PMC10070702_01
T1-weighted contrasted sequences and relative cerebral blood volume MRI sequences of case 1 patient's GB at the time of initial regrowth and presentation to our facility before the re-resection of the de novo disease (A); immediately postoperative result after a near-gross total re-resection (B); 1 week prior to the initiation of chemoradiation with substantial interval disease regrowth appreciated (C); and the time of maximal response with complete disease remission of 6 weeks after the conclusion of radiation therapy and after one cycle of adjuvant TMZ (D).
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An MRI at that time showed substantial enhancing disease regrowth adjacent to the resection cavity, supported by elevated cerebral blood volume and diffusion restriction (Figures 1A1, A2). Given this regrowth, the patient underwent a re-resection 1 week later with a questionable concern for residual disease in the medial resection cavity (Figures 1B1, B2); pathology confirmed the radiographic findings of regrowth and a diagnosis of GB (Figure 2A). Unfortunately, an MRI done 3 weeks later again demonstrated substantial tumor regrowth around the resection cavity (Figures 1C1, C2). An MRI of the head was obtained 6 weeks after the completion of radiation and remarkably demonstrated a complete resolution of the extensive enhancement, associated perfusion, and restricted diffusion previously at the periphery of the left parietal resection cavity (Figures 1D1, D2).
Histology and molecular characteristics of cases. (A) The H&E-stained section from case 1 demonstrates histologic features of a typical high-grade diffuse glial neoplasm, including frequent mitoses and anaplasia. Vascular proliferation and necrosis, grading features diagnostic of GB, were present but not shown. (B) In contrast, an H&E-stained section from case 2 demonstrates a tumor not immediately reminiscent of glioma, with a prominent myxoid background and cells which take on an epithelioid appearance. Florid vascular proliferation is present (arrows). (C) In case 2, the tumor has almost glandular architecture, which is suggestive of metastatic carcinoma. (D) An immunostain for OLIG-2, a marker of glial lineage, nonetheless confirms that the tumor in case 2 is, indeed, glioma. The pathologist diagnosing case 2, given the uncharacteristic appearance of the tumor, felt it necessary to run several confirmatory immunohistochemical markers, including cytokeratins, to rule out entities such as metastatic carcinoma and melanoma. Such prominent myxoid changes have been reported previously in radiation-induced gliomas with molecular characteristics of diffuse pediatric high-grade glioma, H3-wildtype, and IDH-wildtype (scale bars = 100 muM). Chromosomal microarray graphical plots of case 1 (E) and case 2 (F) demonstrating characteristic PDGRA amplification (arrow) and CDKN2A deep deletion (arrowhead). Case 2 has a considerably more complex karyotype with multiple gains, losses, and amplifications.
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T2/FLAIR hyperintense signal, concerning a GB (Figures 3A1, A2). The patient was discharged to our facility where he underwent a craniotomy with subtotal resection 3 days after the initial MRI (Figures 3B1, B2). Pathology was consistent with glioblastoma, IDH-wildtype, and unmethylated MGMT promotor (Figures 2B-D). CDKN2A deep deletion. Chromosomal microarray supported the StrataNGS, identified low-level amplification of PDGFRA, and demonstrated a tetraploid pathology with additional site-specific copy number variations (Figure 2F). One month postoperatively, a pre-therapy MRI of the head revealed increasingly thickened T1 contrast enhancement that was more conspicuous and with new extension posterior to the primary lesion, all demonstrating increased perfusion consistent with postoperative disease growth (Figures 3C1, C2). The T1 contrast-enhanced tumor further decreased 3 months later and was completely resolved 7 months after the completion of radiation (Figures 3D1, D2). The patient maintained functionality during this time and regained minimal right-sided motor function with intensive therapy.
