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Recently, Margot A.
Lazow et al.
of the State University of New York Northern Medical University reported a rare case of diffuse midline glioma with bone metastasis and suspected lung metastasis in children with H3 K27M mutant type, and analyzed its treatment process and genomics results.
Article published online
in the March 2022 issue of the Journal of Pediatric Hematology Oncology.
—Excerpted from the article chapter
【Ref: Lazow MA, et al.
J Pediatr Hematol Oncol.
2022 Mar; 44(2):e597-e604.
doi:10.
1097/MPH.
0000000000002189.
】
Research background
Pediatric high-grade gliomas (pHGGs) account for 20% of childhood brain tumors; Among them, H3 K27M mutant diffuse midline glioma (DMG) accounts for about 80% of childhood midline gliomas, and the median overall survival is only 10-14 months
.
Extraaxial metastases of HGG in children are rare, especially at the time of first diagnosis
.
Recently, Margot A.
Lazow et al.
of the State University of New York Northern Medical University reported a rare case of diffuse midline glioma with bone metastasis and suspected lung metastasis in children with H3 K27M mutant type, and analyzed its treatment process and genomics results.
Article published online
in the March 2022 issue of the Journal of Pediatric Hematology Oncology.
Research methods
12-year-old female patient, previously healthy
.
He was admitted to hospital
in January for progressive numbness and weakness in both lower extremities, back pain, difecal incontinence, and double vision.
Lumbar puncture showed that the pressure of cerebrospinal fluid was increased (>35cmH₂O), the protein content was increased (180mg/dL), the cerebrospinal fluid white blood cell count was normal, and no tumor cells
were found.
Cranial MRI-T2/Flair imaging showed diffuse hyperintensity in bilateral periventricular white matter, medial temporal lobe, optic chiasm, brainstem, and cerebellum; MRI of the thoracic spine shows multifocal intensified lesions inside and outside the dural (Fig.
1), thickening of the spinal cord; At the same time, multiple skeletal lesions were found, and the pathology of thoracic spine and left iliac lesions was consistent with H3 K27M mutant DMG; H3 K27M mutation-specific immunohistochemistry (IHC) showed strong diffuse positivity (Figure 2).
At the same time, targeted sequencing of patients identified H3F3A mutations, as well as several other pathogenic molecular changes, including amplification of MET, CDK6, EMSY, PIK3CG, and TP53 mutations
.
1.
Intracranial and spinal MRI imaging showing lesions Fig.
2.
Pathological staining of neuraxial and skeletal lesions and immunohistochemical staining of H3 K27M mutations
Research results
MRI imaging of the cranial and thoracic spine 1 month after completion of radiotherapy showed good radiotherapy results, with a significant reduction in abnormal signals in the MRI-T2-Flair sequence, and a reduction
in spinal cord enhancement and swelling.
PET-CT showed multiple highly active foci of FDG in the intramedullary, vertebral body, and pelvis, and found two FDG-rich right lung nodules with suspected lung metastasis (Fig.
3).
Targeted therapy
is given in patients whose bone metastases are confirmed in the presence of suspected genetic alterations in tumor sequencing.
After receiving two cycles of cabozantinib treatment, imaging studies showed a significant decrease in FDG activity in bone metastases and pulmonary nodules, basically stable spinal lesions, but a significant increase
in hyperintensity of intracranial abnormal MRI-T2/FLAIR sequences.
PET-CT images after 1 month showed that the FDG activity of extraaxial metastases was further reduced, but the patient's spinal lesions progressed significantly, MRI upper brain signals were abnormal, accompanied by new focal enhancements, and hemorrhagic intracranial
masses.
Cabozantinib was discontinued, and three weeks later, brain/spine MRI showed significant progress of the entire spine and brain lesions without additional treatment
.
The patient died nine months after the first consultation without an autopsy
.
Figure 3.
PET-CT imaging before and after cabozantinib treatment
Conclusion of the study
In summary, diffuse midline gliomas with H3 K27M mutant in children with bone, pleural, and lung metastases are rare but can occur at the time of recurrence; The probability of occurrence at the first visit is low; May result in a poor prognosis
.
Among them, tumors with H3F3A mutations showed a higher tendency of extraaxial spread, while mutations or amplification of MET, CDK6, EMSY, PIK3CG and TP53 may promote tumor invasion and metastasis
.
Therefore, patients with pHGG, especially adolescents complaining of bone pain, should be evaluated for systemic metastases
as soon as possible.
For patients with pHGG with extraaxial metastases, targeted sequencing is important
to identify the molecular drivers of metastasis and potential therapeutic targets.
