T2-Fluid-attenuated inversion recovery (FLAIR) pseudoprogression in patients with anaplastic oligodendrogliomas treated with procarbazine, lomustine and vincristine (PCV) chemotherapy alone.

BACKGROUND: Pseudoprogression in gliomas has been extensively described after radiotherapy with or without chemotherapy, but not after chemotherapy alone. Here we describe the occurrence of pseudoprogression in patients with anaplastic oligodendrogliomas treated with postoperative procarbazine, lomustine and vincristine (PCV) chemotherapy alone. METHODS: We retrospectively reviewed the medical and radiological files of patients with 1p/19q codeleted, IDH-mutant anaplastic oligodendrogliomas treated with PCV chemotherapy alone who presented magnetic resonance imaging (MRI) modifications suggestive of tumour progression and in whom the final diagnosis was a pseudoprogression. RESULTS: We identified six patients. All patients underwent a surgical resection and were treated with PCV chemotherapy without radiotherapy. After a median of 11 months following the initiation of chemotherapy (range: 3-49 months), the patients developed asymptomatic white matter MRI modifications around the surgical cavity leading to the suspicion of a tumour progression. These modifications appeared as hyperintense on T2-fluid-attenuated inversion recovery (FLAIR) sequence, hypointense on T1 sequence, and lacked mass effect (0/6), contrast enhancement (0/6), restriction on diffusion-weighted imaging (0/4), relative cerebral blood volume (rCBV) increase on perfusion MRI (0/4), and hypermetabolism on 18 F-fluoro-L-dopa positron emission tomography (18 F-DOPA PET) scan (0/3). One patient underwent a surgical resection demonstrating no tumour recurrence; the five other patients were considered as having post-therapeutic modifications based on imaging characteristics. After a median follow-up of 4 years all patients were progression-free. CONCLUSIONS: Anaplastic oligodendroglioma patients treated with postoperative PCV chemotherapy alone occasionally develop T2/FLAIR hyperintensities around the surgical cavity that can wrongly suggest tumour progression. Multimodal imaging and close follow-up should be considered in this situation.

Glioma Associated Microglia/Macrophages Distribution is Conserved in Glioblastoma Regrowth: A Morphometric Study.

We compared the morphological aspect of glioblastoma-associated microglia/macrophages cells in 15 paired recurrent glioblastomas to check the ability of glioblastoma to recreate its microenvironment. The absolute number of GAMs is lower in normal tissue (21/mm2) than in the isolated tumor cells area (100-112/mm2) than in the solid tumor area (212-220/mm2) (p < 0.01). The morphology of GAMs remained the same in each tumor area with a reduced covered area by cell processes (196 to 216/mm2) than in normal tissue (708/mm2) (p < 0.01). In paired tumors, GAMs morphology remained the same in successive resections and was not modified by the treatments.

Cyclin D1 expression in ganglioglioma, pleomorphic xanthoastrocytoma and pilocytic astrocytoma.

Ganglioglioma, pleomorphic xanthoastrocytoma (PXA) and pilocytic astrocytoma are rare brain neoplasms with frequent activation of mitogen-activated protein (MAP) kinase pathway. A downstream marker of MAP-kinase pathway activation is cyclin D1. However, the expression of cyclin D1 has not been studied in the differential diagnosis between these brain tumors. The aim of this work is to compare the expression of cyclin D1 in ganglioglioma, PXA, pilocytic astrocytoma. We also compared cyclin D1 expression in giant cell glioblastoma and in IDH wild type glioblastoma. Our work shows that roughly half of gangliogliomas have ganglion cells stained by cyclin D1 while two third of PXA have pleormophic cells stained by cyclin D1 and 15% of giant cell glioblastoma have pleomorphic cells stained by cyclin D1 (p < 0.001). Cyclin D1 never stains normal neurons either in the adjacent cortex of circumscribed tumor, or in entrapped neurons in IDH wild type glioblastomas. The expression of cyclin D1 is correlated to the presence of BRAF V600E mutation in ganglioglioma and PXA (p = 0.002). To conclude, cyclin D1 positivity might be used to confirm the neoplastic nature of ganglion cells. Cyclin D1 is expressed in most cases of BRAF V600E mutated gangliogliomas but also in cases without BRAF mutations suggesting an activation of MAP-kinase pathway through another way. Cyclin D1 immunohistochemistry has currently no or little role in the differential diagnosis of pilocytic astrocytoma. Its role in the differential diagnosis between PXA and giant cell glioblastoma needs to be further investigated on external series.

