Atypical Spitz tumor with SQSTM1::NTRK2 fusion: Report of a case with unique spindled cell features.

A host of signature genetic alterations have been demonstrated in Spitz neoplasms, most notably fusions of kinase genes (including BRAF, ALK, ROS1, NTRK1, NTRK3, RET, MET, MAP3K8) or variants in HRAS. While there are multiple reports of rearrangements involving NTRK1 and NTRK3 in Spitz tumors, there are very few reports of NTRK2-rearranged Spitz nevi in the literature. This report presents an NTRK2-rearranged atypical Spitz tumor with spindled cell features. The patient was a 6-year-old female with a growing pigmented papule on the back. Histopathological evaluation revealed an asymmetric, biphasic, compound proliferation of melanocytes featuring an epithelioid cell population arranged as variably sized nests and single cells along the basal layer with extension down adnexa, as well as a population of spindled melanocytes with desmoplastic features and loss of Melan-A expression in the dermis. There was partial loss of p16 expression in the epidermal component and diffuse loss in the dermal component. Immunohistochemistry for PRAME, ALK, NTRK1, HRAS Q61R, p53, and BRAF V600E were negative. A SQSTM1::NTRK2 fusion was identified by RNA sequencing. No TERT promoter hotspot variants were detected. This case report expands the known histopathologic spectrum of genetic alterations in Spitz neoplasms.

Dermatologic infections in cancer patients treated with checkpoint inhibitors.

BACKGROUND: The incidence of dermatologic infections in patients receiving checkpoint inhibitors (CPIs) has not been systematically described. OBJECTIVE: Identify the incidence of dermatologic infections in patients who received CPIs. METHODS: Retrospective review of dermatologic infections in patients who received CPIs between 2005 and 2020 and were evaluated by dermatologists at Memorial Sloan Kettering Cancer Center. RESULTS: Of 2061 patients in the study, 1292 were actively receiving CPIs (≤ 90 days since the last dose) and 769 had previously been on CPIs (> 90 days since the last dose). The dermatologic infection rate was significantly higher in patients with active CPI treatment (17.5%) than in patients not actively being treated (8.2%; P < .0001). In patients on CPIs, 82 (36.2%), 78 (34.5%), and 48 (21.2%) had bacterial, fungal, and viral infections, respectively, and 18 (8.0%) had polymicrobial infections. Anti-cytotoxic T-lymphocyte-associated antigen-4 monotherapy was associated with the highest risk of infection (hazard ratio, 2.93; 95% confidence interval, 1.87 to 4.60; P < .001). LIMITATIONS: Retrospective design and sample limited to patients referred to dermatology. CONCLUSIONS: Patients actively receiving CPIs are more susceptible to dermatologic infections, with anti-cytotoxic T-lymphocyte-associated antigen-4 monotherapy carrying the highest risk, suggesting that the index of suspicion for infections should be increased in these patients to minimize morbidity and optimize care.

Assessment and Treatment Outcomes of Persistent Radiation-Induced Alopecia in Patients With Cancer.

