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

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

The abscopal effect is a term that has been used to describe the phenomenon in which localized radiation therapy treatment of a tumor lesion triggers a spontaneous regression of metastatic lesion(s) at a non-irradiated distant site(s). Radiation therapy induced abscopal effects are believed to be mediated by activation and stimulation of the immune system. However, due to the brain’s distinctive immune microenvironment, extracranial abscopal responses following cranial radiation therapy have rarely been reported. In this report, we describe the case of 42-year-old female patient with metastatic melanoma who experienced an abscopal response following her cranial radiation therapy for her brain metastasis. The patient initially presented with a stage III melanoma of the right upper skin of her back. Approximately 5 years after her diagnosis, the patient developed a large metastatic lesion in her upper right pectoral region of her chest wall and axilla. Since the patient’s tumor was positive for BRAF and MEK, targeted therapy with dabrafenib and trametinib was initiated. However, the patient experienced central nervous system (CNS) symptoms such as headache and disequilibrium and developed brain metastases prior to the start of targeted therapy. The patient received radiation therapy to a dose of 30 Gy delivered in 15 fractions to her brain lesions while the patient was on dabrafenib and trametinib therapy. The patient’s CNS metastases improved significantly within weeks of her therapy. The patient’s non-irradiated large extracranial chest mass and axilla mass also shrank substantially demonstrating the abscopal effect during her CNS radiation therapy. Following radiation therapy of her residual chest lesions, the patient was disease free clinically and her CNS lesions had regressed. However, when the radiation therapy ended and the patient continued her targeted therapy alone, recurrence outside of her previously treated fields was noted. The disease recurrence could be due to the possibility of developing BRAF resistance clones to the BRAF targeted therapy. The patient died eventually due to wide spread systemic disease recurrence despite targeted therapy.
Adult ; Axilla ; Brain ; Central Nervous System ; Clone Cells ; Diagnosis ; Female ; Headache ; Humans ; Immune System ; Immunization ; Melanoma ; Molecular Targeted Therapy ; Neoplasm Metastasis ; Radiation, Ionizing ; Recurrence ; Skin ; Skin Neoplasms ; Thoracic Wall ; Thorax

BACKGROUND: Pathologic diagnosis of central nervous system (CNS) neoplasms is made by comparing light microscopic, immunohistochemical, and molecular cytogenetic findings with clinicoradiologic observations. Intraoperative frozen cytology smears can improve the diagnostic accuracy for CNS neoplasms. Here, we evaluate the diagnostic value of cytology in frozen diagnoses of CNS neoplasms. METHODS: Cases were selected from patients undergoing both frozen cytology and frozen sections. Diagnostic accuracy was evaluated. RESULTS: Four hundred and fifty-four cases were included in this retrospective single-center review study covering a span of 10 years. Five discrepant cases (1.1%) were found after excluding 53 deferred cases (31 cases of tentative diagnosis, 22 cases of inadequate frozen sampling). A total of 346 cases of complete concordance and 50 cases of partial concordance were classified as not discordant cases in the present study. Diagnostic accuracy of intraoperative frozen diagnosis was 87.2%, and the accuracy was 98.8% after excluding deferred cases. Discrepancies between frozen and permanent diagnoses (n = 5, 1.1%) were found in cases of nonrepresentative sampling (n = 2) and misinterpretation (n = 3). High concordance was observed more frequently in meningeal tumors (97/98, 99%), metastatic brain tumors (51/52, 98.1%), pituitary adenomas (86/89, 96.6%), schwannomas (45/47, 95.8%), high-grade astrocytic tumors (47/58, 81%), low grade astrocytic tumors (10/13, 76.9%), non-neoplastic lesions (23/36, 63.9%), in decreasing frequency. CONCLUSIONS: Using intraoperative cytology and frozen sections of CNS tumors is a highly accurate diagnostic ancillary method, providing subtyping of CNS neoplasms, especially in frequently encountered entities.
Brain Neoplasms ; Central Nervous System Neoplasms ; Central Nervous System ; Cytogenetics ; Diagnosis ; Frozen Sections ; Humans ; Meningeal Neoplasms ; Methods ; Neurilemmoma ; Pituitary Neoplasms ; Retrospective Studies

