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CC BY 4.0 · J Neurol Surg Rep 2025; 86(04): e253-e259
DOI: 10.1055/a-2751-8340
Original Report

Transformation Versus Ascertainment Bias of a Suprasellar Lesion: A Histopathologic Conundrum of BRAF V600E Positive Papillary Craniopharyngioma Versus Rathke's Cleft Cyst with Squamous Metaplasia: A Systematic Review

Authors

  • Hailey Mattheisen 

    1   Department of Neurosurgery, Medical College of Wisconsin and Froedtert Hospital, Wauwatosa, Wisconsin, United States

  • Samon Tavakoli

    1   Department of Neurosurgery, Medical College of Wisconsin and Froedtert Hospital, Wauwatosa, Wisconsin, United States

  • Edward Kelly Mrachek

    2   Department of Pathology, Medical College of Wisconsin and Froedtert Hospital, Wauwatosa, Wisconsin, United States

  • Stephanie Cheok

    1   Department of Neurosurgery, Medical College of Wisconsin and Froedtert Hospital, Wauwatosa, Wisconsin, United States

  • Nathan Zwagerman

    1   Department of Neurosurgery, Medical College of Wisconsin and Froedtert Hospital, Wauwatosa, Wisconsin, United States
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Abstract

Background

Differentiating craniopharyngiomas (CPs) from Rathke's cleft cysts (RCCs) is challenging due to overlapping features. RCCs with squamous metaplasia (SM) may represent a transition to CPs, complicating diagnosis. This study presents a recurrent RCC later confirmed as papillary CP, prompting a systematic review to identify early diagnostic markers. The goal is to improve RCC and CP differentiation, preventing radical resection of true RCCs, and predicting recurrence or transformation to CPs.

Methods

A systematic review was performed with adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Using the PubMed/Medline databases, a search string was created with the keywords “RCC transformation or (RCC and CP) or (RCC to CP) or (RCC to CP) or (Rathke's and CP).” The initial search yielded 489 papers, narrowed by key data points including RCC recurrence with histologic CP confirmation.

Results

The final review included five studies, which detailed cases of initial pathological diagnosis of RCC that were later diagnosed as a CP upon repeat surgery and tissue sampling. Histological examination of primary and secondary surgical resections revealed RCC recurrence with transformation to CPs (two adamantinomatous CPs, two papillary CPs, and one ciliated CP).

Conclusion

RCCs and CPs share overlapping features, complicating preoperative diagnosis and treatment. RCC recurrence with subsequent CP is rare, as our review identified only five recorded cases. Definitive diagnosis requires pathology, though sampling bias poses challenges. Advanced imaging (contrast-enhanced 3D T2-FLAIR MRI) and biomarkers (BRAF V600E, beta-catenin, p53, Ki-67) show promise in improving diagnosis, predicting recurrence, and guiding treatment.

Keywords

CP - RCC - BRAF V600 - histological transformation

Informed Consent

This study was conducted in accordance with institutional and ethical standards of the Medical College of Wisconsin and Froedtert Health System. Institutional Review Board review deemed this study to meet the exemption as it involved retrospective analysis of de-identified data and published literature. Written informed consent was obtained by the patient, outlined in the institutional case section of this paper.




Publication History

Received: 22 April 2025

Accepted: 15 November 2025

Article published online:
10 December 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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