Importance: Persistent radiation-induced alopecia (pRIA) and its management have not been systematically described. Objective: To characterize pRIA in patients with primary central nervous system (CNS) tumors or head and neck sarcoma. Design, Setting, and Participants: A retrospective cohort study of patients from January 1, 2011, to January 30, 2019, was conducted at 2 large tertiary care hospitals and comprehensive cancer centers. Seventy-one children and adults diagnosed with primary CNS tumors or head and neck sarcomas were evaluated for pRIA. Main Outcomes and Measures: The clinical and trichoscopic features, scalp radiation dose-response relationship, and response to topical minoxidil were assessed using standardized clinical photographs of the scalp, trichoscopic images, and radiotherapy treatment plans. Results: Of the 71 patients included (median [range] age, 27 [4-75] years; 51 female [72%]), 64 (90%) had a CNS tumor and 7 (10%) had head and neck sarcoma. Alopecia severity was grade 1 in 40 of 70 patients (56%), with localized (29 of 54 [54%]), diffuse (13 of 54 [24%]), or mixed (12 of 54 [22%]) patterns. The median (range) estimated scalp radiation dose was 39.6 (15.1-50.0) Gy; higher dose (odds ratio [OR], 1.15; 95% CI, 1.04-1.28) and proton irradiation (OR, 5.7; 95% CI, 1.05-30.8) were associated with greater alopecia severity (P < .001), and the dose at which 50% of patients were estimated to have severe (grade 2) alopecia was 36.1 Gy (95% CI, 33.7-39.6 Gy). Predominant trichoscopic features included white patches (16 of 28 [57%]); in 15 patients, hair-shaft caliber negatively correlated with scalp dose (correlation coefficient, -0.624; P = .01). The association between hair density and scalp radiation dose was not statistically significant (-0.381; P = .16). Twenty-eight of 34 patients (82%) responded to topical minoxidil, 5% (median follow-up, 61 [interquartile range, 21-105] weeks); 4 of 25 (16%) topical minoxidil recipients with clinical images improved in severity grade. Two patients responded to hair transplantation and 1 patient responded to plastic surgical reconstruction. Conclusions and Relevance: Persistent radiation-induced alopecia among patients with primary CNS tumors or head and neck sarcomas represents a dose-dependent phenomenon that has distinctive clinical and trichoscopic features. The findings of this study suggest that topical minoxidil and procedural interventions may have benefit in the treatment of pRIA.

Immune checkpoint inhibitor-related dermatologic adverse events.

Immune checkpoint inhibitors have emerged as a pillar in the management of advanced malignancies. However, nonspecific immune activation may lead to immune-related adverse events, wherein the skin and its appendages are the most frequent targets. Cutaneous immune-related adverse events include a diverse group of inflammatory reactions, with maculopapular rash, pruritus, psoriasiform and lichenoid eruptions being the most prevalent subtypes. Cutaneous immune-related adverse events occur early, with maculopapular rash presenting within the first 6 weeks after the initial immune checkpoint inhibitor dose. Management involves the use of topical corticosteroids for mild to moderate (grades 1-2) rash, addition of systemic corticosteroids for severe (grade 3) rash, and discontinuation of immunotherapy with grade 4 rash. Bullous pemphigoid eruptions, vitiligo-like skin hypopigmentation/depigmentation, and psoriasiform rash are more often attributed to programmed cell death-1/programmed cell death ligand-1 inhibitors. The treatment of bullous pemphigoid eruptions is similar to the treatment of maculopapular rash and lichenoid eruptions, with the addition of rituximab in grade 3-4 rash. Skin hypopigmentation/depigmentation does not require specific dermatologic treatment aside from photoprotective measures. In addition to topical corticosteroids, psoriasiform rash may be managed with vitamin D3 analogues, narrowband ultraviolet B light phototherapy, retinoids, or immunomodulatory biologic agents. Stevens-Johnson syndrome and other severe cutaneous immune-related adverse events, although rare, have also been associated with checkpoint blockade and require inpatient care as well as urgent dermatology consultation.

Immune checkpoint inhibitors to treat cutaneous malignancies.

As the incidence of cutaneous malignancies continues to rise and their treatment with immunotherapy expands, dermatologists and their patients are more likely to encounter immune checkpoint inhibitors. While the blockade of immune checkpoint target proteins (cytotoxic T-lymphocyte-associated protein-4, programmed cell death-1, and programmed cell death ligand-1) generates an antitumor response in a substantial fraction of patients, there is a critical need for reliable predictive biomarkers and approaches to address refractory disease. The first article of this Continuing Medical Education series reviews the indications, efficacy, safety profile, and evidence supporting checkpoint inhibition as therapeutics for metastatic melanoma, cutaneous squamous cell carcinoma, and Merkel cell carcinoma. Pivotal studies resulting in the approval of ipilimumab, pembrolizumab, nivolumab, cemiplimab, and avelumab by regulatory agencies for various cutaneous malignancies, as well as ongoing clinical research trials, are discussed.

