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Abstract Background Pleuropulmonary blastoma (PPB) is a rare mesenchymal malignancy of the lung and is the most common pulmonary malignancy in infants and children. Cystic PPB, the earliest form of PPB occurring from birth to approximately two years of age, is often mistaken for a congenital pulmonary airway malformation, as the two entities can be difficult to distinguish on imaging and pathology. Diagnosis of PPB should prompt workup for DICER1 syndrome, an autosomal dominant tumor predisposition syndrome. We report a newborn with a congenital PPB presenting with tachypnea and hypoxia, who was found to have variant of uncertain clinical significance (VUS) in DICER1. Case presentation A term female infant developed respiratory distress shortly after birth. Initial imaging was concerning for a congenital pulmonary airway malformation versus congenital diaphragmatic hernia, and she was transferred to a quaternary neonatal intensive care unit for management and workup. Chest CT angiography demonstrated a macrocytic multicystic lesion within the right lower lobe without systemic arterial supply. The pediatric surgery team was consulted, and the neonate underwent right lower lobectomy. Pathology revealed a type I PPB. Oncology and genetics consultants recommended observation without chemotherapy and single gene sequencing of DICER1, which identified a germline VUS in DICER1 predicted to alter splicing. RNA-sequencing from blood demonstrated that the variant resulted in an in-frame deletion of 29 amino acids in a majority of transcripts from the affected allele. Due to the patient’s young age at presentation and high clinical suspicion for DICER1 syndrome, tumor surveillance was initiated. Renal and pelvic ultrasonography were unremarkable. Conclusion We present the case of a term neonate with respiratory distress and cystic lung mass, found to have a type I PPB with a germline VUS in DICER1 that likely increased her risk of DICER1-related tumors. Nearly 70% of patients with PPB demonstrate germline mutations in DICER1. Review of RNA sequencing data demonstrates the difficulty in classifying splice variants such as this. Penetrance is low, and many patients with pathogenic DICER1 variants do not develop a malignancy. Best practice surgical and oncologic recommendations include an individualized approach and tumor board discussion. This case highlights the importance of a multidisciplinary team approach and the utility of international registries for patients with rare diagnoses.

Inflammatory physiology has been linked to behavioral and emotional symptoms in a variety of contexts and experimental paradigms. Hematopoietic cell transplantation (HCT) represents an intersection of significant immune dysregulation and psychosocial stress, and this biobehavioral relationship can influence important clinical outcomes. For those undergoing HCT with inflammation-related neuropsychiatric symptoms, using targeted agents such as the IL-6 receptor antagonist tocilizumab may be an effective therapeutic approach. We conducted an observational cohort study to explore patient reported outcomes (PROs) and inflammatory biomarkers among allogeneic HCT recipients who received tocilizumab compared to those who did not. Individuals on a larger trial of tocilizumab for prevention of graft-versus-host disease received a single dose of tocilizumab 24 h prior to stem cell infusion. Measures of anxiety, depression, pain, fatigue, and sleep quality and parallel blood samples for inflammatory cytokines were collected from participants and an analogous comparison cohort at baseline and Day 28 after stem cell infusion. Demographic and medical characteristics were reported; an analysis of covariance regression model was fitted to evaluate differences in PROs and distance correlation t-tests assessed for associations between biomarkers and PRO measures. For n = 18 tocilizumab-treated and n = 22 comparison patients, there were no significant differences between patient demographics, but the tocilizumab cohort had a different distribution of primary diagnoses (p = 0.009) with more patients with leukemias and a higher proportion of patients in their first remission (64% vs 28%, p = 0.024). Depression was higher at Day 28 compared to baseline in both groups (comparison group: +5.1 [95% CI 0.14–10, p = 0.045], tocilizumab: +8.6 [95% CI 2.3–15, p = 0.011]), though the difference between groups did not reach statistical significance. The tocilizumab group had significantly increased circulating IL-6 and decreased CRP at Day 28 (all p

A growing body of literature has emphasized the importance of biobehavioral processes – defined as the interaction of behavior, psychology, socioenvironmental factors, and biological processes – for clinical outcomes among transplantation and cellular therapy (TCT) patients. TCT recipients are especially vulnerable to distress associated with pandemic conditions and represent a notably immunocompromised group at greater risk for SARS-CoV-2 infection with substantially worse outcomes. The summation of both the immunologic and psychologic vulnerability of TCT patients renders them particularly susceptible to adverse biobehavioral sequelae associated with the Covid-19 pandemic. Stress and adverse psychosocial factors alter neural and endocrine pathways through sympathetic nervous system and hypothalamic-pituitary-adrenal axis signaling that ultimately affect gene regulation in immune cells. Reciprocally, global inflammation and immune dysregulation related to TCT contribute to dysregulation of neuroendocrine and central nervous system function, resulting in the symptom profile of depression, fatigue, sleep disturbance, and cognitive dysfunction. In this article, we draw upon literature on immunology, psychology, neuroscience, hematology and oncology, Covid-19 pathophysiology, and TCT processes to discuss how they may intersect to influence TCT outcomes, with the goal of providing an overview of the significance of biobehavioral factors in understanding the relationship between Covid-19 and TCT, now and for the future. We discuss the roles of depression, anxiety, fatigue, sleep, social isolation and loneliness, and neurocognitive impairment, as well as specific implications for sub-populations of interest, including pediatrics, caregivers, and TCT donors. Finally, we address protective psychological processes that may optimize biobehavioral outcomes affected by Covid-19.

