PMC8117139_01
Brain MRI of CNS-PTLD. (A) Emergence of CNS-PTLD on day +225. MRI revealed a hypointensity lesion in the left thalamus with ring enhancement (red arrow) on contrast-enhanced T1-weighted imagining. (B) Day +255 (before treatment): the enlarged lesion surrounded by significant edema with the longest diameter of about 53mm (T2 Flair). (C) Day +280 (three weeks after the use of rituximab and MTX): reduction in the size of the lesion and edema with the longest diameter of 36.4mm (T2 Flair). (D) Day +363 (after whole-brain radiotherapy completed): further reduction in the size of the lesion with the longest diameter of 29mm (T2 Flair). (E) Day +477(three months after the start of zanubrutinib): the reduced lesion with the longest diameter of 24mm (T2 Flair). MRI, magnetic resonance imaging; CNS-PTLD, central nervous system post-transplant lymphoproliferative disorder.
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Contrast-enhanced brain magnetic resonance imaging (MRI) demonstrated multiple enhancing hyperintense lesions surrounded by edema in bilateral cerebellar and cerebral hemispheres ( Supplementary Figures 1A-C ). Brain MRI performed 1 month after discharge (on day +153 after HSCT) indicated near resolution of the multiple lesions and perifocal edema ( Supplementary Figures 1D-F ). Babinski sign on the right side. Brain MRI revealed a thalamic ring-enhancing lesion surrounded by edema on the left side ( Figure 1A ). MRI was repeated, which revealed further enlargement of the lesion in the left thalamus, with a maximum diameter of approximately 53 mm ( Figure 1B ). Brain MRI indicated a reduction in lesion size, with the longest diameter of 36mm ( Figure 1C ). Brain MRI showed the remained lesion with the longest diameter of 29mm ( Figure 1D ) and the serum EBV DNA load in the blood reduced to an undetectable level. Follow-up brain MRI revealed that the lesion's size decreased to 24 x 24 x 21 mm ( Figure 1E ) with a response of PR.
Single-voxel 1H-magnetic resonance spectroscopy of the tumor area in the left thalamus showing elevated Cho peak in 3.2 ppm and Lip peak in 1.3ppm with decreased NAA in 2.0 ppm, with corresponding short echo time spectra (A, TE=35ms) and long echo time spectra (B, TE=144ms). Cho, choline compounds; Lip, lipid; NAA, N-acetyl-aspartate.
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Photomicrographs of the brain biopsy demonstrating a monomorphic diffuse large B-cell lymphoma with EBV infection. [hematoxylin and eosin (H&E) stain; original magnification (A) x50; (B) x200]. Immunohistochemical stains showed that the infiltrating lymphocytes were positive for CD20 (C). EBV-encoded RNA in situ hybridization was positive in the infiltrating cells (D).
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The tumor cells stained positive for CD19, CD20, PAX-5, Ki-67 (approximately 65%), CD30, Bcl-2 (approximately 100%), MUM1, c-myc (approximately 25%), CD79a, and CD43 ( Figures 3A-C ). The results of EBV-encoded RNA in situ hybridization were positive ( Figure 3D ).
The clinical treatment process of posttransplant lymphoproliferative disorder (PTLD) after transplantation and the changes of serum EBV-DNA titers. HSCT, hematopoietic stem cell transplantation; CsA, cyclosporine; MTX, methotrexate; WBRT, whole-brain radiotherapy.
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The treatment process and changes of serum EBV-DNA titer are summarized in  Figure 4 .