OBJECTIVE: To investigate the clinical manifestations, imaging and pathological features of gliomatosis and to improve the diagnosis and treatment of this disease. METHODS: A retrospective study was conducted on five patients with gliomatosis admitted to our hospital between 1996 and 2001. RESULTS: The main clinical manifestations of this disease were progressive intracranial pressure increase and recurrent seizures, accompanied by varying degrees of intellectual and mental impairment. Pathological examination showed extensive infiltration of tumor cells into the gray and white matter of the cerebral hemispheres, with infiltrative growth mainly around blood vessels and neurons, without forming tumor masses. All five patients underwent craniotomy, and four died and one survived 10 months after surgery. Conclusion: The diagnosis of gliomatosis can be made with reference to clinical manifestations and imaging examinations, and the confirmation of diagnosis depends on pathological examinations. Gliomatosis is a rare primary tumor of the central nervous system characterized by diffuse growth of glial cells in different stages of development. The disease has a complex clinical presentation with no obvious specificity, and the diagnosis is difficult to confirm by clinical manifestations and imaging examinations alone. Since Nevin first proposed the concept of gliomatosis in 1938, there have been few reports in the domestic and international literature. We summarize the medical records of 5 patients admitted to our department in the past 6 years for retrospective analysis, and report them with the relevant literature as follows. 1. Data and methods (1) General data Five patients, four males and one female, aged 23-45 years old, average 36.8 years old. (2) Clinical manifestations The duration of the disease before admission ranged from 2 weeks to 3 years, with a tendency of progressive aggravation. All patients had different degrees of personality changes, mental abnormalities, mental retardation, hemiparesis, damage to the pyramidal tract and cranial nerve damage. (3) Imaging examination The lesions on CT and MRI scans were extensive, with unclear borders, swelling of brain tissue in the affected areas, shallowing or disappearance of the cerebral sulcus, and small ventricles. The lesion was diffusely isointense or slightly hypointense on CT scan, and the enhancement was not obvious; the MRI scan showed high signal on T2-weighted image and isointense or hypointense on T1-weighted image, with partial enhancement or no enhancement. (4) Laboratory tests Cerebrospinal fluid protein was normal or mildly elevated, and white blood cell count was normal. The EEG showed diffuse slow waves and occasional spikes. (1) Surgery All 5 patients underwent craniotomy under general anesthesia. During the operation, we saw shallowing of the cerebral sulcus, widening of the gyrus, swelling and flattening of the gyrus at the lesion site, and the increase of cerebral pressure was not obvious. The tumor was partially resected in 3 cases and sub-temporal muscle decompression was performed at the same time; most of the tumors were resected in 2 cases and sub-temporal muscle decompression was not performed. (2) Pathological examination: Microscopically, astrocytes were widely infiltrated in the gray and white matter of the cerebral hemispheres, and tumor tissues were infiltrating and growing around blood vessels, neurons and under the soft meninges, without obvious tumor masses. The tumor cells were of different stages with small cell volume and small or moderate amount of cytoplasm. The nucleus morphology was complex, and meganucleated tumor cells were seen, with no mitotic activity in the nucleus. (3) Follow-up and prognosis Four of the five patients died within 10 months after surgery, and one male patient with epilepsy as the main clinical manifestation has been maintained on antiepileptic drugs for 10 months after partial resection of the tumor. 3. Discussion Gliomatosis is a rare primary tumor of the central nervous system. Previously, the nomenclature and concepts of this disease were confusing, such as diffuse glioma of the brain, overgrown glioma, diffuse sclerosing germ cell tumor type, diffuse glial systemic overgrowth of brain neurons, central diffuse Chewang’s cell tumor disease, and diffuse astrocytoma [1].Nevin first introduced the concept of gliomatosis in 1938 [2].Scheinker and Evans in 1943 described the disease as diffuse cerebral glioblastomatosis and described it as having diffuse swelling of the general structure of the brain with proliferation of glial cells spreading only in some of the affected neural tissue [3].Kernohan classification is low grade (grade 1-2) glioma [3, 5, 6, 7].The WHO classification criteria for brain tumors in 1993 classify it as In 1999, the WHO classification of neurological tumors reclassified it as a glioma of undetermined origin among neuroepithelial tissue tumors, with a malignancy grade of 3 [13]. There is a long-standing debate about the origin of the tumor. There are three main hypotheses that are in agreement; one is a congenital developmental disorder of the cerebral glial system that causes