BACKGROUND: The 2016 World Health Organization (WHO) classification of central nervous system (CNS) tumors has been modified to incorporate the IDH mutation and 1p/19q co-deletion in the diagnosis of diffuse gliomas. In this study, we aimed to evaluate the feasibility and prognostic significance of the revised 2016 WHO classification of CNS tumors in Mongolian patients with diffuse gliomas. METHODS: A total of 124 cases of diffuse gliomas were collected, and tissue microarray blocks were made. IDH1 mutation was tested using immunohistochemistry, and 1p/19q co-deletion status was examined using fluorescence in situ hybridization analysis. RESULTS: According to the 2016 WHO classification, 124 cases of diffuse brain glioma were reclassified as follows: 10 oligodendroglioma, IDHmut and 1p/19q co-deleted; three anaplastic oligodendroglioma, IDHmut and 1p/19q co-deleted; 35 diffuse astrocytoma, IDHmut, 11 diffuse astrocytoma, IDHwt, not otherwise specified (NOS); 22 anaplastic astrocytoma, IDHmut, eight anaplastic astrocytoma, IDHwt, NOS; and 35 glioblastoma, IDHwt, NOS, respectively. The 2016 WHO classification presented better prognostic value for overall survival in patients with grade II tumors than traditional histological classification. Among patients with grade II tumors, those with oligodendroglioma IDHmut and 1p/19q co-deleted and diffuse astrocytoma IDHmut showed significantly higher survival than those with diffuse astrocytoma IDHwt, NOS (p<.01). CONCLUSIONS: Mongolian diffuse gliomas could be reclassified according to the new 2016 WHO classification. Reclassification revealed substantial changes in diagnosis of both oligodendroglial and astrocytic entities. We have confirmed that the revised 2016 WHO CNS tumor classification has prognostic significance in Mongolian patients with diffuse gliomas, especially those with grade II tumors.
Astrocytoma ; Brain ; Central Nervous System ; Chromosome Deletion ; Classification ; Diagnosis ; Fluorescence ; Glioblastoma ; Glioma ; Global Health ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Isocitrate Dehydrogenase ; Nervous System Neoplasms ; Nervous System ; Oligodendroglioma ; World Health Organization

Germinoma is the most common type of intracranial germ cell tumors (GCTs). Pineal gland and suprasellar region are the most frequent sites of central nervous system (CNS) involvement. Intracranial masses caused by Langerhans cell histiocytosis (LCH) mimics features of CNS GCTs. LCH frequently involve spine and is the most common cause of vertebra plana in children. A 15-year-old boy presented with progressing symptoms of polydipsia, polyuria, general headache, nausea and severe back pain. Brain MRI showed brain tumor with simultaneous involvement of suprasellar region and pineal gland. An excisional biopsy of suprasellar mass was done. The pathologic assessment confirmed the diagnosis of germinoma. Patient's treatment continued accordingly. A spine MRI, done due to persistent backache, showed a vertebra plana. We reevaluated the primary diagnosis suspecting LCH. Germinoma of CNS was confirmed and a biopsy of vertebral lesion resulted in hemangioma. Thus we report a case of CNS germinoma with co-occurrence of vertebra plana. We emphasized the importance of histopathologic diagnosis of pineal/suprasellar masses and primary investigation of other CNS regions including spine for possible metastasis or comorbidities.
Adolescent ; Back Pain ; Biopsy ; Brain ; Brain Neoplasms ; Central Nervous System ; Child ; Comorbidity ; Diagnosis ; Germinoma* ; Headache ; Hemangioma ; Histiocytosis, Langerhans-Cell ; Humans ; Magnetic Resonance Imaging ; Male ; Nausea ; Neoplasm Metastasis ; Neoplasms, Germ Cell and Embryonal ; Pineal Gland ; Polydipsia ; Polyuria ; Spine*

