Multiple Myeloma With Leptomeningeal Involvement: A Study of Three Cases Exploring Diagnosis and Treatment Challenges

Abstract

Central nervous system (CNS) involvement in multiple myeloma (MM) is a rare but serious complication that poses significant diagnostic and therapeutic challenges. This article presents three cases of leptomeningeal involvement in patients with MM, highlighting the diverse clinical presentations, diagnostic approaches, and treatment strategies employed. The first case is a 54-year-old female who, after initial treatment and autologous hematopoietic stem cell transplant, developed CNS disease. Similarly, a 73-year-old female developed leptomeningeal involvement with progressive neurological symptoms. The third case describes a 63-year-old female with immunoglobulin (Ig)A lambda MM who developed CNS disease after treatment with daratumumab and radiation. In all three cases, leptomeningeal enhancement and atypical plasma cells were identified in cerebrospinal fluid (CSF), with treatment strategies including intrathecal chemotherapy, systemic therapy, radiation, and stem cell transplantation. Despite aggressive management, including novel agents and supportive care, all patients had poor outcomes, with two transitioning to hospice care. The article reviews the limited literature on CNS-MM, noting the lack of standardized treatment protocols and the need for further research. As the survival of MM patients improves, the incidence of CNS involvement is expected to rise, making the development of targeted therapies essential. These cases underscore the urgent need for further investigation into novel treatment options and the importance of early diagnosis and comprehensive management of CNS-MM.

Keywords: leptomeningeal involvement; mm cns; multiple myeloma; multiple myeloma with cns involvement; multiple myeloma with extramedullary disease.

Figure 1. Bone marrow morphology showing bone marrow effacement with plasma cells with plasmablastoid features

Panels A-C: Bone marrow showing effacement with plasma cells exhibiting plasmablastoid features at low, intermediate, and high magnifications, respectively.

Figure 2. MRI imaging of extra-axial mass in the right occipital lobe

Panel A: Axial T2-weighted MRI image showing a new extra-axial mass in the right occipital lobe, extending toward the cerebellum. Panel B: Sagittal T2-weighted MRI image of the same patient, highlighting the continuity of the extra-axial mass from the right occipital lobe to the cerebellum.

Figure 3. Coronal CT and PET imaging of multiple enhancing masses in the left abdomen

Panel A: Coronal CT scan of the abdomen and pelvis showing a conglomerate of multiple enhancing masses (red arrows) located in the left abdomen. Panel B: Coronal PET scan highlighting the same conglomerate of masses (red arrows) with increased metabolic activity, consistent with enhancing lesions. Both imaging modalities demonstrate the presence and localization of the masses in the left abdominal region.

Figure 4. Bone marrow infiltration by plasma cells with plasmablastic features

Panels A-C: Bone marrow showing effacement with plasma cells exhibiting plasmablastic features at low, intermediate, and high magnifications, respectively.

Figure 5. Axial brain MRI in T2-weighted FLAIR sequence demonstrating leptomeningeal enhancement and hyperintensity

Panel A: Axial T2-weighted fluid attenuated inversion recovery (FLAIR) MRI showing extensive abnormal hyperintense signal and leptomeningeal enhancement in the supratentorial compartment (red arrow), raising concern for leptomeningeal involvement. Panel B: Axial T2-weighted FLAIR MRI of the infratentorial compartment exhibiting similar extensive abnormal hyperintense signal and leptomeningeal enhancement (red arrow), further suggesting leptomeningeal disease.

Figure 6. PET scan imaging of hypermetabolic osseous lesions

Panel A: Positron emission tomography (PET) scan showing a lucent lesion in the right head of the humerus, indicated by the arrow, with a standardized uptake value (SUV) max of 4.0. Panel B: PET scan showing a lucent lesion in the right iliac bone (red arrow), depicting a lytic lesion with an SUV max of 5.1.

Figure 7. MRI imaging of osseous lesions in the calvarium and spine consistent with multiple myeloma

Panel A: T2-weighted coronal MRI scan of the brain displaying osseous lesions in the calvarium (red arrows). Panel B: T2/Short Tau Inversion Recovery (T2/STIR) sagittal MRI scan of the spine showing spinal lesions at the cervical and thoracic levels (red arrows).

Figure 8. CSF cytology showing atypical plasma cells

CSF: Ceebrospinal fluid.