A 53‐year‐old female with suprasellar mass

Abstract

1. CLINICAL HISTORY

A 53‐year‐old female was admitted with severe headache for 2 months. The visual fields of both eyes were relatively normal. Magnetic resonance imaging (MRI) revealed a solid oval lesion extending from the posterior pituitary lobe along the pituitary stalk into the suprasellar region, anterior thalamus, and interpeduncular space, approximately 26 mm × 24 mm × 15 mm. The lesion was mildly hypointense on T1‐weighted sequences and hyperintense on T2, with significant homogeneous contrast enhancement (Figure 1A,B). The serum levels of prolactin and thyroid stimulating hormone were elevated to 101.86 ng/ml (reference range, 2.74–19.64 ng/ml) and 8.01 μIU/ml (reference range 0.55–4.78 μIU/ml), respectively, with free thyroxine decreased to 0.80 ng/dl (reference range 0.89–1.76 ng/dl). Other routine laboratory tests did not show further abnormalities. An endoscopic endonasal approach was selected for tumor removal. During the surgery, the lesion was found to originate from the pituitary stalk. Some portions, especially toward the floor of the third ventricle and anterior hypothalamus, appeared to be adherent to neighboring structures. Near‐total resection of the tumor was achieved in an effort to protect the hypothalamus and visual function (Box 1).

FIGURE 1.

Head magnetic resonance imaging (MRI) scans showed a homogeneously enhancing sellar mass with suprasellar extension protruding into interpeduncular space (A, sagittal view) and compressing the right thalamus (B, coronal view).

BOX 1. Virtual glass slide.

Access at https://isn‐slidearchive.org/?col=ISN&fol=Archive&file=BPA‐22‐10‐242.svs

2. FINDINGS

Hematoxylin and eosin (H&E) staining showed a highly cellular tumor with nuclear pleomorphism, high mitotic activity (Figure 2A), focal necrosis (Figure 2B), and microvascular proliferation (Figure 2C). The tumor cells express p53, Olig‐2, and glial fibrillary acidic protein (Figure 2D). Nuclear staining for H3 K27M‐mutant is present in tumor cells (Figure 2E), consistent with mutation at position K27 in the histone coding genes (H3‐3A), confirmed by Sanger sequencing. The K27M substitution results in loss of H3K27me3 expression (Figure 2F). The Ki‐67 proliferation index is 60%. In addition, the tumor is isocitrate dehydrogenase‐wildtype by sequencing and O‐6‐methylguanine‐DNA methyltransferase promoter is unmethylation.

FIGURE 2.

The histological features of the lesion. (A) Hematoxylin and eosin (H&E) staining reveals a highly cellular tumor with nuclear pleomorphic and high mitotic, focal necrosis (B) and microvascular proliferation (C). Virtually all tumor cells express the glial fibrillary acidic protein (D). Strong nuclear staining for K27‐mutant H3 is present in tumor cells (E), which have lost H3K27me3 expression (F) (magnification ×400, all panels).

3. DIAGNOSIS

Diffuse midline glioma (DMG) H3 K27‐altered (central nervous system [CNS] World Health Organization [WHO] Grade 4).

4. DISCUSSION

According to the 2021 WHO classification of CNS tumors, DMG H3 K27‐altered is a diffusely infiltrative midline glioma associated with loss of H3 p.K28me3 (K27me3) leading to PRC2 inhibition. This is the result most commonly of a mutation in one of the histone H3 isoforms, resulting in lysine to methionine substitution at amino acid residue 27 (K27M) [1]. Additional alterations including aberrant overexpression of enhancer of zeste homolog inhibitory protein and epidermal growth factor receptor (EGFR) mutation may have similar effect. DMG H3 K27‐altered is considered a CNS WHO Grade 4 tumor irrespective of its histological features.

DMG H3 K27‐altered involving the sellar‐suprasellar region is exceedingly rare and to our knowledge, a tumor arising from the pituitary stalk has not been previously reported. Although DMG H3 K27‐altered occurs most frequently in children and is listed among pediatric‐type diffuse high grade gliomas in the 2021 WHO classification [2], it is not limited to the pediatric age. According to a recent large series, H3 K27‐mutant DMG occurring in adults involves more frequently the thalamus than the brain stem and shows a higher frequency of ATRX loss and H3.3 K27M mutation compared to children [3]. Although prognosis in this series was slightly more favorable in adults than children, despite multimodal therapies, DMG H3 K27‐altered is a highly aggressive brain tumors with short median survival of usually less than a year.

Current treatments include surgical interventions, standard segmented radiotherapy, or combination chemotherapy [2]. Given the deep midline location of these tumors, the role of surgery is most commonly limited to obtain tissue for diagnosis, including molecular characterization, and reduce tumor burden without harming the patient's neurological status. Conventional high‐dose radiotherapy and chemotherapy using temozolomide are the primary treatment options when complete surgical resection is risky. Some studies on targeted drugs and cellular immunotherapy, such as Imipridone ONC201 and the IDO1 inhibitor Indoximod are in the early phases of clinical activity. In addition, the use of immunotherapy is being trialed as an option. Chimeric antigen receptor T‐cell therapy and immune‐modulating antibodies are also under research.

Our patient, despite surgical resection followed by concurrent chemoradiotherapy, experienced rapid regrowth of the tumor, which lead to her demise 6 months after surgery.

AUTHOR CONTRIBUTIONS

Wenlong Xu analyzed the data, and wrote the manuscript. Lianghong Teng provided essential clinical data and reviewed the manuscript. Xiaohai Liu provided essential material. Mingchu Li and analyzed the clinical data. Ge Chen reviewed the manuscript. All authors approved the final version of the manuscript.

CONFLICT OF INTEREST STATEMENT

The authors declare that they have no conflict of interest.

ETHICS STATEMENT

The study was approved by the ethics committee of Xuanwu Hospital, Capital Medical University, Beijing, China, and was conducted in full compliance with all principles of the Helsinki Declaration.

Xu W, Teng L, Liu X, Li M, Chen G. A 53‐year‐old female with suprasellar mass. Brain Pathology. 2023;33(3):e13152. 10.1111/bpa.13152

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.