Objective: To investigate immunohistochemical patterns of CXorf67 and H3K27me3 proteins in central nervous system germ cell tumors (GCTs) and to assess their values in both diagnosis and differential diagnosis. Methods: A total of 370 cases of central nervous system GCTs were collected from 2013 to 2020 at Huashan Hospital of Fudan University, Shanghai, China. The expression of CXorf67, H3K27me3 and commonly-used GCT markers including OCT4, PLAP, CD117, D2-40, and CD30 by immunohistochemistry (EnVision method) was examined in different subtypes of central nervous system GCTs. The sensitivity and specificity of each marker were compared by contingency table and area under receiver operating characteristic (ROC) curve. Results: Of the 370 cases there were 282 males and 88 females with a mean age of 19 years and a median age of 17 years (range, 2-57 years). Among the GCTs with germinoma, the proportions of male patients and the patients with GCT located in sellar region were both higher than those of GCTs without germinoma (P<0.05), respectively. CXorf67 was present in the nuclei of germinoma and normal germ cells, but not in other subtypes of GCT. H3K27me3 was negative in germinoma, but positive in the nuclei of surrounding normal cells and GCTs other than germinoma. In the 283 GCTs with germinoma components, the expression rate of CXorf67 was 90.5% (256/283), but no cases were positive for H3K27me3. There was also an inverse correlation between them (r²=-0.831, P<0.01). The expression rates of PLAP, OCT4, CD117 and D2-40 were 81.2% (231/283), 89.4% (253/283), 73.9% (209/283) and 88.3% (250/283), respectively. In 63 mixed GCTs with germinoma components, the expression rate of CXorf67 was 84.1% (53/63), while all cases were negative for H3K27me3. The expression rates of PLAP, OCT4, CD117 and D2-40 were 79.4% (50/63), 79.4% (50/63), 66.7% (42/63) and 87.3% (55/63), respectively. The 6 markers with largest area under ROC curve in ranking order were H3K27me3, CXorf67, D2-40, OCT4, PLAP and CD117 (P<0.05). Conclusions: CXorf67 and H3K27me3 have high sensitivity and high specificity in diagnosing germinoma. There is a significant inverse correlation between them. Therefore, they can both be used as new specific immunohistochemical markers for the diagnosis of GCTs.
Adolescent ; Adult ; Brain Neoplasms/pathology* ; Central Nervous System/pathology* ; Central Nervous System Neoplasms/metabolism* ; Child ; Child, Preschool ; China ; Female ; Germinoma/pathology* ; Histones ; Humans ; Male ; Middle Aged ; Neoplasms, Germ Cell and Embryonal/diagnosis* ; Oncogene Proteins ; Transcription Factors/metabolism* ; Young Adult

Objective To analyze the disease spectrum and clinicopathological characteristics of central nervous system(CNS)diseases diagnosed based on pathological findings in Tibet. Methods We collected the data of all the cases with CNS lesions in Tibet Autonomous Region People's Hospital from January 2013 to December 2020.The clinicopathological features were analyzed via light microscopy,immunohistochemical staining,and special staining. Results A total of 383 CNS cases confirmed by pathological diagnosis were enrolled in this study,with a male-to-female ratio of 188∶195 and an average age of(40.03±17.39)years(0-74 years).Among them,127(33.2%)cases had non-neoplastic diseases,with a male-to-female ratio of 82∶45 and an average age of(31.99±19.29)years;256(66.8%)cases had neoplastic diseases,with a male-to-female ratio of 106∶150 and an average age of(44.01±14.87)years.The main non-neoplastic diseases were nervous system infectious diseases,cerebral vascular diseases,meningocele,cerebral cyst,and brain trauma.Among the infectious diseases,brain abscess,granulomatous inflammation,cysticercosis,and hydatidosis were common.The main neoplastic diseases included meningioma,pituitary adenoma,neuroepithelial tumor,schwannoma,metastatic tumor,and hemangioblastoma.The meningioma cases consisted of 95.4%(103/108)cases of grade Ⅰ,3.7%(4/108)cases of grade Ⅱ,and only 1(1/108,0.9%)case of grade Ⅲ.Among the neuroepithelial tumor cases,the top three were glioblastoma,grade Ⅲ diffuse glioma,and ependymoma. Conclusions There are diverse CNS diseases confirmed by pathological diagnosis in Tibet,among which non-neoplastic diseases account for 1/3 of all the cases.Infectious and vascular diseases are the most common non-neoplastic diseases in Tibet,and tuberculosis and parasitic infections are relatively common.The types and proportion of brain tumors in Tibet are different from those in other regions of China,and meningioma is the most common in Tibet,with higher proportion than neuroepithelial tumor.
Adolescent ; Adult ; Aged ; Brain Neoplasms/diagnosis* ; Central Nervous System Diseases/pathology* ; Child ; Child, Preschool ; Ependymoma ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Meningeal Neoplasms ; Middle Aged ; Retrospective Studies ; Tibet/epidemiology* ; Young Adult

