Search

Background: Glioblastoma is one of the most aggressive primary brain tumors, with a poor outcome despite multimodal treatment. Methylation of the MGMT promoter, which predicts the response to temozolomide, is a well-established prognostic marker for glioblastoma. However, a difference in survival can still be detected within the MGMT methylated group, with some patients exhibiting a shorter survival than others, emphasizing the need for additional predictive factors. Methods: We analyzed DIAPH3 expression in glioblastoma samples from the cancer genome atlas (TCGA). We also retrospectively analyzed one hundred seventeen histological glioblastomas from patients operated on at Saint-Luc University Hospital between May 2013 and August 2019. We analyzed the DIAPH3 expression, explored the relationship between mRNA levels and Patient's survival after the surgical resection. Finally, we assessed the methylation pattern of the DIAPH3 promoter using a targeted deep bisulfite sequencing approach. Results: We found that 36% and 1% of the TCGA glioblastoma samples exhibit copy number alterations and mutations in DIAPH3, respectively. We scrutinized the expression of DIAPH3 at single cell level and detected an overlap with MKI67 expression in glioblastoma proliferating cells, including neural progenitor-like, oligodendrocyte progenitor-like and astrocyte-like states. We quantitatively analyzed DIAPH3 expression in our cohort and uncovered a positive correlation between DIAPH3 mRNA level and patient's survival. The effect of DIAPH3 was prominent in MGMT-methylated glioblastoma. Finally, we report that the expression of DIAPH3 is at least partially regulated by the methylation of three CpG sites in the promoter region. Conclusion: We propose that combining the DIAPH3 expression with MGMT methylation could offer a better prediction of survival and more adapted postsurgical treatment for patients with MGMT-methylated glioblastoma.

The role of neuroinflammation in epileptogenesis is extensively investigated, but short-term effects of seizures on established CNS pathologies are less studied and less predictable. We describe the case of a woman with previous recurrent episodes of focal cerebral haemorrhage of unknown cause who developed a pseudo-tumoural oedema triggered by provoked focal status epilepticus. A brain biopsy revealed that the underlying condition was primary angiitis of the CNS. Ictal-induced blood-brain barrier dysfunction allows the entry of water and inflammatory molecules that, in the context of CNS inflammatory diseases, may trigger a self-reinforcing process. Caution should be observed when tapering antiepileptic drugs in patients with such conditions.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) infection, caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), involves several organs through participation of angiotensin-conversion enzyme 2 (ACE2) receptors. The presence of ACE2 receptors in the liver renders this organ a potential target for the novel coronavirus. METHODS: We performed 14 complete autopsies of patients infected with SARS-CoV-2. In each case we stained liver tissue sections with haematoxylin/eosin, Masson blue trichrome stain, periodic acid-Schiff (PAS), Perls, and performed cytokeratin-7 (CK7) immunochemistry. RESULTS: Macroscopically, livers were pale and yellowish in 8 of 14 (57%) patients, and had a nutmeg appearance in the other 6 cases (42%). Histologically, centrolobular necrosis was observed in 12 cases (86%), and was associated with discreet to moderate lobular or portal inflammation. Steatosis was seen in 8 cases (57%), but fibrosis was rare. Cholestasis and discrete bile duct proliferation was observed in 5 cases (36%). DISCUSSION/CONCLUSION: The main histological changes can be explained by the hypoxic status as a result of severe hypoxemic pneumonia leading to death. Drug toxicity may also play a role in certain cases. Other histological changes may be explained by previous hepatic conditions or underlying hepatic diseases. We concluded that COVID-19 infection was not associated with a specific histopathological pattern of the liver.

