Clinical Features and Outcomes of Black Patients With Melanoma.

Importance: Melanoma in Black individuals has an annual incidence of approximately 1 in 100 000 people. Most studies of melanoma in Black patients have used population databases, which lack important, precise clinical details. Objective: To identify patient-level and tumor-level characteristics of melanoma in Black patients. Design, Setting, and Participants: This case series included Black patients with melanoma at 2 tertiary care centers (University of Texas Southwestern [UTSW] Medical Center and Parkland Health), affiliated with a single institution, UTSW in Dallas, Texas. Self-reported Black patients with a histopathologic diagnosis of melanoma were identified between January 2006 and October 2022. Main Outcomes and Measures: The main variables were demographics, clinical characteristics, personal and family medical history, immunosuppression history, comorbidities, histopathology reports, molecular/genetic studies, imaging reports, melanoma treatments and responses, time to progression, metastatic sites, and survival rates. Results: A total of 48 Black patients with melanoma (median [range] age at diagnosis, 62 [23-86] years; 30 [63%] female) were included in the study. Of 40 primary cutaneous melanomas, 30 (75%) were located on acral skin, despite only 10 of 30 (33%) being histologically classified as acral lentiginous melanomas. Compared with those with acral disease, patients with nonacral cutaneous melanomas were more likely to be immunocompromised (4 of 10 [40%] vs 2 of 30 [7%]) or have a personal history of cancer (6 of 10 [60%] vs 5 of 30 [17%]), with all 3 patients with superficial spreading melanoma having a history of both. No patients had more than 1 confirmed primary melanoma. Overall, 13 Black patients (27%) with melanoma developed stage IV disease, of whom 12 died because of disease progression. Those diagnosed with advanced acral melanoma, mucosal/ocular melanoma, or melanoma of unknown primary lacked actionable sequence variations, were nonresponsive to immunotherapy, and had the poorest outcomes. No patients with nonacral cutaneous melanomas developed distant metastases or died of melanoma. Conclusions and Relevance: This single-institution case series highlights several features of melanoma in Black patients that have not been captured in existing population-level registries, including precise anatomic sites, immune status, family and personal cancer history, and genetics. Multi-institutional registries would improve understanding of melanoma in Black patients.

Lymphomatoid papulosis with DUSP22-IRF4 rearrangement: A case report and literature review.

Lymphomatoid papulosis (LyP) with DUSP22-IRF4 rearrangement is a rare, recently described variant of LyP histopathologically characterized by a biphasic growth pattern, with epidermotropic small-to-medium-sized atypical T-cells and dermal large and transformed T-cells diffusely expressing CD30. LyP with DUSP22-IRF4 rearrangement can mimic other cutaneous lymphoproliferative disorders, particularly primary cutaneous anaplastic large cell lymphoma (PCALCL) or transformed mycosis fungoides (MF). Unlike PCALCL or transformed MF, LyP with DUSP22-IRF4 rearrangement shows an indolent clinical behavior, with frequent spontaneous regression of untreated lesions. Thus, it is important to recognize this rare variant of LyP to avoid misclassification, which may potentially lead to unnecessarily aggressive patient management. To our knowledge, only 13 cases of LyP with DUSP22-IRF4 rearrangement have been reported to date in the English literature. Herein, we describe an additional case of LyP with DUSP22-IRF4 rearrangement in a 63-year-old man and provide a comprehensive literature review with regards to the clinical, histopathologic, and molecular features of this novel entity.

Periorbital edema associated with alpelisib.

Alpelisib is an alpha isoform-specific phosphatidylinositol 3-kinase (PI3K) inhibitor approved for use in the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor (HER2)-negative metastatic breast cancer in combination with fulvestrant. Hyperglycemia, rash, and gastrointestinal upset are the most commonly reported adverse events associated with alpelisib. Although rash is a known on-target effect of alpelisib, patients typically present with a morbilliform rash. We describe two cases of periorbital edema associated with alpelisib. We discuss the clinical findings, management, and prognosis of this unique reaction. These cases highlight the importance of early involvement of dermatology to manage adverse cutaneous events associated with alpelisib.

