Background/Aim: The prognosis of patients with brain metastases (BMs) originating from lung cancer remains poor, despite advancements in treatment strategies. The role of tertiary lymphoid structures (TLSs) within the tumor immune microenvironment of BMs has not been extensively explored. Patients and Methods: This study utilized patient-derived clinical samples from 17 patients with histologically confirmed BMs of lung cancer, undergoing surgical resection. Immunohistochemistry was employed to analyze the presence and characteristics of TLS and tumor-infiltrating lymphocytes (TILs) within BM tissues, correlating these with clinical outcomes. Results: TLSs, albeit in their immature form, were identified within BM tissues, distinguishing them from their mature counterparts in primary lung cancer tissues. A significant correlation between TLS density (but not TIL density) and improved postoperative survival was observed, underscoring the potential of TLS density as an independent prognostic marker. Furthermore, TLS density did not correlate with the Graded Prognostic Assessment (GPA) index, suggesting its unique prognostic value beyond conventional predictors. Conclusion: Our findings reveal the presence of TLSs in lung cancer-derived BMs and highlight their prognostic significance, independent of the GPA index. The identification of TLS within the unique central nervous system tumor microenvironment offers new insights into the immune landscape of BMs and suggests potential avenues for immunotherapeutic interventions targeting these structures to improve patient outcomes.

Background/Objectives: Tumor-infiltrating B cells (TIBs) and tissue-resident memory T cells (TRMs) play significant roles in antitumor immunity. However, their prognostic relevance in brain metastases (BMs) derived from gastrointestinal (GI) cancers remains unclear. This study aimed to investigate the prognostic significance of TIBs and TRMs in GI cancer-derived BMs (GIBMs). Methods: Retrospective histopathological analyses were performed on surgically resected GIBM tissues from 13 patients. The densities of tumor-infiltrating lymphocytes (TIL) subsets (TIBs, CD4⁺ T cells, CD8⁺CD103⁺ TRMs, and CD8⁺CD103^- non-TRMs) were quantified and correlated with clinical parameters and overall survival (OS) including the Graded Prognostic Assessment (GPA). Results: TIBs and CD4⁺ T cells were predominantly accumulated in the tumor stroma, particularly around blood vessels, where they formed lymphocyte clusters without characteristics of tertiary lymphoid structures (TLSs). In contrast, TRMs more deeply infiltrated into the tumor epithelium than their counterpart non-TRMs. Positive correlations were found between TIB density and both the prognostic prediction of GPA and overall survival (OS) after BM diagnosis or surgery. Furthermore, increased densities of TIBs and TRMs were associated with enhanced survival after BM diagnosis. Conclusions: TIB and TRM densities in BM tissues could serve as reliable prognostic indicators for survival in patients with GIBMs. This study provides crucial insights for the development of novel immunotherapeutic strategies against this lethal disease.

Background: Rituximab, high‐dose methotrexate (HD‐MTX), procarbazine and vincristine (R‐MPV), has significantly prolonged the survival of patients with primary central nervous system lymphoma (PCNSL), but predictive factors for response to R‐MPV have not yet been investigated. Herein, we investigated the correlation of MYD88 L265P and CD79B Y196 mutations, which are the most frequently found molecular alterations in PCNSL, with prognosis of patients with PCNSL treated with R‐MPV.Methods: We investigated the long‐term clinical course and status of MYD88 and CD79B genes in 85 patients with PCNSL treated with R‐MPV or HD‐MTX treatment, and the correlation of these genetic mutations with prognosis.Results: R‐MPV achieved an excellent tumor control rate (61.6% and 69.9% of 5‐year progression‐free and overall survival rates, respectively). While MYD88 L265P mutation had no significant effect on survival, patients with CD79B Y196 mutations exhibited prolonged survival (p < 0.05). However, the association of CD79B Y196 mutation with a better prognosis was not observed in the HD‐MTX cohort, which indicated that CD79B Y196 mutation was a predictive marker for a favorable response to R‐MPV. Furthermore, we established an all‐in‐one rapid genotyping system for these genetic mutations.Conclusions: In conclusion, CD79B Y196 mutation is a potent predictive marker for favorable response to R‐MPV in PCNSL. The rapid identification of MYD88 L265P and CD79B Y196 mutations can be helpful not only for the accurate molecular diagnosis of PCNSL but also for the prediction of response to R‐MPV.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft-tissue tumors. Intracranial metastasis from MPNSTs is quite rare. OBSERVATIONS: The authors report on a 73-year-old male whose MPNST metastasized to the brain and a 32-year-old male with leptomeningeal metastasis from MPNST and review 41 cases of MPNST that developed intracranial metastasis, as reported in the literature. LESSONS: Brain metastasis and leptomeningeal metastasis of MPNSTs show different clinical courses and require pathology-specific treatment.

Background/Objectives: WHO grade II meningiomas show highly variable growth rates that are difficult to predict using conventional histology. We investigated relationships between immune components within the tumor immune microenvironment (TIME) and explored their association with tumor growth kinetics. Methods: We retrospectively evaluated a small, preselected cohort of 15 patients with WHO grade II meningiomas who underwent initial “watch-and-wait” observation with serial preoperative MRI. Notably, this cohort represents a specific clinical subset—tumors deemed initially observable—and may not be representative of all WHO grade II meningiomas. Densities of Iba1-positive macrophages (TAMs) and B7-H3-positive tumor cells were quantified by digital pathology. The relative growth rate (RGR) was calculated from serial MRI. Results: A strong inverse correlation was observed between TAM density and B7-H3-positive tumor cell density (Spearman’s R = −0.921, p < 0.001). Individual immune components did not show significant linear correlations with RGR; on median-split stratification, high B7-H3-positive tumor cell density was associated with a nominally significant difference in RGR (p = 0.0428, unadjusted). Low TAM density showed a non-significant trend in the same direction. Conclusions: Our findings generate the hypothesis that WHO grade II meningiomas exhibit an inverse relationship between TAMs and B7-H3 and that macrophage-poor/B7-H3-high and macrophage-rich/B7-H3-low patterns may differ in preoperative growth behavior. These observations are derived from a small, preselected cohort of tumors managed with an initial “watch-and-wait” strategy and require validation in broader populations.

BACKGROUND: The management of recurrent brain metastases after initial stereotactic radiosurgery (SRS) remains challenging, with high local recurrence rates following salvage surgery. While preoperative SRS has shown promise for newly diagnosed metastases, its application in post-SRS recurrences is largely unexplored. OBSERVATIONS: The authors treated three patients with recurrent brain metastases using preoperative re-irradiation followed by resection. Gamma Knife SRS was performed at marginal doses of 16–18 Gy, followed by resection within 24–48 hours. Local control was achieved in all patients without radiation-related complications. Histopathological examination confirmed the presence of viable tumor cells and radiation-induced changes. Follow-up magnetic resonance imaging revealed no evidence of tumor recurrence or adverse effects. Two patients remained alive at 35 and 19 months, whereas one died of primary cancer progression at 20 months. LESSONS: Preoperative re-irradiation followed by resection for recurrent brain metastases after initial SRS is feasible and offers promise for short-term safety, local control, and rapid symptom improvement. The ability to promptly implement SRS enables its application in oncological emergencies. These findings suggest that preoperative re-irradiation can be a valuable strategy for managing symptomatic post-SRS recurrent brain metastases that require prompt surgical intervention. https://thejns.org/doi/10.3171/CASE24737