Diffuse Intrinsic Pontine Glioma (DIPG)

 
 

What is the Condition?

  • Pediatric diffuse intrinsic pontine gliomas (DIPGs) are brain tumors that are diagnosed in children (peak incidence 5-9 years old).  They make up around 10% of all pediatric brain tumors.
  • They are found in the pons (the middle portion of the brainstem), and, grow throughout (“infiltrate”) the pons, taking up at least half of this important structure.  They can grow into other area of the brainstem, and grow into the CSF-filled fourth ventricle next to the pons.
  • DIPGs are tumors that arise from precursors of astrocytes – supportive cells of the brain named for their star-like shape. DIPGs are glial tumors (can be grade I through IV) that arise in the pons of the brainstem.  They are fast growing tumors and tend to behave aggressively. 
  • Recent research has shown that 80% of pediatric DIPGs are driven by mutations in  histone genes H3F3A (H3.3) and HIST1H3B (H3.1), which are proteins scaffolds for DNA.  As these mutations have important implications for tumor behavior, treatment, and prognosis, DIPGs with a histone mutation are pathologically diagnosed as "H3 K27M-mutated diffuse midline glioma."
  • Other important genes that are mutated in DIPG include the ACVR1 gene, which is involved in developmental regulation, the tumor suppressor gene TP53 (p53), and other genes that result in growth and proliferation of DIPG cells, including MYCPDGFRA and PI3KCA . The molecular features of a DIPG may impact tumor prognosis and treatment response.   Current investigational therapies are adapted to these molecular features.

What are the Symptoms?

  • Headaches, changes in swallowing, vision, or facial movement, and changes in sensation or strength of the arms and legs are the most common early symptoms of DIPG. Other symptoms may occur depending on the size and location of the tumor.

How is it diagnosed?

  •  Accurate diagnosis is the single most important factor in creating an effective treatment plan for DIPG.
  •  Diagnosis for DIPG may incorporate:
    •  Imaging of the brain (may or may not include spine) with an MRI
    •  If diagnosis remains uncertain after imaging or if the patient/family is interested in obtaining additional molecular information from the tumor, biopsy of is performed and the tumor sample is examined to confirm diagnosis
    • Spinal tap, or lumbar puncture, to remove a small sample of cerebrospinal fluid (CSF) to assess for tumor cells, is occasionally performed.
    • Diagnosis and management of DIPGs may benefit from determination of tumor driving mutations in the DNA or RNA of the tumor cells through sequencing performed on tumor tissue

What is the Condition?

  • Pediatric high-grade gliomas are brain tumors that are diagnosed in children (peak incidence 6-10 years old, but can be found at any age).  High grade glioma includes the following subtypes, which are diagnosed and treated similarly: anaplastic astrocytoma (grade III) and glioblastoma (grade IV). High-grade gliomas arising in the brainstem have distinct biology and clinical management and are discussed above (DIPG).
  • High-grade gliomas are tumors that arise from precursors of astrocytes – supportive cells of the brain named for their star-like shape. Using a microscope, pathologists grade gliomas based on features such as their ability to divide and invade normal tissue.  High-grade gliomas are faster growing tumors and tend to behave more aggressively than lower grade gliomas.  They usually invade locally (only rarely metastasize to other parts of the brain).
  • High grade gliomas are usually found in different locations based on the age of the patient (childhood high-grade glioma is usually in the deeper structures such as the thalamus, while adolescent high-grade glioma is often in the more superficial cortex).
  • Recent research has shown that pediatric high-grade gliomas are frequently driven by mutations in the DNA of the tumor cells, including the histone gene H3F3A (H3.3), the histone chaperone protein ATRX,  the tumor suppressor gene TP53 (p53), and genes involved in cell growth and proliferation, including CDK4/6,  and PDGFRA . The molecular features of a high-grade glioma may impact tumor prognosis and treatment response.  Current investigational therapies are adapted to these molecular features.

What are the Symptoms?

  •  Headaches, seizures, vision changes, and changes in balance are the most common early symptoms of high-grade glioma. Other symptoms may occur depending on the size and location of the tumor.

How is it Diagnosed? 

  • Accurate diagnosis is the single most important factor in creating an effective treatment plan for high-grade glioma.
  • Diagnosis for high-grade glioma may incorporate:
    • Imaging of the brain and spine with an MRI
    • Biopsy or resection of the tumor and examination to confirm diagnosis of a specific type of tumor
    • Spinal tap, or lumbar puncture, to remove a small sample of cerebrospinal fluid (CSF) to assess for tumor cells.
    • Diagnosis and management of high-grade gliomas may benefit from determination of tumor driving mutations in the DNA or RNA of the tumor cells through sequencing performed on tumor tissue