Chronic Lymphocytic Leukemia Presenting with Concurrent Isolated CNS Parenchymal and Leptomeningeal Large B-Cell Lymphoma

Case Report

Ann Hematol Oncol. 2016; 3(6): 1098.

Chronic Lymphocytic Leukemia Presenting with Concurrent Isolated CNS Parenchymal and Leptomeningeal Large B-Cell Lymphoma

Dunbar M

Dilli E

Slack GW

Villa D

1Department of Pediatrics, University of British Columbia, Canada

2Division of Neurology, University of British Columbia, Canada

3Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency, Canada

4Division of Medical Oncology and Centre for Lymphoid Cancer, British Columbia Cancer Agency, Canada

*Corresponding author: Diego Villa, Division of Medical Oncology and Centre for Lymphoid Cancer, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, BC V5Z 4E6, Canada

Received: June 20, 2016; Accepted: August 06, 2016; Published: August 09, 2016


A previously well 59-year-old man presented with two weeks of progressive vertigo, ataxia, vomiting and diplopia. Computed tomography (CT) revealed multifocal areas of cerebral and cerebellar edema with contrast enhancement and magnetic resonance imaging with gadolinium also showed diffuse leptomeningeal enhancement with evidence of parenchymal invasion. Cerebrospinal fluid analysis identified malignant lymphocytes consistent with a large B-cell lymphoma. CT of the neck, chest and abdomen did not demonstrate hepatosplenomegaly or lymphadenopathy and peripheral blood counts showed a mild lymphocytosis. Bone marrow biopsy was consistent with chronic lymphocytic leukemia (CLL). Symptoms initially improved with corticosteroids, but the patient declined active therapy and died one month later of progressive central nervous system (CNS) disease. Patients with CLL may rarely develop CNS involvement. Even more rarely, some of these patients can present with aggressive histology lymphoma in the CNS. There is no standard treatment for CNS CLL or large B-cell lymphoma in these patients; although agents that cross the blood-brain barrier and intrathecal chemotherapy are most commonly used. The presence of large B-cell lymphoma involving the CNS appears to double six-month mortality compared to secondary CNS involvement by CLL.

Keywords: Chronic lymphocytic leukemia; CNS lymphoma; Richter syndrome; Transformation


CT: Computed Tomography; CLL: Chronic Lymphocytic Leukemia; CNS: Central Nervous System; RS: Richter Syndrome; DBLCL: Diffuse Large B-cell Lymphoma; MRI: Magnetic Resonance Imaging; CSF: Cerebrospinal Fluid


The natural history of chronic lymphocytic leukemia (CLL) is variable: approximately one third of patients experience longterm survival without need for treatment, one third are initially asymptomatic but eventually experience disease progression requiring therapy and one third have symptomatic disease requiring immediate treatment [1]. Approximately 2-10% patients may experience transformation to an aggressive lymphoma, commonly known as Richter’s syndrome (RS) [2]. RS is a rare and fatal complication of CLL with an average survival of 8-12 months [3]. The most common aggressive histology is diffuse large B cell lymphoma (DLBCL) [3].

Symptomatic central nervous system (CNS) involvement in CLL is known to be rare, with only 92 cases described in a recent review of the literature [4]. Asymptomatic CNS involvement identified on autopsy is much more common, between 6-50% [5-7]. In most cases, CNS involvement in CLL occurs within five years of diagnosis, although in a very small subset CNS symptoms are the first presentation of CLL [8-16]. RS can rarely present in the CNS with parenchymal invasion causing encephalopathy, seizures and hemiparesis, or with lymphomatous meningitis [17-32]. Regardless of histology, leptomeningeal infiltration is associated with a median overall survival of 4-6 weeks if untreated [33].

It is exceptionally uncommon for patients to present with newlydiagnosed CLL together with DLBCL involving exclusively the CNS [34-36]. Here we present a case of CLL presenting concurrently with large B-cell parenchymal and leptomeningeal involvement and review the clinical characteristics, treatment and prognosis of this uncommon disease presentation.

Case Presentation

A 59 year-old right-handed man of Chinese ancestry presented with a two-week history of worsening vertigo, ataxia, vomiting and diplopia. His past medical history was only significant for mild hypertension and remote smoking.

Temperature was 37 degrees Celsius, blood pressure estimated by an automatic blood pressure monitor was 153/90 mmHg, heart rate was 72 beats per minute and respiratory rate was 16 breaths per minute. There was no peripheral lymphadenopathy or hepatosplenomegaly. Mental status and language were normal. The pupils were equal and reactive to light and funduscopic examination was normal. There was right beating nystagmus upon right, upward and downward gaze. Saccades were hypometric to the right. There was decreased auditory perception in the left ear. The remainder of the cranial nerve exam was normal. In all four limbs, power was intact (grade 5/5), with decreased tone and reduced reflexes. There was bilateral dysmetria, left greater than right, as well as slow rapid alternating movements in the upper extremities. There was marked ataxia in both legs and gait was ataxic and right-veering.

Peripheral blood cell counts showed white blood cells 13.5x109/L (absolute lymphocyte count 4.7x109/L), hemoglobin 134 g/L, platelets 215x109/L. Serum sodium was 140 mmol/L, potassium 3.9 mmol/L, urea 6.7 mmol/L, creatinine 99 mmol/L, alanine aminotransferase 21 U/L, aspartate aminotransferase 10 U/L, lactate dehydrogenase 125 U/L. Hepatitis B, Hepatitis C and Human Immunodeficiency Virus serologies were negative. Computed tomography (CT) of the neck, chest, abdomen and pelvis did not reveal hepatosplenomegaly or lymphadenopathy. CT head demonstrated bilateral multifocal cerebral and cerebellar areas of vasogenic edema with nodular cortical and cerebellar enhancement and increased vascularity on the CT angiogram (Figure 1A). Caudal images of the head/neck CT identified possible paralysis of the left vocal cord. Magnetic resonance imaging (MRI) with gadolinium demonstrated diffuse contrast enhancement throughout the entire subarachnoid space of the brain and spinal canal. There were multiple leptomeningeal foci along the left cerebral hemisphere and superior cerebellum with marked intraparenchymal edema and restricted diffusion suspicious for parenchymal invasion (Figure 1B).