PMC8769414_01
Coronal T1-weighted MR images with contrast enhancement before (A) and after (B) surgery. Two weeks after surgery, the enhancing mass lesion was increased (C). After initial chemoradiation therapy, the enhancing mass lesion was decreased (D). An enhanced CT image (E) showed several nodular metastases in axial slices of both lungs (yellow arrowheads). Sagittal T1-weighted spinal MR images (F, G) revealed an enhanced mass lesion at the Th2 level (arrow, F). The surface of the spinal cord was almost enhanced, suggesting cerebrospinal fluid dissemination (white arrowheads, G). Bone metastasis was seen at the L4-5 spinous process (yellow arrowhead, G). After ICE therapy, the metastatic lung lesion and cerebrospinal fluid dissemination were decreased (yellow arrowheads H, arrow I, white arrowheads J). FDG-PET (K) showed accumulation in the lung tumor (arrow and circle). Hilar lymph node also showed increased accumulation (square). CT: computed tomography, FDG-PET: fluorodeoxyglucose positron emission tomography, ICE: ifosfamide, cisplatin, and etoposide, MR: magnetic resonance.
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F1
Magnetic resonance imaging (MRI) revealed a heterogeneously enhanced mass lesion mainly located in the intra-suprasellar region, invading into the bilateral cavernous sinus, pituitary stalk, and hypothalamus (Fig. 1A). It was removed with residual tumor in the lateral portion of the cavernous sinus (Fig. 1B). AT/RT showing a highly cellular component of rhabdoid cells with mitosis. Although her symptoms improved just after surgery, right oculomotor nerve palsy gradually worsened and MRI showed regrowth of the residual tumor (Fig. 1C). The tumor size decreased after chemoradiation therapy (Fig. 1D); however, the computed tomography (CT) scan revealed multiple lesions in bilateral lungs (Fig. 1E). Lung lesions showed accumulation in fluorodeoxyglucose positron emission tomography (FDG-PET) (Fig. 1K) and CT-guided needle biopsy revealed metastasis of AT/RT. A few days later, she presented with bilateral leg pain and gadolinium-enhanced MRI of the spine demonstrated dissemination along the spinal cord and L4-5 spinous process metastasis (Figs. 1F and 1G). After the first cycle of ICE chemotherapy, the metastatic lung tumor and cerebrospinal fluid dissemination were ameliorated (Figs. 1H-1J), but the primary sellar lesion was unchanged.
Photomicrographs of the tumor. (A and B) The tumor was predominantly composed of dense, diffuse proliferation of small- to medium-sized cells with vesicular nuclei that had prominent nucleoli. Thin-walled branching vessels were observed (A). Rare rhabdoid cells were admixed within (B). (C) Immunohistochemistry. Tumor cells were negative for INI1, whereas endothelial cells were positive for INI1 as an internal control (C). (D-F) Systemic pathological autopsy. The tumor could be seen in the lung (red arrow) (D). Metastasis of sellar AT/RT (E) and vascular invasion (F) were detected in lung pathology. Haematoxylin and eosin staining (A, B, E, F). Original magnification: A, C, D, F: 100x; B, E: 400x. AT/RT: atypical teratoid/rhabdoid tumors.
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F2
Histological examination revealed a densely cellular neoplasm, which was composed of small- to medium-sized cells with vesicular nuclei that had prominent nucleoli (Figs. 2A and 2B). Rare rhabdoid cells with eosinophilic cytoplasm including hyaline inclusions, discrete cell borders, and eccentric nuclei (Fig. 2B) were found among other tumor cells with eosinophilic, pale, clear, or vacuolated cytoplasm. Immunohistochemical examination demonstrated that tumor cells were negative for INI1 compared with endothelial cells as a positive internal control (Fig. 2C). Lung pathology demonstrated multiple metastases and vascular invasion (Figs. 2D-2F). Similar to CNS lesions, rhabdoid cells with eccentric nuclei and eosinophilic cytoplasm were observed and were clearly metastasized (Fig. 2E).
Molecular genetic analyses. (A) Multiplex ligation-dependent probe amplification analysis revealed that there are no copy number changes in the INI1 gene and flanking genes. (B) Sanger sequencing detected two different coding sequence mutations; one mutation was c.144 delC in exon 2, and the other mutation was c.819_820 insT in exon 7.
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F3
Two different mutations were detected, presumably on different alleles (compound heterozygous mutations): one mutation was c.144 delC in exon 2, and the other mutation was c.819_820 insT in exon 7 (Fig. 3A). Copy number changes in exons of the INI1 gene and flanking genes were analyzed by multiplex ligation-dependent probe amplification (MLPA) analysis using the SMARCB1 MLPA test kit P258-C1 (MRC-Holland, Amsterdam, The Netherlands), as previously described, and no copy number change was observed (Fig. 3B).