Atypical teratoid/rhabdoid tumour

Atypical teratoid/rhabdoid tumours (AT/RT) are uncommon WHO grade 4 tumours, which in the vast majority of cases occurs in young children less than two years of age. It most frequently presents as a posterior fossa mass. AT/RT often resembles medulloblastoma by imaging and even H&E microscopy, and the diagnosis requires cytogenetic analysis of the tissue.

Epidemiology

AT/RTs typically present in very young children (median age is less than 2-3 years ^2,13).

Pathology

Microscopic features

Rhabdoid cells are the hallmark of AT/RT, but only comprise a fraction of the tumour and are not required for the diagnosis provided genetic of DNA-methylation changes are compatible (see below) ¹³.

Other portions of the tumour are indistinguishable on imaging and histology from a medulloblastoma or embryonal tumour with multilayered rosettes.

Genetics

The vast majority (~95%) of AT/RTs have inactivation of both copies of SMARCB1 (also known as INI1, BAF47 or hSNF5). In a small minority of cases (< 5%) it is SMARCA4 (also known as BRG1) that is inactivated ¹³. 

Additionally, AT/RTs can be divided into three subgroups according to DNA-methylation profiling: AT/RT-SHH, AT/RT-TYR, and AT/RT-MYC ¹³.

To make the diagnosis, either SMARCB1 or SMARCA4 mutations or compatible DNA-methylation profiling need to identified ¹³. 

Immunophenotype

Rhabdoid cells usually demonstrate:

• EMA: positive
• vimentin: positive
• SMA (smooth muscle actin): positive

Radiographic features

Atypical teratoid/rhabdoid tumours are usually large and very heterogeneous masses. They may be difficult to distinguish from an embryonal tumour with multilayered rosettes by imaging.

Location

• infratentorial: ~50%
  • cerebellum (most common)
  • brainstem
• supratentorial
  • cerebral hemispheres
  • pineal gland region (see pineal mass differential diagnosis)
  • septum pellucidum
  • hypothalamus

CT

• often isodense to grey matter
• may demonstrate heterogeneous enhancement
• calcification is common
• may show associated obstructive hydrocephalus

MRI

Can show necrosis, multiple foci of cyst formation and sometimes haemorrhage:

• T1: iso- to slightly hyperintense to grey matter (haemorrhagic areas can be more hyperintense)
• T2: generally hyperintense (haemorrhagic areas can be hypointense)
• T1 C+ (Gd): heterogeneous enhancement
• MR spectroscopy
  • Cho: elevated
  • NAA: decreased
• DWI
  • almost all restrict diffusion

Leptomeningeal seeding has been described in up to 15-30% of cases and so post-contrast imaging of the entire neuroaxis should be considered in suspected AT/RTs.

Treatment and prognosis

Surgery with debulking can be offered in some cases. Tumours can demonstrate leptomeningeal dissemination. Clinically AT/RTs have a much poorer prognosis than medulloblastomas, with little if any response to chemotherapy and death usually occurring within a year of diagnosis. 

History and etymology

Primary CNS rhabdoid tumour was first identified as a unique entity in the mid/late 1980s. Prior to this, these tumours were likely misdiagnosed as primitive neuroectodermal tumour/medulloblastoma, as they are relatively similar in microscopic appearance ¹². Early reports variably used the term malignant rhabdoid tumour.

Differential diagnosis

Imaging differential considerations include:

• embryonal tumour with multilayered rosettes particularly for supratentorial AT/RTs
• medulloblastoma
  • tends to occur in an older age group ⁶
  • rarely involve cerebellopontine angle
  • haemorrhage is much less frequently seen than in AT/RTs ⁶
• intracranial teratoma