Elsevier

Clinical Radiology

Volume 70, Issue 8, August 2015, Pages 890-897
Clinical Radiology

Pictorial Review
Intracranial involvement by multiple myeloma

https://doi.org/10.1016/j.crad.2015.03.014Get rights and content

Intracranial involvement is a rare complication of multiple myeloma. It results either from direct extra-osseous spread from adjacent skeletal plasmacytomas or extra-medullary disease via haematogenous dissemination. The imaging appearances are non-specific, and dural, leptomeningeal, and parenchymal involvement can all occur. The purpose of this review is to illustrate the various neuroimaging appearances of this rare entity, focusing on MRI.

Introduction

Multiple myeloma (MM) is a neoplastic proliferation of plasma cells. The annual age-adjusted incidence is approximately 5.6 per 100,000, with a median age at diagnosis of approximately 70 years.1 In the majority of patients, it has been shown to evolve from monoclonal gammopathy of unknown significance (MGUS).2 Patients may present early with MGUS or asymptomatic myeloma (also known as smouldering myeloma), neither of which require therapy outside the context of a clinical trial. Alternatively, the diagnosis may be made at a more advanced stage requiring active therapy, such as symptomatic MM or, rarely, plasma cell leukaemia. Skeletal involvement occurs in 80–90% of patients with MM,3 whereas extramedullary disease is relatively uncommon.4 In a large series of 1003 patients with MM, Varettoni et al.4 reported extramedullary disease in 7% of patients at presentation and in a further 6% of patients later in their course, most commonly consisting of a single plasmacytoma, usually within soft tissues surrounding the axial skeleton.4 Treatment of MM typically involves chemotherapy and/or autologous stem cell transplantation. The chemotherapy regimen generally includes a combination of older agents (such as prednisolone and melphalan) and novel therapies (such as thalidomide, lenalidomide, and bortezomib).1

The majority of patients with plasma cell disorders have generalised disease, as outlined above, but a minority (<5%) present with a solitary lesion: either solitary plasmacytoma of bone or, less commonly, solitary extramedullary plasmacytoma.5 Solitary plasmacytoma of bone most commonly affects the axial skeleton, in particular the vertebrae, while solitary extramedullary plasmacytomas most commonly occur in the head and neck.5 The appearances of a solitary plasmacytoma are the same as for a plasmacytoma occurring in the context of MM, hence the diagnosis requires additional investigations to exclude further lesions (for example, with a skeletal survey and magnetic resonance imaging [MRI] of the spine) or systemic involvement (with a full blood count, biochemistry, serum immunoglobulins, serum and urine protein electrophoresis, and bone marrow aspirate and trephine).5 Plasmacytomas are highly radiosensitive, thus these patients are treated with radiotherapy with curative intent, achieving local control rates of 80–100%.5 Both conditions typically occur at a younger age than MM, with the median age at diagnosis about 55 years for solitary plasmacytoma of bone and 60 years for solitary extramedullary plasmacytoma.5, 6 Of the two conditions, solitary plasmacytoma of bone has a worse prognosis, as the majority of patients progress to MM within 2–4 years, whereas progression to MM is less frequent with solitary extramedullary plasmacytoma.5

Spinal cord compression is a common cause of acute neurological symptoms in MM, cited as occurring in 5–20% of patients with MM during the course of their disease, and it may occur at presentation. It is either due to extra-osseous extension of a plasmacytoma or, less frequently, a pathological crush fracture.7, 8 In contrast, direct central nervous system (CNS) involvement is a rare complication of MM. Incidence based on the presence of meningeal myelomatosis (malignant plasma cells in the cerebrospinal fluid) is approximately 1%.9 Patients usually present with cerebral symptoms such as headaches or cognitive dysfunction.10 CNS involvement most commonly results from direct extra-osseous spread from an adjacent skeletal plasmacytoma.11 Extramedullary disease can also occur via haematogenous dissemination, and most commonly involves the leptomeninges.12 Parenchymal involvement is the least common manifestation.10

Historically, CNS involvement presented early in the course of disease. In recent times, however, it is usually a later manifestation occurring after several lines of therapy, including a variety of conventional and novel agents and autologous stem cell transplantation.13 The incidence of CNS involvement appears to be increasing, and it has been hypothesised that novel chemotherapeutic agents may alter the natural history of the disease by changing the tumour microenvironment.13 Other factors contributing to the increased incidence include the greater sensitivity of modern imaging (in particular, the advent of and improvements in MRI), improved survival of patients with MM and clonal selection.4, 14 Disease features associated with CNS involvement include unfavourable cytogenetic abnormalities, high tumour burden, and other extramedullary manifestations.9 There is no standard of care in the management of CNS myeloma, and unfortunately, the prognosis after CNS spread is poor, with a median survival of only a few months despite aggressive modern therapy.13

Section snippets

Skull and dural involvement

Dural involvement is the most-common intracranial manifestation of MM and usually occurs due to direct extension of a plasmacytoma of the skull (Fig 1).11 In contrast, primary dural involvement is rare and can cause diagnostic difficulties by mimicking more common lesions, in particular, meningioma.15 Calvarial plasmacytomas are also non-specific in appearance. Due to their cellularity, they may be hyperdense on pre-contrast computed tomography (CT)16 (Fig 2), similar to differentials such as

Conclusion

In contrast to the relatively common occurrence of acute neurological symptoms in patients with MM due to compression of the spinal cord and cauda equina, intracranial involvement is rare. The incidence of intracranial involvement is increasing, however, and it has a poor prognosis. Dural involvement due to a calvarial plasmacytoma is the most frequent intracranial manifestation of MM, wherease haematogenous disease most commonly affects the leptomeninges. Parenchymal lesions are rare and vary

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      MRI will show linear or nodular leptomeningeal enhancement. Leptomeningeal disease can be confirmed with cerebrospinal fluid analysis and is usually treated with intrathecal chemotherapy, although the prognosis is poor.25–29 Spinal parenchymal myeloma is extremely rare and typically appears as focal lesions with T1 hypointense and variable T2 hyperintensity in relation to the cord but almost all enhance compared with the cord.25–29

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