Cortical stimulation in aphasia following ischemic stroke: toward model-guided electrical neuromodulation.

The aim of this paper is to integrate different bodies of research including brain traveling waves, brain neuromodulation, neural field modeling and post-stroke language disorders in order to explore the opportunity of implementing model-guided, cortical neuromodulation for the treatment of post-stroke aphasia. Worldwide according to WHO, strokes are the second leading cause of death and the third leading cause of disability. In ischemic stroke, there is not enough blood supply to provide enough oxygen and nutrients to parts of the brain, while in hemorrhagic stroke, there is bleeding within the enclosed cranial cavity. The present paper focuses on ischemic stroke. We first review accumulating observations of traveling waves occurring spontaneously or triggered by external stimuli in healthy subjects as well as in patients with brain disorders. We examine the putative functions of these waves and focus on post-stroke aphasia observed when brain language networks become fragmented and/or partly silent, thus perturbing the progression of traveling waves across perilesional areas. Secondly, we focus on a simplified model based on the current literature in the field and describe cortical traveling wave dynamics and their modulation. This model uses a biophysically realistic integro-differential equation describing spatially distributed and synaptically coupled neural networks producing traveling wave solutions. The model is used to calculate wave parameters (speed, amplitude and/or frequency) and to guide the reconstruction of the perturbed wave. A stimulation term is included in the model to restore wave propagation to a reasonably good level. Thirdly, we examine various issues related to the implementation model-guided neuromodulation in the treatment of post-stroke aphasia given that closed-loop invasive brain stimulation studies have recently produced encouraging results. Finally, we suggest that modulating traveling waves by acting selectively and dynamically across space and time to facilitate wave propagation is a promising therapeutic strategy especially at a time when a new generation of closed-loop cortical stimulation systems is about to arrive on the market.

White matter tracts involved by deep brain stimulation of the subthalamic nucleus in Parkinson's disease: a connectivity study based on preoperative diffusion tensor imaging tractography.

Purpose: To depict the specific brain networks that are modulated by deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD), using diffusion tensor imaging-based fibre tractography (DTI-FT).Materials and methods: Nine patients who received bilateral STN-DBS for PD were included. Electrodes were localized by co-registering preoperative magnetic resonance imaging and postoperative computed tomography. The volume of tissue activated (VTA) was estimated as an isotropic, spherical electric field distribution centred at each effective electrode contact's centroid coordinates, taking into account individual stimulation parameters (i.e. voltage, impedance). Brain connectivity analysis was undertaken using a deterministic DTI-FT method, seeded from a single region of interest corresponding to the VTA. The labelling of the reconstructed white matter fibre tracts relied on their path and (sub)cortical termination territories.Results: Six months after surgery, we observed a statistically significant reduction in both the Unified Parkinson Disease Rating Scale part III and L-dopa equivalent daily dose. Areas consistently connected to the VTA included the brainstem (100%), cerebellum (94%), dorsal (i.e. supplementary motor area) and lateral premotor cortex (94%), and primary motor cortex (72%). An involvement of the hyperdirect pathway (HDP) connecting the STN and the (pre)motor cortex was demonstrated.Conclusions: The connectivity patterns observed in this study suggest that the therapeutic effects of STN-DBS are mediated through the modulation of distributed, large-scale motor networks. Specifically, the depiction of projection neurons connecting the stimulated area/STN to the (pre)motor cortex, reinforce the growing evidence that the HDP might be a potential therapeutic target in PD. If further replicated, these findings could raise the possibility that DTI-FT reconstruction of the HDP may critically improve DBS targeting and stimulation parameters selection, through the development of programming tools that incorporate VTA modelling and patient-specific DTI-FT data.

Assessing pain in the postoperative period: Analgesia Nociception IndexTMversus pupillometry.

