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Lesions arising in or around the pineal gland comprise a heterogeneous group of pathologies ranging from benign non-neoplastic cysts to highly malignant neoplasms. Pineal cysts are frequently encountered as an incidental finding in daily radiology practice but there is no universal agreement on the criteria for, frequency of, and duration of follow-up imaging. Solid pineal neoplasms pose a diagnostic challenge owing to considerable overlap in their imaging characteristics, although a combination of radiological appearances, clinical findings, and tumour markers allows for narrowing of the differential diagnosis. In this review, we describe the radiological anatomy of the pineal region, clinical symptoms, imaging appearances, and differential diagnosis of lesions arising in this area, and highlight the clinical management of these conditions.

Cerebrovascular disease is a common cause of death and the general histopathologist will often be responsible for the post mortem examination of stroke-related death. The pathological findings vary depending on the type of stroke, its location and aetiology. The underlying pathology is variable and includes atherosclerosis, cardiogenic embolism and small vessel disease alongside many rarer causes. The adequate post mortem examination of stroke is essential to usefully inform clinical teams, coronial services and relatives and requires proper preparation, familiarity with the range of underlying pathological processes, careful gross examination and judicious use of histology.

Summary Background The genetic basis of variation in the progression of primary tauopathies has not been determined. We aimed to identify genetic determinants of survival in progressive supranuclear palsy (PSP). Methods In stage one of this two stage genome-wide association study (GWAS), we included individuals with PSP, diagnosed according to pathological and clinical criteria, from two separate cohorts: the 2011 PSP GWAS cohort, from brain banks based at the Mayo Clinic (Jacksonville, FL, USA) and in Munich (Germany), and the University College London PSP cohort, from brain banks and the PROSPECT study, a UK-wide longitudinal study of patients with atypical parkinsonian syndromes. Individuals were included if they had clinical data available on sex, age at motor symptom onset, disease duration (from motor symptom onset to death or to the date of censoring, Dec 1, 2019, if individuals were alive), and PSP phenotype (with reference to the 2017 Movement Disorder Society criteria). Genotype data were used to do a survival GWAS using a Cox proportional hazards model. In stage two, data from additional individuals from the Mayo Clinic brain bank, which were obtained after the 2011 PSP GWAS, were used for a pooled analysis. We assessed the expression quantitative trait loci (eQTL) profile of variants that passed genome-wide significance in our GWAS using the Functional Mapping and Annotation of GWAS platform, and did colocalisation analyses using the eQTLGen and PsychENCODE datasets. Findings Data were collected and analysed between Aug 1, 2016, and Feb 1, 2020. Data were available for 1001 individuals of white European ancestry with PSP in stage one. We found a genome-wide significant association with survival at chromosome 12 (lead single nucleotide polymorphism rs2242367, p=7·5 × 10−10, hazard ratio 1·42 [95% CI 1·22–1·67]). rs2242367 was associated with survival in the individuals added in stage two (n=238; p=0·049, 1·22 [1·00–1·48]) and in the pooled analysis of both stages (n=1239; p=1·3 × 10−10, 1·37 [1·25–1·51]). An eQTL database screen revealed that rs2242367 is associated with increased expression of LRRK2 and two long intergenic non-coding RNAs (lncRNAs), LINC02555 and AC079630.4, in whole blood. Although we did not detect a colocalisation signal for LRRK2, analysis of the PSP survival signal and eQTLs for LINC02555 in the eQTLGen blood dataset revealed a posterior probability of hypothesis 4 of 0·77, suggesting colocalisation due to a single shared causal variant. Interpretation Genetic variation at the LRRK2 locus was associated with survival in PSP. The mechanism of this association might be through a lncRNA-regulated effect on LRRK2 expression because LINC02555 has previously been shown to regulate LRRK2 expression. LRRK2 has been associated with sporadic and familial forms of Parkinson's disease, and our finding suggests a genetic overlap with PSP. Further functional studies will be important to assess the potential of LRRK2 modulation as a disease-modifying therapy for PSP and related tauopathies. Funding PSP Association, CBD Solutions, Medical Research Council (UK).

Epithelioid glioblastoma multiforme (eGBM) is a rare and aggressive variant of glioblastoma multiforme (GBM) that predominantly affects younger patients and can be difficult to distinguish from other gliomas. Data on how patients with eGBM might be best treated are limited, although genomic analyses have shown that almost half of tumours harbour activating BRAF gene mutations. Here we present the case of a young female with BRAF V600E-mutant eGBM who had a prolonged response to targeted therapy with the BRAF and MEK1/2 inhibitors dabrafenib and trametinib. We review current knowledge about eGBM, including the emerging role for BRAF- ± MEK1/2- targeted therapy.

Background Metastatic neuroendocrine carcinoma of unknown origin is a rare condition, usually presenting with lesions in the liver and/or lung. We present the first reported case of a metastatic neuroendocrine carcinoma of unknown origin arising in the femoral nerve sheath. Case Description Magnetic resonance imaging demonstrated what was thought to be a schwannoma in the left femoral nerve sheath in the proximal femoral triangle, immediately inferior to the anterior inferior iliac spine. At the time of operation, the tumor capsule was invading surrounding tissue, as well as three trunks of the femoral nerve. The patient underwent a subtotal resection, preserving the integrity of the residual functioning femoral nerve trunks. Histologic evaluation determined that the tumor had features consistent with a metastatic neuroendocrine carcinoma of unknown primary origin. The patient recovered well postoperatively, and subsequent radiologic evaluation failed to demonstrate a potential primary site. Unfortunately, the patient re-presented with disease progression and was subsequently referred to palliative care. Conclusions We recommend that there is a definite role for surgery in the management of solitary neuroendocrine carcinoma of unknown origin.