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Background & objectives: Diagnosis of myelodysplastic syndromes (MDS) is subjective in low-grade cases with 1 cell compartment could diagnose most MDS patients. Patients with high flow scores had high R-IPSS scores. Patient with flow score ≥3 and borderline cytomorphology should be observed closely for the development of MDS.

The Myelodysplastic/myeloproliferative category of myeloid neoplasms includes clinical, laboratory, and morphologic features that overlap between MDS and MPN. In this category are included MDS/MPN with ring sideroblasts with marked thrombocytosis, atypical CML, (BCR-ABL1 negative), and chronic myelomonocytic leukemia. JMML and unclassifiable MDS/MPN. In MDS/MPN the karyotype is often normal or shows abnormalities in common with MDS. Mutations are seen in a high proportion of cases, most common being SRSF2, TET2, and or ASXL1 in more than 80% cases. Co-mutation of SRSF2 and TET2 is highly specific for patients with CMML.

Progression of Chronic Myeloid Leukemia from chronic phase to accelerated phase to blast crisis is often associated with secondary chromosomal aberrations, such as trisomy 8, trisomy 19, duplication of Ph chromosome, isochromosome 17 q, acquisition of t(1;21) or translocations and inversions associated with AML/Myelodysplasia and show complex karyotypes.

Cytogenetic studies have become a critical factor in the workup of hematologic neoplasms. They provide invaluable information for diagnosis, prognosis, and clinical decision-making for the disease.

Molecular diagnostic testing has virtually become a routine part of characterization of hematologic malignancies. In addition to confirming or refining or establishing new diagnoses, it is used extensively to stage patients, to follow them for response to therapy and disease recurrence as well as for predicting prognosis.

CLL is often marked by cytogenetic aberrations (up to 80% of patients may show abnormalities by FISH) which are critical in risk stratification. Among them, deletions of 11q, 13q, 17p, and trisomy 12 play an important role in CLL pathogenesis and evolution determining patient outcomes and therapeutic strategies. FISH analysis has been implemented as the gold standard for diagnosis. It has also been used very effectively in the diagnosis of non-Hodgkin’s Lymphoma employing BCL-2, BCL-6, and MYC gene alterations for classification and defining the subgroups of NHLs for determining therapeutic strategies.

The use of Next Generation Sequencing is being increasingly sought to be included in routine clinical use for more differentiated disease classification, risk stratification and therapeutic decisions, particularly in AML, MDS, and MPNs. But unexpected challenges are being faced towards interpretation and implementation of the results obtained.

Acute promyelocytic leukemia is a distinct subset of acute myeloid leukemia with characteristic clinical, morphological and genetic features. The gene product PML-RAR alpha resulting from reciprocal t(15;17) translocation, plays a pivotal role in the pathogenesis of acute promyelocytic leukemia and classified as favorable cytogenetic features. We are describing an unusual additional chromosomal abnormality t(2;3) in APL patient.

Hereditary spherocytosis (HS) is the most common congenital hemolytic anemia, characterized by anemia, jaundice, and splenomegaly. The diagnosis of HS relies on symptoms of hemolysis, a family history of HS, and a positive laboratory test which is usually the osmotic fragility test (OFT). We conducted a study to assess the utility of mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), mean sphered cell volume (MSCV), and mean reticulocyte volume (MRV) in the diagnosis of HS and if these are helpful in distinguishing cases of HS from immune hemolytic anemia.A total of 102 patients suspected to have HS were enrolled. In addition 10 cases of immune hemolytic anemia (IHA) were included in the study and performance of the above screening tests was evaluated. The diagnosis of HS was based on incubated OFT, eosin 5'-maleimide (EMA) dye binding test, and flowcytometric OFT.A total of 29 patients were diagnosed as having HS. The sensitivity and specificity for diagnosis HS by MCHC 35 g/dL was 44.82%, and ΔMCV-MSCV 10 fL has a sensitivity and specificity of 82.75% and 95.9% for diagnosis of HS. Using an algorithm of ΔMCV-MSCV 10 fL and ΔMRV-MSCV 25, for the differentiation of HS from IHA had sensitivity of 68.9% and specificity of 98.8%.

A 66-year-old woman presented with melena for 5 months with an episode of haematemesis. Ultrasonography revealed hepatosplenomegaly. Her complete blood count showed anaemia (haemoglobin of 44 g/L), hyperleucocytosis (total leucocyte count 323.99×109/L) and thrombocytopenia (platelets of 40×109/L

Background: The use of novel agents for induction prior to autologous stem cell transplantation (ASCT) has considerably improved the complete response (CR) rate in multiple myeloma (MM) patients. There are very few studies from the developing countries on the use of novel agents followed by ASCT. Aims and Objectives: The current study was aimed for retrospective evaluation of the efficacy and response rates of induction with bortezomib (Velcade) plus dexamethasone (VD regimen) followed by ASCT in Indian patients. Materials and Methods: Ten patients with newly diagnosed, symptomatic MM who had received four cycles of VD induction before stem cell collection were evaluated. High dose melphalan was given for conditioning followed by stem cell transfusion. Thalidomide or lenalidomide was used as post-transplantation maintenance treatment. Results: Post VD induction, the overall response rate (ORR) was 90% including 20% CR, 40% very good partial response (VGPR), and 30% partial response (PR). Post ASCT, the ORR was 100%, including 80% CR and 20% VGPR. The 5-year overall survival and progression free survival rates were 65.6% and 57.1%, respectively. Conclusions: The VD induction regimen was effective and well tolerated in this retrospective analysis of Indian patients with newly diagnosed MM. It significantly improved the post-induction and post-transplant response rates without affecting stem cell collection. Asian Journal of Medical Sciences Vol.7(4) 2016 44-48

