Lymphknotenmetastase eines IDH-mutierten Astrozytoms Grad 4: Fallbericht und systematische Übersicht der relevanten Literatur

Metastatic growth of primary brain tumors outside of the CNS is considered exceedingly rare. Most cases of extra-axial dissemination were reported for glioblastoma, while clinical and genomic analysis for IDH-mutant gliomas defined by the WHO 2021 classification are lacking.

A 18-year-old man presented with a right T2-hyperintense lesion of the primary motor cortex, and a stereotactic biopsy was consistent with an IDH-mutant astrocytoma grade 2. While the lesion was initially monitored, the patient was lost to follow-up. After seventeen years, the patient developed a progressive left-sided hemiparesis and MRI showed local progression. A subtotal resection was provided, and histology demonstrated an astrocytoma grade 4 (IDH1-mutated, MGMT promotor methylated). While the patient underwent adjuvant radiochemotherapy followed by consolidation chemotherapy with temozolomide, a painless swelling of a right cervical lymph node occurred. Biopsy was scheduled; immunohistochemistry and next-generation sequencing (NGS) of the tissue was performed. Pertinent literature was systematically searched.

On histology, diffuse infiltration of the lymph node by a pleomorphic neoplasm with brisk mitotic activity was seen. While no expression of markers for epithelial cell-lineage (AE1/3, CK18, CK7) was shown, immunostaining confirmed glial tumour lineage and the presence of an IDH1-mutation. On NGS, a somatic pArg132Ser missense mutation of IDH1 (allele frequency: 13%) and a nonsense pArg273Cys mutation of TP53 (allele frequency: 39%) were identified. Given that identical mutations were found in cerebral tissue specimens, diagnosis of a lymph node metastasis from the astrocytoma was established. Temozolomide was continued and lymph node-directed radiotherapy provided; however, the patient deceased within months. Only 22 cases of extra-axial metastasis from IDH-mutant gliomas have been reported, including 15 astrocytomas. No patient described in the literature responded to treatment.

Despite rarely encountered, extra-axial metastasis may also occur in IDH-mutant gliomas and characterize a late disease stage. Given that no durable treatment response has yet been document, establishing an accurate diagnosis mainly serves to inform patient guidance towards end-of-life care. With novel IDH-targeting treatments on the horizon, it remains to be seen whether such approaches represent a valuable option to improve outcome of affected patients.