Enfortumab vedotin-induced cutaneous eruption: Ring mitotic figures as a distinctive histopathologic feature.

Enfortumab vedotin (EV), a nectin-4-binding agent that affects microtubules, has become standard therapy for advanced urothelial carcinoma. The agent, now given in combination with pembrolizumab, frequently induces cutaneous reactions. Here, we report a severe EV-induced cutaneous eruption. A 58-year-old woman with metastatic urothelial carcinoma developed a rash after receiving simultaneous first doses of EV and pembrolizumab. The eruption began on the flank and spread to involve her trunk and extremities with prominent involvement of folds, including the axillae and medial thighs. Skin biopsy revealed extensive vacuolar alteration of the basal epidermis and numerous epidermal keratinocytic mitotic figures, often suprabasilar, including ring and "starburst" forms. The findings supported a diagnosis of EV-induced eruption. With EV cessation and systemic corticosteroids, the rash resolved over a few weeks. Pembrolizumab was restarted as monotherapy, and the patient's cancer showed a significant radiographic treatment response at 3 months. An emerging literature of small series and case reports, largely from oncologic literature, presents the histopathology of EV-induced cutaneous eruption as a vacuolar interface dermatitis with the inconsistently reported feature of arrested mitotic figures. This case study demonstrates distinctive clinical and histopathologic features of EV-induced eruption, which may inform dermatologic and oncologic management.

Screening, Diagnosis, and Initial Care of Asian and White Patients With Lung Cancer.

BACKGROUND: Data on the care of Asian patients with lung cancer in the US are limited; however, lung cancer is the leading cause of cancer death in this population. METHODS: Demographics, low-dose computed tomography (LDCT) screening, disease characteristics, and treatment history were compared between Asian and White patients newly diagnosed with lung cancer from 2014 to 2019 identified from Tufts Medical Center cancer registry. The influence of race on presenting stage was assessed via ordinal logistic regression. Time to treatment initiation (TTI) and overall survival (OS) were analyzed via log-rank tests. The impact of race on OS was evaluated via multivariable Cox regression. RESULTS: Asian patients (N = 144) were more likely to prefer non-English languages, use interpreters, be never-smokers, and harbor EGFR alterations, compared to White patients (N = 472), and to be diagnosed with later-stage lung cancer (odds ratio: 2.14, P < .001), had longer median TTI (early stage: 2.30 vs. 1.43 months, P = .035; curative stage: 1.88 vs. 1.20 months, P = .041) and more often did not receive cancer-directed therapy (12.6% vs. 5.7%, P = .01). Screening LDCT was done only in 11.9% of Asian and 21.4% of White patients (P = .20) who would have met screening criteria prior to diagnosis (N = 215). Median OS was similar between Asian and White patients (not reached vs. 74.8 months, P = .17). Multivariable Cox model suggested better OS for Asian patients (hazard ratio: 0.57, P = .01). CONCLUSION: In our study, Asian patients presented with later-stage lung cancer, had treatment delays, and more often did not receive treatment, compared to White patients, yet did not have inferior survival.

Atherosclerotic Cardiovascular Disease Risk and Longitudinal Risk Factor Management Among Patients With Breast Cancer.

BACKGROUND: Cardiovascular disease is the leading cause of noncancer mortality for breast cancer survivors. Data are limited regarding patient-level atherosclerotic cardiovascular disease (ASCVD) risk estimation and preventive medication use. This study aimed to characterize ASCVD risk and longitudinal preventive medication use for a cohort of patients with nonmetastatic breast cancer. PATIENTS AND METHODS: This retrospective cohort study included 326 patients at an academic medical center in Boston, Massachusetts diagnosed with nonmetastatic breast cancer or ductal carcinoma in situ from January 2009 through December 2015. Patient demographics, clinical characteristics, laboratory studies, medication exposure, and incident cardiovascular outcomes were collected. Estimated 10-year ASCVD risk was calculated for all patients from nonlaboratory clinical parameters. RESULTS: Median follow up time was 6.5 years (IQR 5.0, 8.1). At cancer diagnosis, 23 patients (7.1%) had established ASCVD. Among those without ASCVD, 10-year estimated ASCVD risk was ≥20% for 77 patients (25.4%) and 7.5% to <20% for 114 patients (37.6%). Two-hundred and sixteen patients (66.3%) had an indication for lipid-lowering therapy at cancer diagnosis, 123 of whom (57.0%) received a statin during the study. Among 100 patients with ASCVD or estimated 10-year ASCVD risk ≥20%, 92 (92.0%) received an antihypertensive medication during the study. Clinic blood pressure >140/90 mmHg was observed in 33.0% to 55.6% of these patients at each follow up assessment. CONCLUSION: A majority of patients in this breast cancer cohort had an elevated risk of ASCVD at the time of cancer diagnosis. Modifiable ASCVD risk factors were frequently untreated or uncontrolled in the years following cancer treatment.

Expression and alternative splicing of classical and nonclassical MHCI genes in the hippocampus and neuromuscular junction.

The major histocompatibility complex class I (MHCI) is a large gene family, with over 20 members in mouse. Some MHCIs are well-known for their critical roles in the immune response. Studies in mice which lack stable cell-surface expression of many MHCI proteins suggest that one or more MHCIs also play unexpected, essential roles in the establishment, function, and modification of neuronal synapses. However, there is little information about which genes mediate MHCI's effects in neurons. In this study, RT-PCR was used to simultaneously assess transcription of many MHCI genes in regions of the central and peripheral nervous system where MHCI has a known or suspected role. In the hippocampus, a part of the CNS where MHCI regulates synapse density, synaptic transmission, and plasticity, we found that more than a dozen MHCI genes are transcribed. Single-cell RT-PCR revealed that individual hippocampal neurons can express more than one MHCI gene, and that the MHCI gene expression profile of CA1 pyramidal neurons differs significantly from that of CA3 pyramidal neurons or granule cells of the dentate gyrus. MHCI gene expression was also assessed at the neuromuscular junction (NMJ), a part of the peripheral nervous system (PNS) where MHCI plays a role in developmental synapse elimination, aging-related synapse loss, and neuronal regeneration. Four MHCI genes are expressed at the NMJ at an age when synapse elimination is occurring in three different muscles. Several MHCI mRNA splice variants were detected in hippocampus, but not at the NMJ. Together, these results establish the first profile of MHCI gene expression at the developing NMJ, and demonstrate that MHCI gene expression is under tight spatial and temporal regulation in the nervous system. They also identify more than a dozen MHCIs that could play important roles in regulating synaptic transmission and plasticity in the central and peripheral nervous systems.