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.

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.

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.

Cutaneous graft-versus-host disease incidence is similar in haploidentical and matched unrelated hematopoietic transplant recipients: A retrospective cohort study.

BACKGROUND: Cutaneous graft-versus-host disease (GVHD) is common after hematopoietic cell transplants. Haploidentical transplants (Haplo) have historically higher rates of GVHD with overall outcomes improved with the use of posttransplant cyclophosphamide. Specific cutaneous outcomes have not been explored in haploidentical versus matched unrelated donor (MUD) transplants. OBJECTIVE: We sought to examine the incidence of GVHD in MUD and Haplo transplants. METHODS: This is a retrospective cohort study of patients' records that received MUD or Haplo transplants between 2010 and 2015 with determination of GVHD severity and features by one investigator. RESULTS: The Haplo cohort included more minorities (22.7% vs 6.8%; P < .001). The incidence of acute cutaneous GVHD was similar (Haplo 47.7% [95% confidence interval {CI} 37.0-58.6%] vs MUD 42.6% [95% CI 37.9-47.3%]; P = .41). Chronic GVHD was also similar (Haplo 17.1% [95% CI 9.9-26.6%] vs MUD 12.8% [95% CI 9.9-16.3%]; P = .31). The Haplo group had lower rates of sclerosis (13.3% [95% CI 1.7-4.05%] vs 50.9% [95% CI 37.3-64.4%]; P = .0095). Other secondary outcomes showed no difference. LIMITATIONS: Severity of GVHD was determined retrospectively and not all patients were seen by a dermatologist. CONCLUSIONS: No difference was observed between rates or severity of acute or chronic GVHD. Sclerosis was less common in the Haplo group.