The prognosis of Diffuse midline gliomas, H3 K27-altered was poor, even if histopathology showed WHO grade II or grade III, which was the same as that of grade WHO IV gliomas. Therefore, Diffuse midline gliomas, H3 K27-altered are classified as WHO grade IV regardless of their histopathological manifestations [1].
The age of the patients and location of the tumors
Diffuse midline glioma, H3K27-altered often occurs in children and adolescents, with few cases in middle-aged and elderly individuals, and there is no significant sex difference [7]. This group of patients was consistent with previous studies. Diffuse midline gliomas, H3 K27-altered are commonly found in the thalamus, brainstem and spinal cord [8]. Other rare sites include the third ventricle, hypothalamus, pineal region, cerebellar hemisphere and so on [9]. This group of patients showed that the location of the diffuse midline gliomas, H3 K27-altered was significantly different from gliomas in the midline without H3 K27-altered. This is consistent with previous studies. In this group of patients, brain tissue outside the midline structure was involved in both the H3 K27-altered group and the no H3 K27-altered group, indicating that diffuse midline glioma is not limited to only the midline area [10].
The clinical manifestation of diffuse midline glioma is related to its location but not to the type of tumor. Infratentorial tumors are often characterized by motor and sensory abnormalities, ataxia, cerebral neurological symptoms and so on. Supratentorial tumors often have symptoms such as increased intracranial pressure, hemiplegia, and blurred vision. The clinical manifestations of the Diffuse midline gliomas, H3 K27-altered and gliomas without H3 K27-altered included blurred vision, limb weakness, limb numbness, strabismus, headache, dizziness, facial paralysis, unstable walking and so on, [11].
MR findings
In this group of patients, the Diffuse midline gliomas, H3K27-altered had regular shape and clear boundary when the tumors only located in the midline area, but the shape of the masses was irregular, and the boundary was not clear, when they invaded the extramidline tissues. However, gliomas without H3 K27-altered did not have this imaging feature. This feature has not been reported in previous studies, and its mechanism is not clear. It is speculated that this may be because Diffuse midline gliomas, H3K27-altered originate from the midline, so most of the gliomas confined to the midline are in the early stage or are weakly invasive, while the gliomas involving structures outside the midline are mostly in the late stage or have strong infiltration. This needs to be further studied. In this group, the “basilar artery wrapped sign” was only found in patients with Diffuse midline gliomas, H3 K27-altered. This sign is most common in high-grade gliomas located in the pons [12]. Therefore, if there is a “basilar artery wrapped sign”, it indicates that the tumor has a high degree of malignancy, and the possibility of Diffuse midline gliomas, H3 K27-altered should be considered.
Similar to that of other high-grade gliomas, the signal intensity of most Diffuse midline gliomas, H3 K27-altered is often uneven. The cystic part of the tumor showed obvious low signal intensity on T1WI and high signal intensity on T2WI, while the solid part of the tumor showed slightly low signal intensity on T1WI and slightly high signal intensity on T2WI. The tumor is prone to cyst degeneration, necrosis and hemorrhage [9], which may be related to the rapid growth of the tumor or to ischemia, hypoxia or other reasons. we found that Diffuse midline gliomas, H3 K27-altered were prone to cyst degeneration and necrosis as gliomas without H3 K27-altered. We found that the Diffuse midline gliomas, H3K27-altered which only located in the midline area had less cyst degeneration and necrosis, but when they invaded the extramidline tissues, the tumors had more cystic degeneration and necrosis, and the cystic degeneration and necrosis always only located in the extramidline region of the tumor. The reasons for this phenomenon need to be further studied.
