IDH1-mutant primary intraventricular gliosarcoma: Case report and systematic review of a rare location and molecular profile

Abstract

Background: Gliosarcoma (GS) is classified as an IDH-wild-type variant of glioblastoma (GBM). While GS is already an unusual presentation of GBM, IDH1-mutant cases are especially rare. We present an IDH1-mutant primary intraventricular GS case report and a systematic review of the molecular profile in GS correlating to the prognostic and pathogenesis of IDH1/2 mutations.

Case description: A 44-years-old man presented with ongoing fatigue symptoms and a new-onset intense occipital headache. The patient complained of memory loss, dyscalculia, and concentration difficulties. An MRI revealed a bihemispheric intraventricular mass crossing the midline through the corpus callosum and infiltrating the trigone of the lateral ventricles, hypointense, and hyperintense on the T1- and T2-weighted image. We performed a microsurgical resection with a transparietal transsulcal approach; however, the contralateral mass was attached to vascular structures and we decided to reoperate the patient in another moment. The histopathological study showed a Grade IV tumor and the immunohistochemistry confirmed the diagnosis of GS. The patient presented progressive neurologic decline and died 45 days after the surgical approach.

Conclusion: We did two systematic reviews studies from PubMed, EMBASE, MEDLINE, Cochrane, and SCOPUS databases, and included molecular and intraventricular studies of GS. We performed further meta-analysis using OpenMetaAnalyst™ software. We conducted a forest plot with the molecular profile of GS. When correlated IDH1 mutation versus tp53 mutation, we found an odds ratio (OR) of 0.018 (0.005-0.064) and P < 0.001. Moreover, we compared IDH1 mutation versus MGMT methylation (P = 0.006; OR = 0.138 [0.034-0.562]). The studies evaluating the molecular profile in GS prognostics are often extended from all GBMs despite specifics GBM variants (i.e., GS). We found a correlation between IDH1 mutation expression with tp53 and MGMT expression in GS, and future studies exploring this molecular profile in GS are strongly encouraged.

Keywords: Case report; Cerebral ventricle neoplasms; Gliosarcoma; Human IDH1 protein; Systematic review.

Figure 1:

Preoperative MRI dated 1 month before surgery. (a) Axial T1WI MRI showing extensive amorphic heterogeneous mass invading both lateral ventricles with a commitment of midline. (b) Axial T1WI Gd MRI demonstrates the same lesion with ring and internal enhancement. (c) Coronal T1WI Gd MRI showing better the internal enhancement and commitment of both lateral ventricles. (d) Axial T2WI MRI exhibiting heterogeneous intratumoral signal and irregular-margin enhancement. Note hypointense signal surrounding the lesion suggesting extensive vasogenic edema. (e) Axial DWI shows nonimpaired diffusion. (f) ADC Map demonstrating high signal.

Figure 2:

Immediate postoperative Control MRI. (a-c) T1WI Gd MRI exhibiting residual mass on the left ventricle atrium. (d-f) T2WI MRI demonstrating residual mass on the left ventricle atrium. The inclusion criteria in our first systematic review were case series studies with at least ten patients containing GS with molecular profile study (IDH1/2, ATRX, tp53, TERT, 1p19q, or Ki-67). Cases series without any molecular profile were excluded from the study.

Figure 3:

(a) Sarcomatous component, with marked pleomorphic spindle cells and mitotic activity (H and E, ×10). (b) Glial component, presenting hypercellularity, pleomorphism, mitotic figures, and nuclear atypia (H and E, ×20). (c) Glial component. Featuring hypercellularity, a high degree of anaplasia, presence of bizarre multinucleated cells, nuclear atypia, and evident mitotic figures (H and E, ×40). (d) Sarcomatous component, presenting mitotic figures, and nuclear atypia (H and E, ×20).

Figure 4:

Immunohistochemical stains. (a) Focal positivity for GFAP, only in glial component (×10). (b) IDH was positive in the glial component (×10). (c) SMA (Smooth Muscle Actin) was positive in the sarcomatous component (×10). (d) Partial loss of ATRX expression (intact) in tumor cells (×10). (e) S100 was positive in the glial component (×10). (f) Vimentin was positive in the sarcomatous component (×20). (g) Diffuse positivity for p53 stain - approximately 80% of neoplastic cells (×10). (h) Ki-67 stain showed more than 60% proliferative activity in the tumor nuclei - 35% of neoplastic cells (×10). (i) Gomori silver stain highlights reticulin, negative in the glial component, and positive in the sarcomatous component.

Figure 5:

Postoperative MRI one month after surgery. (a-c) Axial T1WI Gd MRI showing notorious residual lesion growth.

Figure 6:

PRISMA 2009 flow diagram – Gliosarcoma molecular profile study.

Figure 7:

PRISMA 2009 flow diagram – Gliosarcoma intraventricular location.

Figure 8:

Forest plot of the molecular profile of gliosarcoma. (a) IDH1 versus p53. (b) IDH1 versus MGMT.