Atypical teratoid rhabdoid tumor
Atypical teratoid rhabdoid tumor (ATRT), a WHO grade IV lesion, is a rare and highly aggressive intracranial tumor usually occurring in young children. First identified in 1987, these tumors bear pathological resemblance to malignant rhabdoid tumors of the kidney (9). The central nervous system is the most common non-renal location for rhabdoid tumor, and usually involves the posterior fossa. On MR imaging, most ATRT are hypointense in T1-weighted imaging, has variable T2 signal, and show inhomogeneous contrast enhancement. Presence of central cystic or necrotic areas and calcification is common. Diffusion restriction is usually present, and spectroscopy typically shows elevated levels of choline and decreased N-acetylaspartate. Incidence of hemorrhage is quoted at 40-60%. Altogether, these are features of a high-grade tumor and by themselves not specific for an ATRT. (1)
ATRT is an embryonal tumor consisting of rhabdoid cells admixed with cells resembling medullobastoma, primitive neuroectodermal tumor (PNET), spindle-shaped mesenchyme, and/or epithelial tissue. Recognized as a separate entity by the WHO in 2000, diagnosis is based on the absence of gene products (INI-1) from the tumor-suppressor gene (SMARCB1/INI1/SNF5/BAF47) on chromosome 22q11.2, and/or by the detection of monosomy 22 or deletions/mutations involving this gene segment. The INI-1 protein is a member of the ATP-dependent switching/sucrose non-fermentable (SWI/SNF) complex involved in chromatin remodeling and cell cycle regulation. This protein is generally ubiquitous in the cell nucleus, and the encoding tumor-suppressor gene SMARCB1 is inactivated or lost in most ATRT, a pathognomonic feature also shared with its renal counterpart, and serves as key to distinguish ATRT from PNET or medulloblastoma. (3) (2)
However, the loss of SMARCB1 expression is non-specific and has also been observed in a number of tumors, including epithelioid sarcomas, undifferentiated pediatric sarcomas, myoepithelial carcinoma, and some neuroepithelial tumors. (5) (8) (6) In addition, a rare number of ATRT, despite classic ATRT histological appearances, retains the nuclear expression of the INI-1 protein. In the genetic analyses of such a case, Schneppenheim et al have found another potential causative gene to be SMARCA4/BRG1, which encodes for another protein in the SWI/SNF complex, further supporting the important role of the SWI/SNF complex in the generation of the ATRT histophenotype. (10) The current ISN-Haarlem guidelines recommend that an integrated diagnosis of ATRT be made only in the presence of either INI-1 or BRG1 loss of protein expression or mutation. (7)
ATRT carries a poorer prognosis than PNET or medulloblastoma, and early literature suggests a median survival of 12 months from time of diagnosis to death with standard therapy. More recent reports show possible prolongation of survival using more aggressive therapies involving surgery, chemotherapy with or without stem-cell rescue, intrathecal chemotherapy, and early radiotherapy. (4) Because of its rarity and poor outcome, clear treatment guidelines are still in the process of development.
Contributed by Wai Kiu Tang, Ho Keung Ng, Danny Tat-Ming Chan, Xian Lun Zhu, Wai-Sang Poon