Lee-Fomenib syndrome with bilateral thalamic glioma in one case

Raffaella Messina et al.
of the Department of Basic Medicine, Neuroscience and Department of Sensory Organs, Department of Basic Medicine, Neuroscience and Sensory Organs, Barrioldo Moreau, Italy, reported 1 case of LFS with bilateral thalamic glioma; The article was published in the April 2021 issue
of Neurology International.

——Excerpt from the article chapter

【Ref: Messina R, et al.
Neurol Int.
2021 Apr 22; 13(2):175-183.
doi: 10.
3390/neurolint13020017.
】

Research background

Li-Fraumeni syndrome (LFS) is a rare high penetrance autosomal dominant disease caused by mutations in the TP53 gene, which is easy to induce the early occurrence of a variety of malignancies, such as sarcoma, osteosarcoma, breast cancer and pheochromocytoma, etc.
, and in central nervous system (CNS) tumors, the most common are low-grade glioma, medulloblastoma and choroid plexus carcinoma in children.
and adult high-grade gliomas (HGG
).

Some patients develop multiple tumors
from childhood.

It is estimated that about 10% of children with CNS tumors have underlying cancer susceptibility syndrome, the most common of which is LFS, with a prevalence of 1:5000-20000
.

The diagnosis of LFS requires that the following three criteria or TP53 gene mutation test be positive at the same time: (1) Diagnosis of sarcoma before the age of 45; (2) Have a first-degree relative who was diagnosed with any cancer before the age of 45; (3) Have a first- or second-degree relative
who was diagnosed with any cancer before the age of 45 or diagnosed sarcoma at any age.

The Joppret Revision Standard integrates
the classic standards for LFS test indications.

Raffaella Messina et al.
of the Department of Basic Medicine, Neuroscience and Department of Sensory Organs, Department of Basic Medicine, Neuroscience and Sensory Organs, Barrioldo Moreau, Italy, reported 1 case of LFS with bilateral thalamic glioma; The article was published in the April 2021 issue
of Neurology International.

Research Methods

The child is pregnant at term and is healthy after birth; Swelling
of the left rectus femur appears at 18 months.

The child was given a tissue biopsy with a pathological result of rhabdomyosarcoma, chemotherapy was given, and the tumor
was extensively removed after 9 months.

At 18 months postoperatively, follow-up MRI showed complete resection of the
tumor.

Family histories include the maternal great-grandmother having ovarian cancer and the father's 52-year-old cousin having leukemia, which does not meet the classic diagnostic criteria for LFS
.

At 20 months, the child began to have resting intention tremor of the right upper extremity, and the cranial MRI showed bilateral thalamic malignancy; Stereotactic biopsy results are high-grade gliomas
.

Further immunohistochemical tests were positive for acid gliofibrillar protein (GFAP) and positive for p53 protein; B-RAF, intermuscular mitoprotein, and IDH-1 are all negative
.

H3.
3K27M protein is not expressed
.

The NTRK1 gene fusion transcript is missing, while the NTRK2 gene is present
.

At this time, it is highly suspected that the child's tumor is caused
by a genetic mutation.

Genetic testing was then performed, and the results showed the 7th exon mutation of the TP53 gene, which finally confirmed the diagnosis
of LFS.

The child was unable to undergo surgery and eventually died
two months after receiving 17 radiation treatments.

Results of the study

The authors searched the PubMed and MeSH databases for "Lee-Fomene syndrome" and "pediatric glioma" and obtained a total of 6 cases of pediatric LFS with HGG, and the results showed that the median age of tumor diagnosis was 8 years
.

Of the five children with a history of cancer, 4 had no previous history of other malignancies and 1 had been diagnosed with osteosarcoma
.

Five cases of tumor locations involved the cerebral hemisphere and 1 case involved the thalamus
.

Three children with glioblastoma died, and one patient with glioblastoma survived, but the disease progressed
after 4 months of follow-up.

Two cases were diagnosed with anaplastic astrocytoma, of which 1 died after 17 months and the other was followed for 8 months with no signs
of disease progression.

Studies have shown that the median age of brain tumors in patients with LFS is 16 years old, and about 40% of children develop cancer
at the age of 18.

Thalamus HGG accounts for 13% of HGG in children and has a very poor prognosis
.

The authors reported a child with LFS with bilateral thalamic HGG as the first child, whose family history at the time of the discovery of rhabdomyosarcoma did not show any criteria that could be diagnosed as LFS, so the child was not genetically screened
.

However, according to the new "Joplet Revision Criteria", LFS should be highly suspected when patients are diagnosed with interembryonic degeneration subtypes of rhabdomyosarcoma, while regular cranial MRI screening may become early diagnosis
.

Conclusion of the study

In summary, LFS combined with HGG is extremely rare in the pediatric population and its survival rate is extremely low, especially if
surgery is not possible.

The pathogenesis of LFS combined with HGG has yet to be further studied genetically to seek effective multimodal treatments
.

In addition, this case is also the first case of a child glioma with simultaneous mutations
in the TP53 gene and NTRK2 gene.

The authors hope to conduct in-depth studies of challenging cases in order to provide patients with the best possible treatment options
.