BACKGROUND: Potential methods for objective assessment of postoperative pain include the Analgesia Nociception Index™ (ANI), a real-time index of the parasympathetic tone, the pupillary light reflex (PLR), and the variation coefficient of pupillary diameter (VCPD), a measure of pupillary diameter (PD) fluctuations. Until now, the literature is divided as to their respective accuracy magnitudes for assessing a patient's pain. The VCPD has been demonstrated to strongly correlate with pain in an obstetrical population. However, the pain induced by obstetrical labour is different, given its intermittent nature, than the pain observed during the postoperative period. The aim of the current study was to compare the respective values of these variables at VAS scores ≥4. METHODS: After approval by the Ethics Committee, 345 patients aged on average 50 (SD 17) yr (range: 18-91 yr) of age were included. The protocols of general anaesthesia and postoperative analgesia were left to the anaesthetist's discretion. Some 40 min after tracheal intubation, VAS, ANI, PD, PLR, and VCPD values were recorded. RESULTS: VCPD correlates more strongly (r=0.78) with pain as assessed with the VAS than ANI (r=-0.15). PD and PLR are not statistically correlated with VAS. The ability of VCPD to assess the pain of patients (VAS≥4) is strong [area under the curve (AUC): 0.92, confidence interval (CI): 0.89-0.95], and better than for ANI (AUC: 0.39, CI: 0.33-0.45). CONCLUSIONS: Our study suggests that VCPD could be a useful tool for monitoring pain in conscious patients during the postoperative period. CLINICAL TRIAL REGISTRATION: NCT03267979.

Robot-Guided Neuronavigated Repetitive Transcranial Magnetic Stimulation (rTMS) in Central Neuropathic Pain.

OBJECTIVES: To confirm and extend previous results involving repetitive transcranial magnetic stimulation (rTMS) aimed at alleviating refractory central neuropathic pain (CNP). To evaluate pain relief in detail and to assess ongoing benefits after one year of treatment. DESIGN: Prospective observational study. SETTING: University hospital. Outpatient settings. PARTICIPANTS: Patients (N=80) with chronic central pain after brain or spinal cord injuries. INTERVENTIONS: High-frequency (20Hz) neuronavigated-rTMS sessions were applied on the primary motor cortex using a figure-of-eight coil positioned by a robotized arm. Patients received a minimum of 4 consecutive sessions, each separated by 3-4 weeks. MAIN OUTCOME MEASURES: Percentage of pain relief (%R), duration of pain relief (DPR), numeric rating scale (NRS), neuropathic pain symptom inventory (NPSI), and pain relief score (PRS). RESULTS: Seventy-one patients completed the study. On average, after the first 4 sessions, %R was 28% and DPR was 11 days. Fifty-four patients (76%) were responders with a permissive threshold of ≥10%R and 61% (43 patients) with a stringent threshold ≥30%R. After 12 months of treatment (15 sessions) we observed a cumulative effect on %R (48%), DPR (20d), and on the prevailing NPSI sub-score (-28%). This effect reached significance after 4 sessions and was further maintained over 12 months. Across participants, more than 1000 rTMS sessions were delivered over 6 years without any adverse effect. CONCLUSION: These results confirm that multiple rTMS sessions are both safe and have potential as a treatment for CNP. An ongoing randomized controlled trial will allow teasing out of this effect from placebo analgesia.

Hearing eyeball and/or eyelid movements on the side of a unilateral superior semicircular canal dehiscence.

Hearing of eyeball movements has been reported in superior semicircular canal dehiscence (SSCD), but not hearing of eyelid movements. Our main objective was to report the hearing of eyeball and/or eyelid movements in unilateral SSCD. Our secondary objective was to access its specificity to SSCD and discuss the underlying mechanism. Six patients with SSCD who could hear their eyeball and/or eyelid movements were retrospectively reviewed. With the aim of comparisons, eight patients with an enlarged vestibular aqueduct (EVA), who share the same mechanism of an abnormal third window, were questioned on their ability to hear their eyeball and/or eyelid movements. Three patients with SSCD could hear both their eyeball and eyelid movements as a soft low-pitch friction sound. Two patients with SSCD could hear only their eyelid movements, one of whom after the surgery of a traumatic chronic subdural hematoma. The latter remarked that every gently tapping on the skin covering the burr-hole was heard in his dehiscent ear as the sound produced when banging on a drum, in keeping with a direct transmission of the sound to the inner ear via the cerebrospinal fluid. One patient with SSCD, who could hear only his eyeball movements, had other disabling symptoms deserving operation through a middle fossa approach with an immediate relief of his symptoms. None of the eight patients with EVA could hear his/her eyeball or eyelid movements. Hearing of eyeball and/or eyelid movements is highly suggestive of a SSCD and do not seem to occur in EVA. In case of radiological SSCD, clinicians should search for hearing of eyeball and/or eyelid movements providing arguments for a symptomatic dehiscence. The underlying mechanism is discussed particularly the role of a cerebrospinal fluid transmission.

