The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor ...reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients.
The 2017 World Health Organization (WHO) classification proposes to type and subtype primary adenohypophyseal tumours according to their cell lineages with the aim to establish more uniform tumour ...groups. The definition of atypical adenoma was removed in favour of high-risk adenoma, and the assessment of proliferative activity and invasion was recommended to diagnose aggressive tumours. Recently, the International Pituitary Pathology Club proposed to replace adenoma with the term of pituitary neuroendocrine tumour (PitNET) to better reflect the similarities between adenohypophyseal and neuroendocrine tumours of other organs. The European Pituitary Pathology Group (EPPG) endorses this terminology and develops practical recommendations for standardised reports of PitNETs that are addressed to histo- and neuropathologists. This brief report presents the results of EPPG’s consensus for the reporting of PitNETs and proposes a diagnostic algorithm.
La grande majorité des « adénomes » hypophysaires sont des tumeurs bénignes. Encore aujourd’hui, le caractère « malin » d’un « adénome » hypophysaire, n’est retenu qu’à l’apparition d’une métastase. ...Avec cette définition restreinte, seul 0,2 % des tumeurs hypophysaires peuvent être qualifier de « malignes » (carcinomes hypophysaires ou tumeurs neuroendocrines hypophysaires/PitNETs métastatiques). Cela signifie-t-il que tous les autres « adénomes » hypophysaires sont bénins ? Cette définition restrictive empêche la reconnaissance de véritables tumeurs malignes hypophysaires « non-métastatiques ». Selon l’European Society of Endocrinology (ESE), une tumeur hypophysaire “agressive” se caractérise par une invasion radiologique, un taux de croissance rapide et une résistance aux traitements conventionnels. Mais qui dit « agressivité » ne dit pas forcément « malignité ». Parmi ces tumeurs agressives, seule une petite partie pourrait correspondre à de véritables tumeurs malignes « non-métastatiques ». D’un point de vue anatomo-pathologique, les tumeurs hypophysaires agressives et les tumeurs malignes hypophysaires partagent des caractéristiques communes (sur-représentation du type corticotrope, index de prolifération MIB1 ≥ 3 %, immunopositivité de la p53). D’un point de vue biologique, elles peuvent toutes deux présenter des mutations des gènes TP53 et ATRX (deux gènes impliqués dans la cancérogenèse) et une instabilité génomique. L’un des enjeux actuels en pathologie tumorale hypophysaire est donc d’établir des critères histopathologiques et biologiques fiables afin d’identifier les tumeurs malignes avant qu’elles n’aient pu métastaser.
Tumors of the spinal cord are rare and some can be confused with each other. We report a rare spinal cord solitary fibrous tumor/hemangiopericytoma (SFT/HPC), and propose keys to differentiate spinal ...cord tumors from each other.
A 67-year-old man presented weakness with recent diffuse sensory disorders in the right lower limb. Spinal MRI revealed a T8-T9 intradural extramedullary mass with spinal cord compression. Gross total resection of a poorly vascularized intradural tumor was achieved. It was an encapsulated extramedullary tumor, which was difficult to separate from the spinal cord due to the presence of pial adhesions. Definitive diagnosis was grade 1 SFT/HPC of the spinal cord. One-year follow-up MRI revealed complete excision without any evidence of residual tumor.
SFT/HPC is a very rare spinal tumor that can be extramedullary, intramedullary or both. It may perfectly mimic meningioma. The maximal resection is the best treatment, but can be challenging because of the tumor's firm consistency and pial adherences to the spinal cord. Outcome is good in case of gross total resection, but there is a risk of very late recurrence, requiring long-term follow-up.
Papillary tumor of the pineal region (PTPR), recently described as a distinct clinicopathological entity, can show aggressive biological behavior. The optimal therapeutic approach of PTPR has not ...been well defined. The role of surgery, radiotherapy, and chemotherapy in the treatment of PTPR was analyzed in a large multicenter series. In order to determine factors that influence prognosis, outcome data of a series of 44 patients with histopathologically proven PTPR were retrospectively analyzed. Of the 44 patients, 32 were still alive after a median follow-up of 63.1 months. Twelve patients experienced progressive disease, with seven undergoing two relapses and five more than two. Median overall survival (OS) was not achieved. Median progression-free survival (PFS) was 58.1 months. Only gross total resection and younger age were associated with a longer OS, radiotherapy and chemotherapy having no significant impact. PFS was not influenced by gross total resection. Radiotherapy and chemotherapy had no significant effect. This retrospective series confirms the high risk of recurrence in PTPR and emphasizes the importance of gross total resection. However, our data provide no evidence for a role of adjuvant radiotherapy or chemotherapy in the treatment of PTPR.
