Leptomeningeal Myelomatosis: A Rare but Devastating Manifestation of Multiple Myeloma Diagnosed Using Cytology, Flow Cytometry, and Fluorescent in situ Hybridization

Abstract

Introduction: Involvement of the central nervous system in patients with multiple myeloma is a rare event. We evaluated the diagnostic workup and prognosis of patients with leptomeningeal myelomatosis (LMM). Methods: Between April 2005 and April 2016, we identified 16 cases with LMM. The involvement was diagnosed by magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) cytology as well as flow cytometry. Fluorescence in situ hybridization (FISH) was used in 8/16 cases. In 1 case, genome-wide screening for genetic alterations using single-nucleotide polymorphism (SNP) array analysis was performed. Results: The median time from initial diagnosis until the occurrence of LMM was 434 days. At diagnosis, the median age was 60 years. The median cell count was 21/µL (range 1–1,333/µL). All CSF samples showed malignant pleocytosis, confirmed by flow cytometry in 12/16 patients. FISH revealed high-risk features in the majority of samples. Treatment for LMM consisted of intrathecal chemotherapy and radiation therapy. Genome-wide screening assays revealed different subclones. The outcome was dismal with a median overall survival after the diagnosis of LMM of 82 days. Conclusion: By combining several technical procedures, it is possible to identify most patients with LMM. Management of affected patients is challenging and the survival short after a diagnosis of LMM.

Multiple myeloma with central nervous system relapse

“…Cytological techniques can detect atypical plasma cells and flow cytometry can detect monoclonal CD38/CD138 expressing cells in CSF in approximately 90% of CNS-MM cases, thus confirming the disease. 8,41 CSF cytology and flow cytometry are both particularly useful since the former can employ immunocytochemistry to identify unknown tumors, 42 and the latter can be used to distinguish the clonal plasma cells found in MM from polyclonal plasma cells present in CSF in other conditions. 43 Furthermore, the presence of a paraprotein, including clonal free light chains (FLC), in CSF obtained from a clean lumbar puncture, can be diagnostic.…”

Thiotepa intrathecal injections for myelomatous central nervous system involvement

“…Thus, overall survival after CNS-MM treatment appears to be at least twice that observed in previously published studies, of which more than half used intrathecal injection with methotrexate, cytarabine and methylprednisolone. [3][4][5][6][7][8][9] These encouraging results could be explained by a majority of focal invasive dural damage. However, the biological and radiological evidence surrounding this clinical outcome appears to reflect the efficiency of the alkylating agent thiotepa.…”

“…2 In particular, central nervous system (CNS) involvement is a critical prognostic indicator, with overall survival of less than 6 months. [3][4][5][6][7][8][9] Because of its rarity, there is no consensus on the optimal treatment. Radiotherapy is the subject of controversy, in terms of both efficacy and toxicity.…”

Isolated Leptomeningeal Recurrence of Multiple Myeloma

“…1 The median onset from MM diagnosis to LMM is approximately 390 to 434 days. 1,2 Our patient is atypical because LMM was diagnosed 7 years after his MM diagnosis. This prolonged latency is rare.…”

“…Neuroimaging may be negative in 30% of cases. 2 Although the optimal therapy is unestablished, treatment typically involves intrathecal chemotherapy and sometimes craniospinal radiotherapy. 3…”