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Clinical presentation and diagnosis of secondary central nervous system lymphoma

Ephraim Hochberg, MD
Fred H Hochberg, MD
Section Editor
Arnold S Freedman, MD
Deputy Editor
April F Eichler, MD, MPH


Systemic non-Hodgkin lymphoma (NHL) may involve the nervous system at every level, including peripheral nerve, spinal nerve root, spinal cord, meninges, and brain. Such involvement may include direct invasion or compression of these structures, as well as non-invasive paraneoplastic effects of NHL. Whereas involvement of the central nervous system (CNS) complicates the course of a significant minority of patients, peripheral nervous system involvement is rare. (See "Overview of paraneoplastic syndromes of the nervous system".)

NHL can involve the CNS either as the sole area of disease (ie, primary CNS lymphoma) or as secondary spread of systemic disease. Secondary involvement of the CNS by NHL can present in many ways, and rapid control of CNS involvement is necessary to prevent neurologic morbidity and preserve quality of life. As such, clinicians must keep this entity high on their differential diagnosis in patients with NHL presenting with neurologic complaints. The most common manifestations of NHL involvement of the CNS include leptomeningeal disease and parenchymal brain involvement.

The clinical features and diagnosis of secondary CNS lymphoma will be discussed here. Treatment of secondary CNS lymphoma and primary CNS lymphoma are discussed separately. (See "Treatment, prognosis, and prophylaxis of secondary central nervous system lymphoma" and "Clinical presentation, pathologic features, and diagnosis of primary central nervous system lymphoma" and "Treatment and prognosis of primary central nervous system lymphoma" and "AIDS-related lymphomas: Primary central nervous system lymphoma".)


There are limited data regarding the cellular or molecular interactions that facilitate trafficking of lymphoma cells to the central nervous system (CNS). Lymphoma cells are thought to enter the CNS by hematogenous spread, direct extension from adjacent bone metastases, or by centripetal growth along neurovascular bundles. It has also been hypothesized that lymphoma cells could spread from retroperitoneal lymph nodes or bone marrow to the leptomeninges via the intervertebral venous plexus [1], although confirmatory evidence for this mode of spread is lacking.

Most episodes of CNS involvement by non-Hodgkin lymphoma (NHL) occur in the setting of relapsed disease [2]; however, a significant percentage may have had subclinical CNS involvement at the time of diagnosis. This is suggested by the high rate of CNS involvement within six months of initial therapy in many patients with aggressive NHL [3]. In addition, late CNS recurrences of NHL may represent second primary tumors. Support for this hypothesis comes from molecular studies in which immunoglobulin heavy chain (IgH) rearrangement analysis suggested a separate clonal origin for some CNS tumors arising more than three years after the initial diagnosis of NHL [4].

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Literature review current through: Nov 2017. | This topic last updated: Jul 26, 2017.
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