After enhancement, the enhancement range of diffuse midline gliomas is different, which can only be shown as spot enhancement, circular enhancement, and obvious enhancement in large patches [9]. The enhancement degree of Diffuse midline gliomas, H3K27-altered was lower than that of no H3 K27-altered midline glioma. This is different from the enhancement of high-grade gliomas, which are often significantly enhanced [13]. The peritumoral edema of Diffuse midline gliomas, H3K27-altered was not obvious, and some did not have edema at all. This may be because the tumor is classified as WHO grade IV, but the histopathological features of some tumors are the same as those of WHO grade I and II tumors, and peritumoral edema is closely related to the pathological classification of tumors [14]. The vascular endothelium and intercellular connections of low-grade gliomas are relatively close, while the endothelial cells of high-grade gliomas are dysplastic and loosely connected; the higher the malignant degree of tumor cells is, the more immune and inflammatory factors secreted, thus aggravating brain edema. At the same time, high-grade gliomas grow faster, peritumoral edema will further oppress the surrounding brain tissue, and the venous reflux of the peritumoral tissue will be blocked, thus aggravating the degree of peritumoral edema [15, 16]. This group of patients showed that the peritumoral edema in the Diffuse midline gliomas, H3 K27-altered was mild or there was not edema, and the degree of peritumoral edema was significantly milder than that of gliomas without H3K27-altered, this was consistent with previous studies.
DWI can evaluate tumor tissue structure from the microscopic level, and the ADC value can better reflect the degree of tumor cell density and cell edema, which is highly consistent with the malignant degree of tumors, so it can predict the glioma grade [17]. we found that the ADC value of the tumor and its ratio to the normal brain tissue of Diffuse midline gliomas, H3 K27-altered were lower than those of gliomas without H3K27-altered. This reflects the dense cells, high nuclear/cytoplasmic ratio and high degree of malignancy of Diffuse midline gliomas, H3 K27-altered, which is in accordance with the histological characteristics of high-grade gliomas. Therefore, the ADC value can be used as a reference index for the diagnosis of Diffuse midline gliomas, H3 K27-altered.
In conclusion, for patients with gliomas in the midline area, those with H3K27-altered are younger in age. Compared with gliomas without H3 K27-altered, Diffuse midline gliomas, H3K27-altered are more likely to occur in the thalamus and brainstem. When the Diffuse midline gliomas, H3K27-altered only located in the midline area,,they often have regular shapes,, clear boundaries, and less cyst degeneration and necrosis. But when they invaded the extramidline tissues, the tumors often have irregular shape and unclear boundary and have more cystic degeneration and necrosis, in addition, the cystic degeneration and necrosis always only located in the extramidline region of the tumor. However, gliomas without H3 K27-altered did not have such imaging feature. Compared with gliomas in the midline without H3 K27-altered, H3K27M-mutant diffuse midline gliomas have less peripheral edema and less enhancement. The “basilar artery wrapped sign” is often seen in H3K27M-mutant midline gliomas located in the pons. The ADC value is helpful for preoperative tumor grading,
Treatment and prognosis
At present, the treatment of Diffuse midline gliomas, H3K27-altered is mainly surgery, radiotherapy and chemotherapy. In recent years, there have been an increasing number of studies on gene targeting therapy, and some of these approaches have been used in the clinic [18], Some studies have shown that ONC201, a small molecule selective antagonist of dopamine receptor D2/3 (DRD2/3), may be effective for Diffuse midline gliomas, H3K27-altered [19]. The prognosis of patients with Diffuse midline gliomas, H3K27-altered is poorer than that of patients with glioma without H3 K27-altered [20]. This group of patients also showed that the survival time of Diffuse midline gliomas, H3K27-altered was significantly shorter than that of gliomas without H3 K27-altered, which was consistent with previous studies. Feng et al. [21] found that the prognosis of Diffuse midline gliomas, H3 K27-altered in different anatomic sites was different, and the prognosis of patients with Diffuse midline gliomas, H3K27-altered in the brainstem was worse than that in those with gliomas in the thalamus. This feature was not found in this group of patients, which may be related to the small sample size. However, Karremann et al. [22] found that H3K27M gene mutation was the only factor for poor prognosis in Diffuse midline gliomas, H3K27-altered and had nothing to do with the location, tumor grade or extent of involvement. Therefore, some scholars suggest that H3K27M mutation detection should be performed for all gliomas in the midline region in addition to histopathology and routine immunohistochemical detection [23].
Limitations of this study:The number of cases in this study is relatively small, and some imaging features still need to be verified by large samples of cases.Some features,like the degree of enhancement, were assessed by the observer subjectively. Therefore, there may be some slight inaccuracies. The volume of tumors was calculated by formula, the automatic method is not used. Although this method is convenient for clinical application, its accuracy is not as good as the automatic method.