Brachyury Expression in Atypical Teratoid/Rhabdoid Tumor

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, highly aggressive central nervous system tumor of childhood with variable morphologic features, which is characterized by alterations in SWI/SNF complex, such as SMARCB1/INI1 or SMARCA4/BRG1 loss. Poorly differentiated chordoma is the differential diagnosis, particularly in the infratentorial region of older children and the use of brachyury in such conditions is under debate. We investigated the brachyury expression in 44 samples of AT/RT from 40 patients. All AT/RTs except 2 infratentorial tumors were negative for brachyury (2 clones: A-4 and EPR18113). Both brachyury-positive tumors (one diffuse and one patchy expression) involved the clivus of children younger than 2 years old. The DNA methylation profile of one of these tumors showed epigenetic similarity to reference examples of chordoma in 2 public unsupervised and one supervised analysis systems. The second tumor exhibited a classical epigenetic microarray pattern found in samples with degraded DNA. We revised 2 initial AT/RT diagnoses as poorly differentiated chordoma based on the morphology, brachyury expression, topographical features, and methylation profile. Differentiating poorly differentiated chordoma from AT/RT could be challenging; brachyury expression can be useful in diagnosing poorly differentiated chordoma over AT/RT in suitable clinical and radiological settings.