En pathologie tumorale, un marqueur théranostique peut être défini comme un outil diagnostique permettant au pathologiste d’identifier les tumeurs qui ont le plus de chance de répondre à un ...traitement spécifique. Dans le cadre de la prise en charge personnalisée des tumeurs neuroendocrines/adénomes hypophysaires, le pathologiste dispose de différents marqueurs immunohistochimiques qui peuvent aider l’endocrinologue à sélectionner le traitement le plus adéquat pour son patient et lui éviter de prescrire un traitement inefficace aux effets secondaires non-négligeables. La détection immunohistochimique des récepteurs à la somatostatine SSTR2A et SSTR5 apporte des informations sur la sensibilité des tumeurs somatotropes aux analogues de la somatostatine (AS) tels que le lanréotide et le pasiréotide. L’expression de SSTR5 dans les tumeurs corticotropes avec Cushing est à la base de leur traitement par pasiréotide. La détection de SSTR5 dans certaines tumeurs à prolactine peut faire ponctuellement discuter l’utilisation des AS dans leur prise en charge thérapeutique. Le traitement des tumeurs neuroendocrines hypophysaires agressives et des carcinomes hypophysaires peut nécessiter l’utilisation d’agents alkylants comme le témozolomide (TMZ). Le lien entre détection par immunohistochimie de l’enzyme MGMT (O6-methylguanine-ADN méthyl-transférase) dans la tumeur et résistance au TMZ reste controversé. D’autres marqueurs comme la protéine MSH6 (MutS Homolog 6), impliquée dans la réparation des mésappariements de l’ADN, ont été proposés dans ce cadre. Enfin, la détection de PD-L1 (Programmed Death-Ligand 1) dans les tumeurs hypophysaires ouvre une voie à l’utilisation de l’immunothérapie anti-checkpoint (point de contrôle) dans leur traitement et notamment celui des tumeurs agressives résistantes au TMZ.
•Complete surgical removal of posterior fossa ependymoma still is the most important prognostic factor for survival.•Second-look surgery must be done in case of incomplete removal.•Aggressive surgery ...is associated with a higher rate of postoperative sequelae but is justified to improve the patient's survival.•Clinical trials with new-targeted therapy are essential to improve the prognosis.
Ependymomas in the posterior fossa have poor prognosis. This study reports a single-center pediatric series, focusing on the value of surgical resection.
A single-center retrospective study included all patients operated on by the senior author (CM) for posterior fossa ependymoma from 2002 to 2018. Medical and surgical data were extracted from the hospital's medical database.
Thirty-four patients were included. Age ranged from 6 months to 18 years, with a median of 4.7 years. Fourteen patients underwent initial endoscopic third ventriculocisternostomy before the direct surgical resection. Surgical removal was complete in 27 patients. There were 32 surgeries for second-look, local recurrence or metastasis despite complementary chemotherapy and/or radiotherapy. Twenty patients were WHO grade 2 and 14 grade 3. Sixteen patients showed recurrence (47%). Overall survival was 61.8% at a mean 10.1 years’ follow-up. Morbidities comprised facial nerve palsy, swallowing disorder, and transient cerebellar syndrome. Fifteen patients had normal schooling, 6 had special assistance; 4 patients reached university, 3 of whom experienced difficulties. Three patients had a job.
Posterior fossa ependymomas are aggressive tumors. Complete surgical removal is the most important prognostic factor, despite risk of sequelae. Complementary treatment is mandatory, but no targeted therapy has so far proved effective. It is important to continue the search for molecular markers in order to improve outcomes.
Highlights • Using a model of neonatal excitotoxic brain injury, we shows an early opening of the BBB that likely contributes to damage. • In this model, we demonstrate that melatonin specifically ...prevents this early BBB alteration. • Our study shows an early BBB disruption in perinatal damage and further extend the neuroprotective profile of melatonin.
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