Neoplastic Plasma Cells Are Demonstrable at Bone Marrow Sites Distant to Solitary Plasmacytoma of Bone and Predict for Progression to Multiple Myeloma.
Authors: Hill Quentin A. , de Tute Ruth M. , Child J. Anthony , Rawstron Andy C. , Owen Roger G. 
Published: October 2019

Abstract
Solitary plasmacytoma of bone (SPB) typically present as single destructive lesions within the spinal column or long bones. Local radiotherapy is the treatment of choice but approximately 50% of patients progress to myeloma. Many patients have a monoclonal protein detectable in their serum and/or urine at diagnosis and persistence of this for greater than 1 year after radiotherapy predicts for progression to myeloma. Identification of high risk patients at the time of diagnosis is clearly desirable as it would enable risk stratification and more careful monitoring of patients. Although prophylactic adjunctive chemotherapy has not definitively been shown to benefit unselected patients with SPB, future therapeutic advances might be targeted on patients with a high risk of progression. Interestingly it has recently been shown that patients positive for serum free light chains are at greater risk of progression to myeloma. We and others have previously demonstrated that neoplastic bone marrow plasma cells are distinguishable from their normal counterparts by virtue of their lack of CD19 expression and/or their aberrant expression of CD56. We have developed a multiparameter flow cytometry assay which predicts outcome following autologous transplantation in myeloma patients and risk of progression in patients with MGUS. In this study we have applied this assay to assess the staging bone marrow specimens from patients with biopsy proven SPB for the presence of occult disease at sites distant to the primary lesion. 52 patients were included in this analysis (31 male, 21 female; median age 65) and in each case the staging bone marrow aspirate and trephine biopsy (obtained from a site distant from the SPB, typically the right iliac crest) was not indicative of myeloma (<10% plasma cells). Plasma cells comprised a median of 0.6% (0.05–6.2%) of bone marrow leucocytes while distinct populations with a neoplastic immunophenotype (>30% CD19− and/or CD56+ as per convention) were demonstrable in 35/52 (67%). Neoplastic plasma cells when present comprised a median of 70% (35–100%) of bone marrow plasma cells. 21 patients (40%) developed myeloma with a median time to progression of 476 days (range 18–1632). Progression occurred in 18 of the 35 (51%) patients with neoplastic plasma cells in their staging marrows and in 3/17 (18%) patients with a normal phenotypic profile. The difference was significant using Chi-square analysis with Yates’ correction for continuity (p=0.04). The overall risk of progression was similar in patients with a “myeloma pattern” in which >90% of bone marrow plasma cells had a neoplastic phenotype (5/12, 42%) and those with an MGUS or mixed pattern in which distinct populations of both normal and neoplastic cells are demonstrable (13/23, 57%). We would conclude that neoplastic plasma cells are frequently found at bone marrow sites distant to SPB and that their presence predicts for progression to multiple myeloma. Trials of adjuvant systemic therapy are warranted in this group.