Inter-individual variations and hemispheric asymmetries in structural connectivity patterns of the inferior fronto-occipital fascicle: a diffusion tensor imaging tractography study.

PURPOSE: Precise knowledge of the structural connectivity of white matter fascicles could yield new insights into function and is important for neurosurgical planning. Therefore, we aimed to provide a detailed map of the cortical terminations of the inferior fronto-occipital fascicle (IFOF), with special emphasis on putative inter-individual variations and hemispheric asymmetries. METHODS: Deterministic diffusion tensor imaging-based tractography was used to perform virtual dissection of the IFOF in 20 healthy subjects. The IFOF was probed from a single seed region of interest placed within the external/extreme capsule, i.e. the white matter region of "obligatory passage" along the known path of the IFOF. This enabled to reconstruct all the fibers belonging to the IFOF and to provide the complete map of their cortical terminations. RESULTS: We observed widespread projections over a total of 11 cortical territories within the occipital, parietal, temporal and frontal lobes. Importantly, compared to previous studies we consistently found some inter-individual variability with several distinct patterns connecting subsets of the 11 cortical territories, and tangible differences between the two hemispheres. IFOF terminations within the superior parietal lobule were rightward lateralized, whereas terminations within the inferior frontal gyrus were leftward lateralized. CONCLUSIONS: Our results provide a clinically relevant map of IFOF's cortical terminations, including intra- and inter-individual variations. Right-left differences in connectivity patterns might be related to known functional asymmetries in the human brain, and reinforce the general evidence that the IFOF likely supports distinct clinical features and functional roles according to the (affected) hemisphere, such as language and spatial attention.

Ex vivo confocal microscopy imaging to identify tumor tissue on freshly removed brain sample.

Confocal microscopy is a technique able to realize "optic sections" of a tissue with increasing applications. We wondered if we could apply an ex vivo confocal microscope designed for dermatological purpose in a routine use for the most frequent brain tumors. The aim of this work was to identify tumor tissue and its histopathological hallmarks, and to assess grading criteria used in neuropathological practice without tissue loss on freshly removed brain tissue. Seven infiltrating gliomas, nine meningiomas and three metastases of carcinomas were included. We compared imaging results obtained with the confocal microscope to frozen sections, smears and tissue sections of formalin-fixed tissue. Our results show that ex vivo confocal microscopy imaging can be applied to brain tumors in order to quickly identify tumor tissue without tissue loss. It can differentiate tumors and can assess most of grading criteria. Confocal microscopy could represent a new tool to identify tumor tissue on freshly removed sample and could help in selecting areas for biobanking of tumor tissue.

New insights into the functional significance of the frontal aslant tract: an anatomo-functional study using intraoperative electrical stimulations combined with diffusion tensor imaging-based fiber tracking.

We used the method of direct electrostimulation combined with navigated tractography to map the frontal "aslant" tract, enabling us to perform reliable anatomo-functional correlation in a patient undergoing awake surgery to remove a left frontal glioma. The findings enhanced our understanding of the organization of language within the human brain.

Intraoperative visualisation of language fascicles by diffusion tensor imaging-based tractography in glioma surgery.

BACKGROUND: For gliomas, the goal of surgery is to maximise the extent of resection (EOR) while minimising the postoperative morbidity. The purpose of this study was to evaluate the benefits of a protocol developed for the surgical management of gliomas located in language areas, where tractography-integrated navigation was used in conjunction with direct electrical stimulations (DES). METHODS AND MATERIALS: The authors included ten patients suffering of gliomas located in language areas. The preoperative planning for multimodal navigation was done by integrating anatomical magnetic resonance images and subcortical pathway volumes generated by diffusion tensor imaging. Six white matter fascicles implicated in language functions were reconstructed in each patient, including fibres for phonological processing (i.e. the arcuate fasciculus), fibres for lexical-semantic processing (i.e. the inferior frontooccipital fasciculus, inferior longitudinal fasciculus and uncinate fasciculus), and two premotor fasciculi involved in the preparation of speech movements (the subcallosal medialis fasciculus and cortical fibres originating from the medial and lateral premotor areas). During surgery, language fascicles were identified by direct visualisation on tractography-integrated navigation images and by observing transient language inhibition after subcortical DES. Language deficits were evaluated preoperatively and postoperatively, and compared with the EOR. RESULTS: Tractography was successfully performed in all patients, preoperatively demonstrating the relationships between the tumours to resect and the language fascicles to preserve from injury. With the use of the tractography-integrated navigation system and intraoperative DES, language functions were preserved in all patients. The mean volumetric resection was 93.0 ± 10.4 % of the preoperative tumour volume, with a gross total resection in 60 % of patients. CONCLUSION: The intraoperative combination of tractography and DES contributed to maximum safe resection of gliomas located in language areas.

