The role of BRAF testing of Rathke's cleft cysts to identify missed papillary craniopharyngioma.

Aim: The differential diagnosis of cystic sellar/suprasellar lesions includes craniopharyngioma (CP) and Rathke's cleft cyst (RCC). Histological differentiation between cystic papillary craniopharyngioma (pCP) and RCC using light microscopy alone is challenging. A major point of difference is that virtually all pCPs are clonal for the BRAF V600E variant, whereas RCCs are not. Noting that BRAF testing of RCCs is not current standard practice, we hypothesised that routinely performing BRAF studies in RCCs might uncover otherwise missed pCPs.

Method: We performed a retrospective cohort study of all RCCs operated on at Flinders Medical Centre, the Memorial and Royal Adelaide Hospitals, between 2001 and 2023. In cases with sufficient tissue, we performed BRAF V600E immunohistochemistry (IHC) and BRAF next generation sequencing (NGS) of extracted tumour DNA.

Results: Of eleven patients with suitable operative specimens, one patient with an initial diagnosis of RCC was revised to pCP following BRAF testing with equivocal positivity on BRAF IHC and clear identification of the V600E variant on NGS. The patient's subsequent clinical course was aggressive and more compatible with pCP than RCC.

Conclusion: This study highlights the potential value of BRAF testing in RCCs to identify missed pCP, which is an especially timely finding given the advent of primary medical therapy with BRAF inhibition for pCP. In the absence of guidelines advising on the use of BRAF studies in sellar lesions, we suggest consideration of BRAF testing of all RCCs, particularly if there is squamous metaplasia or disease recurrence.