PMC8769401_01
T2-weighted MRI performed on admission showed a high-intensity area in the pontine lesion (A). Contrast-enhanced T1-weighted MRI revealed a hypointense lesion in the left pons, which did not exhibit enhancement (E). T2-weighted MRI (B) and contrast-enhanced T1-weighted MRI (F) performed after the initial treatment revealed that the size of the lesion had decreased slightly. T2-weighted (C) and contrast-enhanced T1-weighted (G) MRI performed at 48 months after the initial diagnosis showed that the high-intensity area in the pontine lesion had decreased in size. At this point, the 24 courses of adjuvant temozolomide had completed. T2-weighted (D) and contrast-enhanced T1-weighted (H) MRI performed at 57 months after the initial diagnosis revealed a large recurrent tumor in the pons and cerebellum. MRI: magnetic resonance imaging.
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F1
Magnetic resonance imaging (MRI) revealed a high-intensity lesion, extending from the pons to the medulla, on T2-weighted (Fig. 1A). T1-weighted imaging, no enhancement was seen (Fig. 1E). The symptoms were gradually progressive. After initial treatment with local radiotherapy (total dose: 54 Gy/30 fractions) and concurrent (75mg/m2/day, 43 days) temozolomide-based chemotherapy, the tumor decreased in size slightly (Fig. 1B and 1F). TMZ was considered good. Therefore, total of 24 cycles of adjuvant (150-200mg/m2/day, 5 days every 4 weeks) temozolomide were administered, and the size of the tumor significantly decreased (Fig. 1C and 1G). T1-weighted MRI detected a large tumor, extending from the pons to the left cerebellar hemisphere (Fig. 1D and 1H). The left cerebellar lesion was subtotally removed via left lateral suboccipital craniotomy and histologically diagnosed as a glioblastoma, IDH mutant.
A histological examination of the tumor involving hematoxylin and eosin staining demonstrated moderately increased cellularity and mild pleomorphism, and the absence of necrosis and microvascular proliferation (A, x200). Immunohistochemical analysis showed that the tumor was positive for IDH1 R132H (B) and H3K27me3 (C) and negative for H3K27M (D).
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F2
A pathological examination involving hematoxylin and eosin (HE) staining showed moderate proliferation of atypical astrocytes (Fig. 2A). The tumor cells were also immunopositive for H3K27me3 and IDH1 R132H and immunonegative for H3K27M (Fig. 2B-D).
A histological examination of the cerebellar recurrent tumor involving hematoxylin and eosin staining revealed high cellularity, mitosis, microvascular proliferation, and necrosis (A, x200). Immunohistochemical analyses of IDH1 R132H (B), H3K27me3 (C), H3K27M (D), p53 (E), and ATRX (F) expression were performed. The tumor cells were positive for IDH1 R132H (B), H3K27me3 (C), and p53 (E) and negative for H3K27M (D). The loss of nuclear ATRX expression was observed (F). Additionally, the tumor cells were immunopositive for MLH1 (G) and PMS2 (I), immunonegative for MSH2 (H) and MSH6 (J).
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F3
Therefore, glioblastoma, WHO grade IV, was diagnosed, which disagreed with the initial pathological findings (Fig. 3A). The tumor cells were immunopositive for IDH1 R132H, H3K27me3, and p53 and immunonegative for H3K27M and the transcriptional regulator ATRX (Fig. 3B-3F). The tumor cells were immunonegative for MSH2 and MSH6 (Fig. 3G-3J).
DNA sequencing of the IDH1 gene. The IDH1 R132H mutation was detected.
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F4
Although the IDH1 R132H mutation was detected, no other hotspot mutations were found (Fig. 4).