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The pathogenesis of histiocytic neoplasms is driven by mutations activating the MAPK/ERK pathway, but little is known about the transcriptional and post-transcriptional alterations involved in these neoplasms. We analyzed microRNA (miRNA) expression in plasma samples and tissue biopsies of Erdheim&ndash, Chester disease (ECD) and Langerhans cell histiocytosis (LCH) patients. In silico analysis revealed a potential role of miRNAs in regulating gene expression in these neoplasms as compared with healthy controls (HC). NanoString analysis revealed 101 differentially expressed plasma miRNAs in 16 ECD patients as compared with 11 HC, 95% of which were downregulated. MiRNAs-15a-5p, -15b-5p, -21-5p, -107, -221-3p, -320e, -630, and let-7 family miRNAs were further evaluated by qRT-PCR in an extended cohort of 32 ECD patients, seven LCH and 15 HC. Six miRNAs (let-7a, let-7c, miR-15a-5p, miR-15b-5p, miR-107 and miR-630) were highly expressed in LCH plasma and tissue samples as compared with ECD. Pathway enrichment analysis indicated the miRNA contribution to inflammatory and pro-survival signaling pathways. Moreover, the let-7 family members were downregulated in untreated ECD patients as compared with HC, while treatment with MAPK/ERK signaling inhibitors for 16 weeks resulted in their upregulation, which was in parallel with the radiologic response seen by PET-CT. The study highlights the potential contribution of miRNA to the inflammatory and neoplastic characteristics of ECD and LCH.

OBJECTIVE To investigate patients’ and physicians’ perceptions of lumbar puncture (LP) and tolerability. METHODS Adult patients were surveyed prior to and after the procedure regarding patient perceptions and actual experience of LP. Presence of symptoms pre- and post-LP were compared by McNemar test; symptom severity score was rated 0–10, compared by Wilcoxon test; and relative risks were compared by Fisher’s exact test. In addition to patient surveys, email requests to complete an eight-question survey regarding LP tolerability was sent to faculty physicians at two academic centers. RESULTS A total of 154 patients and 302 physicians completed the surveys during 1/2017-5/2019. Ninety-one patients (59%) reported anxiety prior to-LP compared to 52 (34%) who reported anxiety after the LP (p< 0.0001). Whereas 74% of patients predicted LP to be painful prior to LP, only 48% reported that LP was painful after the procedure (p< 0.0001). On an 11-point scale, patients anticipated significantly greater pain from LP than they reported after the procedure (mean 3.4 and 2.0 respectively, p< 0.0001). Patients who anticipated pain were more likely to experience pain (RR=1.65, 95% CI 1.07–2.73). There was no significant difference in symptoms such as headache, nausea, generalized pain, vision or gait disturbance before and after the procedure. After the LP, 117 patients (77%) answered they would repeat LP if recommended by their doctors. Out of 302 physicians (40% women), the majority (81%) felt that the LP induces anxiety or worry in patients, and 50% answered that the LP is painful for patients in general. CONCLUSION We observed that although anticipation of pain contributed to pre-procedure anxiety, LP was generally well-tolerated. The majority of patients experienced minimal pain. The results of this study suggest that measures to reduce pre-procedure anxiety may improve the tolerability of LP, an important diagnostic tool in neuro-oncology.

BACKGROUND: For patients with incurable cancer, prognostic awareness (PA) is associated with favorable psychological states and end-of-life outcomes. Malignant glioma (MG) is a devastating cancer with uniformly poor prognosis, however prospective and systematic measurement of (1) patients' and caregivers' PA and (2) evaluation of prognostic communication (PC) has not been attempted. METHODS: Cross-sectional study of fully-oriented (Glasgow Coma Scale 15/15) MG patients and a subset of caregivers. Participants underwent a semi-structured assessment of their awareness of incurability and life expectancy and evaluated PC with Likert-scale responses. Interviews were audio-recorded and consensus-scored by two independent raters. Patients underwent multi-domain neurocognitive testing and screening for anxiety and depression. RESULTS: 34 patients with 20 matched caregivers have participated. No patients withdrew consent or refused to discuss PA. Fifteen (44%) had zero or one recurrence of disease and 19(56%) were multiply-recurrent. Fourteen (41%) patients demonstrated full PA (awareness of incurability and estimated life expectancy). Of the 20 (59%) patients with limited or no PA, 10 (50%) had multiply-recurrent MG; 8 (40%) indicated that they desired more PC and 9(45%) rated the quality of PC as satisfactory, fair, or poor. Full PA was not associated with anxiety or depression as compared to limited/no awareness (36% versus 32% and 43% versus 42%, respectively). There was no significant difference in cognitive performance between those with full versus limited/no awareness. Fourteen (70%) of caregivers had full PA. CONCLUSIONS: Candid discussion of prognostic information is feasible in MG. A significant proportion of MG patients are unaware of their life expectancy, even in the setting of multiply-recurrent disease. Absence of awareness does not appear related to lower importance attributed to PC, or to worse cognitive function, as compared to full awareness. Full awareness is not associated with psychological distress. Further study of PA and associated outcomes in MG is necessary.