Multiparametric flow cytometry (MFC) allows discrimination between normal and neoplastic plasma cells (NeoPCs) within the bone marrow plasma cell (BMPC) compartment. This study sought to characterize immunophenotypes and quantitate the proportion of NeoPCs in BMPCs to diagnose plasma cell myeoma (PCM) and evaluate the prognostic impact of this method. We analyzed the MFC data of the bone marrow aspirates of 76 patients with PCM and 33 patients with reactive plasmacytosis. MFC analysis was performed using three combinations: CD38/CD138/-/CD45; CD56/CD20/CD138/CD19; and CD27/CD28/CD138/CD117. The plasma cells of patients with reactive plasmacytosis demonstrated normal immunophenotypic patterns. Aberrant marker expression was observed in NeoPCs, with negative CD19 expression observed in 100% of cases, CD56+ in 73.7%, CD117+ in 15.2%, CD27- in 10.5%, CD20+ in 9.2%, and CD28+ in 1.3%. In PCM patients, more than 20% of NeoPCs/BMPCs were significantly associated with factors suggestive of poor clinical outcomes. Patients who were CD27- or CD56+/CD27-, demonstrated shorter overall survival than patients of other CD56/CD27 combinations. Our results support the clinical value of immunophenotyping and quantifying NeoPCs in PCM patients. This strategy could help to reveal poor prognostic categories and delineate surrogate markers for risk stratification in PCM patients.
Adult ; Aged ; Aged, 80 and over ; Antigens, CD27/metabolism ; Antigens, CD56/metabolism ; Asian Continental Ancestry Group ; Bone Marrow Cells/*cytology/metabolism ; Female ; Flow Cytometry ; Humans ; *Immunophenotyping ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Multiple Myeloma/metabolism/mortality/*pathology ; Neoplasm Staging ; Neoplastic Stem Cells/*cytology/metabolism ; Prognosis ; Republic of Korea ; Risk Factors

BACKGROUND: Myelomatous pleural effusion (MPE) is rare in myeloma patients. We present a consecutive series of patients with MPE in a single institution. METHODS: We retrospectively reviewed the medical records of 19 patients diagnosed with MPE between 1989 and 2008 at the Asan Medical Center. Diagnoses were confirmed by cytologic identification of malignant plasma cells in the pleural fluid. RESULTS: Our patients showed dominance of IgA (36.8%) and IgD (31.6%) subtypes. Of 734 myeloma patients, the incidence of MPE was remarkably high for the IgD myeloma subtype (16.7%), compared to the other subtypes (1.4% for IgG and 4.6% for IgA). At the time of diagnosis of MPE, elevated serum beta2-microglobulin, anemia, elevated serum lactate dehydrogenase, and elevated creatinine levels were found in 100%, 89.5%, 83.3%, and 57.9% of the patients, respectively. Approximately one-third (31.3%) of the patients had adenosine deaminase (ADA) activities in their pleural fluid exceeding the upper limit of the reported cutoff values for tuberculous pleural effusion (55.8 U/L). Chromosome 13 abnormality was seen in 77.8% of the tested patients. The median survival period from the development of MPE was 2.8 months. CONCLUSIONS: Patients with MPE have aggressive clinical and laboratory characteristics. The preponderance of IgD myeloma in MPE patients is a noteworthy finding because IgD myeloma is a rare subtype. Elevated ADA activity in the pleural fluid is also noteworthy, and may be helpful for detecting MPE. Physicians treating myeloma patients should monitor the development of MPE and consider the possibility of a worse clinical course.
Adenosine Deaminase/metabolism ; Adult ; Aged ; Chromosomes, Human, Pair 13 ; Creatine/blood ; Diagnosis, Differential ; Female ; Humans ; Immunoglobulin A/metabolism ; Immunoglobulin D/metabolism ; L-Lactate Dehydrogenase/blood ; Male ; Middle Aged ; Multiple Myeloma/diagnosis ; Plasma Cells/pathology ; Pleural Effusion, Malignant/*diagnosis/mortality/pathology ; Retrospective Studies ; Survival Rate ; beta 2-Microglobulin/blood

BACKGROUND: Angiogenesis is important for the proliferation and survival of multiple myeloma (MM) cells. Bone marrow (BM) microvessel density (MVD) is a useful marker of angiogenesis and is determined by immunohistochemical staining with anti-CD34 antibody. This study investigated the prognostic impact of MVD and demonstrated the relationship between MVD and previously mentioned prognostic factors in patients with MM. METHODS: The study included 107 patients with MM. MVD was assessed at initial diagnosis in a blinded manner by two hematopathologists who examined three CD34-positive hot spots per patient and counted the number of vessels in BM samples. Patients were divided into three groups according to MVD tertiles. Cumulative progression-free survival (PFS) and overall survival (OS) curves, calculated by using Kaplan-Meier method, were compared among the three groups. Prognostic impact of MVD was assessed by calculating Cox proportional hazard ratio (HR). RESULTS: Median MVDs in the three groups were 16.8, 33.9, and 54.7. MVDs were correlated with other prognostic factors, including beta2-microglobulin concentration, plasma cell percentage in the BM, and cancer stage according to the International Staging System. Multivariate Cox regression analysis showed that high MVD was an independent predictor of PFS (HR=2.57; 95% confidence interval, 1.22-5.42; P=0.013). PFS was significantly lower in the high MVD group than in the low MVD group (P=0.025). However, no difference was observed in the OS (P=0.428). CONCLUSIONS: Increased BM MVD is a marker of poor prognosis in patients newly diagnosed with MM. BM MVD should be assessed at the initial diagnosis of MM.
Aged ; Antigens, CD34/metabolism ; Bone Marrow/metabolism/*pathology ; Disease-Free Survival ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Male ; Microvessels/*physiopathology ; Middle Aged ; Multiple Myeloma/*diagnosis/mortality ; Neoplasm Staging ; Neovascularization, Pathologic ; Plasma Cells/cytology ; Prognosis ; Proportional Hazards Models ; Regression Analysis ; Risk Factors