<sup>89</sup>Zr‐rituximab PET/CT to detect neurolymphomatosis
Authors: Antoinette de Jong, Rogier Mous, Guus A.M.S. van Dongen, Otto S. Hoekstra, Rutger A.J. Nievelstein, Bart de Keizer
Journal: American Journal of Hematology (2016)

A 58-year-old woman presented with progressive loss of strength in her left leg. Ten years earlier, she had been successfully treated for a CD20 positive diffuse large B-cell lymphoma (DLBCL) located in the right L5 nerve root with chemo-immunotherapy followed by radiotherapy. Physical examination showed muscle weakness and sensory loss in the left leg. White blood cell count, bone marrow biopsy, and cerebrospinal fluid (CSF) analyses were unremarkable. 18F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG PET/CT) showed increased glucose metabolism in the left sciatic nerve (Fig. 1A,B), and magnetic resonance imaging (MRI) showed enhancement and restricted diffusion of the left sciatic nerve. Since a tissue biopsy had a high risk of permanent nerve damage, a 89Zirconium-rituximab PET/CT (89Zr-rituximab PET/CT) was performed to determine the most likely diagnosis. The 89Zr-rituximab PET/CT showed uptake in the left sciatic nerve (Fig. 1C,D), indicating CD20 positive tissue. Furthermore, 89Zr-rituximab uptake was seen in all visible lymph nodes and the spleen (Fig. 1E), which was considered as physiological CD20 positive B-cell presence as these lymph nodes and spleen were negative on FDG PET/CT. PET and PET/CT scans before and after six cycles of chemo-immunotherapy. Coronal reconstruction of pathological FDG uptake in the left sciatic nerve on PET (A) and fused PET/CT (B). Pathological 89Zr-rituximab binding in the left sciatic nerve on PET (C) and fused PET/CT (D), and intense physiological 89Zr-rituximab uptake in all visible lymph nodes and the spleen (E). The FDG PET/CT after six cycles of chemo-immunotherapy showed normalization of FDG uptake on PET (F) and fused PET/CT images (G). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] Neurolymphomatosis is a rare neurological manifestation of non-Hodgkin lymphoma (NHL) or leukemia, with an unknown incidence 1. It comprises a neuropathy that is caused by infiltration of tumor cells (mainly of DLBCL origin) into peripheral nerves, nerve roots, plexus, or cranial nerves 1. Distinction between other neuropathies is challenging because CSF cytology is positive in 40% of all cases, and biopsy can only be performed in less than half of the patients 1, 2. MRI is the most sensitive and specific imaging tool 1, 3, and FDG PET/CT can be a useful adjunct 4. However, diagnostic tests need to be improved as in almost half of the patients the diagnosis is not established until autopsy 2. B-cells are characterized by the surface phosphoprotein CD20, which is also expressed in most B-cell neoplasms. Recently, 89Zr-rituximab was proven to target CD20 positive B-cells in a humanized transgenic mouse model 5. Clinical studies to determine the diagnostic and prognostic value of 89Zr-rituximab PET/CT in malignant lymphoma are ongoing 6. The 89Zr-rituximab PET/CT in our case showed uptake in the left sciatic nerve. In case of neuro-inflammatory diseases (auto-immune, paraneoplastic) or diabetic neuropathies, the inflammatory response mainly consists of T-cells (90%) so less uptake would be expected. Hypothetically, the 89Zr-rituximab uptake could also be the result of binding between the rituximab Fc receptor and other cells expressing Fc receptors, for example macrophages. However, with regard to the previously diagnosed CD20 positive DLBCL this uptake made neurolymphomatosis the most likely diagnosis. Our patient was treated with intravenous rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP) and high-dose intravenous methotrexate (HD-MTX). After four cycles, therapy was changed to rituximab, dexamethasone, cytarabine, and carboplatin (R-DHAC) and HD-MTX due to cisplatin nephrotoxicity. After six cycles, the neurological complaints almost resolved, and the FDG PET/CT showed normalization of FDG uptake (Fig. 1F,G). A.J. wrote the manuscript; R.M. treated the patient and contributed significantly to the writing; G.A.M.S.D, O.S.H, and R.A.J.N. analyzed data and significantly contributed to the writing; B.K. performed the research study and significantly contributed to the writing.