High prevalence of oncogenic MYD88 and CD79B mutations in diffuse large B-cell lymphomas presenting at immune-privileged sites.

Activating mutations in CD79 and MYD88 have recently been found in a subset of diffuse large B-cell lymphoma (DLBCL), identifying B-cell receptor and MYD88 signalling as potential therapeutic targets for personalized treatment. Here, we report the prevalence of CD79B and MYD88 mutations and their relation to established clinical, phenotypic and molecular parameters in a large panel of DLBCLs. We show that these mutations often coexist and demonstrate that their presence is almost mutually exclusive with translocations of BCL2, BCL6 and cMYC, or Epstein-Bar virus infection. Intriguingly, MYD88 mutations were by far most prevalent in immune-privileged site-associated DLBCL (IP-DLBCL), presenting in central nervous system (75%) or testis (71%) and relatively uncommon in nodal (17%) and gastrointestinal tract lymphomas (11%). Our results suggest that MYD88 and CD79B mutations are important drivers of IP-DLBCLs and endow lymphoma-initiating cells with tissue-specific homing properties or a growth advantage in these barrier-protected tissues.

Skeletal muscle ultrasonography in children with a dysfunction in the oxidative phosphorylation system.

OBJECTIVE: The aim of this prospective study was to investigate the diagnostic value of quantitative skeletal muscle ultrasonography in children suspected of having a mitochondrial disorder. METHODS: Muscle thickness and quantitatively determined echo intensity of four muscles were established in 53 children with symptoms indicative of a mitochondrial disorder. RESULTS: A sensitivity of 25 to 46 % was found, depending on the chosen cut-off point (abnormal or borderline abnormal), with a specificity of 85 to 100 %. Except for one, all abnormal ultrasound scans were found in children over five years of age. Within the group of patients with a mitochondrial disorder, a significant correlation was found between muscle echo intensity and age (r = 0.38; p = 0.047). CONCLUSIONS: We conclude that skeletal muscle ultrasound can be of additional value in the diagnosis of children with suspected mitochondrial disorders, especially in children over five years of age. With its low sensitivity, it is not suitable for screening purposes. However, since all abnormal ultrasound scans were found in children with a mitochondrial disorder, and no significant correlation with the MDC score was found, muscle ultrasound can be used complementary to this scoring system to facilitate the decision-making in pursuing further invasive diagnostics.