Multiple intra-axial lesions in a 57-year-old male with a history of B-cell chronic lymphocytic leukemia

A 57-year-old male with a recent history of B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (BCLL/SLL), developed a persistent left-frontal headache. One month after the onset of headache and 2 days after the second dose of anti-SARS-CoV2 mRNA vaccine, he developed a persistent high fever. He was monitored for the following days and 20 days later, he experienced tonic–clonic seizures with post-critical coma (Day 1). CT and MRI scans showed multiple sub and supra-tentorial intra-axial edematous lesions with contrast enhancement and without mass effect, as shown in Figure 1. He started dexamethasone and levetiracetam with subsequent total recovery of vigilance on Day 3 (Box 1).

On Day 6, a stereotactic biopsy of the major frontal lesion showed the presence of necrotic tissue. Following clinical improvement, on Day 9 he was discharged, with dexamethasone taping from Day 20. On Day 40 a control RMI showed edema reduction, but new nodules appeared. He was admitted again and underwent CSF analysis, lymphocyte characterization, blood culture, and total body ¹⁸FDG-PET-CT, all non-contributive.

Still, under steroid tapering, the patient became unresponsive and febrile again, so corticosteroid dosing was increased. After initial improvement he went into hyponatremic coma, consistent with inappropriate ADH secretion syndrome. A new MRI showed a further increase in the lesions and expanded edema. On Day 67 a new open biopsy of the left frontal lesion was performed. After histologic diagnosis, the patient was referred to the Onco-Hematology department where a bone marrow biopsy confirmed a modest infiltration by BCLL/SLL (10% of cellularity). Chemotherapy with MATRix regimen was started with only mild improvement. He ultimately succumbed to the disease on Day 98.

On hematoxylin–eosin the lesion showed extensive necrosis with predominantly medium-sized, atypical lymphoid cells with irregular nuclei, moderate amount of pale cytoplasm with vascular proliferation and histiocytic elements (Figure 2A–C). The neoplastic cells displayed angiocentric growth, mitoses, and apoptotic bodies. CD3 (Figure 2D) and CD2 were positive in neoplastic cells (Figure 2E) as well as Beta-F1 for the αβ T-cell receptor (TCR) dimer; CD20, PAX5, CD5, CD7, CD4, CD8, TdT, CD56, Tia-1, and TCR-γ dimer were negative. Epstein–Barr virus-encoded small RNAs were not detected at in situ hybridization. TCR Gamma rearrangement (TRG) was analyzed by GeneScanning and two distinct reproducible peaks were detected (Figure 2E) interpreted as either a biallelic or biclonal rearrangement.

Peripheral T cell lymphoma, Not Otherwise Specified (NOS) consistent with Primary CNS T cell lymphoma.

Peripheral T-cell lymphoma (PTCLs) accounts for 2%–4% of primary CNS lymphomas in Europe. Immunodeficiency might play a role in the etiology of the disease in a subset of patients. Involved sites include the frontal and temporal lobes, cerebellum, pituitary, and (rarely) leptomeninges. Involvement can be single or multifocal.

Clonal proliferation, extensive necrosis, prominent angiocentric growth, histological and genomic heterogeneity, phenotypic aberrancy, and cytotoxic phenotype are typical hallmarks of biopsy-proven PTCLs, while symptoms and neuroradiological examinations are often nonspecific. Therefore the awareness of this entity is important for distinction with other intra-axial tumors.

The main differential diagnosis is with other primary CNS lymphomas with medium-to-large cell composition, frequently of B-cell derivation, including primary CNS diffuse large B-cell lymphoma (CNS-DLBLC), Burkitt lymphoma, and EBV+ large B-cell lymphomas. Other nodal or extranodal B-cell and T-cell lymphomas can involve the CNS, such as anaplastic T-cell lymphoma, most commonly in refractory/advanced-stage patients. Immunophenotype is crucial, with minimal contribution from morphology or clonality analysis (TCR-γδ is detected in only 50% of primary CNS T-cell lymphomas).

Matteo Martinoni: acquisition of data. Elena Sabattini, Rocco Liguori, and Caterina Tonon: revising the manuscript. Sofia Asioli, Luisa Di Sciascio, and Lina Cardisciani: study design, drafting design, interpretation of pathological results, revising the manuscript.

The authors declare no conflict of interest.