Choroid plexus tumors are uncommon brain tumors that primarily occur in children. Most of these tumors originate from the intraventricular area, and the most common clinicalpresentation is increased intracranial pressure. Dissemination through the cerebrospinal fluid space is the inevitable natural course of the disease. Here, we present 2 rare cases of adult choroid plexus carcinoma (CPC), each with distinct clinical presentation and progression. The first case was a 40-year-old male who presented with multiple intraventricular masses. After surgical biopsy, radiation and intrathecal chemotherapy failed to elicit any response. The patient progressed with spinal cord dissemination and expired 1 year later. The second case presented with visual disturbance, and brain MRI revealed a large ovoid juxtaventricular mass with peritumoral edema. This 49-year-old female patient underwent craniotomy for what was thought to be a high-grade glioma; however, the mass was connected to the choroid plexus at the operative field. Her pathology specimen was diagnosed as CPC, and adjuvant systemic chemotherapy was administered. She has now been free of recurrence for 10 months. The description of the presentation and progression of these rare adult-onset CPC provides insight for the diagnosis and treatment of other rare instances of choroid plexus tumors.
Adult ; Biopsy ; Brain ; Brain Neoplasms ; Cerebrospinal Fluid ; Child ; Choroid Plexus Neoplasms ; Choroid Plexus ; Choroid ; Craniotomy ; Diagnosis ; Drug Therapy ; Edema ; Female ; Fourth Ventricle ; Glioma ; Humans ; Intracranial Pressure ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Pathology ; Recurrence ; Spinal Cord

Bilateral thalamic gliomas (BTGs) are rare brain tumors. In general, the prognosis is poor because of the involvement of bilateral thalami and limitations of surgical excision. Consequently, patients with symptoms of personality changes and memory impairment must be differentiated from others. Magnetic resonance imaging (MRI) is essential for the diagnosis of BTGs and reveals a hypo-intense lesion on T1-weighted images and a hyper-intense lesion on T2 images. We report a case of a 17-year-old female patient suffering from progressive cognitive dysfunction and personality changes and subsequent rehabilitation treatment. Brain MRI showed an enlarged bilateral thalamus, with hyperintensity on T2-weighted images and iso-intensity on T1-weighted images. A biopsy was performed, and the pathology revealed a high-grade glioma. The patient was referred for radiotherapy and chemotherapy. She also underwent rehabilitation treatment for 5 weeks and showed improvement in standing balance, endurance, and speech fluency. The patient's Modified Barthel Index scores also improved. Cancer rehabilitation is important in brain tumor patients because they have a higher incidence of neurological sequelae than others. Rehabilitation of patients with a malignant brain tumor is also important for improving health-related quality of life by maintaining the general condition and preventing complications during and after cancer treatment.
Adolescent ; Biopsy ; Brain ; Brain Neoplasms ; Diagnosis ; Drug Therapy ; Female ; Glioma ; Humans ; Incidence ; Magnetic Resonance Imaging ; Memory ; Memory Disorders ; Neurobehavioral Manifestations ; Pathology ; Prognosis ; Quality of Life ; Radiotherapy ; Rehabilitation ; Thalamus

Recent discoveries of brain tumor-related genes and fast advances in genomic testing technologies have led to the era of molecular diagnosis of brain tumor. Molecular profiling of brain tumor became the significant step in the diagnosis, the prediction of prognosis and the treatment of brain tumor. Because traditional molecular testing methods have limitations in time and cost for multiple gene tests, next-generation sequencing technologies are rapidly introduced into clinical practice. Targeted sequencing panels using these technologies have been developed for brain tumors. In this article, focused on pediatric brain tumor, key discoveries of brain tumor-related genes are reviewed and cancer panels used in the molecular profiling of brain tumor are discussed.
Brain Neoplasms ; Brain ; Diagnosis ; High-Throughput Nucleotide Sequencing ; Pathology, Molecular ; Pediatrics ; Prognosis