The World Health Organization (WHO) classification of central nervous system (CNS) tumors was revised in 2016 with a basis on the integrated diagnosis of molecular genetics. We herein provide the guidelines for using molecular genetic tests in routine pathological practice for an accurate diagnosis and appropriate management. While astrocytomas and IDH-mutant (secondary) glioblastomas are characterized by the mutational status of IDH, TP53, and ATRX, oligodendrogliomas have a 1p/19q codeletion and mutations in IDH, CIC, FUBP1, and the promoter region of telomerase reverse transcriptase (TERTp). IDH-wildtype (primary) glioblastomas typically lack mutations in IDH, but are characterized by copy number variations of EGFR, PTEN, CDKN2A/B, PDGFRA, and NF1 as well as mutations of TERTp. High-grade pediatric gliomas differ from those of adult gliomas, consisting of mutations in H3F3A, ATRX, and DAXX, but not in IDH genes. In contrast, well-circumscribed low-grade neuroepithelial tumors in children, such as pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and ganglioglioma, often have mutations or activating rearrangements in the BRAF, FGFR1, and MYB genes. Other CNS tumors, such as ependymomas, neuronal and glioneuronal tumors, embryonal tumors, meningothelial, and other mesenchymal tumors have important genetic alterations, many of which are diagnostic, prognostic, and predictive markers and therapeutic targets. Therefore, the neuropathological evaluation of brain tumors is increasingly dependent on molecular genetic tests for proper classification, prediction of biological behavior and patient management. Identifying these gene abnormalities requires cost-effective and high-throughput testing, such as next-generation sequencing. Overall, this paper reviews the global guidelines and diagnostic algorithms for molecular genetic testing of brain tumors.
Adult ; Astrocytoma ; Brain Neoplasms* ; Brain* ; Central Nervous System ; Child ; Classification ; Diagnosis ; Ependymoma ; Ganglioglioma ; Genes, myb ; Glioblastoma ; Glioma ; Humans ; Molecular Biology ; Neoplasms, Neuroepithelial ; Neurons ; Oligodendroglioma ; Promoter Regions, Genetic ; Telomerase ; World Health Organization

Adult ; Central Nervous System Neoplasms ; diagnosis ; surgery ; Female ; Humans ; Lymphoma ; diagnosis ; surgery ; Magnetic Resonance Imaging ; methods

BACKGROUND: Normalized cerebral blood volume (nCBV) can be measured using manual or semiautomatic segmentation method. However, the difference in diagnostic performance on brain tumor differentiation between differently measured nCBV has not been evaluated. PURPOSE: To compare the diagnostic performance of manually obtained nCBV to that of semiautomatically obtained nCBV on glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL) differentiation. MATERIALS AND METHODS: Histopathologically confirmed forty GBM and eleven PCNSL patients underwent 3T MR imaging with dynamic susceptibility contrast-enhanced perfusion MR imaging before any treatment or biopsy. Based on the contrast-enhanced T1-weighted imaging, the mean nCBV (mCBV) was measured using the manual method (manual mCBV), random regions of interest (ROIs) placement by the observer, or the semiautomatic segmentation method (semiautomatic mCBV). The volume of enhancing portion of the tumor was also measured during semiautomatic segmentation process. T-test, ROC curve analysis, Fisher's exact test and multivariate regression analysis were performed to compare the value and evaluate the diagnostic performance of each parameter. RESULTS: GBM showed a higher enhancing volume (P = 0.0307), a higher manual mCBV (P = 0.018) and a higher semiautomatic mCBV (P = 0.0111) than that of the PCNSL. Semiautomatic mCBV had the highest value (0.815) for the area under the curve (AUC), however, the AUCs of the three parameters were not significantly different from each other. The semiautomatic mCBV was the best independent predictor for the GBM and PCNSL differential diagnosis according to the stepwise multiple regression analysis. CONCLUSION: We found that the semiautomatic mCBV could be a better predictor than the manual mCBV for the GBM and PCNSL differentiation. We believe that the semiautomatic segmentation method can contribute to the advancement of perfusion based brain tumor evaluation.
Area Under Curve ; Biopsy ; Blood Volume ; Brain Neoplasms ; Central Nervous System* ; Diagnosis, Differential ; Glioblastoma* ; Humans ; Lymphoma* ; Magnetic Resonance Imaging* ; Methods* ; Perfusion* ; ROC Curve

Adult ; Central Nervous System Neoplasms ; diagnosis ; Ciliary Body ; pathology ; Humans ; Male