With the advent of affordable and accessible genomic sequencing, molecular and genetic
information have become cornerstones in the diagnosis and treatment of brain tumors.
Craniopharyngiomas have two histologically distinct subtypes: papillary and adamantinous.
Studies show that 90% of papillary craniopharyngioma contain BRAF V600E mutations,
providing a molecular marker for pharmacological targeting. A phase II trial of BRAF
V600E+ papillary craniopharyngioma treated with BRAF/MEK inhibitors showed 94% response
rate and 91% tumor volume reduction. During resection of craniopharyngioma, disruption
of the pituitary/hypothalamic axis is often inevitable, requiring permanent hormone
replacement. Determination of tumor genotype prior to proceeding with surgical resection
can alter the treatment options and quality-of-life outcomes. Despite interest in
the development of “liquid-biopsy” for noninvasive preoperative detection and diagnosis
of CNS tumors, results thus far have been unsuccessful.
We present the case of a 29-year-old female with chronic headaches and progressively
worsening left lower quadrant vision loss, found to have a 3-cm solid contrast-enhancing
suprasellar mass encasing the pituitary stalk concerning for craniopharyngioma ([Fig. 1]). The absence of calcification and cystic components in the mass were suggestive
of papillary craniopharyngioma.
Fig. 1: Coronal and sagittal post-contrast MRI sequences.
A standard endoscopic endonasal approach was pursued for trans-tuburcular biopsy of
the suprasellar mass. The bone over the tuberculum was removed for a planned minimal
dural opening. The tumor was visualized with the infundibulum draped over the anterior
aspect. We dissected along the left side of the stalk to gain access for safe biopsy
([Fig. 2]). The biopsy was performed using cup forceps and sent for permanent pathology and
ultra-rapid BRAF PCR analysis. In approximately 15 minutes the PCR resulted as positive
suggesting a BRAF positive papillary craniopharyngioma. As a result the decision was
made to close and not resect further. The skull base was repaired using an alloderm
plug and nasoseptal flap. The patient was noted to have normal pituitary function
on testing postoperatively and discharged home on POD 3 with no supplementation necessary.
She began BRAF-MEK inhibitor therapy POD 14.
Fig. 2 Intraoperative image of suprasellar lesion. Pituitary stalk (yellow arrow) and tumor
(blue arrow) visualized.
Bead homogenization in the presence of a detergent-free DNA extraction buffer was
used to lyse the cells. The cells were incubated at 98°C for 2.5 minutes and centrifuged
to isolate DNA from associated proteins and cellular debris. An ultra-rapid ddPCR
based assay was used to determine the mutational status intraoperatively. Standard
histopathological analysis using H&E and immunohistochemistry were performed on permanent
pathology specimen for confirmation.
Ultra-rapid ddPCR assay was positive for BRAF V600E mutation. These findings were
corroborated by H&E and standard immunohistochemistry ([Fig. 3]).
Fig. 3 Immunohistochemistry staining for BRAF V600E mutation.
Through the use of an intraoperative ultra-rapid PCR, we identified a BRAF V600E mutation
within minutes, confirming the diagnosis of papillary craniopharyngioma. Further surgical
resection was aborted in lieu of medical therapy and pituitary function was preserved.
The use of ultra-rapid PCR for BRAF mutation detection presents an innovative approach
for intraoperative diagnosis of papillary craniopharyngioma, with profound treatment
implications.
