Oral Presentation ESA-SRB-ANZBMS 2024 in conjunction with ENSA

A new indication for BRAF testing: identification of the V600E variant to revise the diagnosis of Rathke’s cleft cyst to papillary craniopharyngioma (#198)

Nicholas G Candy 1 , Esther Quick 2 , Barbara Koszyca 3 , Ian Chapman 4 , David Torpy 4 , Nicholas Vrodos 5 , Stephen Santoreneos 1 , Sunita De Sousa 4 , Edward Mignone 6
  1. Neurosurgery, Central Adelaide Local Health Network, Adelaide, South Australia
  2. Pathology, Flinders Medical Centre, Adelaide, SA
  3. Pathology, Royal Adelaide Hospital, Adelaide, South Australia
  4. Endocrinology, Central Adelaide Local Health Network, Adelaide, SA, Australia
  5. Neurosurgery, Flinders Medical Centre, Adelaide, South Australia, Australia
  6. Central Adelaide Local Health Network, Adelaide, SA, Australia

Aim

The differential diagnosis of cystic sellar/suprasellar lesions include Rathke’s cleft cyst (RCC) and craniopharyngioma (CP) (1). The papillary subtype (pCP) can be difficult to differentiate from RCC due to similar radiological and histological features, but the distinction is vital as RCC are non-neoplastic lesions readily curable by surgery, whereas CP is a locally invasive neoplasm usually necessitating aggressive management(2). 

We aimed to determine whether BRAF testing of RCCs might reveal some of these lesions to in fact be pCP, noting that the BRAF V600E variant  is detectable in ~95% of pCPs(3).

Method

We undertook a retrospective cohort study of all RCCs resected by two pituitary neurosurgeons (SS and NV) over 2001-2023. In cases with sufficient operative specimens, we performed BRAF V600E immunohistochemistry (IHC) using paraffin sections and BRAF next generation sequencing (NGS) using extracted tumour DNA.

Results

Eleven patients had suitable specimens. BRAF IHC was performed in all 11 cases. BRAF NGS was undertaken in 8/11 cases, with insufficient tissue in the remaining 3 cases (Table 1). 

A single case had a diagnosis of RCC revised to pCP through BRAF testing, with equivocal epithelial BRAF IHC staining (Fig1) and confirmation of the V600E variant by NGS. Another patient had positive epithelial BRAF IHC but was negative by NGS. 

Separate to the epithelial findings, all cases unexpectedly exhibited BRAF V600E IHC positivity in adjacent anterior pituitary tissue (Fig2).

Conclusion

BRAF testing has the potential to revise the diagnosis of RCC to pCP, with substantial prognostic and therapeutic implications. This finding is especially timely given the emerging paradigm shift to BRAF inhibitors instead of surgical management of pCPs (4). We accordingly recommend consideration of BRAF testing in RCCs, noting that BRAF V600E staining in anterior pituitary tissue appears to be a normal finding that should not be mistaken for neoplasia.

 

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