Diffuse Large B Cell Lymphoma in an Adolescent: A Challenging Case with Intracerebral and Retinal Involvement

Diffuse large B-cell lymphoma (DLBCL) is a rare lymphoma type in pediatric patients with usually good prognosis. We present the difficult diagnostic procedure and the complicated course in an adolescent patient with DLBCL.

Case report: The 16-year-old female patient presented with a history of fever episodes during the past 3 weeks, hepatosplenomegaly, leukopenia, anemia, hypertriglyceridemia, massive hyperferritinemia and elevation of lactate dehydrogenase. Leukemia was excluded by bone marrow puncture. Initially, no significant lymph node enlargement was detected by imaging of the mediastinum and the abdomen but a pathological signal of the bone marrow could be observed in magnetic resonance imaging (MRI). Hemophagocytic lymphohistiocytosis (HLH) was diagnosed and the patient was treated with prednisone 0.5 mg/kg per day. The overall condition and the laboratory values improved but deteriorated on cessation of the steroid treatment. The result of the bone marrow biopsy then revealed an infiltration of a malignant B-cell lymphoma. Diagnosis of a DLBCL, Non-GCB-type with a BCL6-break was subsequently made in a biopsy of a lymphnode which had shown increased uptake in PET scan. Treatment according to the current NHL-BFM registry including administration of Rituximab was started. The course of disease was complicated by HLH symptoms with persistent fever and pancytopenia, renal failure, severe Methotrexate excretion failure requiring Carboxypeptidase treatment and Herpes virus encephalitis. After recovery progression of DLBCL was found and the treatment was switched to DA-EPOCH regimen and repeated systemic Rituximab administrations. Five months after diagnosis the girl suffered from visual impairment and convulsions. Ophthalmoscopy revealed retinal lesions and intracerebral lesions were detected by MRI but no abnormalities of cerebrospinal fluid (CSF) were found. Biopsy of a brain lesion confirmed cerebral involvement of DLBCL. Intensified treatment included high- dose steroids, cranio-spinal irradiation, high-dose Cytarabin and intrathecal Rituximab. Response of the cerebral lesions but no improvement of the visual impairment was found. Salvage treatment with Gemcitabin, Cisplatin and Rituximab was administered because of persistent nodal and extranodal lymphoma manifestations. The patient finally died due to refractory disease and severe bone marrow failure.

Conclusion: This case of DLBCL in an adolescent girl is extraordinary in many ways. DLBCL, especially the non-GCB type, is a rare disorder in pediatric patients. Predominant bone-marrow involvement has been described in only few older patients with non-GCB-type DLBCL and mostly aggressive clinical course. HLH as a presenting feature is rather observed in T- or NK-cell lymphoma than in DLBCL. Finally, central nervous system (CNS) relapse occurs in only about 6% of adults with DLBCL regardless of CNS prophylaxis. Retinal and intraparenchymal CNS involvement without abnormalities in the CSF has been typically described for primary CNS lymphoma in adults. All these conditions have contributed to the adverse outcome in our patient.