A 19-year-old woman with intermittent headache and dizziness and a large temporal lobe mass

Abstract

A 19-year-old woman had a 3-month history of intermittent headaches and dizziness. MRI revealed a 7.7 × 6.8 × 6.2 cm right temporal lobe mass involving the choroid plexus, compressing the lateral ventricle with midline shift. The lesion was T1-hypointense (Figure 1), T2-hyperintense, heterogeneously enhancing with mild diffusion restriction. Intraoperatively, the tumor was located in the temporal lobe parenchyma, extending into the lateral ventricle without a capsule. Subsequently, the patient underwent microscopic total tumor resection.

Pathological examination revealed an ependymoma-like pattern, characterized by perivascular pseudorosettes (Figure 2A, Box 1) and microcystic areas containing basophilic secretions (Figure 2B). The tumor exhibited high cellularity, nuclear atypia, and increased mitoses (up to 6/mm² in hotspots) in ependymoma-like pattern regions. Necrosis (Figure 2A, inset) and hyalinized stroma (Figure 2B, inset) were seen locally. Although supratentorial ependymoma was initially suspected, the diagnosis was not fully supported by the minimal focal expression of GFAP, EMA, and S100, along with negative FISH testing for ZFTA::RELA. Meanwhile, RNA-seq identified only a SAMD5::SASH1 fusion transcript (Figure 2F). An extensive immunohistochemical panel showed diffuse positivity for BCOR (Figure 2C), vimentin (Figure 2C, inset), CD56 (Figure 2D, inset), and CD99, and a Ki-67 index of 40% (Figure 2D), suggesting a CNS tumor with BCOR internal tandem duplication (ITD). Subsequent whole-genome sequencing confirmed a heterozygous ITD in BCOR exon 15 (Figure 2E). No hotspot mutations (e.g., in IDH1/2, TERT, ATRX, TP53, CDKN2A/B) or structural variations (e.g., in MN1 or CIC) were detected.

Postoperatively, she underwent radiotherapy (56Gy/28f) for 1 year without signs of local recurrence. One year after radiotherapy, she began to experience a persistent cough, dyspnea, and CT scan showed multiple lung nodules and left pleural effusion, pathologically confirmed as metastases. Despite aggressive treatment and chemotherapy, she succumbed to respiratory failure 1 month later.

CNS tumor with BCOR internal tandem duplication (ITD).

The 2021 WHO classification defines CNS tumors with BCOR ITD as malignant embryonal neoplasms of uncertain origin, characterized by a heterozygous ITD in BCOR exon 15 and a solid growth patterns of oval-spindle cells with a dense capillary network and focal pseudorosettes [1]. BCOR ITDs also occur in certain sarcomas, such as primitive myxoid mesenchymal tumor of infancy, clear cell sarcoma of the kidney, and undifferentiated round cell sarcomas in infants, and the nosological relationship among these entities continues to be debated [1].

Somatic heterozygous BCOR ITD is a key oncogenic driver, often as the sole alteration, although additional mutations in EP300, SMARCA2, STAG2, and BCORL1 may contribute [2]. These CNS tumors have poor prognosis, and gross total resection serves as a favorable prognostic factor [2]. Their clinical course is aggressive yet heterogeneous. In one cohort (n = 24), overall survival was poor (8 deaths; survival range: 0.2–6.3 years) [1, 2] and among the 19 patients with follow-up data, 9 (47.4%) experienced recurrence at variable intervals [2]. While metastatic disease at diagnosis is unreported, leptomeningeal dissemination, bone metastases, and inoculation metastases along the neurosurgical access route have been observed at relapse [1]. Notably, some patients achieved long-term survival, with disease-free follow-up exceeding 14 years in one case, and may respond favorably to multimodal therapy [2].

SAMD5::SASH1 fusion is a novel entity with an unknown pathogenic mechanism. Its identification in advanced/metastatic colorectal cancer and sarcoma [3] suggests it is an oncogenic fusion potentially linked to metastasis, a hypothesis requiring experimental validation.

Extracranial metastasis (ECM) in high-grade primary CNS tumors is exceptionally rare, leading to unpredictable symptoms and often underrecognition. Common sites of ECM include the lungs, pleura, lymph nodes, bones, bone marrow, and liver. Its infrequency results from the typically rapid and often fatal intracranial progression, which precludes clinical ECM presentation, along with the protective barriers of the CNS (e.g., the blood–brain barrier and sparse extracellular matrix) that limit tumor cell escape, and the potential inability of disseminated cells to survive in distant organ niches. Proposed mechanisms for ECM include neurosurgical intervention, hematogenous dissemination, and lymphatic spread. While neurosurgery may facilitate seeding, cases in treatment-naïve patients indicate some tumors have innate metastatic potential, with surgery acting as an accelerator or revealing event. Therefore, vigilant monitoring for signs of metastatic spread in patients with high-grade CNS tumors is crucial, as early detection could potentially improve survival rates.

Sha-Sha Hu wrote the main manuscript text. Wei Yan and Bo Wang revised the manuscript. Sha-Sha Hu performed the histological and immunohistological analysis. Sha-Sha Hu and Wei Yan analyzed the molecular assay results. Sha-Sha Hu and Bo Wang reviewed and edited the manuscript. All authors approved the final version of the paper.

The authors declare no conflicts of interest.

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.