Unusual Cauda Equina and Intramedullary Disease Spread as the Only Site of Disease Recurrence in a Case of Diffuse Large B-cell Lymphoma

INTRODUCTION

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for approximately 30%–40% of all NHL cases.^[1] It can arise in lymph nodes or extranodal sites, including the gastrointestinal tract, testes, thyroid, skin, breast, bone, brain, and other organs. Among the serious but uncommon complications of DLBCL is central nervous system (CNS) involvement, which has been reported in 5%–20% of cases.^[2,3]

CNS lymphoma can occur as either primary CNS lymphoma (PCNSL), comprising 0.2%–2% of all lymphomas, or more commonly as secondary CNS lymphoma (SCNSL), seen in 1%–7% of systemic DLBCL cases.^[4] Both forms carry a poor prognosis. If left untreated, PCNSL has a median survival of only 1.5 months and a 5-year survival rate of approximately 30%.^[5] Patients with SCNSL also face a grim outlook, with reported incidence rates between 2% and 27% in aggressive NHL and a median survival of just 2.2 months.^[6]

Isolated CNS relapse without systemic recurrence is particularly rare, with only 10–30 such cases reported in the literature.^[7-10] While earlier studies suggested leptomeningeal disease as most common, recent data indicate parenchymal involvement in 40%–60% of cases, leptomeningeal disease in 20%–30%, and combined involvement in about 10%.^[11-14]

Here, we present a rare case of isolated secondary CNS relapse in an immunocompetent patient with high-risk DLBCL, initially in complete remission. The diagnosis was made based on ¹⁸F-fluorodeoxyglucose positron emission tomography/ computed tomography (¹⁸F-FDG PET/CT) findings and confirmed by cerebrospinal fluid (CSF) cytology. This case underscores the value of advanced imaging in detecting atypical CNS involvement and guiding timely management.

CASE REPORT

A 58-year-old immunocompetent female presented with a 2-month history of fever, unintentional weight loss, and bilateral cervical, axillary, and inguinal lymphadenopathy. A biopsy confirmed a diagnosis of DLBCL, activated B-cell subtype.

Initial staging with 18F-FDG PET/CT revealed extensive hypermetabolic lymphadenopathy above and below the diaphragm, diffuse splenic uptake, and extranodal involvement of the nasopharynx, ileocecal junction, cecum, ascending colon, and focal bone marrow involvement in the sternum [Figure 1].

Close

Figure 1:

(a) F-18 fluorodeoxyglucose positron emission tomographycomputed tomography maximum intensity projection image at initial staging, (b-e) Positron emission tomographycomputed tomography transaxial images revealed extensive hypermetabolic lymphadenopathy above and below the diaphragm, diffuse splenic uptake, and extranodal involvement of the nasopharynx, ileocecal junction, and focal bone marrow involvement in the sternum

Export to PPT

She was treated with six cycles of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). End-of-treatment ¹⁸F-FDG PET/CT showed a complete metabolic response.

Four months aft er treatment completion, the patient developed new-onset neurological symptoms including headache, visual disturbances, lower limb weakness, and backache. Brain magnetic resonance imaging (MRI) was unremarkable. Given the clinical suspicion of disease relapse, a restaging ¹⁸F-FDG PET/CT was performed. Maximum intensity projection images demonstrated intense linear FDG uptake along the lower vertebral column, corresponding to the spinal cord and cauda equina [Figure 2a]. Corresponding sagittal and axial PET/CT images [Figure 2b-g] showed metabolically active, discrete, and confluent intramedullary lesions in the lumbar spinal cord and focal hypermetabolic areas in the lower thoracic spine – findings suggestive of CNS lymphomatous recurrence.

Close

Figure 2:

The maximum intensity projection image revealed (a) intense linear fluorodeoxyglucose uptake along the lower part of the abdominal cavity in the midline corresponding to the region of spinal cord and cauda equina and (b,c) the corresponding sagittal and (d-g) transaxial images showed its location in the spinal canal. It reveals metabolically active discrete and confluent lesions noted involving the intramedullary region in the lumbar spine with focal areas of hypermetabolism in the lower dorsal spine

Export to PPT

CSF analysis confirmed the diagnosis. Cytology revealed lymphomatous infiltration. Immunophenotyping demonstrated 100% lymphocytes, with up to 60% B-lymphocytes expressing CD19, CD20, CD22, CD38, CD10 (variable), CD43, and CD49d. The cells were negative for CD5, CD23, CD56, CD11c, CD200, CD103, kappa, and lambda light chains. These findings were consistent with CNS involvement by DLBCL.

