Neuroimaging features of primary central nervous system post-transplantation lymphoproliferative disorder following hematopoietic stem cell transplant in patients with β-thalassemia: a case series and review of literature

Abstract

Purpose: Primary central nervous system post-transplantation lymphoproliferative disorder (PCNS-PTLD) is a rare but serious complication of hematopoietic stem cell transplantation (HSCT) in patients with severe β-thalassemia. This study aimed to assess the clinical presentation, pathological characteristics, neuroimaging findings, and treatment strategies in patients with β-thalassemia who developed PCNS-PTLD and to compare a case series from our transplant center to reported cases from literature.

Methods: We retrospectively reviewed our hospital database and identified four cases of pathologically confirmed PCNS-PTLD without a history of systemic PTLD in patients with severe β-thalassemia after HSCT. We also performed a relevant literature review on PCNS-PTLD.

Results: The median time from transplantation to diagnosis of PCNS-PTLD was 5.5 months. Intracerebral lesions were usually multiple involving both supratentorial and infratentorial regions with homogeneous or rim enhancement. All patients had pathologically confirmed PCNS-PTLD with three patients having diffuse large B-cell lymphoma and the fourth patient having plasmacytic hyperplasia. There was low response to treatment with a median survival of 83 days.

Conclusion: PCNS-PTLD should be considered in the differential diagnosis of patients with β-thalassemia who had an intracranial lesion on neuroimaging after HSCT.

Critical relevance statement: This case series with a comprehensive review of neuroimaging and clinical characteristics of children with primary central nervous system post-transplantation lymphoproliferative disorder should advance our understanding and improve management of this rare yet severe complication following transplant for β-thalassemia.

Key points: • We assessed clinical presentation, treatment strategies, and neuroimaging characteristics of PCNS-PTLD in patients with β-thalassemia after transplantation. • Patients with β-thalassemia may have post-transplantation lymphoproliferative disorder presenting as brain lesions on neuroimaging. • Neuroimaging findings of the brain lesions are helpful for prompt diagnosis and proper management.

Keywords: Central nervous system; Hematopoietic stem cell transplantation; Magnetic resonance imaging; Post-transplantation lymphoproliferative disorder; β-thalassemia.

Fig. 1

Brain MRI and CT images for the case 1. a–d Axial CT image showing lesions in the right cerebellar hemisphere, left occipital lobe, pons and frontal-parietal lobes with slight hyperdensity (white arrows), patchy hypodense edema, and hyperdensity. e–h Axial T1-weighted imaging showing hypointense and heterogeneous hypo- and hyperintense lesions (white arrows) with high signal indicating hemorrhage. i–l Axial T2-weighted imaging showing extensive peri-lesional edema (white arrows). m–p Axial T2-fluid-attenuated inversion recovery images showing extensive peri-lesional edema (white arrows). q–t Sagittal T2-weighted image showing extensive peri-lesional edema (white arrows)

Fig. 2

Brain MRI and pathological findings for case 2. Brain CT showing multiple isodensity or hyperdensity lesions (a–d). Brain MRI with axial-T1-weighted (e), T2-weighted (f), and fluid-attenuated inversion recovery image (g) showing multiple intraparenchymal lesions (white, yellow, and black arrows), contrast-enhanced T1-weighted images (h, i) showing multiple rim-enhancing lesions (white arrows) in the subcortical white matter, diffusion-weighted image (j) and apparent diffusion coefficient image (k) showing restricted diffusion of the enhancing rim of the brain lesions (white and black arrows), microscopic presentation of hemorrhage and necrosis accompanied by lymphoid and plasma cell infiltration in a pathology slide (HE × 100) (l)

Fig. 3

Brain MRI findings for case 3. Brain MRI images (a–d) at the time of initial diagnosis showing a homogenous lesion (white arrows) being hypointense on T1-weighted imaging (a), isointense on T2-weighted imaging (b), with mild homogeneous enhancement (c, d), MRI images (e–h) obtained 18 days after an initial presentation showing the lesion (white arrows) being enlarged in size (e), more heterogeneous in appearance (f), and having a new rim-enhancing feature (g, h)

Fig. 4

Brain MRI findings for case 4. Brain MRI with axial T1-weighted imaging (a–d), T2W-weighted imaging (e–h), and T2-fluid-attenuated inversion recovery image (i–l) showing multiple intraparenchymal lesions (white arrows) and the T2-weighted image and T2-fluid-attenuated inversion recovery images (e–l) showing extensive peri-lesional edema (white arrows). The enhance scan (m–p) showing mild to moderate heterogenous enhancement of the lesions (white arrows)