In clinical practice, neurosurgeons often lack a correct judgment of some difficult CNS occupying lesions, and some imaging physicians have difficulty in grasping the imaging characteristics of difficult CNS occupying lesions. In the past 10 years, with the help of our neurosurgery stereotactic surgery, the pathological diagnosis of CNS difficult occupying lesions has also been made with the formation of a multidisciplinary consultation center for difficult neurological diseases in our department over the past 5 years, with clinical neurology, imaging, and (neuro)pathology as the main components. With the development of the “three-dimensional one” consultation mode, we have more perceptual and rational understanding of CNS difficult occupying lesions, and summarized some effective clinical experience, and the following is the analysis and experience sharing of relevant diagnostic ideas. Neuroepithelial tumor diagnosis and differentiation Neurosurgery and imaging physicians are used to simply use “glioma” to represent primary neuroepithelial tumors in the brain, but in fact, in 2007, neuroepithelial tumors were divided into nine categories, including astrocytic tumors, oligodendrocytic tumors and ventricular canal cell tumors [1]. Astrocytic tumors are further divided into seven types such as hairy cell type, diffuse astrocytic, glioblast, and gliomatosis cerebri. Clinicians should use the concept of pathological classification to define the brain tumor to be diagnosed, which requires that some pathological knowledge should be acquired. Without knowledge of brain tumor pathology, it is difficult to fully understand the corresponding characteristics and differentiation of tumor and non-tumor lesions. For example, some multicentric growth astrocytomas are easily misdiagnosed as multiple infectious lesions (parasites), multiple sclerosis or multiple metastases, etc. If we know the growth characteristics, clinical symptoms and imaging features of brain tumors, it is not difficult to make the corresponding judgment. For example, hairy cell astrocytoma is more common in children and adolescents, with the midline brainstem and cerebellum as the preferred sites. Although the brainstem is filled with tumor cells, the patient’s activities are basically normal, only slightly unstable walking or dizziness [Figure 1], which is due to the growth of tumor cells in the nerve fibers and does not destroy the normal structure, but if it is a brainstem demyelinating disease, even if it is only a small part, the patient’s clinical symptoms can be more obvious [Figure 2a-2c]. Tumors of neuroepithelial tissue can be slightly or densely localized on CT, whereas demyelinating disease or encephalitis tend to be hypointense changes; therefore, CT hyperintensity can help distinguish tumors from non-tumorigenic lesions [2,3]. Gliomatosis cerebri (GC) is one of the astrocytic tumors, and its clinical symptoms are diverse due to the extent of the lesion and present late and atypically, which also poses a great challenge for clinical diagnosis. Because tumors rarely form clusters, tumor cells are scattered and nuclear heterogeneity is not significant in the early stage, some GCs are not found in clusters of tumor cells despite brain biopsy, and pathology is mostly reported as “glial cell hyperplasia”. The diagnosis of GC is not difficult when combined with the clinical manifestations (some often have high cranial pressure), especially the foggy-like lesions on imaging [Figure 3a,3b], which often involve the cortex, and the lesions rarely intensify. The duration of GC is mostly within 2-3 years, but a few of them can be 5-8 years, and some of them are easily misdiagnosed as viral encephalitis due to seizures, but the patients are less febrile and have relatively good overall intelligence, which is not consistent with viral encephalitis. Some GCs have also been diagnosed as demyelinating disease, cerebral infarction, etc [5]. 2, Clinical imaging features of primary central nervous system lymphoma Primary central nervous system lymphoma [PCNSL] often has a chronic or subacute clinical onset, generally over 50 years of age, and can develop in both men and women, with rapid progression in the later stages, and is partially characterized clinically by unresponsiveness, PCNSL is usually chronic or subacute in onset, usually in men and women over 50 years of age, and progresses rapidly in later stages. The lesions are most likely to involve the midline and paramedian structures of the brain parenchyma, mostly centered on the basal ganglia, thalamus, brainstem, and paraventricular area, and may have an occupying effect, or may grow in a patchy infiltrative pattern in the subcortical white matter area, and very rarely PCNSL may invade the meninges alone, or nerve roots, or grow near the cavernous sinus. PCNSL in the spinal cord is rare, and the one case of spinal cord PCNSL seen by the author is considered to be a downward disseminated implant from the brain rather than a primary in the spinal cord [8]. The CT scan of the brain may show low, equal, or high density signal.MRI may show long slightly