La DM est une maladie inflammatoire auto-immune touchant la peau et les muscles, dont l’étiologie reste souvent inconnue. Les DM induites par des agents biologiques comme les inhibiteurs du tumor necrosis factor alpha sont rares, décrites principalement chez des patients souffrant d’affections auto-immunes ou de néoplasies sous-jacentes. Nous rapportons le cas d’une patiente âgée de 57 ans, développant une DM à anticorps anti-SAE 1/2 suite à un traitement par adalimumab instauré dans le cadre d’une maladie de Verneuil réfractaire. Notre patiente présentait des lésions cutanées typiques (rash héliotrope, papules de Gottron), des arthralgies, des gonflements articulaires, une faiblesse musculaire proximale et une dysphagie. La biologie montrait un faible syndrome inflammatoire, une hypergammaglobulinémie polyclonale, une hypoalbuminémie, des LDH élevés, des CK, GOT et GPT normales. Les anticorps spécifiques des myosites reviennent positifs pour les anticorps anti-SAE 1/2. L’EMG et la biopsie musculaire montrent une myopathie inflammatoire. Une corticothérapie systémique a été démarrée, avec une amélioration des douleurs articulaires et de la force musculaire après 7 jours. Une récidive clinique de la pathologie survient lors de la dégression de la corticothérapie, nécessitant l’instauration d'un traitement par azathioprine avec une bonne réponse clinique et biologique., [Anti-SAE ½ antibody-associated dermatomyositis on adalimumab treatment: a case report] Dermatomyositis (DM) is an autoimmune inflammatory disorder affecting the skin and muscles, whose etiology is often unknown. While DM induced by biological agents like anti-tumor necrosis factor-alpha agents is uncommon, this disorder is mainly seen in patients with autoimmune disorders or underlying neoplasms. We report the case of a 57-year-old female patient who developed DM with anti-small ubiquitin-like modifier-1 activating enzyme (anti-SAE 1/2) antibodies following an adalimumab treatment on account of refractory hidradenitis suppurativa. Our patient presented typical cutaneous findings consisting of heliotrope rash, Gottron papule, arthralgia, joint swelling, proximal muscle weakness, and dysphagia. Laboratory studies showed mild inflammatory syndrome, polyclonal hypergammaglobulinemia, hypoalbuminemia, high LDH levels, yet normal CK, AST, and ALT levels. Myositis-specific antibody assay was found to be positive for anti-SAE 1/2 antibodies. The electromyogram (EMG) and muscle biopsy revealed inflammatory myopathy. Systemic corticosteroid therapy was initiated. As a result, the patient’s joint pain and muscle strength both improved following 7 days of treatment. A clinical recurrence of the pathology occurred during the gradual regression of corticosteroid therapy, requiring the initiation of azathioprine with both good clinical and biological responses.

A 78-year-old woman was admitted for acute dyspnoea. One year before, she had been treated with cisplatin and gemcitabine for a high grade urothelial carcinoma. Immunotherapy was discussed 9 months later due the progression of bone metastases but could not be administered before this episode of respiratory distress. There was a major discrepancy between the findings of a limited pulmonary embolism at thoracic tomodensitometry and the severity of a recently developed pulmonary hypertension at echocardiography. The patient presented cardiac arrest on day 6 and post-mortem findings were consistent with diffuse pulmonary tumor thrombotic microangiopathy, a rare complication of urothelial carcinoma.

No abstract available

INTRODUCTION : Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described pathological entity featured by a specific histological, immunohistochemical and molecular profile combining an oligodendroglial-like component, a diffuse CD34 expression, and an alteration of the MAP-kinase signalling pathway. That entity was so far rarely described. We would like to report an additional case. [...]

A middle-aged man with an addiction to alcohol met with sudden death at home. Additional clinical information was not available. In particular, there was no radiological examination prior to death. The local authorities requested an autopsy because the deceased had been involved in a car accident 3 days before, which was presumed to be related to his excessive alcohol consumption. Two forensic pathologists performed a medico-legal autopsy. No abnormalities were found at autopsy of the major organs (heart, lungs, liver, kidneys, and spleen). Signs of tuberous sclerosis were lacking. More specifically, characteristic skin lesions, renal cysts, angiomyolipomas, cardiac rhabdomyomas, or cystic pulmonary formations were absent. A certified neuropathologist performed the brain exam. External examination of the brain did not show any particularities, except for an insignificant temporal and cerebellar pressure cone, probably caused by hypoxia during agony [...]

BACKGROUND: Type IIIb dysplasia is a subtype of focal cortical dysplasia associated with a tumor, most frequently with gangliogliomas then with dysembryoplastic neuroepithelial tumors (DNETs). Their preoperative diagnosis often remains equivocal since specific features are missing. The functional results (i.e., seizure free) is good with 81%-87% of Engel Ia at 5-year follow-up. CASE DESCRIPTION: A 4-year-old boy presented with a 1-year history of severe, invalidating, drug-resistant epilepsy. Imaging workup demonstrated a huge left limbic lesion, of which diagnosis remained speculative. Because of worsening neurological status, resective surgery was recommended after multidisciplinary discussion. The resection was performed through left transtemporal approach under neuronavigation (C.R.). Postoperative magnetic resonance imaging assessed uncomplicated near-total resection. Histopathological analysis showed combined features of a DNET of nonspecific type and a focal cortical dysplasia. CONCLUSION: We describe a rare condition of type IIIb dysplasia combining a focal cortical dysplasia with a DNET. Preoperative diagnosis of the lesion was of utmost difficultly, thereby rendering mandatory a thorough histopathological examination of resected specimen in the vast majority of cases. Increased recognition of the condition brings up the hypothesis of a genetic continuum or linkage between the 2 conditions. Functional results on seizure activity after ablative surgery are good and maximal safe resection should be the goal.