Treatment Outcomes of Immune-Related Cutaneous Adverse Events.

PURPOSE: The aim of the current study was to report the efficacy of topical and systemic treatments for immune-related cutaneous adverse events (ircAEs) attributed to checkpoint inhibitors in an uncontrolled cohort of patients referred to oncodermatology clinics. METHODS: A retrospective analysis of patients with ircAEs evaluated by dermatologists from January 1, 2014, to December 31, 2017, at three tertiary care hospitals and cancer centers were identified through electronic medical records. Clinicopathologic characteristics, dermatologic therapy outcome, and laboratory data were analyzed. RESULTS: A total of 285 patients (median age, 65 years [range, 17 to 89 years]) with 427 ircAEs were included: pruritus (n = 138; 32%), maculopapular rash (n = 120; 28%), psoriasiform rash (n = 22; 5%), and others (n = 147; 34%). Immune checkpoint inhibitor class was associated with ircAE phenotype (P = .007), where maculopapular rash was predominant in patients who received combination therapy. Severity of ircAEs was significantly reduced (mean Common Terminology Criteria for Adverse Events grade: 1.74 v 0.71; P < .001) with dermatologic interventions, including topical corticosteroids, oral antipruritics, and systemic immunomodulators. A total of 88 ircAEs (20%) were managed with systemic immunomodulators. Of these, 22 (25%) of 88 persisted or worsened. In seven patients with corticosteroid-refractory ircAEs, improvement resulted from targeted biologic immunomodulatory therapies that included rituximab and dupilumab. Serum interleukin-6 (IL-6) was elevated in 34 (52%) of 65 patients; grade 3 or greater ircAEs were associated with increased absolute eosinophils (odds ratio, 4.1; 95% CI, 1.3 to 13.4) and IL-10 (odds ratio, 23.8; 95% CI, 2.1 to 262.5); mean immunoglobulin E serum levels were greater in higher-grade ircAEs: 1,093 kU/L (grade 3), 245 kU/L (grade 2), and 112 kU/L (grade 1; P = .043). CONCLUSION: Most ircAEs responded to symptom- and phenotype-directed dermatologic therapies, whereas biologic therapies were effective in patients with corticosteroid-refractory disease. Increased eosinophils, IL-6, IL-10, and immunoglobulin E were associated with ircAEs, and they may represent actionable therapeutic targets for immune-related skin toxicities.

Inflammatory dermatoses, infections, and drug eruptions are the most common skin conditions in hospitalized cancer patients.

BACKGROUND: Dermatologic conditions cause morbidity and mortality among hospitalized cancer patients. An improved understanding is critical for implementing clinical and research programs in inpatient oncodermatology. OBJECTIVE: To characterize inpatient dermatology consultations at a large comprehensive cancer center. METHODS: Retrospective database query of new admissions and medical record review of initial inpatient dermatology consultations comparing inpatients consulted and not consulted during January-December 2015. RESULTS: In total, 412 of 11,533 inpatients received 471 dermatology consultations (54% male, median age 59.5 years). Patients with hematologic cancers were 6 times more likely to receive dermatologic consultations compared with nonhematologic cancers (odds ratio 6.56, 95% confidence interval 5.35-8.05, P < .0001). Patients consulted by a dermatologist had a significantly longer length of stay than inpatients not consulted by dermatology (median 11 vs 5 days, P < .0001). Among the 645 dermatologic conditions diagnosed, the most common categories were inflammatory diseases, infections, and drug reactions; the most frequent conditions were contact dermatitis, herpes zoster, and chemotherapy-induced drug eruptions. LIMITATIONS: The study's retrospective nature and single-institution setting are potential limitations. CONCLUSION: Hematologic malignancies are a significant risk factor for dermatology inpatient consultations. A significantly longer length of stay was associated with dermatology consultations, suggesting high comorbidities in these patients. Increased dermatologic care of these inpatients might improve quality of life, dermatologic health, and ability to receive anticancer agents.