neuroglial cells to become tumorigenic, resulting in a centrifugal-like diffuse distribution of the tumor. The second is a multicentric tumor distribution. The tumor has a multicentric origin and further centrifugal spread in a diffuse infiltration. Thirdly, the tumor is formed by intrafocal proliferative spread or regional metastatic spread [5,6,7]. Recently, Kattan et al. speculated from the analysis of tumor clones that the tumor may originate from an oligoclonal process or a discordant combination of multiple gliomas [8]. The clinical features of this disease are subacute onset, variable duration, progressive development, and can develop at any age. Initial onset may be without positive neurological signs. The clinical presentation is dominated by psychiatric symptoms, increased intracranial pressure, seizures, and hemiparesis [3, 5, 7, 12]. In Jennins et al.’s review of 160 patients reported in 85 papers, corticospinal tract involvement was found in 58%, hypo-intelligence or dementia in 44%, headache in 39%, epilepsy in 38%, cranial nerve damage in 37%, increased intracranial pressure in 34%, and cerebrospinal involvement in 33% [6]. in 33% of cases [6]. Imaging lesions usually invade more than 2-3 brain lobes. They are mainly located in the frontal lobe, temporal lobe and corpus callosum, and can sometimes involve the basal ganglia, parieto-occipital lobe, brainstem, cerebellum, spinal cord and soft meninges [1, 3, 4, 12]. Lesion sites are predominantly cortical and subcortical white matter damage, and symmetrical diffuse infiltrates adjacent to midline brain structures are more common, with insignificant occupational effects. CT scans show diffuse isointense or slightly hypointense foci that may or may not intensify, CT shows only non-specific diffuse intracranial lesions, which are difficult to accurately reflect the lesions and their extent, and shows a smaller lesion than MRI. T1-weighted images are isosignal or hyposignal, and the tumor is partially enhanced or non-enhanced on enhanced scans [9, 12]. this presentation on MRI may be related to diffuse tumor infiltration and white matter demyelination changes [1, 11, 12]. Pathological examination of the gross specimen showed swelling and widening of the cerebral gyrus at the tumor site and flattening of the cerebral sulcus. The lesion was extensive, with both gray and white matter of the brain involved, and the demarcation between the two was unclear. Microscopically, the tumor cells infiltrated extensively in the gray and white matter, mainly in the blood vessels, perineurons and submural infiltrative growth, without forming local tumor clusters. The tumor cells were generally astrocytic series, and different stages of cells were seen. The tumor cells were small in size, with a small or moderate amount of cytoplasm. The nuclei are morphologically diverse and pleomorphic, with oval, round, spindle, bipolar and polygonal prominence, and meganucleated tumor cells are also seen, with no mitotic activity in the nucleus, and normal neural tissue may be mildly damaged at the site of tumor tissue infiltration [1,9, 12]. Electron microscopy revealed that gliomatosis is a tumor-like process of small, uniform cells, i.e., an excessive form of astrocytes to oligodendrocytes, which are tumor cells at various stages of development originating from astrocytes [10]. The clinical presentation has a tendency to be highly malignant because of the extensive involvement of this tumor and its severe infiltration of normal brain tissue. The diagnosis of this disease should be made by a comprehensive analysis of its clinical manifestations and imaging examinations, and pathological examination is the key to diagnosis. In the differential diagnosis, it should be differentiated from encephalitis, multiple sclerosis, glioma, cerebral leukodystrophy, motor neuron disease, and primary intracranial lymphoma [4, 12]. In the treatment of this disease, a review of the literature and follow-up of the five patients in our group revealed that surgical resection was not effective. Radiotherapy and chemotherapy were not effective, with an average survival of 6-9 months, only 8.8% of patients survived longer than 12 months, and 52% of patients died 12 months after diagnosis [5,6,11]. However, Kim et al. reported 15 patients who received 57GY radiotherapy and survived an average of 38 months except for one death, and concluded that radiotherapy may be an effective treatment [9]. Zhang Yi et al. reported the treatment experience of 13 cases and concluded that the efficacy of radiotherapy after puncture biopsy was significantly lower than that of those who underwent craniotomy, and the analysis concluded that the reasons were that low-grade gliomas were insensitive to radiotherapy and the patients’ diffuse blood-brain barrier was destroyed, and radiotherapy often caused cranial hypertension to aggravate the disease, and suggested that the tumor should be removed under the principle of preserving neurological function as much as possible in craniotomy, and reducing the total number of tumor cells could help improve the radiation effect and at the same time can also relieve cranial hypertension.