Brain ; blood supply ; pathology ; surgery ; Diagnosis, Differential ; Humans ; Middle Aged ; Pituitary Neoplasms ; cerebrospinal fluid ; complications ; diagnosis ; Stroke ; cerebrospinal fluid ; complications ; diagnosis ; Tuberculosis ; cerebrospinal fluid ; complications ; diagnosis

Intracranial lesions may show contrast enhancement through various mechanisms that are closely associated with the disease process. The preferred magnetic resonance sequence in contrast imaging is T1-weighted imaging (T1WI) at most institutions. However, lesion enhancement is occasionally inconspicuous on T1WI. Although fluid-attenuated inversion recovery (FLAIR) sequences are commonly considered as T2-weighted imaging with dark cerebrospinal fluid, they also show mild T1-weighted contrast, which is responsible for the contrast enhancement. For several years, FLAIR imaging has been successfully incorporated as a routine sequence at our institution for contrast-enhanced (CE) brain imaging in detecting various intracranial diseases. In this pictorial essay, we describe and illustrate the diagnostic importance of CE-FLAIR imaging in various intracranial pathologic conditions.
Arachnoid Cysts/*diagnosis/pathology ; Brain/*pathology ; Brain Neoplasms/*diagnosis/pathology ; Contrast Media ; Humans ; Magnetic Resonance Imaging/*methods

OBJECTIVETo discuss the clinicopathologic features of rhabdoid glioblastoma of the brain and its differential diagnoses.

METHODSA 10-year-old and a 45-year-old female both presented with gradually worsening headache, limbs twitch and blurred vision. MRI scan revealed a contrast enhancing tumor in the right temporal lobe and left cerebellum respectively. Both patients underwent tumor resection, followed by postoperative radiotherapy and chemotherapy.

RESULTSMicroscopic examination of both tumors showed rhabdoid tumor cells with an eccentric nuclei and eosinophilic cytoplasms. Both tumors had areas of classic glioblastoma with microvascular proliferation and necrosis. Immunohistochemical staining showed the rhabdoid tumor cells were positive for vimentin diffusely and GFAP, EMA, CK focally. Integrase interactor (INI-1) was expressed in most tumor cells, but IDH1 R132H was not detected in both tumors. Fluorescence in situ hybridization revealed 1p/19q co-deletion in one case. One patient was alive without tumor recurrence after 16 months follow-up, the other patient died of intraspinal tumor dissemination 9 months after surgery.

CONCLUSIONSRhabdoid glioblastoma is a rare glial cell tumor with specific rhabdoid tumor cells, a highly aggressive clinical course and poor prognosis. Combining histological features, a panel of selected immunostains including vimentin, GFAP, CK, EMA, SMA and INI-1 is helpful in making an accurate diagnosis for those diagnostically challenging cases with rhabdoid features in central nervous system.

Biomarkers, Tumor ; metabolism ; Brain Neoplasms ; pathology ; Child ; Diagnosis, Differential ; Female ; Glioblastoma ; pathology ; Humans ; In Situ Hybridization, Fluorescence ; Magnetic Resonance Imaging ; Middle Aged ; Necrosis ; Neoplasm Recurrence, Local ; Rhabdoid Tumor ; pathology ; Temporal Lobe ; pathology

PURPOSE: To evaluate patterns of macular retinal ganglion cell (RGC) loss measured by spectral domain optical coherence tomography in patients with neurologic lesions mimicking glaucoma. METHODS: We evaluated four patients with neurological lesions who showed characteristic patterns of RGC loss, as determined by ganglion cell thickness (GCT) mapping. RESULTS: Case 1 was a 30-year-old man who had been treated with glaucoma medication. A left homonymous vertical pattern of RGC loss was observed in his GCT map and a past brain magnetic resonance imaging (MRI) revealed a hemorrhagic lesion around the right optic radiation. Case 2 was a 72-year-old man with a pituitary adenoma who had a binasal vertical pattern of RGC loss that corresponded with bitemporal hemianopsia. Case 3 was a 77-year-old man treated for suspected glaucoma. His GCT map showed a right inferior quadratic pattern of loss, indicating a right superior homonymous quadranopsia in his visual field (VF). His brain MRI revealed a left posterior cerebral artery territory infarct. Case 4 was a 38-year-old woman with an unreliable VF who was referred for suspected glaucoma. Her GCT map revealed a left homonymous vertical pattern of RGC loss, which may have been related to a previous head trauma. CONCLUSIONS: Evaluation of the patterns of macular RGC loss may be helpful in the differential diagnosis of RGC-related diseases, including glaucoma and neurologic lesions. When a patient's VF is unavailable, this method may be an effective tool for diagnosing and monitoring transneuronal retrograde degeneration-related structural changes.
Adult ; Aged ; Brain Injuries/diagnosis ; Cerebral Infarction/diagnosis ; Diagnosis, Differential ; Female ; Glaucoma/*diagnosis ; Hemianopsia/diagnosis ; Humans ; Magnetic Resonance Imaging ; Male ; Nerve Fibers/*pathology ; Nervous System Diseases/*diagnosis ; Pituitary Neoplasms/diagnosis ; Retinal Ganglion Cells/*pathology ; Retrospective Studies ; Tomography, Optical Coherence ; Tonometry, Ocular ; Visual Acuity ; Visual Field Tests ; Visual Fields

