Characteristics of SCNSL patients at initial systemic disease diagnosis：
Clinical findings are shown in Table 1. Half of the SCNSL patients (n=13) were older than 60 years old when diagnosed with systematic aggressive B cell lymphoma. Extranodal involvement was observed in 14 (53.8%) patients, breast involvement in 15.4% (n=4), testicular involvement in 11.5% (n=3), and involvement of the intestines, parotid gland, oral cavity, rhino, orbit and spleen in 26.9% (n=7). The histological findings were DLBCL in 92.3% (n=24) of the patients, mantle-cell lymphoma in 3.5% (n=1), and follicular lymphoma in 3.5% (n=1). For the initial treatment prior to CNS involvement, 22 patients with isolated CNS disease received chemotherapy prior to CNS disease. 42.3% (n=11) of the patients used Rituximab-containing therapy. Only 7.7% (n=2) of the patients received intravenous HD-MTX for CNS prophylaxis. As for 4 SCNSL patients with combined disease, two patients had breast and CNS involvement, the other two had bone marrow and CNS involvement. They did not receive any treatment prior to CNS involvement due to they initially presented with CNS lesions, and were diagnosed as SCNSL later.
Clinical and physiological findings, relapse site, pathological findings, and treatment at CNS relapse：
All patients presented with brain parenchymal lesions, and one patient also had spinal cord compression. The symptoms of CNS relapse varied with location; the most common symptom was headache, and no epilepsy was observed in our study. Eye symptoms, such as blurred vision, were observed in 26.9% (n=7) of the patients. The time from clinical presentation to a definite diagnosis ranged from 4 to 180 days (median 30 days). One patient died of post-operation intracranial hemorrhage. Three patients presented to our center initially as PCNSL but were later detected as having systemic disease and were distributed to SCNSL.
In this study, 80.8% (n=21) of the patients were categorized as having isolated CNS relapse, 3.8% (n=1) had CNS with disease progression，15.4%（n=4）had combined disease, and those in whom CNS involvement was found after the first year of systemic disease were more likely to have isolated CNS relapse (p=0.034) (Table 2). Regarding the time of relapse, 73.1% (n=19) had CNS relapse within the first five years after diagnosis with systemic disease with a median CNS relapse time of 3 years (Fig. 1). 88.5% (n=23) patients underwent stereotactic biopsy, only 3.8%(n=1) patient received intracranial tumor resection, and 7.7%(n=20) were diagnosed with enhanced MRI. Pathological results showed that all were DLBCL, and of these, 92.3% (n=24) were non-germinal center DLBCL subtypes, while others were germinal center B cell(GCB) subtype. BCL2 and BCL6 expression was detected in 75% (n=18) of the patients, MYC was positive in 15 out of 16 (93.7%) of the SCNSL patients, and 93.75% presented with Ki-67 higher than 90%.
Clinical and physiological findings, pathological findings of PCNSL patients:
All PCNSL patients had parenchymal diseases , their median age was 56.5years (range28-82years). 96.2% (n=25) patients underwent stereotactic biopsy, 3.8%(n=1) patient was diagnosed with intracranial tumor resection. As for pathological findings, all were DLBCL, with 92.3% (n=24) non-germinal center DLBCL subtypes, and 7.7%(n=2) germinal center B cell(GCB) subtype.
MRI findings in SCNSL and PCNSL patients (Table 3).
All PCNSL patients avoided steroid treatment before MRI and surgery while 6 SCNSL patients with isolated CNS disease used corticosteroids before diagnosis.
Multiplicity and localization Parenchymal involvement was present in all SCNSL patients, with multiple lesions found in 76.9% (n=20) of the cases; in PCNSL, this proportion was 42.3% (n=11) (p=0.023). The SCNSL lesions were located in the deep gray matter in 68% (n=17) and in the white matter in 84% (n=21) of the patients; in PCNSL, these ratios were 46.2% (n=12) and 65.4% (n=17). Brainstem involvement was detected in only 12% (n=3) of SCNSL cases but was observed in 34.6% (n=9) of PCNSL patients (p=0.097). In SCNSL, supratentorial lesions were seen in 64% (n=16) of the cases and concomitant supratentorial and infratentorial lesions in 36% (n=9), and none of them had solitary infratentorial lesions. Among the PCNSL patients, 23.1% (n=6) had solitary infratentorial lesions (p=0.017).
Signal characteristics The signal characteristics of SCNSL and PCNSL were quite similar. On T1-weighted (T1W) images, lesions were hypointense in 79.2% (n=19), hyperintense in 4.2% (n=1), and isointense in 12.5% (n=3) of SCNSLs. The T2-weighted (T2W) signal of the lesions was hyperintense in 66.7% (n=16) of SCNSL and 92.3% (n=24) of PCNSL patients. T2 Flair hyperintensity was detected in 84.6% (n=11) of the patients. Diffusion-weighted imaging (DWI) hyperintensity was found in 81.3% (n=13) of the SCNSL patients, while all of the PCNSL patients presented with hyperintensity on DWI (p=0.049).
Enhancement pattern In the SCNSL group, the enhancement pattern was homogenous nodular in 61.5% (n=16), patchy in 23.1% (n=6) and ring-like in 7.7% (n=2) of the cases. Notably, 7.7% (n=2) of the patients presented with lesions without enhancement (Fig. 2). One SCNSL patient initially had no enhancement on MRI and was diagnosed with anti-NMDA-receptor encephalitis, but eventually, with the progression of the disease, the tumor developed enhancement, and stereotactic biopsy confirmed DLBCL with CNS involvement (Fig. 3).