MFI-11 Predicts Post-Operative Serious Complications in Patients Undergoing Surgery for Odontoid Fractures.

STUDY DESIGN: Retrospective Cohort. OBJECTIVES: The objective of this study was to analyze postoperative complications in different mFI-11 groups after surgery for odontoid fractures in a geriatric population. METHODS: A single center retrospective review of odontoid fractures surgery (between 2013 and 2022) in patients aged 65 years and older was conducted. The primary outcome was the occurrence of a major complication (Calvien-Dindo ≥4) within 30 days post-surgery. The secondary outcome was the occurrence of a major complication within 3 months after surgery, and death within 1-month post-surgery. Survival curve, multi-variate analysis was performed and adjusted receiver operating characteristic curves were generated. RESULTS: There were 92 patients included in this study, with a mean age of 80.5 years. Serious complication occurred for 16 patients (17%) during hospitalization. Multivariate analysis demonstrated an mFI 11 >.27 was strongly and independently associated with serious complications within 1-month post-surgery (OR = 16.7, 95% CI = 4.50-83), as well as serious complications within 3 months post-surgery (OR = 11.8, 95% CI = 3.48-49.1) and death within 1 month post-surgery (OR = 11.7; 95% CI = 3.02-60.4). The Receiver Operator Characteristics (ROC) curves for the three models all have an Area Under the Curve (AUC) value greater than 0.7. CONCLUSIONS: The mFI-11 is a straightforward and validated tool that can be used during the preoperative period to identify the patient's level of frailty and assess their risk of postoperative complications. Patients with mFI-11 ≥.27 are at greater risk of serious complications within 1 and 3 months' post-surgery and death within 1 month post-surgery.

Improved dexterity after chronic electrical stimulation of the motor cortex for central pain: a special relevance for thalamic syndrome.

OBJECTIVES: To demonstrate that motor cortex stimulation (MCS) could improve motor function in patients with neuropathic pain. METHODS: In this prospective clinical study of 38 patients referred for MCS as treatment for their neuropathic pain, we collected any declaration of improvement in motor performance that could be attributed to MCS. RESULTS: Ten patients (26%) declared a benefit in their motor function. Eight presented objective evidence of recovered dexterity for rapid alternating movements. A minor proportion had improvement in dystonic posture (n = 2), but none had detectable increased motor strength or tonus changes. Overall, 73% of the patients with limb ataxia declared a benefit after MCS. In 6 out of 10 patients (60%), the anatomic lesion responsible for pain was restricted to the lateral aspect of the thalamus. All of them had either clinical or electrophysiological evidence of lemniscal dysfunction (proprioceptive ataxia). No correlation was found between the scores of pain relief and the modification of motor status. The correlation between thalamic lesions and benefits in motor performance was significant (Fisher's exact test, two-tailed, p = 0.0017). CONCLUSIONS: Up to 26% of patients estimated that MCS improved their motor outcome through recovered dexterity and in cases of lateral thalamic lesions.

Margin-free, en bloc resection of a multilevel cervical chordoma with C-2 involvement: case report with 2-year follow-up and description of operative technique.

The purpose of this technical/case report is to demonstrate that the appropriate oncological principle of margin-free, tumour en bloc removal can be successfully achieved in a large multilevel chordoma with C-2 involvement, with limited morbidity. Although technically challenging, such an approach offers the patient's best chance for cure.

Solitary fibrous tumors of the central nervous system: report of five cases with unusual clinicopathological and outcome patterns.

