Cerebrospinal Fluid (CSF) Involvement By Plasma Cell Dyscrasias – Single Center Experience

Introduction:

Central nervous system (CNS) involvement by plasma cell dyscrasias (PCD) is uncommon but poses significant clinical challenges and has a dismal prognosis. Lumbar puncture (LP) is typically performed only for patients with neurologic signs or symptoms and data on patients with CNS involvement are rather scarce. Here, we report a retrospective single institution review of clinicopathological features and treatment outcomes in the setting of cerebrospinal fluid (CSF) involvement by PCD.

Methods:

We identified consecutive patients with plasma cell disorders who had abnormal cytology or flow cytometry results in the CSF in the Department of Hematopathology database at Moffitt Cancer Center from 1997 to 2014. Cytology slides [Wright-Giemsa (WG) and Papanicolaou (Pap) stained preparations] and the corresponding flow cytometry were reviewed to confirm the diagnosis. Four-color flow cytometry was performed using antibodies against CD38, CD138, CD56, CD117, CD19, and cytoplasmic kappa and lambda light chains, withadditional markers added when necessary. Clinical variables were abstracted from the patient medical records. Overall survival was estimated from the time CSF involvement was identified using the Kaplan-Meier method.

Results:

Sixty-seven Pap-stained cytology smeas/cytospins and WG stained cytospins from 65 patients who underwent LP for clinical suspicion of CSF involvement were reviewed. Flow cytometry was preformed on 48 cases positive for atypical plasma cells by cytology. Sixteen of 67 (23.9%) were suspicious or diagnostic for PCD (median age of 58 years (range 44 – 75), 56% were male). However, only 4 of 16 cases (25%) were diagnosed as PCD by cytology without additional flow cytometry study. Median tumor load of PCD by flow cytometry was 81% (range 4 - 99%). PCD included 14 patients (88%) with multiple myeloma [MM; 1 patient progressed to secondary plasma cell leukemia (PCL)], 1 with primary PCL, and 1 with Waldenström macroglobulinemia (Neel-Bing syndrome). Of the 14 MM patients, 57% had high-risk disease by cytogenetics/FISH, and immunophenotypes were IgA (50%), IgG (29%), and light chain (21%). All MM patients had Durie-Salmon stage 3 disease. Median number of prior therapies was 2 (1-4), and 44% received stem cell transplant prior to CSF involvement. Median time from diagnosis to CSF involvement was 23 (range, 6 – 78) months. Presenting symptoms included diplopia/vision loss (31%), headache (25%), and leg weakness (cauda equina/cord compression) (19%). Two patients presented with gross orbital involvement and new/enlarging scalp lesions. On radiologic imaging, 5 (31%) had leptomeningeal, 4 (25%) had epi- or extra-dural, and 2 (13%) had dural enhancement/lesions. None had CSF involvement at the time of initial PCD diagnosis. Treatment included intrathecal chemotherapy (methotrexate, cytarabine or triple regimen; 86%), radiation therapy (including whole brain, craniospinal, radiosurgery or involved field; 63%) and systemic chemotherapy (65%). One patient did not receive treatment due to poor performance status. For 5 patients who had repeat CSF analyses, only one had no evidence of disease on cytology but flow cytometry remained positive. Six-month overall survival rate was 20.2% (95% CI 4.4 – 43.5). At the time of data review, only 2 patients were alive.

Conclusions:

CSF involvement by PCD carries extremely limited prognosis and represents advanced stage of the disease. Patients may be treated with systemic therapy as well as CNS-directed therapy, though the outcomes are dismal. Careful assessment of patients’ neurologic symptoms and low threshold for performing LP is required for early detection of CSF involvement. Application of flow cytometry appears to be a useful tool in the diagnosis of CSF involvement by PCD; improving sensitivity and specificity over cytology alone, particularly when the tumor load is low or cytologically equivocal for atypical plasma cells. Further research is needed to improve the outcomes of these patients.