Recurrent mutations of CD79B and MYD88 are the hallmark of primary central nervous system lymphomas.

AIMS: Primary central nervous system lymphoma (PCNSL) manifest aggressive clinical behaviour and have poor prognosis. Although constitutive activation of the nuclear factor-κB (NF-κB) pathway has been documented, knowledge about the genetic alterations leading to the impairment of the NF-κB pathway in PCNSLs is still limited. This study was aimed to unravel the underlying genetic profiles of PCNSL. METHODS: We conducted the systematic sequencing of 21 genes relevant to the NF-κB signalling network for 71 PCNSLs as well as the pyrosequencing of CD79B and MYD88 mutation hotspots in a further 35 PCNSLs and 46 glioblastomas (GBMs) for validation. RESULTS: The results showed that 68 out of 71 PCNSLs had mutations in the NF-κB gene network, most commonly affecting CD79B (83%), MYD88 (76%), TBL1XR1 (23%), PRDM1 (20%) and CREBBP1 (20%). These mutations, particularly CD79B and MYD88, frequently coincided within each tumour in various combinations, simultaneously affecting diverse pathways within the network. No GBMs had hotspot mutation of CD79B Y196 and MYD88 L265. CONCLUSIONS: The prevalence of CD79B and MYD88 mutations in PCNSLs was considerably higher than reported in systemic diffuse large B-cell lymphomas. This observation could reflect the paucity of antigen stimuli from the immune system in the central nervous system (CNS) and the necessity to substitute them by the constitutive activation of CD79B and MYD88 that would initiate the signalling cascades. These hotspot mutations may serve as a genetic hallmark for PCNSL serving as a genetic marker for diagnose and potential targets for molecular therapy.

Recurrent craniopharyngioma with nasopharyngeal extension.

We report the case of a 10-year-old boy having a recurrent craniopharyngioma with nasopharyngeal extension during a course of growth hormone therapy, in whom the nasopharyngeal craniopharyngioma was totally resected despite its extensive growth by using a transbasal approach. There has been no evidence of recurrence during 6 years of follow-up. A literature review was made with respect to nasopharyngeal extension of craniopharyngiomas, and the efficacy of the transbasal approach for those tumors is discussed.

Clustered lipid droplets in the endomyocardial biopsies from a patient with neuroleptic malignant syndrome.

Neuroleptic malignant syndrome is caused by serious adverse effects of antipsychotic agents and occurs only rarely. Endomyocardial biopsies documented unique clustered lipid droplets in a Japanese man with this disease. After administration of haloperidol, he had symptoms of high fever, respiratory dysfunction, and cardiogenic shock, and subsequently suffered from multiple organ failure. Fortunately, he was completely cured with intensive therapy. In the convulsant stage, left ventricular endomyocardial biopsies were performed that yielded the interesting discovery of unique clustered lipid droplets among the myofibrils. It was suggested that although the pathomechanism of neuroleptic malignant syndrome is unknown, this disease may be characterized by a lipid metabolic disorder of the cardiac muscle cell.