PMC9339260_01
Initial radiological and histopathological images of Case 1. Magnetic resonance (MR) images of the patient studied for medical checkups (A, B). Axial FLAIR image obtained 10 years before when the patient was 48 years old shows no abnormality (A). Axial FLAIR scan at this time showing a hyperintensity lesion in the right hippocampus and uncus (B). MR images taken 4 months after the discovery of the right hippocampal lesion. Axial FLAIR image (C), axial Gd-enhanced T1-weighted image (D), and coronal Gd-enhanced T1-weighted image (E) indicating no enhancement of the hippocampus. Perfusion-weighted axial image showing no aggregation of cerebral blood flow (F). A postoperative FLAIR image indicating removal area containing almost the whole area of the lesion (G). Hematoxylin and eosin staining (H) showing no proliferation of atypical cells. Immunohistochemical staining for Ki-67 (I), original magnification: x40. A result of Sanger sequencing of the specimen (J), showing 27.8% had C250T TERT promoter mutation.
2188-4226-9-0199-g001.jpg
PMC9339260_01_2188-4226-9-0199-g001.jpg
g001
Case 1: A 58-year-old right-handed woman, whose MR imaging was normal 10 years ago (Fig. 1A), was referred to our institution because of a hyperintense lesion on T2-weighted MR images in the right mesial temporal lobe and amygdala detected incidentally (Fig. 1B). Further investigation revealed that it was nonenhancing by Gd and showed no significant elevation of rCBF (Fig. 1C-F). Removal of the hyperintensity area on T2WI was confirmed via immediate postoperative MR imaging (Fig. 1G). Histopathologically, the specimen showed normocellularity, and there was no evidence of atypical cells, indicating nonneoplastic features (Fig. 1H). Immunohistochemically, no positive cells for Ki-67 (Fig. 1I) and p53 were found. The result of the molecular investigation was IDH-wildtype, H3-wildtype, and pTERT mutated (Fig. 1J) (molecular GBM signature), and pMGMT unmethylated.
Radiological and histopathological images after the recurrence of Case 1. An axial FLAIR (A) and coronal Gd-enhanced image (B) showing solid enhanced mass, typical findings of GBM just the same place as the removed lesion at the initial operation. Perfusion image (C) showing elevated blood flow. Hematoxylin and eosin staining showing necrosis (D), microvascular proliferation (E), and proliferation of atypical cells (F), original magnification: x10 (D, E), x40 (F). Immunohistochemical staining for Ki-67 (G), p53 (H), IDH1 (R132H) (I), ATRX (J), original magnification: x40. A result of Sanger sequencing of the specimen (K), showing 17.0% had C250T TERT promoter mutation.
2188-4226-9-0199-g002.jpg
PMC9339260_01_2188-4226-9-0199-g002.jpg
g002
MR images revealed a massive large enhanced mass with high blood flow that had a maximum diameter of 45 mm located in the previous surgical cavity (Fig. 2A-C). This time, a histopathological diagnosis of GBM was made because necrosis, microvascular proliferation, and atypical cells were evident (Fig. 2D-F). Immunohistochemically Ki-67 labeling index was approximately 15% (Fig. 2G), p53 was positive for only a few tumor cells (Fig. 2H), IDH1 (R132H) was negative (Fig. 2I), ATRX was positive (retained) (Fig. 2J), and GFAP was positive (figure not shown). Molecular analysis again revealed a molecular GBM signature that was completely the same as the initial one: IDH-wildtype, H3-wildtype, pTERT mutated (Fig. 2K), and pMGMT unmethylated.
PMC9339260_02
Radiological and histopathological images of Case 2. An MR image taken 8 years before showing multiple deep white matter hyperintensity (A). An MR image taken 1 year before also showing deep white matter hyperintensity (B). MR images showing the emergence of T2WI hyperintensity lesion in the left frontal white matter (C, arrowhead) that are hypointensity in T1WI (D) and not enhanced with Gd (E). MR images 3 months after the operation indicating that the hyperintensity area was elongating toward the corpus callosum (F) but was not enhanced with Gd (G). Note that the removal cavity of the operation is seen in exactly the same loci of the T2WI hyperintensity lesion in C. Histopathological findings indicating a slight increase in cell density in HE (H), and scarce positive cells for Ki-67 staining (I), and negative for p53 (J) and IDH1 (R132H) (K), and positive for ATRX (L). Original magnification: x20 (H, I), x40 (J, K, L). A result of Sanger sequencing of the specimen (M), showing 13.3% had C228T TERT promoter mutation. Radiological images after disease progression of Case 2. Ten months after the operation, images revealed a massive enhanced lesion next to the operative cavity (N, O).
2188-4226-9-0199-g003.jpg
PMC9339260_02_2188-4226-9-0199-g003.jpg
g003
This 50-year-old right-handed woman annually underwent MR imaging as a medical checkup since the FLAIR image detected multiple hyperintensity lesions in the deep white matter 8 years ago (Fig. 3A). The white matter lesions were asymptomatic, and the FLAIR image remain unremarkable until a year ago (Fig. 3B). Nevertheless, this time aggregation of the T2WI/FLAIR hyperintensity area developed in the left frontal white matter (Fig. 3C, arrowheads). Additional imaging showed the lesion was slightly hypointensity in T1WI and was not enhanced with Gd (Fig. 3D and E). The correctness of the surgical removal of the lesion was confirmed by postoperative MR images (Fig. 3F and G). On immunohistochemical analysis, those cells were positive for ATRX, and negative for IDH1 (R132H) and p53, and the Ki-67 labeling index was 0.8% (Fig. 3H-L). In the molecular diagnosis, molecular GBM signature, IDH-wildtype, H3-wildtype, and pTERT mutated (Fig. 3M), and unmethylated pMGMT, was detected. Five months after the operation, elongation of the T2WI hyperintensity tail toward the corpus callosum was detected (Fig. 3F and G). However, during maintenance chemotherapy with TMZ, she got progressive cognitive decline and MR images obtained 10 months after the operation revealed a ring-enhancing lesion in the left frontal lobe (Fig. 3N and O).