A previously healthy 16-year-old girl presented with hemoptysis in the setting of a persistent cough for two months. Imaging identified a large mediastinal mass with cystic and solid components, calcifications and fat suggestive of a germ cell tumor. There was associated right middle lobe consolidation with an air-fluid level concerning for a necrotizing pneumonia, right upper lobe bronchiectasis, hilar lymphadenopathy, and right upper lobe and right pleural-based nodules concerning for disseminated disease. Histologic analysis of a percutaneous biopsy revealed skeletal muscle, fibroadipose tissue, skin, and keratinous debris consistent with a mature germ cell tumor. Rigid and flexible bronchoscopy were performed and identified inspissated, purulent, and fibrinous material in the right upper and middle lobe bronchi. Microbial cultures grew Staphylococcus aureus. After 3 weeks of antibiotics, complete surgical resection was performed. No malignant components were identified. Her post-operative course was uncomplicated, and she remains without evidence of disease 6 months after resection. While mediastinal teratomas are common, rupture is uncommon with fewer than 60 reported cases in the literature. Rupture can be associated with inflammation and/or infection, resulting in diagnostic and treatment challenges.

The stress response influences the development and trajectory of cancer through a host of complex neuroimmune mechanisms. Basic, translational, and clinical research has elucidated these biobehavioral connections and offers a new paradigm for scientific investigation and patient care. Using a biobehavioral approach could offer new diagnostic and therapeutic opportunities in oncology, and this approach will be particularly impactful for adolescent and young adult (AYA) patients with cancer. To date, nearly all biobehavioral oncology research has been done in the adult population. And yet, AYAs have traditionally poorer mental health and cancer-related outcomes, and thus represent a population that could benefit from parallel psychosocial and biomedical intervention. Future biobehavioral work in oncology should focus on the AYA population, integrating new cancer therapies and technology into the next generation of research.

Background Heart Rate Variability (HRV) is a valid, scalable biomarker of stress. We aimed to examine associations between HRV and psychosocial outcomes in adolescents and young adults (AYAs) with cancer. Methods This was a secondary analysis of baseline data from a randomized trial testing a resilience intervention in AYAs with cancer. Two widely used HRV metrics, the standard deviation of normal to normal beats (SDNN) and root mean square of successive differences (RMSSD), were derived from electrocardiograms. Patient-reported outcome (PRO) survey measures included quality of life, anxiety, depression, distress, and resilience. Linear regression models were used to test associations between HRV and PRO scores. The Wilcoxon rank sum test was used to test differences in median HRV values among participant subgroups. Results Among the n = 76 patients with available electrocardiograms, the mean age was 16 years (SD 3y), 63% were white, and leukemia/lymphoma was the most common diagnosis. Compared to healthy adolescents, AYAs with cancer had lower median HRV (SDNN [Females: 31.9 (12.8–50.7) vs 66.4 (46.0–86.8), pConclusion In this secondary analysis, we did not find an association between HRV and psychosocial PROs among AYAs with cancer. HRV measures were lower than for healthy adolescents. Larger prospective studies in AYA biopsychosocial research are needed.

BackgroundHeart Rate Variability (HRV) is a valid, scalable biomarker of stress. We aimed to examine associations between HRV and psychosocial outcomes in adolescents and young adults (AYAs) with cancer.MethodsThis was a secondary analysis of baseline data from a randomized trial testing a resilience intervention in AYAs with cancer. Two widely used HRV metrics, the standard deviation of normal to normal beats (SDNN) and root mean square of successive differences (RMSSD), were derived from electrocardiograms. Patient-reported outcome (PRO) survey measures included quality of life, anxiety, depression, distress, and resilience. Linear regression models were used to test associations between HRV and PRO scores. The Wilcoxon rank sum test was used to test differences in median HRV values among participant subgroups.ResultsAmong the n = 76 patients with available electrocardiograms, the mean age was 16 years (SD 3y), 63% were white, and leukemia/lymphoma was the most common diagnosis. Compared to healthy adolescents, AYAs with cancer had lower median HRV (SDNN [Females: 31.9 (12.8-50.7) vs 66.4 (46.0-86.8), pConclusionIn this secondary analysis, we did not find an association between HRV and psychosocial PROs among AYAs with cancer. HRV measures were lower than for healthy adolescents. Larger prospective studies in AYA biopsychosocial research are needed.