Molecular characterization of CNS paragangliomas identifies cauda equina paragangliomas as a distinct tumor entity.

Paragangliomas/pheochromocytomas are rare neuroendocrine tumors that arise from the adrenal gland or ganglia at various sites throughout the body. They display a remarkable diversity of driver alterations and are associated with germline mutations in up to 40% of the cases. Comprehensive molecular profiling of abdomino-thoracic paragangliomas revealed four molecularly defined and clinically relevant subtypes. Paragangliomas of the cauda equina region are considered to belong to one of the defined molecular subtypes, but a systematic molecular analysis has not yet been performed. In this study, we analyzed genome-wide DNA methylation profiles of 57 cauda equina paragangliomas and show that these tumors are epigenetically distinct from non-spinal paragangliomas and other tumors. In contrast to paragangliomas of other sites, chromosomal imbalances are widely lacking in cauda equina paragangliomas. Furthermore, RNA and DNA exome sequencing revealed that frequent genetic alterations found in non-spinal paragangliomas-including the prognostically relevant SDH mutations-are absent in cauda equina paragangliomas. Histologically, cauda equina paragangliomas show frequently gangliocytic differentiation and strong immunoreactivity to pan-cytokeratin and cytokeratin 18, which is not common in paragangliomas of other sites. None of our cases had a familial paraganglioma syndrome. Tumors rarely recurred (9%) or presented with multiple lesions within the spinal compartment (7%), but did not metastasize outside the CNS. In summary, we show that cauda equina paragangliomas represent a distinct, sporadic tumor entity defined by a unique clinical and morpho-molecular profile.

Prediction of 30-day mortality in spontaneous cerebellar hemorrhage.

BACKGROUND: Cerebellar hemorrhage is a potentially life-threatening condition and an understanding of the factors influencing outcome is essential for sound clinical decision-making. METHODS: We retrospectively evaluated data from 50 consecutive patients who suffered a first spontaneous cerebellar hemorrhage (SCH) from 2005 to 2014, analysing their short-term outcomes and identifying possible clinical, radiological and therapeutic risk factors for poor prognosis and death within 30 days. RESULTS: Among 50 patients with first SCH, the mean age was 72 ± 10 years. Median Glasgow Coma Scale (GCS) score on admission was 11 [interquartile range (IQR) = 7-11]. Among 50 patients, 19 patients (38%) underwent surgical hemorrhage evacuation with placement of an external ventricular drain (EVD), 12 patients (24%) received an EVD only and 19 patients (38%) were treated conservatively. The 30-day mortality rate was 36%. In multivariate analysis only the GCS score on admission was a significant predictor of 30-day mortality [odds ratio (OR) = 0.598; 95% confidence interval (CI) = 0.406-0.879; P = 0.009]. For prediction of 30-day mortality, receiver operating characteristic curve analysis confirmed that the best cut-off point was a GCS score of 10 on admission [area under the curve: 0.882, 95% CI = 0.717-1, P < 0.001]. CONCLUSION: Lower GCS score on admission was associated with increased 30-day mortality and poorer short-term outcome in patients with SCH. For patients with a GCS score <10 on admission, it is important to balance the possibility of survival afforded by further therapy against the formidable risk of significant functional disability and poor quality of life.

Spontaneous Involution of a Presumably Rathke's Cleft Cyst in a Patient with Slight Subclinical Hypopituitarism: A Case Report and Review of the Literature.

Rathke cleft cyst is described as benign intrasellar cyst. They are mostly small and asymptomatic; they may become large enough to cause symptoms by compression of intrasellar or suprasellar structures. We report on a case of spontaneous regression of a symptomatic RCC with subsequent recovery of preexisting endocrine dysfunction and resolution of headaches. A 60-year-old man complained about headaches. Laboratory investigation revealed a partial hypopituitarism with a slight central hypothyroidism without need for substitution. An MRI study showed a cystic, T2-hyperintense, sellar lesion compatible with a RCC. At one year follow-up, the patient had no complaints and the hormone work-up revealed a regression of the previous slight hypopituitarism. The MRI study showed a complete regression of the cystic lesion and a normal sized and shaped pituitary gland. The spontaneous regression of cystic sellar lesions is rare. The exact mechanism of the possible spontaneous involution of RCC is until now not well understood. However, spontaneous regression is possible and justifies the conservative therapy with regular clinical and radiological follow-up for asymptomatic patients or patients with symptoms not caused by the mass effect of these lesions.