutations of FLT3 and IDH2 (R140Q). The patient developed skin rash on the right flank with the clinical differential diagnosis of herpes simplex virus or varicella-zoster virus infection/reactivation versus leukemia cutis. A skin biopsy showed leukemia cutis in mid and deep dermis. Immunohistochemistry positive for CD4, CD33, CD117, and myeloperoxidase (MPO) supported myeloid and monocytic differentiation. Clusters of Langerhans cells positive for S100, CD1a, CD4, langerin and aberrant CD33 and MPO were found admixed with the AML cells. Langerhans cells were negative for BRAF V600E by immunohistochemistry. The diagnosis of leukemia cutis and concomitant LCH was established. The aberrant expression of CD33 and MPO shared by AML and LCH suggests a possible relationship among these 2 lesions. No LCH or Langerhans cell differentiation was found in the bone marrow. The patient achieved complete remission 4 months after chemotherapy and the skin lesions resolved. To our knowledge, we present for the first time a case of concomitant cutaneous LCH and leukemia cutis.

Diverse types of dermatologic toxicities from immune checkpoint blockade therapy.

Immunomodulatory drugs that leverages host immune mechanisms to destroy tumor cells have been met with great promise in the treatment of cancer. Immunotherapy, targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have shown tremendous improvements in the survival of patients with advanced solid tumors. However, the development of dermatologic toxicity (DT) is a consequence to immunotherapy. Review of published reports of the DT to immunotherapy revealed patients receiving anti-CTCLA-4 antibody or anti-PD-1/PD-L1 antibody often develop a DT of any type and grade. In this article, of the 3825 patients who were treated with anti-PD-1 and of 556 patients receiving anti-PD-L1, DT of any type and grade were reported in 1474 (∼39%) and 95 (∼17%) of patients, respectively. The emergence of specific types of DT to immunotherapy is beginning to be recognized can be categorized into four groups: (a) inflammatory, (b) immunobullous, (c) alteration of keratinocytes and (d) alteration of melanocytes. Lichenoid dermatitis and bullous pemphigoid appear to be DT more associated with anti-PD-1/PD-L1 antibody. The DT profile in patients receiving immunotherapy is diverse, and early recognition of specific types of DT that clinicians may encounter is critical for optimal patient care.

Cross-species identification of genomic drivers of squamous cell carcinoma development across preneoplastic intermediates.

Cutaneous squamous cell carcinoma (cuSCC) comprises 15-20% of all skin cancers, accounting for over 700,000 cases in USA annually. Most cuSCC arise in association with a distinct precancerous lesion, the actinic keratosis (AK). To identify potential targets for molecularly targeted chemoprevention, here we perform integrated cross-species genomic analysis of cuSCC development through the preneoplastic AK stage using matched human samples and a solar ultraviolet radiation-driven Hairless mouse model. We identify the major transcriptional drivers of this progression sequence, showing that the key genomic changes in cuSCC development occur in the normal skin to AK transition. Our data validate the use of this ultraviolet radiation-driven mouse cuSCC model for cross-species analysis and demonstrate that cuSCC bears deep molecular similarities to multiple carcinogen-driven SCCs from diverse sites, suggesting that cuSCC may serve as an effective, accessible model for multiple SCC types and that common treatment and prevention strategies may be feasible.

Autoimmune dermatologic toxicities from immune checkpoint blockade with anti-PD-1 antibody therapy: a report on bullous skin eruptions.

Monoclonal antibodies against the immune checkpoint programmed cell death receptor 1 (PD-1) improve the hosts' antitumor immune response and have showed tremendous promise in the treatment of advanced solid tumors and hematologic malignancies. Reports of serious autoimmune dermatologic toxicities from immune checkpoint blockade therapy, however, are emerging. We report our experience with five patients who presented with pruritic vesicles and blisters on the skin while treated with anti-PD-1 antibody immunotherapy with either nivolumab or pembrolizumab. Four of the patients' skin biopsies revealed subepidermal bullae with immunohistochemical study for type IV collagen labeling the floor of the blister cavity and direct immunofluorescence studies (in three of the four patients tested) decorated linear IgG and C3 immune deposits on the blister roof, diagnostic of bullous pemphigoid. One patient developed bullous erythema multiforme. All patients had partial or complete resolution of skin lesions following treatment with systemic corticosteroid and cessation of checkpoint blockade. Recognition and treatment of rare immune-related bullous dermatologic toxicities will become increasingly important as more patients are treated with effective and newer immune checkpoint blockade therapy.

Multifocal extramammary Paget's disease-associated adenocarcinoma: a rare condition of flexoral skin of multiple sites.

Extramammary Paget disease (EMPD) is a rare malignant neoplasm of apocrine sweat glands that is morphologically and histologically identical to Paget disease of the breast. The primary lesion is usually a solitary, well-demarcated, erythematous, scaly plaque that may contain crust, erosions, or ulcerations. The vulva is the most common site, but any area containing apocrine sweat glands may be involved. We present a case of triple extramammary Paget disease of the groin and bilateral axillae in a diabetic patient whose axillary lesions appeared consistent with acanthosis nigricans. This case demonstrates the need to consider EMPD in the evaluation of acanthosis of the axilla given its ability to mimic more common conditions.

