Glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA): a molecularly distinct brain tumor type with recurrent NTRK gene fusions.

Glioneuronal tumors are a heterogenous group of CNS neoplasms that can be challenging to accurately diagnose. Molecular methods are highly useful in classifying these tumors-distinguishing precise classes from their histological mimics and identifying previously unrecognized types of tumors. Using an unsupervised visualization approach of DNA methylation data, we identified a novel group of tumors (n = 20) that formed a cluster separate from all established CNS tumor types. Molecular analyses revealed ATRX alterations (in 16/16 cases by DNA sequencing and/or immunohistochemistry) as well as potentially targetable gene fusions involving receptor tyrosine-kinases (RTK; mostly NTRK1-3) in all of these tumors (16/16; 100%). In addition, copy number profiling showed homozygous deletions of CDKN2A/B in 55% of cases. Histological and immunohistochemical investigations revealed glioneuronal tumors with isomorphic, round and often condensed nuclei, perinuclear clearing, high mitotic activity and microvascular proliferation. Tumors were mainly located supratentorially (84%) and occurred in patients with a median age of 19 years. Survival data were limited (n = 18) but point towards a more aggressive biology as compared to other glioneuronal tumors (median progression-free survival 12.5 months). Given their molecular characteristics in addition to anaplastic features, we suggest the term glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (GTAKA) to describe these tumors. In summary, our findings highlight a novel type of glioneuronal tumor driven by different RTK fusions accompanied by recurrent alterations in ATRX and homozygous deletions of CDKN2A/B. Targeted approaches such as NTRK inhibition might represent a therapeutic option for patients suffering from these tumors.

Accessory nerve schwannoma extending into the fourth ventricle: case report and review of literature.

Accessory nerve schwannoma is a rare entity in patients presenting with cranial nerve (CN) deficits. Most of these tumours arise from the cisternal segment of the eleventh CN and extend caudally. Herein, we report the third case of an accessory schwannoma extending cranially into the fourth ventricle. A 61-year-old female presented with a history of variable headaches. Cerebral magnetic resonance imaging (cMRI) revealed a large inhomogeneous contrast-enhancing lesion at the craniocervical junction extending through the foramen of Magendi and concomitant hydrocephalus due to obstruction of the foramina of Luschkae. Microsurgical tumour resection was performed in the half-sitting position. Intraoperatively, the tumour arose from a vestigial fascicle of the spinal accessory nerve. At three month follow-up, neither radiological tumour recurrence nor neurological deficits were observed.

Therapeutic duplication of anticoagulants: a retrospective study of frequency and consequences in a tertiary referral hospital.

BACKGROUND: Anticoagulants are commonly prescribed in medical practices and could be of significant harm in the case of medication errors. We conducted a retrospective observational study to determine the frequency and consequences of the therapeutic duplication of anticoagulants (TDA). As a secondary objective, we aimed to determine the characteristics of the population in which TDA occurs. METHODS: We conducted a retrospective observational study among admitted patients who concomitantly received at least two anticoagulants from August 2017 to August 2018. RESULTS: A total of 107 patients with TDA are included in the research. The patients with TDA have a mean age of 73. The TDA population has a high rate of associated comorbidities with 69% of patients having arterial hypertonia, 40% with chronic kidney disease, 26% with a history of malignancy, and 20.5% with a history of stroke. More than 65% of patients were under anticoagulation before admission, mostly due to atrial fibrillation. The TDA occurred in more than 95% of cases in the first week or the last week of hospitalization. Patients had a high risk of bleeding prior to the TDA-event with about 62.5% of TDA patients having a HAS-BLED score at least 3. A total of 8 patients showed a significant Hemoglobin (Hb)-drop of at least 10 g/L within 24 h after TDA-event. Two patients had a new or worsened hematuria following TDA-event. CONCLUSION: TDA occurred in 0.8% of patients who were under anticoagulation and in 6.7% of patients who received direct oral anticoagulants (DOACs). TDA led in about 7.4% of cases to hemoglobin-relevant bleeding. The old patients with significant comorbidities and a high HAS-BLED score were mainly affected. The female gender and presence of anemia independently predicted the occurrence of bleeding following TDA.