The patient was initiated on CNS-directed chemotherapy; however, her condition rapidly deteriorated, and she succumbed to the disease shortly thereaft er.

DISCUSSION

Isolated CNS relapse is an uncommon manifestation of DLBCL. Common sites of CNS involvement include the brain parenchyma, meninges, cranial nerves, eyes, and spinal cord. These sites pose therapeutic challenges due to the restrictive nature of the blood–brain and blood–retinal barriers.

Approximately 40% of SCNSL cases are diagnosed de novo, while the remaining 60% occur at relapse – either as isolated CNS involvement or in conjunction with systemic disease.^[11,12] The clinical presentation varies depending on the site of involvement. Common symptoms include motor deficits, headaches, cognitive decline, cranial nerve palsies, and neuropsychiatric disturbances.^[15,16] Blurred vision and floaters may occur in patients with ocular involvement.

The gold standard for diagnosing SCNSL remains histopathological confirmation via stereotactic brain biopsy or cytological examination of CSF.^[17] While the International Primary CNS Lymphoma Collaborative Group recommends contrast-enhanced MRI for the evaluation of PCNSL, its role in SCNSL is less well-established.^[18] In contrast, ¹⁸F-FDG PET/ CT has proven valuable for disease monitoring and detecting relapse in lymphoma. PET/CT is oft en more sensitive than MRI in identifying involvement of cranial nerves, nerve roots, and the cauda equina.^[19] Furthermore, it assists in disease mapping by revealing occult systemic involvement.

Definitive diagnosis typically includes CSF analysis with cell counts, protein and glucose levels, cytology, and flow cytometry, alongside evaluation of peripheral blood.^[20] Most relapses occur within 6–9 months following completion of treatment, likely due to occult CNS disease present at diagnosis or inadequate CNS prophylaxis and systemic therapy.^[21]

To better identify patients at risk for CNS involvement, the CNS International Prognostic Index (IPI) has been developed.^[22] This model incorporates the five IPI factors – age >60 years, elevated lactate dehydrogenase, Eastern Cooperative Oncology Group performance status >1, more than one extranodal site, and advanced stage (III/IV) – as well as involvement of the kidneys and/or adrenal glands. Based on the number of risk factors, patients are stratified into three groups:

• Low risk (0–1 factor): 2-year CNS relapse risk of 0.6%

• Intermediate risk (2–3 factors): 2-year risk of 3.4%

• High risk (4–6 factors): 2-year risk of 10.2%.^[23]

Our patient fell into the intermediate-risk category, with multiple extranodal sites and advanced-stage disease at diagnosis. Notably, she experienced an isolated CNS relapse within the spinal cord, which is a rare pattern. Even more uncommon was the multifocal intramedullary and cauda equina involvement, without systemic recurrence.

This case underscores the pivotal role of ¹⁸F-FDG PET/CT in diagnosing suspected SCNSL. While brain MRI was normal, PET/CT identified metabolically active lesions in the spinal cord and cauda equina, leading to prompt CSF evaluation and diagnosis confirmation. PET/CT offers superior sensitivity over MRI, detecting additional lesions that influence prognosis and therapeutic decisions. Early detection of CNS relapse through PET/CT is crucial for guiding treatment and improving outcomes in DLBCL.

CONCLUSION

This case highlights the crucial role of 18F-FDG PET/CT in detecting isolated CNS relapse in DLBCL, particularly when MRI may miss metabolically active lesions. The patient’s rare spinal cord and cauda equina involvement without systemic recurrence emphasizes the need for vigilant monitoring in high-risk patients. 18F-FDG PET/CT offers superior sensitivity, enabling early diagnosis and timely treatment, ultimately improving outcomes in these challenging cases.