A Comparative Study Between Smartphone-Based Microscopy and Conventional Light Microscopy in 1021 Dermatopathology Specimens.

CONTEXT: The incorporation of high-resolution cameras into smartphones has allowed for a variety of medical applications including the use of lens attachments that provide telescopic, macroscopic, and dermatoscopic data, but the feasibility and performance characteristics of such a platform for use in dermatopathology have not been described. OBJECTIVE: To determine the diagnostic performance of a smartphone microscope compared to traditional light microscopy in dermatopathology specimens. DESIGN: A simple smartphone microscope constructed with a 3-mm ball lens was used to prospectively evaluate 1021 consecutive dermatopathology cases in a blinded fashion. Referred, consecutive specimens from the community were evaluated at a single university hospital. The performance characteristics of the smartphone platform were calculated by using conventional light microscopy as the gold standard. The sensitivity and specificity for the diagnosis of melanoma, nonmelanoma skin cancers, and other miscellaneous conditions by the phone microscopy platform, as compared with traditional light microscopy, were calculated. RESULTS: For basal cell carcinoma (n = 136), the sensitivity and specificity of smartphone microscopy were 95.6% and 98.1%, respectively. The sensitivity and specificity for squamous cell carcinoma (n = 94) were 89.4% and 97.3%, respectively. The lowest sensitivity was found in melanoma (n = 15) at 60%, although the specificity was high at 99.1%. The accuracy of diagnosis of inflammatory conditions and other neoplasms was variable. CONCLUSIONS: Mobile phone-based microscopy has excellent performance characteristics for the inexpensive diagnosis of nonmelanoma skin cancers in a setting where a traditional microscope is not available.

Grape Cells (Multinucleated Keratinocytes) in Noninfectious Dermatoses: Case Series and Review of the Literature.

Multinucleated keratinocytes (also known as multinucleated epidermal giant cells) are a frequently overlooked histological finding in noninfectious inflammatory dermatoses. They are sometimes found in conditions characterized by chronic rubbing and pruritus, such as lichen simplex chronicus or prurigo nodularis, and may be a helpful clue in making the clinical diagnosis. This finding must be differentiated from other conditions characterized by multinucleated keratinocytes on histopathology, specifically herpes simplex, varicella zoster, or measles viral infections. The authors present a case series of 2 patients with unique clinical noninfectious diagnoses but similar histopathologic findings on biopsy. The histopathologic findings on both cases demonstrated multinucleated keratinocytes, which were related to manipulation of the epidermis.

Morphea-like complications to illicit gluteal silicone injections.

We present a case of a 39-year-old Hispanic woman who was referred to our clinic for treatment of several indurated plaques on her buttocks that developed one year prior to presentation, after she received injections of an unknown substance for augmentation. Biopsy of one nodule revealed silicone in the dermis.

Panniculitis With Necrotizing Granulomata in a Patient on BRAF Inhibitor (Dabrafenib) Therapy for Metastatic Melanoma.

There have been major developments in targeted therapeutics with the clinical development of selective BRAF inhibitors (BRAFi) for patients with metastatic BRAF V600E mutant melanoma. Objective response rate of almost 50% has been witnessed in BRAFi clinical trials. Frequent side effects range from squamoproliferative lesions, including hyperplasia, keratoacanthomas, and squamous cell carcinomas to second primary melanomas. We describe a 50-year-old Hispanic woman with BRAF V600E mutant metastatic melanoma who was treated with surgery, radiation therapy, interleukin-2, and was enrolled on a BRAFi (dabrafenib) trial. Two months after initiation, she developed multiple erythematous, indurated, tender subcutaneous nodules bilaterally on the anterior thighs, posterior arms, and left dorsal forearm without overlying epidermal change. Punch biopsy revealed panniculitis with necrotizing granulomata. Infectious and other causes for panniculitis were excluded. We believe the histology likely represents a reaction to BRAFi therapy based on the temporal relationship of its onset to initiation of BRAFi therapy and previously reported cases of neutrophilic panniculitis associated with BRAFi therapy. Panniculitis has been emerging as an important unusual side effect of BRAFi therapy. Our case illustrates a unique presentation of BRAFi-associated panniculitis demonstrating necrotizing granulomata.

Emerging clinical applications of selected biomarkers in melanoma.

Melanoma is a lethal skin disease with a mostly predictable clinical course according to a known constellation of clinical and pathologic features. The distinction of melanoma from benign melanocytic nevus is typically unequivocol; however, there is a subset of tumors known for its diagnostic challenges, development of late metastases, and difficulties in treatment. Several melanocytic tissue biomarkers are available that can facilitate the histopathologic interpretation of melanoma as well as provide insight into the biologic potential and mutational status of this disease. This review describes the clinical application of some of these established and emerging tissue biomarkers available to assess melanocytic differentiation, vascular invasion, mitotic capacity, and mutation status. The selected tissue biomarkers in this review include MiTF, Sox10, D2-40, PHH3, H3KT (anti-H3K79me3T80ph), anti-BRAFV600E, and anti-BAP-1.