Interstitial granulomatous dermatitis and concurrent immunotherapy associated encephalitis with nivolumab and ipilimumab.

Immune-related adverse events (irAEs) are common in patients receiving immune checkpoint inhibitors for metastatic melanoma and other advanced malignancies. Cutaneous, gastrointestinal, and endocrine (thyroid) irAEs are most prevalent, whereas neurologic irAEs are rare. We present a 73-year-old man with dementia and metastatic melanoma who developed immunotherapy-associated encephalitis and subsequently, interstitial granulomatous dermatitis with nivolumab/ipilimumab. High-dose corticosteroids successfully treated both conditions, though he never regained his baseline mental status. We review the literature on interstitial granulomatous dermatitis and encephalitis with immunotherapy.

Diverse landscape of dermatologic toxicities from small-molecule inhibitor cancer therapy.

BACKGROUND: Advances in molecular biology and genetics have contributed to breakthrough treatments directed at specific pathways associated with the development of cancer. Small-molecule inhibitors (Nibs) aimed at a variety of cellular pathways have been efficacious; however, they are associated with significant dermatologic toxicities. METHODS: We conducted a comprehensive review of dermatologic toxicities associated with Nibs categorized into the following five groups: (a) mitogen-activated protein kinase; (b) growth factor/multi-tyrosine kinase; (c) cell division/DNA repair; (d) signaling associated with myeloproliferative neoplasms; and (e) other signaling pathways. Prospective phase I, II, or III clinical trials, retrospective literature reviews, systematic reviews/meta-analyses, and case reviews/reports were included for analysis. RESULTS: Dermatologic toxicities reviewed were associated with every class of Nibs and ranged from mild to severe or life-threatening adverse skin reactions. Inflammatory reactions manifesting as maculopapular, papulopustular/acneiform, and eczematous lesions were frequent types of dermatologic toxicities seen with Nibs. Squamous cell carcinoma with keratoacanthoma-like features was associated with a subset of Nibs. Substantial overlap in dermatologic toxicities was found between Nibs. CONCLUSIONS: Dermatologic toxicities from Nibs are diverse and may overlap between classes of Nibs. Recognition of the various types of toxicities from Nibs is critical for patient care in the era of "oncodermatology/dermatopathology."

Biologic therapies for checkpoint inhibitor-induced cutaneous toxicities: a single-institution study of 17 consecutively treated patients.

PURPOSE: Treatment options for corticosteroid-refractory and/or high-grade checkpoint inhibitor (CPI)-induced cutaneous adverse events (CAEs) are limited; however, anecdotal reports of biologic therapies have been successful. We aim to characterize the appropriate treatment scenarios and safety and efficacy profiles of biologics used to treat patients with CPI-induced CAEs at a single institution. METHODS: This is a retrospective case series of patients from January 1st, 2015 to October 20th, 2020, with CPI-induced CAEs who were treated with biologics at a single cancer center. Patients were identified using institutional electronic medical record who underwent CPI therapy with subsequent CAEs that necessitated biologic therapy. Diagnostic criteria utilized for CAEs were based on documentation by four board-certified dermatologists, in combination with detailed chart reviews and pathology findings. Primary study outcome measurements include CAE response, tumor response, and adverse events during biologics treatment. RESULTS: We identified 17 patients who fit study criteria. Sixteen patients experienced some degree of CAE improvement on biologics, with 10 of 10 patients reaching CAE resolution at 6 months post biologics. Eight patients needed new systemic treatment post biologics treatment, while 9 patients received no further treatment or stayed on the CPI. Thirteen patients tolerated biologics well with no significant adverse events or blood abnormalities, with only 2 patients experiencing biologic dose delays. CONCLUSION: In our cohort, biologics appear to be extremely efficacious in the treatment of severe-grade and/or steroid refractory CAEs. They also appeared to be well-tolerated without overtly negative effects on tumor response. In patients with limited cancer treatment options and good tumor response to CPIs, biologics should be considered for severe-grade and/or refractory CAEs.