BACKGROUND: This is a retrospective study of 11 patients harboring a solitary fibrous tumor (SFT) of the central nervous system (CNS), with special emphasis on unusual clinicopathological and outcomes patterns. METHOD: Between 2000 and 2008, 11 patients harboring CNS SFTs were treated at our institution. Patient charts were retrospectively reviewed and tumor location, clinical presentation, imaging characteristics, extent of resection, dural origin, pathological features, adjuvant treatment, and follow-up data were collected, focusing on five atypical cases (four intracranial and one within the spine). FINDINGS: One intracranial SFT arose from the sella turcica and relapsed threefold during the 6 years following partial removal. Disease progressed as successive isolated local recurrences treated by subsequent surgical interventions and gamma-knife radiosurgery. The MiB-1 labeling index analysis showed a steady increase in these sequential recurrences (ranging from less than 3% up to 6%) without obvious malignant transformation. The second SFT occurred in the cerebellopontine angle and exhibited a high MiB-1 index (10%) without noticeable features of malignancy. It relapsed twice during the 5 years following gross total resection without demonstrating a more aggressive histological pattern. The third SFT arose from the cerebellar tentorium, widely invaded the lateral sinus and adjacent bone, had a low MiB-1 index, and has not recurred within the 2 years after incomplete resection. The two remaining SFTs presented with unusual clinicoradiological features. We described a extremely rare case of intraventricular SFT, and a case of extradural SFT of the thoracic spine (T8-T9) radiologically consistent with a schwannoma. Immunohistochemistry confirmed that all tumors were SFTs. CONCLUSIONS: These atypical presentations gave us the opportunity to provide further information about the variability of the clinicoradiological patterns and natural histological course of CNS SFTs.

Heterogeneity of PD-L1 expression in lung adenocarcinoma metastasis is related to histopathological subtypes.

OBJECTIVES: The heterogeneity of PD-L1 expression and its relationship with histopathological subtype has recently been shown on primary tumor but has not been evaluated on metastases. The aim of our work is to analyze PD-L1 expression within each histopathological pattern on resected metastases. MATERIAL AND METHODS: 136 patients were included in this retrospective study. Immunohistochemistry was performed with 22C3 laboratory-developed test. The Tumor Proportion Score was evaluated on each subtype. RESULTS: The most frequent major histopathological subtype was solid (n = 69, 50.7 %), followed by acinar (n = 37, 27.2 %), micropapillary (n = 14, 10.3 %) and papillary (n = 10, 7.3 %). Mean percentage of PD-L1 expression for each subtype was at 28+/-4.8 % for solid subtype, 5.3+/-1.9 % for acinar subtype, 5+/-1.9 % for papillary subtype and 23.6+/-4.1 % for micropapillary subtype. Mean percentage of PD-L1 expression was different between solid pattern and acinar pattern (p < 0.001), solid pattern and papillary pattern (p = 0.007), micropapillary pattern and acinar pattern (p < 0.001) and micropapillary pattern and papillary pattern (p = 0.015). CONCLUSION: To conclude, we have showed firstly that several patterns are present in metastases of lung adenocarcinoma, secondly that the evaluation of patterns and PD-L1 stain on different patterns is reproducible, thirdly that pattern heterogeneity is related to PD-L1 staining, fourthly that in metastatic lung adenocarcinoma with at least two patterns, solid and micropapillary subtypes have higher levels of PD-L staining, fifthly that PD-L1 heterogeneity between different patterns is not a rare event. These results might explain discrepancies of PD-L1 results between biopsies and surgical samples and the fact that some patients might respond to checkpoint inhibitors even though PD-L1 expression is low or absent.

The Immune Microenvironment of Chordomas: An Immunohistochemical Analysis.

Chordomas are rare sarcomas that are usually treated by surgery and/or radiotherapy since these are chemo-resistant tumors, but immunotherapy could be a possible option for chordoma patients. However, few reports investigating the composition of the chordoma immune microenvironment exist. We immunohistochemically studied 81 chordomas regarding their immune microenvironment factors and compared them with clinicopathological data. Macrophages and CD4 cells were the most prominent inflammatory cell populations, followed by CD8 T cells, while CD20 B cells and high endothelial venules (MECA-79+) were less frequently found. PD-L1 (22C3) expression by inflammatory cells was found in 21 (26%) tumors and was associated with a larger tumor size. None of the cases showed the expression of PD-L1 by tumor cells. Survival analysis showed that younger patients had a better overall survival. Considering the immunohistochemical factors studied, higher CD8, the presence of PD-L1+ immune cells, and higher vascular density were adverse prognostic factors, but in multivariate analysis, only PD-L1+ immune cells retained prognostic significance. To conclude, chordoma tumor cells do not express PD-L1, but PD-L1+ immune cells seem to play a negative prognostic role, supporting the need for further studies in this field and the possible beneficial role of immunotherapy in these patients.