A disease warranting attention from neurosurgeons: primary central nervous system post-transplant lymphoproliferative disorder

Abstract

Background: Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) is a rare condition, posing diagnostic and treatment challenges, with histological biopsy essential for diagnosis. Standardized treatment protocols are lacking. This disease requires urgent attention due to the increasing number of organ transplant surgeries and the use of immunosuppressive agents.

Methods: From 2020 to 2023, our center diagnosed five patients with PCNS-PTLD. We reviewed their clinical records and conducted a comprehensive analysis of 22 literatures on PCNS-PTLD cases following renal transplantation or allogeneic hematopoietic stem cell transplantation (HSCT).

Results: Four patients had previously received a kidney transplant, one had undergone allogeneic HSCT. The median time from the last transplant surgery to the diagnosis of PCNS-PTLD differs between kidney transplant (21.5 years) and allogeneic HSCT (9 months). Common symptoms included motor weakness (n = 4), headache (n = 2), confusion (n = 2), and nausea (n = 2), with ring-enhancing (n = 5), typically solitary (n = 3) and supratentorial (n = 3) lesions on imaging. Diagnosis involved robot-assisted stereotactic brain biopsy (n = 4) or craniotomy (n = 1), all showing Epstein-Barr virus and CD20 positivity. Most cases (n = 4) were monomorphic diffuse large B-cell lymphoma. Treatment included rituximab (n = 3), surgical resection (n = 2), zanubrutinib (n = 1), whole-brain radiation (n = 1), and methotrexate (n = 1). At the last follow-up, the median duration of follow-up for all patients was 19 months. During this time, 3 patients had died and 2 patients were still alive.

Conclusion: In patients with a history of kidney transplantation or allogeneic HSCT who are on long-term immunosuppressive therapy, any neurological symptoms, particularly the presence of supratentorial ring-enhancing masses in the brain on imaging, whether solitary or multiple, should raise high suspicion for this disease, warranting a timely brain biopsy. Additionally, we found that besides reducing immunosuppressants, zanubrutinib may be a potential, safe, and effective treatment for this condition. Moreover, post-surgical administration of rituximab in conjunction with whole-brain radiotherapy also appears to be a potentially safe and effective approach.

Keywords: brain tumor; hematopoietic stem cell transplantation; kidney transplant; primary central nervous system post-transplant lymphoproliferative disorder; robot-assisted stereotactic brain biopsy.

Figure 1

MRI findings of patient 1. Irregular ring enhancement lesion in the right frontal lobe on T1-weighted images (A). Extensive perilesional edema in the right frontal lobe on T2-weighted images (B).

Figure 2

Histopathological features of patients 1 and 3. Hematoxylin and eosin staining in patient 1 [(A) magnification × 400]. The atypical cells demonstrated positive staining for CD20 in patient 1 (B). Detection of Epstein-Barr virus (EBV) encoded small RNA positive cells was observed in patient 1 (C). Hematoxylin and eosin staining in patient 3 exhibited sheets of atypical cells with prominent nuclear division, visible nucleoli in some cells, and extensive areas of necrosis, indicative of monomorphic PTLD, diffuse large B-cell lymphoma [(D) magnification × 400]. The atypical cells in patient 3 stained positive for CD20 (E). Presence of cells positive for EBV-encoded small RNA in patient 3 was confirmed (F).

Figure 3

MRI findings of patient 2. Preoperative enhanced MRI prior to brain biopsy showed a ring-enhancing lesion in the right basal ganglia area on T1-weighted images (A), with extensive edema surrounding the lesion in the right basal ganglia area on T2-weighted images (B), and abnormal signal intensity in the left cerebellum on T1-weighted images [(C) white arrows]. Enhanced MRI scans obtained four months after the diagnosis of PCNS PTLD, persistent ring enhancement lesion in the right basal ganglia on T1-weighted images (D). Continued perilesional edema in the right basal ganglia on T2-weighted images (E). Additionally, the abnormal signal intensity in the left cerebellum persisted on T1-weighted images [(F) blue arrows].

Figure 4

MRI findings of patient 3. Preoperative enhanced MRI prior to brain biopsy showed ring-enhancing lesions affecting the left cerebral peduncle, thalamus, and basal ganglia on T1-weighted images (A, B), with surrounding edema around the left cerebral lesion on T2-weighted images (C).

Figure 5

MRI findings of patient 4. Preoperative enhanced MRI prior to brain biopsy showed a ring-enhancing lesion in the right basal ganglia area on T1-weighted images (A), with extensive edema surrounding the lesion in the right basal ganglia area on T2-FLAIR images (B). On follow-up enhanced MRI images obtained 3 months after the diagnosis of PCNS PTLD, the ring-enhancing lesion in the right basal ganglia area appeared reduced on T1-weighted images (C), and the edema surrounding the lesion in the right basal ganglia area decreased on T2-weighted images (D).

Figure 6

MRI findings of patient 5. Preoperative enhanced MRI images showed a ring-enhancing lesion in the left parietal lobe on T1-weighted images (A), a circular lesion in the right parietal lobe (B), and extensive edema surrounding the lesion in the left parietal lobe on T2-weighted images (C).