The genomic and transcriptional landscape of primary central nervous system lymphoma

Primary lymphomas of the central nervous system (PCNSL) are mainly diffuse large B-cell lymphomas (DLBCLs) confined to the central nervous system (CNS). Molecular drivers of PCNSL have not been fully elucidated. Here, we profile and compare the whole-genome and transcriptome landscape of 51 CNS lymphomas (CNSL) to 39 follicular lymphoma and 36 DLBCL cases outside the CNS. We find recurrent mutations in JAK-STAT, NFkB, and B-cell receptor signaling pathways, including hallmark mutations in MYD88 L265P (67%) and CD79B (63%), and CDKN2A deletions (83%). PCNSLs exhibit significantly more focal deletions of HLA-D (6p21) locus as a potential mechanism of immune evasion. Mutational signatures correlating with DNA replication and mitosis are significantly enriched in PCNSL. TERT gene expression is significantly higher in PCNSL compared to activated B-cell (ABC)-DLBCL. Transcriptome analysis clearly distinguishes PCNSL and systemic DLBCL into distinct molecular subtypes. Epstein-Barr virus (EBV)+ CNSL cases lack recurrent mutational hotspots apart from IG and HLA-DRB loci. We show that PCNSL can be clearly distinguished from DLBCL, having distinct expression profiles, IG expression and translocation patterns, as well as specific combinations of genetic alterations

Incidental pulmonary emboli in stage IV melanoma patients: Prevalence in CT staging examinations and improved detection with vessel reconstructions based on dual energy CT.

OBJECTIVES:Malignancy is the strongest predictor for venous thromboembolism. Dual energy CT (DECT) can support assessment of pulmonary emboli (PE) by providing vessel reconstructions (DECT-VR) and highlighting thrombi. Purpose was to determine prevalence and risk factors of PE in staging examinations of stage IV-melanoma patients and to evaluate the potential of DECT-VR to improve PE diagnosis. MATERIAL AND METHODS:This retrospective study was approved by IRB. Contrast-enhanced, conventional grey scale CT (cCT) and DECT-VR of 200 stage IV-melanoma patients were reviewed by three radiologists in consensus. Overall prevalence was determined. One-sided Wilcoxon-test was performed to compare the number of detected emboli between cCT and cCT with supplementary DECT-VR. Frequencies of risk factors were compared with χ2 test. RESULTS:On cCT, 9 PE were detected (6 patients, correlating to 3% of the study population with 0.05 emboli per patient). With the supplementary DECT-VR, number of diagnosed emboli increased from 9 to 17 (p < 0.05) (in total 9 patients, correlating to 0.09 emboli per patient). Emboli on DECT-VR were mainly subsegmentally (7 of 8). There was no significant difference in the frequency of risk factors. CONCLUSIONS:The prevalence of pulmonary emboli in our cohort of 200 stage IV melanoma patients was 5%. DECT-VR improved significantly diagnosis of PE, especially when located subsegmentally

Incidental pulmonary emboli in stage IV melanoma patients: Prevalence in CT staging examinations and improved detection with vessel reconstructions based on dual energy CT - Fig 3

<p>Pulmonary artery embolus in right upper lobe of a male patient (75y), clearly highlighted in dual energy CT (DECT) vessel reconstruction (a), but not detected on grey scale CT (b). Further pulmonary, subsegmental embolus in the right lower lobe of a male patient (77y), highlighted in red in the DECT vessel reconstruction (c). Retrospectively, a filling defect can be seen in thin-slice (1 mm) reconstructions of the corresponding grey scale CT (d).</p

Potential risk factors for pulmonary emboli (PE).

<p>Potential risk factors for pulmonary emboli (PE).</p

Follow up examination of patient Nr. 4 (see Table 2) 12 months later.

<p>While the CT evaluated in this study showed only a small subsegmental peripheral embolus (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0199458#pone.0199458.g003" target="_blank">Fig 3c</a>), the follow up CT demonstrated multiple lobar and central pulmonary emboli.</p

Platelet counts and international normalized ratio (INR) (measured within 4 weeks before the CT examination).

<p>Platelet counts and international normalized ratio (INR) (measured within 4 weeks before the CT examination).</p

Number of Emboli (z-axis) detected on Dual Energy CT-vessel reconstructions (DECT-VR, bars on the left) and on conventional grey scale CT (bars on the right), subdivided into their anatomical location (yellow: lobar, blue: segmental, red: subsegmental).

<p>Emboli detected on DECT-VR were mainly subsegmentally located.</p

Distribution and clinical features of incidental pulmonary emboli in stage IV melanoma patients.

<p>Distribution and clinical features of incidental pulmonary emboli in stage IV melanoma patients.</p