Reliable intraoperative diagnostic methods for PCNSL: utility of combining intraoperative immunohistochemistry, cytology, and flow cytometry in achieving optimal treatment.

Background: Primary central nervous system lymphoma (PCNSL) is a rapidly growing malignant tumor that typically shows sensitivity to high-dose methotrexate-based chemotherapy. Rapid diagnosis and early chemotherapy are thus essential to obtain the best outcome. To accomplish this, we have performed intraoperative rapid immunohistochemistry (IHC) as an examination method for obtaining accurate diagnosis during surgery. Here, to markedly enhance the accuracy of intraoperative rapid IHC, the utility of adding intraoperative rapid examinations of cytology and flow cytometry (FCM) in addition to rapid IHC was investigated.

Methods: From April 2020 to January 2024, we performed intraoperative rapid IHC in 35 patients with intracranial lesions, including PCNSL. In the last 17 of these cases, intraoperative cytology and FCM were also performed simultaneously. We examined the utility of examination methods in determining treatment strategies for brain tumors, particularly early therapeutic intervention for PCNSL.

Results: Postoperative final pathological diagnoses from paraffin-embedded sections were as follows: 20 PCNSLs, 9 glioblastomas, 4 diffuse gliomas, 1 meningioma, and 1 inflammatory disorder. In all cases, results from intraoperative rapid IHC were consistent with final pathological diagnoses from paraffin-embedded sections. In two cases, results from conventional intraoperative rapid pathological diagnoses based on morphological assessments using frozen sections changed with the addition of intraoperative rapid IHC. Further, the time from surgery to initiation of chemotherapy for PCNSL was significantly reduced by adding cytology and FCM to rapid IHC alone (only rapid IHC group: 7.3 days, combination group: 1.6 days; p = 0.015).

Conclusions: The combination of rapid intraoperative IHC, cytology, and FCM contributes to deciding appropriate treatment strategies and facilitating early initiation of chemotherapy for PCNSL. These examination methods may allow new therapeutic strategies for not only PCNSL, but also other brain tumors.