The current standards in radiotherapy of high-grade gliomas (HGG) are based on anatomic imaging techniques, usually computed tomography (CT) scanning and magnetic resonance imaging (MRI). The guidelines vary depending on whether the HGG is a histological grade 3 anaplastic glioma (AG) or a grade 4 glioblastoma multiforme (GBM). For AG, T2-weighted MRI sequences plus the region of contrast enhancement in T1 are considered for the delineation of the gross tumor volume (GTV), and an isotropic expansion of 15 to 20 mm is recommended for the clinical target volume (CTV). For GBM, the Radiation Therapy Oncology Group favors a two-step technique, with an initial phase (CTV1) including any T2 hyperintensity area (edema) plus a 20 mm margin treated with up to 46 Gy in 23 fractions, followed by a reduction in CTV2 to the contrast enhancement region in T1 with an additional 25 mm margin. The European Organisation of Research and Treatment of Cancer recommends a single-phase technique with a unique GTV, which comprises the T1 contrast enhancement region plus a margin of 20 to 30 mm. A total dose of 60 Gy in 30 fractions is usually delivered for GBM, and a dose of 59.4 Gy in 33 fractions is typically given for AG. As more than 85% of HGGs recur in field, dose-escalation studies have shown that 70 to 75 Gy can be delivered in 6 weeks with relevant toxicities developing in <10% of the patients. However, the only randomized dose-escalation trial, in which the boost dose was guided by conventional MRI, did not show any survival advantage of this treatment over the reference arm. HGGs are amongst the most infiltrative and heterogeneous tumors, and it was hypothesized that the most highly aggressive areas were missed; thus, better visualization of these high-risk regions for radiation boost could decrease the recurrence rate. Innovations in imaging and linear accelerators (LINAC) could help deliver the right doses of radiation to the right subvolumes according to the dose-painting concept. Advanced imaging techniques provide functional information on cellular density (diffusion MRI), angiogenesis (perfusion MRI), metabolic activity and cellular proliferation [positron emission tomography (PET) and magnetic resonance spectroscopy (MRS)]. All of these non-invasive techniques demonstrated good association between the images and histology, with up to 40% of HGGs functionally presenting a high activity within the non-contrast-enhanced areas in T1. New LINAC technologies, such as intensity-modulated and stereotactic radiotherapy, help to deliver a simultaneous integrated boost (SIB) > 60 Gy. Trials delivering a SIB into a biological GTV showed the feasibility of this treatment, but the final results, in terms of clinical benefits for HGG patients, are still pending. Many issues have been identified: the variety of MRI and PET machines (and amino-acid tracers), the heterogeneity of the protocols used for image acquisition and post-treatment, the geometric distortion and the unreliable algorithms for co-registration of brain anatomy with functional maps, and the semi-quiescent but highly invasive HGG cells. These issues could be solved by the homogenization of the protocols and software applications, the simultaneous acquisition of anatomic and functional images (PET-MRI machines), the combination of complementary imaging tools (perfusion and diffusion MRI), and the concomitant addition of some ad hoc targeted drugs against angiogenesis and invasiveness to chemoradiotherapy. The integration of these hybrid data will construct new synthetic metrics for fully individualized treatments.
Antineoplastic Agents, Alkylating ; therapeutic use ; Brain Neoplasms ; diagnosis ; pathology ; radiotherapy ; Dacarbazine ; analogs & derivatives ; therapeutic use ; Diffusion Tensor Imaging ; Glioblastoma ; diagnosis ; drug therapy ; pathology ; radiotherapy ; Glioma ; diagnosis ; pathology ; radiotherapy ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Neoplasm Grading ; Particle Accelerators ; Positron-Emission Tomography ; Radiotherapy Dosage ; Radiotherapy, Intensity-Modulated ; methods