Objective:To observe and analyze the atypical magnetic resonance imaging (MRI) findings and misdiagnosis reasons of primary central nervous system lymphoma (PCNSL), and to explore the value of conventional MRI signs combined with minimum apparent diffusion coefficient value (ADCmin) and imaging features of magnetic resonance spectroscopy (MRS) in the diagnosis and differentiation of atypical PCNSL.Methods:The clinical and imaging data of 15 patients with atypical PCNSL confirmed by clinical and pathological findings from Lianyungang Second People′s Hospital and the Affiliated Hospital of Xuzhou Medical University from January 2015 to December 2020 was collected. All cases were examined by plain MRI, enhanced and diffusion weighted imaging (DWI), and 3 cases were examined by MRS. The conventional MRI features, DWI signal features and MRS imaging features of 15 cases of atypical PCNSL were observed and analyzed, and the MRI findings of atypical PCNSL and the causes of misdiagnosis were summarized and analyzed. The ADCmin of tumor parenchyma, the mean ADC values of proximal peritumor, distal peritumor and contralateral white matter were detected and compared to explore the variation rules of ADC values in different regions.Results:Of the 15 cases of PCNSL, 14 cases were single and 1 case was multiple, with a total of 21 lesions. (1) Single lesions in rare sites: 4 cases in the superficial part of the brain, 1 case in the bridge arm, 1 case in the cerebellar hemisphere, 1 case in the suprasellar saddle, and 1 case in the third ventricle. (2) Atypical MRI findings: cystic degeneration or necrosis in 5 lesions (5/21), accompanied by hemorrhage in 1 lesion (1/21); There were 3 isosensitive lesions on DWI, and isosensitive lesions on ADC false color images. There were 5 ring enhancement lesions and 3 sheet enhancement lesions. (3) Multi-center growth pattern: 1 case with a total of 7 lesions, located in the right thalamus, basal ganglia and corona radiata, showing multiple nodules and ring enhancement. 1H-MRS examination showed that choline (Cho) peak increased, creatine (Cr) peak decreased, N-acetyl aspartate (NAA) peak decreased, and obvious Lip peak appeared in all the 3 cases with single lesions. 2 cases showed high Lip peak as the first peak. The ADCmin values of tumor parenchyma, proximal peritumor, distal peritumor and contralateral white matter showed a parabola pattern of first rise and then decline, as follows: (0.54±0.06)×10 -3 mm 2/s, (1.55±0.10)×10 -3 mm 2/s, (1.45±0.09)×10 -3 mm 2/s, (0.85±0.03)×10 -3 mm 2/s, overall difference was statistically significant ( F=630.570, P<0.001). The pairwise comparison was statistically significant (all P<0.05). Conclusions:Atypical PCNSL is easy to be misdiagnosed. Conventional MRI feature analysis combined with DWI and MRS imaging features and comparison of ADC values in different tumor areas are helpful for the diagnosis and differentiation of PCNSL and are expected to improve diagnostic accuracy.