Redefinition of tumor capsule: Rho-dependent clustering of cancer-associated fibroblasts in favor of tensional homeostasis.

Fibroblasts are the most frequent cells of the connective tissues. Having the ability to sense and respond to mechanical stimuli in addition to the biochemical ones makes them crucial for such a composite-like and tension-preserving tissue. Over the last decade, the investigation of the role of these cells in tumor progression was a hot topic of research in tumor biology. Literatures almost unanimously describe the re-education of stromal fibroblasts by tumor cells in favor of tumor progression, which resulted in the birth of a new nomenclature, the cancer-associated fibroblasts. On the other hand, some studies reported anti-tumor roles for these cells. Herein, author suggests that the previously described pro-migratory and pro-contractile contexts, which respectively results in divergent and convergent distribution of fibroblasts by changing Rho-Rac1 balance, could be applied for cancer-associated fibroblasts as well. Based on this proposed concept, stromal fibroblasts could represent different roles, either pro-tumor or anti-tumor, during the course of tumor progression. In the earlier phases, they tend to assemble along tumor-stroma interface in the form of tumor capsules in order to resist tumor growth and to maintain tensional homeostasis in stroma. But in later phases, after being chronically subjected to tumor-induced chemical and mechanical stimuli, they will gradually lose their substantial abilities to oppose tumor expansion and, in contrary, will promote tumorigenesis. In summary, this paper redefines tumor capsule from chemical and mechanical standpoints as Rho-dependent clustering of cancer-associated fibroblasts in favor of tensional homeostasis. Furthermore, it proposes that stromal fibroblasts will undergo some irreversible epigenetic changes in Rac1- and Rho-related proteins through tumor-stroma crosstalk, which irreversibly diminish their ability of capsule formation. Finally, the author discusses the possible researches helping us to assess the proposed concept and its clinical implications.

Pilocytic Astrocytoma of Fornix Mimicking a Colloid Cyst: Report of 2 Cases and Review of the Literature.

BACKGROUND: Colloid cyst is a gelatin-containing cyst in the brain almost always found in the third ventricle. The specific shape and location of these cysts, a round well-delineated mass in the rostral part of the third ventricle adjacent to the foramen of Monro, on imaging are the main findings for diagnosis. Several masses of the third ventricle masquerading colloid cysts on images have been reported. Based on different surgical approaches, preoperative misdiagnosis of colloid cyst may have great impact on prognosis. METHODS: We report 2 cases that presented with severe headache and hydrocephalus, and their preoperative images were highly indicative of colloid cyst. RESULTS: Histopathologic investigations after tumor resection showed pilocytic astrocytoma of fornix in both cases. CONCLUSIONS: Fifteen cases of colloid cyst misdiagnosis with other masses have been reported thus far; among them, 2 cases were pilocytic astrocytoma. In this study we report 2 other cases. Furthermore, we discuss additional clues helping to differentiate pilocytic astrocytoma from colloid cyst on images.

Bilateral Choroid Plexus Metastasis from Papillary Thyroid Carcinoma: Case Report and Review of the Literature.

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. It has an indolent clinical course and favorable prognosis. Brain metastasis is uncommon and complicates about 0.1%-5% of PTCs. Metastasis to the choroid plexus of the lateral ventricles has been reported in 7 cases of thyroid malignancies, all of which were unilateral. METHODS: We report a case of a 52-year-old woman with a history of PTC who presented with severe headache, nausea and vomiting, right hemiparesis, and speech disturbance. Imaging studies depicted lesions in both lateral ventricles. RESULTS: The patient underwent microsurgical tumor resection. Histopathologic examination revealed choroid plexus metastasis from PTC. CONCLUSIONS: Metastases to the choroid plexus from extracranial tumors are very rare, with only a few cases reported thus far. A demographic analysis of these cases suggests there may be a tropism of some extracranial carcinomas, such as renal cell carcinoma, for choroid plexus, especially in the lateral ventricles. We report the eighth case of choroid plexus metastasis, but it is the first bilateral one arising from thyroid cancer.