Tumors & Cysts

Astrocytomas

• • A slow-growing astrocytic tumor composed of bipolar “hair-like” (pilocytic) cells.
  • Most common glioma in children.
  • Associated with tuberous sclerosis, neurofibromatosis type 1 (NF1), and Li-Fraumeni syndrome.
    • Optic nerve and chiasm glioma are associated with NF1.
  • Often presents with symptoms of increased ICP (headache, nausea/vomiting), vision loss, ataxia, or cranial nerve deficits depending on location.
  • Imaging: Cystic mass with a contrast rim-enhancing nidus or mural nodule with minimal vasogenic edema, dorsally exophytic. Most commonly found in the cerebellum.

    • Also prefers midline structures such as the brainstem, optic chiasm, hypothalamus, and deep gray matter (basal ganglia).

      

  • KIAA1549-BRAF gene fusion is characteristic of this tumor type.

• • 90% 10-year overall survival. It can be treated with surgical resection alone, and rarely progresses to malignant glioma.
  • Classic patient presentation: child presenting with increased ICP/ataxia found to have a cerebellar cystic mass lesion with enhancing mural nodule.

• Subependymal giant cell astrocytoma (SGCA or SEGA)

  • WHO grade 1 tumor almost exclusively seen in pediatric patients with tuberous sclerosis (TS) and before the age of 20.
    • Seen in 5-15% of patients with TS.
  • Often asymptomatic, but when symptomatic presents with obstructive hydrocephalus due to location in the foramen of Monro.
  • Imaging: Well circumscribed, partially-calcified intraventricular contrast-enhancing mass near the foramen of Monro.

    

• • Generally treated initially with mTOR inhibition with everolimus.
    • If acute symptomatic or growing, can be treated with surgical resection.
  • Tuberous Sclerosis Review: classically presents with seizures, mental retardation, and adenoma sebaceum. Associated with TSC2/tuberin (most cases) or TSC1/hamartin with cortical or subependymal tubers, hamartomas, renal angiomyolipomas, and cardiac rhabdomyomas.

• Pleomorphic xanthoastrocytoma (PXA)

  • Found in young patients who present with temporal lobe epilepsy.
  • Imaging: Supratentorial peripheral cystic and contrast-enhancing mass abutting the leptomeninges with enhancing dural tail sign and scalloping of overlying bone.

• • Associated with BRAFV600E mutations and homozygous CDKN2A/B deletions.
  • Treated with surgical resection. However, local recurrence and malignant transformation are common so post-operative radiation is indicated for grade 3 tumors.

• Adult-type diffuse gliomas

  • • Astrocytoma, IDH-mutant (grades 2-4)
      • Patients present with progressive neurologic symptoms dependent on tumor location and/or with seizures.
      • Imaging: T2-FLAIR mismatch sign often present, with T2 hyperintensity and relative hypointensity on FLAIR sequences.
        • MR Spectroscopy will have an elevated choline peak, low NAA peak, and elevated choline:creatinine ratio.
      • Pathology:
        • Grade 2: mitotic activity absent or low without microvascular proliferation, necrosis, or genetic markers that would upgrade the tumor (homozygous deletion of CDKN2A/B).
        • Grade 3:  mitotic activity present without microvascular proliferation, necrosis, or genetic markers that would upgrade the tumor.
          • Formally known as anaplastic astrocytoma.
        • Grade 4: microvascular proliferation, necrosis, or genetic markers that would upgrade the tumor present.
    • Glioblastoma, IDH-wildtype (grade 4)
      • Formally known as glioblastoma multiforme (GBM).
      • The most common and also most destructive of the diffuse gliomas.
      • Imaging: Contrast ring-enhancing lesions with significant vasogenic edema. Lesions can also have internal necrosis and can extend through the corpus callosum (butterfly lesion).

• • • • Genetics:
        • IDH-1/2 mutations are associated with secondary GBM arising from a lower-grade glioma.
        • Tumors without microvascular proliferation or necrosis can still be classified as “molecular” glioblastoma if genetic testing shows TERT promotor mutation, EGFR gene amplification, or gain of 7/loss of 10 chromosome copy number alterations.
      • Pathology: Cells with increased mitotic activity with pseudopalisading necrosis and microvascular endothelial proliferation.

• • • • Treatment: Maximal safe resection followed by intensity-modulated radiation therapy (IMRT) plus concomitant temozolomide (alkylating chemotherapy) followed by adjuvant temozolomide.
        • Methylation of the MGMT gene is associated with better treatment response to temozolomide.
        • Bevacizumab, a monoclonal antibody that inhibits vascular endothelial growth factor (VEGF)  can be used in recurrent or progressive GBM.
        • Another alkylating agent, lomustine, is often used as a second-line treatment or in recurrent gliomas.

Table of High-Yield Gliomas:

CharacteristicWHO GradeCell of OriginTypical AgeLocationImagingKey Molecular MarkersMGMT StatusHistologyPrognosisTreatment

Pilocytic Astrocytoma (Grade 1)	Diffuse Astrocytoma (Grade 2)	Anaplastic Astrocytoma (Grade 3)	Glioblastoma (Grade 4)
1	2	3	4
Astrocytes	Astrocytes	Astrocytes	Astrocytes
Children, young adults	30-40 years	40-50 years	50-60 years
Cerebellum, optic pathway	Cerebral hemispheres	Cerebral hemispheres	Cerebral hemispheres
Cystic mass with enhancing nodule	T2/FLAIR hyperintense, non-enhancing	T2/FLAIR hyperintense, may enhance	Enhancing mass with necrosis and edema
BRAF-KIAA1549 fusion	IDH mutation, ATRX loss	IDH mutation, ATRX loss	IDH wildtype (primary), EGFR amplification
Not typically assessed	Often methylated	Often methylated	Variable
Biphasic (compact and loose areas), Rosenthal fibers	Low cellularity, no mitoses	Increased cellularity, mitoses	High cellularity, mitoses, necrosis, microvascular proliferation
Excellent, often curable	5-year survival: 65-70%	5-year survival: 25-30%	Median survival: 12-15 months
Surgery alone often curative	Surgery, RT if progression	Surgery, RT, +/- chemotherapy	Surgery, RT, chemotherapy (TMZ)

Abbreviations: IDH: Isocitrate dehydrogenase, ATRX: Alpha-thalassemia/mental retardation syndrome X-linked, EGFR: Epidermal growth factor receptor, MGMT: O6-methylguanine-DNA methyltransferase
RT: Radiation therapy, TMZ: TemozolomidePilocytic astrocytoma (PA)