INTRODUCTION: Additional robust criteria to predict early postoperative recurrence of non-functioning pituitary macroadenomas (NFMAs) are needed. Recently, a new classification of pituitary tumors has been proposed, which is based on both radiological and histological criteria and allows the grading into 5 groups of different potential aggressiveness. The aim of this study was to use this classification to further characterize predictive factors of recurrence in an independent series of NFMA. CASES AND METHODS: 120 patients operated for a NFMA were analyzed retrospectively. For each of them, the invasion of the cavernous and/or sphenoidal sinuses by the tumor was studied on the preoperative MRI and the proliferative character was based on precise histological and immunohistological examination. RESULTS: 26% (n = 31) of the adenomas were proliferative and 57% (n = 68) were invasive. The invasive lesions were larger (P < 0.001) and their removal was complete in only 82% of the cases. The distribution of NFMAs was as follows: 32% grade 1a, 11% (proliferative) grade 1b, 42% (invasive) grade 2a and 15% (proliferative and invasive) grade 2b. Their probability of recurrence at 5 years was 20, 39, 44 and 66%, respectively. A young age, the atypical character and the presence of postoperative residual tumor were all independent risk factors of recurrence (P < 0.025). DISCUSSION: The new clinicopathological classification proves to be very useful in predicting the risk of recurrence of non-functioning pituitary macroadenomas after a first surgery. In particular, grade 2b lesions showed an overall likelihood of recurrence that was 8.6 times greater than those of grade 1a.

In spite of aggressive multimodal treatment, survival for patients with glioblastoma (GBM) remains short. Nevertheless, some patients survive much longer than expected and become long- term survival patients. The extent of resection (EoR), Karnofsky Performance Scale (KPS), age and methyl-guanine methyltransferase gene (MGMT) methylation are well-defined prognostic factors, but the characteristics of patients with long-term survival (LTS, survival of at least three years after diagnosis) has not been fully determined yet. That is the reason why we analyzed the GBM patients with LTS at our center. We retrospectively reviewed all consecutive patients who underwent surgery for GBM between January 2002 and November 2011, including patients treated with surgical resection under neuronavigation with or without intraoperative MRI (ioMRI) and those who had stereotactic biopsy. We identified and further analysed those patients with LTS. A total of 127 patients underwent surgery for GBM during the study period. 101 (79.6%) of whom had surgical resection and 26 (20.4%) of whom had stereotactic biopsy. Of the 101 patients who were treated with surgical resection, 12 had LTS. After two other pathologists reviewed the patients' cases, they confirmed that 11 (11%) of the 12 patients had a GBM (female/male ratio 4.5; average age 50 years; pre-op Karnofsky score 82%), and one patient had an anaplastic glioma. The mean survival in the LTS patients with confirmed GBM was 74 (36-150) months. Seven of the LTS patients (63.6%) had a gross total resection (GTR), including two with an additional resection after ioMRI. Three (27.3%) had a near total resection (NTR: residue ≤ 5%) and one (9.1%) had a partial resection. Ten (90.9%) patients had a methylation of MGMT, only two (18.8%) had an IDH1 mutation, and seven (63.6%) received a full Stupp protocol. Among patients with a GBM who were treated with one or more resections, 11% had LTS with 90.9% with at least a near total resection (36% wit

A 26-year-old woman presented with severe postpartum headaches. Magnetic resonance imaging (MRI) revealed a symmetric, heterogeneous enlargement of the pituitary gland. Three months later, she developed central diabetes insipidus. A diagnosis of postpartum hypophysitis was suspected and corticosteroids were prescribed. Six months later, the pituitary mass showed further enlargement and characteristics of a necrotic abscess with a peripheral shell and infiltration of the hypothalamus. Transsphenoidal surgery was performed, disclosing a pus-filled cavity which was drained. No bacterial growth was observed, except a single positive blood culture for , considered at that time as a potential contaminant. A short antibiotic course was, however, administered together with hormonal substitution for panhypopituitarism. Four months after her discharge, severe headaches recurred. Pituitary MRI was suggestive of a persistent inflammatory mass of the sellar region. She underwent a new transsphenoidal resection of a residual abscess. At that time, the sellar aspiration fluid was positive for and she was treated with antibiotics for 6 weeks, after which she had complete resolution of her infection. The possibility of a pituitary abscess, although rare, should be kept in mind during evaluation for a necrotic inflammatory pituitary mass with severe headaches and hormonal deficiencies. The possibility of a pituitary abscess, although rare, should be kept in mind during evaluation for a necrotic inflammatory pituitary mass with severe headaches and hormonal deficiencies.In a significant proportion of cases no pathogenic organism can be isolated.A close follow-up is necessary given the risk of recurrence and the high rate of postoperative pituitary deficiencies.

Rasmussen encephalitis is a rare, devastating condition, typically presenting in childhood. Cases of adult-onset Rasmussen have also been described, but the clinical picture is less defined, rendering final diagnosis difficult. We present a case of adult-onset Rasmussen encephalitis with dual pathology, associated with focal cortical dysplasia and encephalitis. We interpreted the Rasmussen encephalitis to be caused by severe and continuous epileptic activity due to focal cortical dysplasia. The best therapeutic approach for such cases remains unclear.

info:eu-repo/semantics/nonPublished