pRB immunostaining in the differential diagnosis between pleomorphic xanthoastrocytoma and glioblastoma with giant cells

Abstract

Aims: Pleomorphic xanthoastrocytoma (PXA) is a rare circumscribed glioma, characterized by frequent BRAF p. V600E mutation, and classified as grade 2 or 3. Owing to overlapping clinical-pathological features, the histological distinction from glioblastoma (GBM) with giant cells (GCs) is challenging. Based on the high frequency of TP53 and RB1 alterations in the latter, this study aimed to assess the value of BRAF, p53, and pRB immunostainings in the differential diagnosis.

Methods and results: In 37 GBMs with ≥30% GCs and in eight PXAs, we assessed the alterations of 409 cancer-related genes and immunostainings for BRAF, p53, and pRB. GBMs with GCs were TP53-mutated in 30 cases, RB1-altered in 11, and BRAF-mutated in none. PXAs were BRAF-mutated in six cases, TP53-mutated in three, and RB1-altered in none. pRb immunostaining was lost in 25 GBMs (11 RB1-altered and 14 RB1-unaltered), retained in all PXAs and six GBMs, and inconclusive in six GBMs. pRb loss had 100% specificity and 80.6% sensitivity for GBM with GCs. P53 immunostaining was observed in 22 TP53-mutated GBMs and in one TP53-mutated PXA. It showed 87.5% specificity and 60% sensitivity to identify GBM with GCs. BRAF immunostaining corresponded to BRAF mutation status and it had 100% specificity and 75% sensitivity for detecting PXA.

Conclusion: This study shows for the first time that loss of pRB immunostaining is sensitive and specific for distinguishing GBM with GCs from PXA in routine practice. Thus, it could complement an immunohistochemical panel that includes BRAF and p53 immunostainings for the differential diagnosis.

Keywords: RB1; giant cell; glioblastoma; pRB; pleomorphic xanthoastrocytoma.

Figure 1

Clinical‐pathological features, gene alterations, and immuno‐expression of pRB, p53, and BRAF p.V600E in 37 GBMs with GCs and 8 PXA. Samples are sorted by ID number and histological diagnosis. EGB, eosinophilic granular bodies.

Figure 2

Different immunostainings for pRB, p53, and BRAF p. V600E in PXA and GBM with GCs. PXA retains nuclear pRB immunostaining, is negative (<10% stained cells) for p53, and shows cytoplasmic staining for BRAF p. V600E. GBM with GCs is negative for pRB, shows p53 staining, and lacks BRAF p. V600E staining. H&E: ×200 magnification; pRB: ×400 magnification; p53: ×200 magnification; BRAF p. V600E: ×200 magnification.