PMC9580084_01
Imaging studies and intraoperative findings. (A) MRI axial T2WI revealed intraparenchymal hemorrhage with mild edematous changes in the right frontal lobe adjacent to falx. (B) MRI axial Gd-T1WI showed a heterogeneously enhancing mass lesion at the medial margin of hematoma. (C) Intraoperative snapshot of the tumor (*), which was soft, reddish, and vascular-rich. No continuity between the tumor and falx was observed. (D and E) MRI Gd-T1WI obtained immediately after the first surgery (D) and 2.5 months later (E). The latter revealed a well-demarcated, homogeneously enhancing relapsed tumor. (F) MRI Gd-T1WI performed after the completion of radiotherapy and 5 cycles of chemotherapy.
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Computed tomography scanning and subsequent magnetic resonance imaging (MRI) T2-weighted images (T2WI) showed intraparenchymal hematoma at the right frontal lobe with surrounding edema (Figure 1A). T1-weighted images (T1WI) revealed an enhancing mass lesion at the medial margin of the hematoma (Figure 1B), indicating a tumorous lesion as the bleeding source. The patient had a prior medical history of uterine myoma and hypothyroidism, and no previous history of severe head injury or cranial irradiation. The intraoperative findings revealed that the tumor mass was fibrous and hemorrhagic; discontinuity between the tumor and falx was confirmed by direct observation (Figure 1C). Because the tumor residue was very small (Figure 1D), a wait-and-see strategy was applied first. MRI T1WI revealed a well-demarcated enhancing lesion, suggesting tumor regrowth (Figure 1E). The patient is doing well and her disease remains stable at 14 months after initiating postoperative treatment (Figure 1F). The cells were immuno-negative for epithelial membrane antigen (EMA), progesterone receptor (PgR), and signal transducer and activator of transcription 6 (STAT6), which indicated inconsistency with meningioma and SFT/HPC (Figure 1C and D). The possibility of glioma, schwannoma, melanoma, and myosarcoma also appeared unlikely because of the negative-staining for glial fibrillary acidic protein (GFAP), S-100 protein, human melanoma black-45 (HMB-45), desmin, and alpha-smooth muscle antigen (alphaSMA) (Figure 1E). The possibility of spindle cell rhabdomyosarcoma was also thought to be low as rhabdomyoblasts or rhabdomyoblast-like cells were not observed morphologically, however, the possibility was not eliminated since we could not assess MyoD1 staining with this case. Although the tumor cells were immune-positive for vimentin, which is consistent with mesenchymal tumors, the marker is non-specific and less helpful for excluding other possible diagnoses (Figure 1F).
Histopathological findings. (A and B) Hematoxylin and eosin staining section of the recurrent tumor at low-(A) and high-(B) magnification. Morphologically, the tumor comprised dense, spindle-shaped cells with hyperchromatic nuclei arranged in interlacing fascicles-like pattern. (C-H) IHC findings. Tumor cells were stained negatively for EMA (C), STAT-6 (D), and alphaSMA (E), while stained positively for vimentin (F). Loss of ATRX expression was noted, consistently with the mutation of the gene (G). Heterogeneously positive staining for MDM2 was observed, reflecting its overexpression (H). Scale bars indicate 200 microm (A) and 50 microm (B), respectively.
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Both tumor tissues comprised dense, spindle-shaped neoplastic cells with hyperchromatic, irregular nuclei, arranged in an interlacing fascicle-like pattern (Figure 2A and B). IHC (Figure 2H). In addition, the CN analysis also revealed the loss of heterozygosity (LOH) of chromosome 22q which contains the NF2 gene locus. ATRX mutation was validated by IHC, showing loss of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) expression (Figure 2G). In particular, the presence of ATRX mutation further minimized the possibility of meningioma, since the mutation has been reported to be extremely rare in the disease. Any other mutations diagnostically critical or typical for meningiomas and SFT/HPC were not detected.
DNA methylation array data analyses. (A), CN analysis revealed aberrant chromosomal instability accompanied by MDM2 (12q15) amplification and chromosome 22q loss. (B), Unsupervised clustering of the combined cohort (present case, n = 1; mesenchymal tumors from DKFZ-CNS-MES cohort, n = 198; and TCGA-SARC cohort, n = 206) using t-SNE dimensionality reduction. Individual samples are shape/color-coded based on histological diagnosis. The present case was plotted closely to the cases with DDLPS and ULMS.
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On the other hand, the copy number (CN) variation profile elucidated aberrant chromosomal instability, including murine double minute 2 (MDM2) (12q15) amplification (Figure 3A).