Clear cell renal cell carcinoma (ccRCC) is characterized by BAP1 and PBRM1 mutation, which are associated with tumors of different grade and prognosis. However, whether BAP1 and PBRM1 loss causes ccRCC and determines tumor grade is unclear. We conditionally targeted Bap1 and Pbrm1 (with Vhl) in the mouse using several Cre drivers. Sglt2 and Villin proximal convoluted tubule drivers failed to cause tumorigenesis, challenging the conventional notion of ccRCC origins. In contrast, targeting with Pax8, a developmental lineage-specific transcription factor, led to ccRCC of different grade. Bap1-deficient tumors were high grade and showed greater mTORC1 activation than Pbrm1-deficient tumors, which exhibited longer latency. Disrupting one allele of the mTORC1 negative regulator, Tsc1, in Pbrm1-deficient kidneys triggered higher grade ccRCC. This study establishes Bap1 and Pbrm1 as lineage-specific drivers of ccRCC and histological grade, implicates mTORC1 as a tumor grade rheostat, and suggests that ccRCC may arise from Bowman capsule cells.

A screening protocol including direct nasal endoscopy, noncontrast chest CT, and abdominal ultrasound was effective in detecting invasive mold infections in at-risk patients. Nasosinal involvement often occurs before specific symptoms develop, and sinus CTs are insensitive and nonspecific. Bedside nasal endoscopy precludes radiation exposure associated with sinus CT and was associated with decrease in mold-related mortality, likely due to earlier diagnosis and initiation of appropriate antifungal therapy.

Alopecia areata (AA) and immune thrombocytopenia (ITP) are autoimmune conditions occasionally encountered by pediatricians, but their simultaneous occurrence is rare. We describe here a 7-year-old female who acutely developed both AA and ITP. Within 3 months both conditions resolved spontaneously, suggesting a pathophysiologic relationship.

ImportanceLittle is known about the risk of post–COVID-19 multisystem inflammatory syndrome in children (MIS-C) in the setting of childhood cancer.ObjectiveTo evaluate factors associated with MIS-C and describe the clinical course of COVID-19 in the setting of MIS-C.Design, Setting, and ParticipantsMultisite observational cohort study of a registry representing more than 100 US pediatric oncology sites. All included patients were registered between April 1, 2020, and May 18, 2022. Sites submitted deidentified data surrounding sociodemographics, cancer diagnosis and treatment, and COVID-19 course (symptoms, maximum support required, outcome). Patients with MIS-C (n = 24) were compared with matched controls (n = 96). Children (<21 years) with cancer who developed COVID-19 while receiving cancer treatment or within 1 year of completing treatment were characterized based on their development of MIS-C.Exposures(1) Clinical and sociodemographic characteristics of children with cancer and COVID-19; and (2) MIS-C.Main Outcomes and Measures(1) Development of MIS-C among children with cancer and COVID-19; and (2) symptoms and disease severity associated with MIS-C.ResultsAmong 2035 children with cancer and COVID-19, 24 (1.2%) developed MIS-C. COVID-19 occurred at a median (IQR) age of 12.5 (5.5-17.1) years in those with MIS-C and 11 (6-16) years among matched controls (P = .86). The majority of children with MIS-C had a hematologic cancer (83.3% [n = 20]), were publicly insured (66.7% [n = 16]), and were Hispanic (54.2% [n = 13]). Half (n = 12) had 1 or more noncancer comorbidity. Those with comorbidities were more likely to develop MIS-C than those without (odds ratio [OR], 2.5 [95% CI, 1.1-5.7]). Among children with MIS-C, 100% (n = 24) were admitted to the hospital and 54.2% (n = 13) to the intensive care unit (ICU), while COVID-19 contributed to the death of 20.1% (n = 5); cancer therapy was changed in 62.5% (n = 15). Compared with matched controls, those with MIS-C had higher odds of symptoms classified as systemic (OR, 4.7 [95% CI, 1.4-15.8]) or gastrointestinal (OR, 5.0 [95% CI, 1.7-14.6]) along with higher odds of hospitalization (OR, 42.9 [95% CI, 7.1-258]), ICU admission (OR, 11.4 [95% CI, 3.6-36.4]), and changes to cancer therapy (OR, 24.9 [95% CI, 6.5-94.8]).Conclusions and RelevanceIn this cohort study among children with cancer and COVID-19, those with MIS-C had a more severe clinical course than those without MIS-C. The risk of MIS-C and its severity are important to consider as clinicians monitor patients with COVID-19. These findings can inform their conversations with families regarding COVID-19 risks and the benefits of prevention strategies that are pharmacologic (vaccination) and nonpharmacologic (masking), as well as treatment (antivirals, monoclonal antibodies).