Effect of p16 Status on Survival Outcomes in Sinonasal Squamous Cell Carcinoma.

OBJECTIVE: Evaluate the effect of p16 status on disease-free survival (DFS) and overall survival (OS) in patients with sinonasal squamous cell carcinoma (SCC) undergoing treatment with curative intent; and to assess how p16 status may affect patterns of recurrence. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary medical center. METHODS: Patients with sinonasal SCC treated with curative intent from 2012 to 2018 were identified. Independent variable of interest was p16 status, which was assessed using immunohistochemistry (IHC) with a 70% staining cutoff for positivity. Kaplan Meier survival curve was plotted to assess correlation between p16 status and DFS and OS. Association between recurrence patterns and p16 status was conducted using chi square and fisher's exact tests. Multivariable Cox proportional hazard analysis was conducted to assess association between independent variables and DFS. RESULTS: Fifty patients with sinonasal SCC met inclusion criteria. Patients were p16 positive in 28/50 (56%) of cases. Kaplan Meier survival curve revealed no statistically significant association between p16 status and DFS or OS survival (P = .780, P = .474). There was no difference in recurrence patterns in patients with p16 positive versus negative tumors. CONCLUSION: p16 status did not have prognostic value on DFS and OS in our cohort of patients with sinonasal SCC undergoing treatment with curative intent. There was no difference in recurrence patterns between the 2 populations. Based on the results of this study, p16 status should not impact counseling of patients as it relates to their prognosis from SNM.

GATA1 controls numbers of hematopoietic progenitors and their response to autoimmune neuroinflammation.

GATA-binding factor 1 (GATA1) is a transcription factor that governs the development and function of multiple hematopoietic cell lineages. GATA1 is expressed in hematopoietic stem and progenitor cells (HSPCs) and is essential for erythroid lineage commitment; however, whether it plays a role in hematopoietic stem cell (HSC) biology and the development of myeloid cells, and what that role might be, remains unclear. We initially set out to test the role of eosinophils in experimental autoimmune encephalomyelitis (EAE), a model of central nervous system autoimmunity, using mice lacking a double GATA-site (ΔdblGATA), which lacks eosinophils due to the deletion of the dblGATA enhancer to Gata1, which alters its expression. ΔdblGATA mice were resistant to EAE, but not because of a lack of eosinophils, suggesting that these mice have an additional defect. ΔdblGATA mice with EAE had fewer inflammatory myeloid cells than the control mice, suggesting that resistance to EAE is caused by a defect in myeloid cells. Naïve ΔdblGATA mice also showed reduced frequency of CD11b+ myeloid cells in the blood, indicating a defect in myeloid cell production. Examination of HSPCs revealed fewer HSCs and myeloid cell progenitors in the ΔdblGATA bone marrow (BM), and competitive BM chimera experiments showed a reduced capacity of the ΔdblGATA BM to reconstitute immune cells, suggesting that reduced numbers of ΔdblGATA HSPCs cause a functional deficit during inflammation. Taken together, our data show that GATA1 regulates the number of HSPCs and that reduced GATA1 expression due to dblGATA deletion results in a diminished immune response following the inflammatory challenge.

CSF-1 maintains pathogenic but not homeostatic myeloid cells in the central nervous system during autoimmune neuroinflammation.

The receptor for colony stimulating factor 1 (CSF-1R) is important for the survival and function of myeloid cells that mediate pathology during experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). CSF-1 and IL-34, the ligands of CSF-1R, have similar bioactivities but distinct tissue and context-dependent expression patterns, suggesting that they have different roles. This could be the case in EAE, given that CSF-1 expression is up-regulated in the CNS, while IL-34 remains constitutively expressed. We found that targeting CSF-1 with neutralizing antibody halted ongoing EAE, with efficacy superior to CSF-1R inhibitor BLZ945, whereas IL-34 neutralization had no effect, suggesting that pathogenic myeloid cells were maintained by CSF-1. Both anti­CSF-1 and BLZ945 treatment greatly reduced the number of monocyte-derived cells and microglia in the CNS. However, anti­CSF-1 selectively depleted inflammatory microglia and monocytes in inflamed CNS areas, whereas BLZ945 depleted virtually all myeloid cells, including quiescent microglia, throughout the CNS. Anti­CSF-1 treatment reduced the size of demyelinated lesions and microglial activation in the gray matter. Lastly, we found that bone marrow­derived immune cells were the major mediators of CSF-1R­dependent pathology, while microglia played a lesser role. Our findings suggest that targeting CSF-1 could be effective in ameliorating MS pathology, while preserving the homeostatic functions of myeloid cells, thereby minimizing risks associated with ablation of CSF-1R­dependent cells.

Mucormycosis Leading to Cerebral Edema and Cerebellar Tonsillar Herniation after Allogeneic Bone Marrow Transplant: A Case Report.

INTRODUCTION: Mucormycosis following hematopoietic stem cell transplant (HSCT) carries a very high mortality rate. Pulmonary mucormycosis often leads to systemic dissemination and eventual death. It is imperative for transplant providers to have a high level of suspicion for mucormycosis and initiate early treatment. Here, we present a 64-year-old woman who died of disseminated mucormycosis 13 days following her allogeneic HSCT. CASE PRESENTATION: A 64-year-old female with a history of acute myeloid leukemia (AML) presented for allogeneic HSCT and passed away from intracerebral hemorrhage secondary to mucormycosis infection 13 days following her transplant. On autopsy, it was found she had angioinvasive mucormycosis in her frontal lobe leading to cerebral edema which eventually led to tonsillar herniation and brainstem infarction. Her lungs were the likely source of infectious dissemination. DISCUSSION: This case represents an unusual course of events following HSCT in that no other published case shows tonsillar herniation resulting from mucormycosis-related intracerebral swelling. We also report this case because it is believed mucormycosis in HSCT patients is underreported. Additionally, our case highlights the importance of increased vigilance for mucormycosis in patients with prolonged neutropenia prior to HSCT and the potential link of voriconazole prophylaxis and increased risk for mucormycosis.