Severe de novo pustular psoriasiform immune-related adverse event associated with nivolumab treatment for metastatic esophageal adenocarcinoma.

Breakthrough targeted therapies have produced significant improvements in survival for cancer patients, but have a propensity to cause cutaneous immune-related adverse events (irAEs). Psoriasiform irAEs, representing about 4% of dermatologic toxicities associated with immune checkpoint inhibitor (ICI) therapy, are usually mild, occur in older patients and present as an exacerbation of existing psoriasis after several doses of ICI therapy. We report a case of a 58-year-old woman with metastatic esophageal adenocarcinoma and no prior history of psoriasis who developed a pustular psoriasiform irAE, beginning 3 days after initiation of nivolumab and progressing to confluent erythroderma with pustules over 2 weeks despite topical steroid use. She had concurrent acrodermatitis enteropathica, clinically diagnosed and confirmed with a low serum zinc level, that improved with supplementation. Her psoriasiform irAE was refractory to systemic steroids and acitretin, prompting discontinuation of nivolumab and treatment with ustekinumab and concomitant slow taper of acitretin and prednisone. Pustular psoriasiform irAE is a rare but severe dermatologic toxicity resulting from ICI therapy. Given the diverse morphologic types of cutaneous irAEs that can occur during ICI therapy, a clinical and histopathologic examination of dermatologic toxicities is critical to identify patients who may benefit from biologic therapy.

Surgical Intervention for Paronychia Induced by Targeted Anticancer Therapies.

BACKGROUND: Paronychia is a common toxicity associated with targeted anticancer therapies. Antibiotics and steroids are the standard treatments for severe paronychia, yet they are often inadequate, prolonging the patient's suffering and resulting in changes to effective cancer therapy. OBJECTIVE: This article describes the clinical course of drug-induced paronychia and attempts to identify circumstances under which nail surgery may be beneficial. MATERIALS AND METHODS: This is a retrospective case series from a single institution's electronic medical record for patients on paronychia-inducing anticancer therapies with nail disease visit diagnosis codes. RESULTS: The authors identified 36 nail procedures performed on 12 patients, all of whom were managed with conservative steroid and antibiotic therapy with varying degrees of improvement; however, no further improvement was seen after 90 days. Partial matricectomy, nail avulsion, debridement/clipping, and incision and drainage were performed with resolution rates of 100% (11/11), 38.5% (5/13), 12.5% (1/8), and 0% (0/4), respectively. The average time to surgical intervention was 196 days, and the average time to resolution was 268 days. CONCLUSION: This series highlights the prolonged course of severe drug-induced paronychia and the importance of surgical intervention to reduce pain and impact on cancer treatment. Partial matricectomy should be considered for paronychia unresponsive to conservative therapy by 3 months.

Case Report: Enfortumab Vedotin for Metastatic Urothelial Carcinoma: A Case Series on the Clinical and Histopathologic Spectrum of Adverse Cutaneous Reactions From Fatal Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis to Dermal Hypersensitivity Reaction.

Enfortumab vedotin is a Nectin-4 directed antibody-drug conjugate approved in metastatic urothelial carcinoma following progression on a platinum-containing chemotherapy and immune checkpoint blockade. On-target dermatologic toxicity may occur from Nectin-4 expression in the skin. We highlight a case of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis following enfortumab infusions that was ultimately fatal. The second case describes an erythema multiforme-like rash with interface dermatitis related to enfortumab. Dermatologic findings, immunohistochemistry studies, and immune profiling are detailed. These cases demonstrate the potentially catastrophic outcomes in some patients treated with enfortumab. Patients must be monitored for cutaneous toxicities with early involvement of dermatology and dermatopathology.