EC Clinical and Medical Case Reports

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma (NHL) with a male-predominant incidence. Several techniques have been implemented to ensure an appropriate diagnosis of the pathology, including biological, histological, radiological, and molecular analyses. Neuromeningeal infiltration of DLBCL is a rare presentation of the pathology with a poor prognosis limiting patient survival. We report a case of neuromeningeal dissemination of DLBCL with a review of the literature.

Case Presentation: H.M., a 54-year-old patient with no particular history, followed for high-grade diffuse large B-cell lymphoma, CG stage IV A, IPI at 3 and CNS IPI at 4 with renal involvement. In partial remission after 4 R-CHOP courses and in progression after C4 RDHAOX (Rituximab-Dexamethasone-Cytarabine-Oxaliplatin), admitted to the clinical hematology department for his 2^nd RICE course (Rituximab-Ifosfamide-Carboplatin-Etoposide). Clinically, hemodynamically and the rest of the clinical examination was without any particularities. Biologically, there were no notable particularities apart from an increased LDH of 523.

During his hospitalization, the patient presented neurological signs such as: lower limb pain of the sciatic type, tingling and paresthesia with peripheral facial paralysis. The neurographic examination was in favor of a length-dependent sensory-motor axonal polyneuropathy, predominantly sensory. A brain CT scan was performed showing neurological involvement.

The cytological study of the CSF showed lymphomatous hypercellularity estimated at 58%, very often large in size with an irregular nucleus related to his lymphoma, which confirm the diagnosis of neuromeningeal dissemination of DLBCL.

After chemotherapy, the patient presented respiratory distress with a left basal opacity on chest X-ray, which badly progressed, leading to the patient's death.

Conclusion: Neuromeningeal infiltration of DLBCL is a rare complication of this pathology characterized by its aggressiveness and rapid progression. A precise diagnosis can be made using various available techniques. A comprehensive CSF examination is crucial, including conventional cytology, flow cytometry, and cytokine assays.

Collaboration between biologists, pathologists, hematologists, and radiologists effectively contributes to early detection, reducing diagnostic errors, and developing specific and individualized management plans.

Keywords: Neuromeningeal Infiltration; Diffuse Large B-Cell Lymphoma; Flow Cytometry

1. Swerdlow SH., et al. “WHO classification of tumours of haematopoietic and lymphoid tissues”. 4^th Lyon: IARC (2017).
2. Alaggio R., et al. “The 5^th edition of the World Health Organization classification of haematolymphoid tumours: lymphoid neoplasms”. Leukemia7 (2022): 1720-1748.
3. Swerdlow SH., et al. “The 2016 revision of the World Health Organization classification of lymphoid neoplasms”. Blood20 (2016): 2375-2390.
4. Bernstein SH., et al. “Natural history of CNS relapse in patients with aggressive non-Hodgkin’s lymphoma: a 20-year follow-up analysis of SWOG 8516”. Journal of Clinical Oncology 1 (2009): 114-119.
5. Kanas G., et al. “Epidemiology of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in the United States and Western Europe: population-level projections for 2020-2025”. Leukemia and Lymphoma 1 (2022): 54-63.
6. H Hami., et al. “Epidemiology of non-Hodgkin’s lymphoma in Morocco”. British Journal of Hematology1 (2014): 31.
7. Thandra KC., et al. “Epidemiology of non-Hodgkin’s lymphoma”. Medical Science (Basel)1 (2021): 5.
8. Abid MB., et al. “Diffuse large B cell lymphoma (DLBCL) in Pakistan: an emerging epidemic?” Asian Pacific Journal of Cancer Prevention 4 (2005): 531-534.
9. Hamda K. “Facteurs pronostiques du lymphome B diffus à grandes cellules à l’ère du rituximab: à propos de 140 cas”. [Thèse/mémoire].
10. Alderuccio JP., et al. “How I treat secondary CNS involvement by aggressive lymphomas”. Blood21 (2023): 1771-1783.
11. Ghose A., et al. “Influence of rituximab on central nervous system relapse in diffuse large B-cell lymphoma and role of prophylaxis: a systematic review”. Clinical Lymphoma, Myeloma and Leukemia 8 (2015): 451-457.
12. Shi Y., et al. “Clinical features and outcomes of diffuse large B-cell lymphoma based on nodal or extranodal primary sites of origin”. Chinese Journal of Cancer Research 1 (2019): 152-161.
13. Ferreri AJ., et al. “Central nervous system dissemination in immunocompetent patients with aggressive lymphomas: incidence, risk factors and therapeutic options”. Hematological Oncology 2 (2009): 61-70.
14. Tomita N., et al. “Secondary central nervous system lymphoma”. International Journal of Hematology 2 (2006): 128-135.
15. Tang C., et al. “Diffuse large B-cell lymphoma with concurrent involvement of central and peripheral nervous system: a case report and literature review”. Heliyon7 (2024): e28552.
16. Peñalver FJ., et al. “Guidelines for diagnosis, prevention and management of central nervous system involvement in diffuse large B-cell lymphoma patients by the Spanish Lymphoma Group (GELTAMO)”. Haematologica2 (2017): 235-245.
17. Rozenblum L., et al. “Rôle de la TEP dans la prise en charge des lymphomes primitifs du système nerveux central”. Médecine Nucléaire 4 (2021): 245-249.
18. Zheng W., et al. “Cerebrospinal fluid proteins facilitate the differential diagnosis of CNS diffuse large B-cell lymphoma”. Journal of Cancer 17 (2017): 3631-3640.
19. Zhu S., et al. “Overcoming missed diagnoses of primary CNS lymphoma: the key role of CSF cytology”. Diagnostic Pathology 1 (2025): 29.
20. Song Y., et al. “Cerebrospinal fluid IL-10 and IL-10/IL-6 as diagnostic biomarkers for primary CNS large B-cell lymphoma”. Scientific Reports 6 (2016): 38671.
21. Yi JH., et al. “Pre-treatment serum IL-10 predicts secondary CNS involvement in diffuse large B-cell lymphoma”. Cytokine 129 (2020): 155048.
22. Gu J., et al. “CSF IL-6 and IL-10 as diagnostic and prognostic biomarkers for secondary CNS lymphoma”. BMC Cancer1 (2024): 1443.
23. Ungureanu A., et al. “CSF interleukin-6 distinguishes inflammatory CNS diseases from primary CNS lymphoma”. Journal of Neurology 8 (2021): 2890-2894.
24. Subira D., et al. “Flow cytometric analysis of CSF samples in routine clinical practice”. American Journal of Clinical Pathology 6 (2002): 952-958.
25. French C., et al. “Diagnosing lymphoproliferative disorders in CSF using flow cytometry”. Diagnostic Cytopathology 6 (2000): 369-374.
26. Bromberg JE., et al. “CSF flow cytometry improves diagnostic accuracy in CNS hematologic malignancies”. Neurology20 (2007): 1674-1679.
27. Hegde U., et al. “High incidence of occult leptomeningeal disease detected by flow cytometry in newly diagnosed aggressive B-cell lymphomas at risk for central nervous system involvement: the role of flow cytometry versus cytology”. Blood2 (2005): 496-502.
28. Kraan J., et al. “Flow cytometric immunophenotyping of cerebrospinal fluid”. Current Protocols in Cytometry Chapter 6 (2008): Unit 6.25.
29. Talaulikar D., et al. “Clinical role of flow cytometry in redefining bone marrow involvement in DLBCL”. Histopathology3 (2008): 340-347.
30. Bode-Lesniewska B. “Flow cytometry and effusions in lymphoproliferative processes”. Acta Cytologica 4 (2016): 354-364.