PMC10070702_02
Histology and molecular characteristics of cases. (A) The H&E-stained section from case 1 demonstrates histologic features of a typical high-grade diffuse glial neoplasm, including frequent mitoses and anaplasia. Vascular proliferation and necrosis, grading features diagnostic of GB, were present but not shown. (B) In contrast, an H&E-stained section from case 2 demonstrates a tumor not immediately reminiscent of glioma, with a prominent myxoid background and cells which take on an epithelioid appearance. Florid vascular proliferation is present (arrows). (C) In case 2, the tumor has almost glandular architecture, which is suggestive of metastatic carcinoma. (D) An immunostain for OLIG-2, a marker of glial lineage, nonetheless confirms that the tumor in case 2 is, indeed, glioma. The pathologist diagnosing case 2, given the uncharacteristic appearance of the tumor, felt it necessary to run several confirmatory immunohistochemical markers, including cytokeratins, to rule out entities such as metastatic carcinoma and melanoma. Such prominent myxoid changes have been reported previously in radiation-induced gliomas with molecular characteristics of diffuse pediatric high-grade glioma, H3-wildtype, and IDH-wildtype (scale bars = 100 muM). Chromosomal microarray graphical plots of case 1 (E) and case 2 (F) demonstrating characteristic PDGRA amplification (arrow) and CDKN2A deep deletion (arrowhead). Case 2 has a considerably more complex karyotype with multiple gains, losses, and amplifications.
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T2/FLAIR hyperintense signal, concerning a GB (Figures 3A1, A2). The patient was discharged to our facility where he underwent a craniotomy with subtotal resection 3 days after the initial MRI (Figures 3B1, B2). Pathology was consistent with glioblastoma, IDH-wildtype, and unmethylated MGMT promotor (Figures 2B-D). CDKN2A deep deletion. Chromosomal microarray supported the StrataNGS, identified low-level amplification of PDGFRA, and demonstrated a tetraploid pathology with additional site-specific copy number variations (Figure 2F). One month postoperatively, a pre-therapy MRI of the head revealed increasingly thickened T1 contrast enhancement that was more conspicuous and with new extension posterior to the primary lesion, all demonstrating increased perfusion consistent with postoperative disease growth (Figures 3C1, C2). The T1 contrast-enhanced tumor further decreased 3 months later and was completely resolved 7 months after the completion of radiation (Figures 3D1, D2). The patient maintained functionality during this time and regained minimal right-sided motor function with intensive therapy.
T1-weighted contrasted sequences and relative cerebral blood volume MRI sequences of case 2 patient's GB at the time of initial diagnosis (A); immediate postoperative results following a subtotal resection (B); 1-month postoperative results prior to the initiation of radiation with evidence of substantial persistent disease with the evidence of interval progression (C); and the time of maximal response in the brain with complete disease remission 7 months after the conclusion of radiation therapy (D).
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T2/FLAIR hyperintense signal, concerning a GB (Figures 3A1, A2). The patient was discharged to our facility where he underwent a craniotomy with subtotal resection 3 days after the initial MRI (Figures 3B1, B2). One month postoperatively, a pre-therapy MRI of the head revealed increasingly thickened T1 contrast enhancement that was more conspicuous and with new extension posterior to the primary lesion, all demonstrating increased perfusion consistent with postoperative disease growth (Figures 3C1, C2). The T1 contrast-enhanced tumor further decreased 3 months later and was completely resolved 7 months after the completion of radiation (Figures 3D1, D2). The patient maintained functionality during this time and regained minimal right-sided motor function with intensive therapy.
T1-weighted fat-saturated post-contrast sequences of the lumbar spine for the patient in case 2 immediately following radiation to the brain lesion (A); 7 months later following the development of new lower back pain which revealed leptomeningeal drop metastases at the level of T12 extending to the terminus of the thecal sac (T12 to L3 predominant lesions represented graphically) (B); approximately 2 months after the completion of 30 Gy of radiation in 10 fractions to T10-S4 with a significant reduction in lesion size (C); and approximately 4 months after the completion of spinal radiation (D).
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T12 extending to the terminus of the thecal sac 7 months after the completion of brain radiation (Figure 4B). T10-S4 was treated with radiation to 30 Gy in 10 fractions with significant disease response observed on MRI 2 months later (Figure 4C). New cervical and thoracic leptomeningeal drop metastases outside the prior radiation field were observed 2 months later in previously non-irradiated regions as well as slightly increased conspicuity of several previously treated lumber lesions, most notably at the L2 level (Figure 4D).