T1, slightly long T2 signal, slightly high signal on DWI, and rarely hemorrhagic signal.CT or MRI enhancement mostly shows homogeneous masses, nodules, or cloudy enhancement. In some cases, PCNSL has a specific presentation, with MRI showing diffuse lesions in the bilateral cerebral hemispheres without significant mass lesions, similar to white matter encephalopathy-like changes, which can be non-enhancing in the early stage, and clinically, cognitive impairment such as unresponsiveness and memory loss is the main manifestation. Some pathologies are characterized by diffuse lymphocytic infiltration in the white matter of the brain without clear mass formation, which is characteristic of lymphomatosis cerebri [9] and can be easily confused with GC. Two of the PCNSL cases in the group summarized in this issue had clinical and imaging manifestations [Figure 4a-4c] that were consistent with the presenting features of cerebral lymphomatosis [7]. Therefore, we must understand the concept and clinical imaging features of cerebral lymphomatosis and pay attention to the diagnosis and differential diagnosis in practice. 3. diagnostic differentiation of pseudotumor-like demyelinating lesion In recent years, with the improved understanding of pseudotumor-like demyelinating lesion (TDL) [2], the rate of correct clinical diagnosis has become higher. However, insufficient mastery of its imaging judgment criteria has also brought about diagnostic generalization or misdiagnosis, and some cases of brain tumors (PCNSL or astrocytoma) are often diagnosed and treated as TDL. For this reason, the author’s list further compares the clinical and imaging aspects of TDL with PCNSL and astrocytoma for easy grasp (Table 1). TDL, also known as tumor-like inflammatory demyelinating disease (TIDD). Its MRI imaging presentation correlates with the stage of clinical onset, and the clinical presentation correlates with the site of involvement. In the acute phase (within 2 weeks of onset), MRI of the brain reveals a markedly enhanced lesion with punctate or lamellar enhancement, which can easily be considered as PCNSL or astrocytoma. In the subacute phase (within 1.5 months of disease onset), TDL foci with peripheral enhancement are more common and can be semi-annular or circumferential. This issue of CPC provides a case of TDL in the acute stage [10], and its imaging presentation is typical of the acute stage of TDL. DWI reveals high signal changes in the lesion regardless of the acute or subacute phase. After the chronic phase, the DWI signal of the lesion gradually decreases over time, and enhancement is not obvious. However, the DWI signal of PCNSL or malignant astrocytoma shows more pronounced high signal over time [Figure 4c], and the enhancement becomes more obvious. 4. Other occupancy-like encephalopathies From the classification of 195 pathologically confirmed intracranial occupancy-like lesions by pathology summarized by Qinwen Dong [11], the three common occupancy-like encephalopathies mentioned above accounted for 117 cases, or 60%. In addition, there were also intracranial infectious diseases (34 cases, 17.4%), 8 cases of encephalopathy of vascular origin (4 cases of cerebral infarction, 3 cases of venous system thrombosis, and 1 case of cerebral hemorrhage), 7 cases each of mitochondrial encephalomyopathy and primary central nervous system vasculitis, and a few other non-neuroepithelial tumors. For example, in primary angiitis of the central nervous system (PACNS), the brain lesions mainly involve cortical and subcortical structures, and sometimes the lesions are clearly occupying and can be easily confused with brain tumors or TDL. However, PACNS lesions are low signal on CT and generally do not enhance significantly. MRI shows that there are often small scattered hemorrhagic signals between long T1 and long T2 signals, which is different from brain tumors. Germ cell tumors tend to be seen on CT with high density in the lesion. Nodular cell gliomas tend to occur in children with recurrent seizures that are not well controlled by medications, and the lesions are often in the temporal lobe and may also have calcification on imaging. Brain metastases are sometimes similar to brain abscesses on MRI and can be easily confused, but DWI of MRI can clearly distinguish them. The central pus cavity of a brain abscess is high signal on DWI, whereas the central necrotic area of a brain metastasis is low signal or isosignal on DWI. In addition, PWI and MRS are also helpful in differentiating low-grade glioma from malignant glioma [12]. Above, the diagnostic ideas, differentiation methods and means of some related diseases are provided for difficult occupying lesions in the central nervous system, especially the clinical imaging features of some common occupancy-like diseases are compared meticulously, which may be helpful for clinicians’ work. It is believed that in the future, these experiences and summaries will be further compensated and improved, and clinicians are also welcome to actively summarize their experiences and communicate frequently to facilitate better service to patients.