Observation on frequency & clinico-pathological significance of various cytogenetic risk groups in multiple myeloma: an experience from India.

BACKGROUND & OBJECTIVES: Multiple myeloma (MM) is a plasma cell malignancy characterized by cytogenetic heterogeneity. In comparison with conventional karyotyping, fluorescence in situ hybridization (FISH) can efficiently detect various genetic changes in non-cycling plasma cells in 50-90 per cent of MM cases. The present study was undertaken in MM patients to evaluate the frequency and clinico-pathological significance of various cytogenetic abnormalities in the Indian population. METHODS: Interphase FISH was applied on purified plasma cells of 475 patients with MM using specific probes. Interphase FISH for 1q gain/1q amplification was performed on a separate group of 250 newly diagnosed MM patients. RESULTS: Low frequency of Δ13 [-13/del(13q)] (32%) and t(11;14) (5%) was observed in our 475 patients probably due to ethnic diversity. Clustering of Δ13, del(17)(p13.1) and IgH translocations in non-hyperdiploidy confirmed prognostic significance of ploidy in MM. t(4;14) and del(17)(p13.1) were high-risk groups due to correlation with high serum ß2-microglobulin, increased plasma cells and advanced disease. Hyperdiploidy and t(14;16) were associated with higher age group. In a separate group of 250 patients, 1q amplification [amp(1q)] in combination with Δ13 and/or del(17p) with t(4;14) revealed association with adverse clinico-laboratory features, which confirmed progressive role of amp(1q) with adverse prognostic impact. Amp(1q) was clustered at 1q21 and 1q25 loci. INTERPRETATION & CONCLUSIONS: Based on our findings, it appears that comprehensive analysis of various cytogenetic aberrations by interphase FISH is a powerful strategy being adapted for risk stratification of MM.

Clinical impact of prostate specific antigen (PSA) inter-assay variability on management of prostate cancer.

PURPOSE: To evaluate the inter-assay variability of six commercially available prostate specific antigen (PSA) assays, its clinical impact in prostate cancer (PCa) and comparison of automated versus manual assays. PATIENTS AND METHODS: Sera from 495 patients (425 with PCa and 70 men with Benign Prostatic Hyperplasia (BPH), were measured with six different assays [three automated assays (a-PSA) and three manual ELISA based assay (m-PSA)]. Variability, agreement and bias were measured and compared among assays using Bland Altman plots and Passing and Bablok regression analysis. The possible impact of inter-assay variability on important clinical scenarios was also studied. RESULTS: All the assays were well correlated (r: 0.88-0.98); however there was significant disagreement and bias between the systems, which were more pronounced among the a-PSA assays. The Bland Altman plot showed that the variability was high between the m-PSA assays and the standard Abbott system with mean difference of 3.8-5.8ng/ml. In contrast, the a-PSA had better agreement with mean difference of 0.8-2.3ng/ml. Beckman Coulter showed the best agreement to the institutional reference (slope-1.097; 95% CI: 1.06-1.14; p<0.05, and intercept-0.20; 95% CI-0.38-0.58; p<0.05, Passing Bablok). It led to significant variability in PCa risk stratification and failure to detect biochemical failure in more than 50% cases. CONCLUSIONS: The discrepancies between the assays lead to significant clinical misinterpretation with risk group migration and detection of biochemical failure post radiotherapy. There are significant discordances between automated and ELISA based assays.

Immunophenotypic profile of plasma cell leukemia: a retrospective study in a reference cancer center in India and review of literature.

BACKGROUND: Plasma cell leukemia (PCL) is a rare but aggressive subtype of plasma cell dyscrasia. It is known to present with highly variable morphological features and may mimic with other lymphoid neoplasms. Multicolor flow cytometry (MFC) with availability of newer markers is highly useful in the diagnosis of the plasma cell leukemia. We present an immunophenotypic profile in ten cases of PCL along with their clinical and laboratory findings. MATERIALS AND METHODS: We retrospectively studied immunophenotypic profile of 10 cases of plasma cell leukemia (out of 4615 cases of hematolymphoid neoplasms) using five parameter, three color flow cytometric analysis. We also studied their clinical presentation and other laboratory findings. RESULTS: Common clinical features at presentation were weakness, bone pain, anemia, thrombocytopenia and osteolytic lesions. Plasma cell population was identified on strong expression of CD38 and co-expression of CD38 and CD138. CD56 was expressed in 44% cases. CD19 and CD20 were negative in all cases. Surface light chain restriction was seen in 50% cases and in remaining 50% cases revealed cytoplasmic light chain restriction. CD117 was expressed in one out of two cases studied. CONCLUSIONS: MFC immunophenotyping is highly useful to differentiate Plasma cell leukemia from other chronic lymphoproliferative disorders with plasmacytoid morphology as well as from non-neoplastic reactive PC and co-expression of CD38 and CD138 is a best combination to identify the plasma cells by MFC.