Introduction Hereditary spherocytosis (HS) is the most common inherited hemolytic anemia with heterogeneous clinico-laboratory manifestations. We evaluated the flow-cytometric tests: eosin-5'-maleimide (EMA) and flow-cytometric osmotic fragility test (FOFT) and the conventional osmotic fragility tests (OFT) for the diagnosis of hereditary spherocytosis (HS). Methods One hundred two suspected HS patients underwent EMA, FOFT, incubated OFT (IOFT), and room temperature OFT (RT-OFT). In addition, 10 cases of immune hemolytic anemia (IHA) were included, and performance of the above 4 tests was evaluated. For EMA and FOFT, 5 normal controls were assessed together with the patients and cutoffs were calculated using receiver-operator-characteristics curve (ROC) analysis. Results The best cutoff for %EMA decrease was 12.5%, and for FOFT, %residual red cells (%RRC) was 25.6%. The sensitivity and specificity of RT-OFT was 62.06% and 86.3%, respectively, while that of IOFT was 79.31% and 87.67%, respectively. Both flow cytometric tests performed better. Sensitivity and specificity of EMA was 86.2% and 93.9% respectively, and that of FOFT was 96.6% and 98.63%, respectively. The combination of the FOFT with IOFT or EMA dye-binding test yields a sensitivity of 100%, but with EMA, it had a higher specificity. Hb/MCHC was a predictor of the severity of the disease while %EMA decrease and %RRC did not correlate with severity of the disease. Conclusion Flow-cytometric osmotic fragility test is the best possible single test followed by EMA for diagnosis of HS. A combination of FOFT and EMA can correctly diagnose 100% patients. These tests are likely to replace conventional OFTs in future.

Title: "A prospective observational study of clinico-pathological features, prognostic factors and treatment response to primary therapy in Multiple Myeloma at a tertiary care centre" Background: Multiple myeloma (MM) is characterised by the neoplastic proliferation of plasma cells leading to excess monoclonal immunoglobulins. The incidence of multiple myeloma in India ranges from 1.2 to 1.8 per 100,000. There is paucity of cytogenetic data from this part of subcontinent. The aim of our study is to report various clinicopathological features, evaluate biological markers of prognostication including cytogenetic variables and assess treatment response after standard primary therapy. Methods and Materials: The study was carried out at a tertiary care center in Northern India. After final diagnosis of multiple myeloma was established, each patient was risk stratified via FISH cytogenetic analysis as per the revised ISS. Definitive management plan was individualised, including assessment for high dose therapy with peripheral blood stem cell support. Treatment response were recorded as per standard IMWG response criteria. Significant toxicities associated with treatment were also recorded. Results: Eighty consecutive patients with newly diagnosed multiple myeloma were enrolled prospectively from April 2017 to November 2018. The median age at diagnosis was 63 years, and number of males & females were equal. The most common presenting symptom was back pain (67.8 % patients) and most frequent clinical sign was pallor (86.4 %). All four CRAB features were documented only in 16.9% patients. M-Band was present in 96.6% patients and on SFLC assay 59.3% and 40.7% were kappa and lambda light chain restricted respectively. Most common heavy chain abnormality detected was IgG. Seventy percent patients had lytic lesions on imaging while only 3% suffered skeletal related events. Cytogenetic evaluation by interphase FISH was carried out in all patients upfront. No chromosomal abnormality was documented in 61.25 % while among those with chromosomal abnormalities, most commonly detected was del13q14.3 (23.75 %). Overall, 66.6% patients were stratified as standard risk, 28.1% as intermediate risk and only 3 (5.3%) patients were categorised as high risk. Most common induction regimen was VRD. Overall response rate was 94.9 % and VGPR or better responses were observed in 77.9% patients. Most common adverse effect of therapy was peripheral neuropathy of all grades. Of the 77 patients who completed primary therapy, 21.4% patients underwent high dose therapy with peripheral blood stem cell support while 67.7% patients were started on maintenance therapy. Four (5.1 %) non-responder was started on 2nd line treatment. On univariate analysis, higher deeper responses (VGPR or better) were observed in patients with IgA & IgG related myeloma and better overall response rates were seen in IgG related myeloma. Those with kappa light chain myeloma had 5.67 times higher likelihood of achieving response as compared to lambda light chain myeloma. Also, patients with kappa light chain myeloma achieved higher VGPRs as compared to lambda light chain myeloma. There was 17 times high risk of non-response in the presence of local bony tenderness. None of the findings were found to be significant on multivariate analysis. Conclusions: Use of interphase FISH to identify various cytogenetic markers help in stratification & staging of the disease which in turn act as a marker for prognostication. They should be a part of standard care in multiple myeloma. In majority we could administer treatment in accordance to standard practice guidelines and response rates were similar to those reported my seminal studies. Our study in a longer follow up will yield some useful information which will help in the better care of the patients. Disclosures No relevant conflicts of interest to declare.

Non-immune haemolysis is a rare manifestation of acute leukaemia and more so in acute myeloid leukemia. Here, we report a case of non-immune and non-fragmentation haemolysis as the initial presenting manifestation in a 55-year-old female with acute myeloid leukaemia (AML-M6). All other potential aetiologies of haemolysis were excluded, including drugs, paroxysmal nocturnal haemoglobinuria, immune and other known congenital and acquired causes of haemolytic anaemia. This case shows that malignant haematopoietic disorders should be considered in patients with newly diagnosed haemolysis.

Fanconi anemia (FA) is a genetically and phenotypically heterogeneous recessive disorder characterized by diverse congenital malformations, progressive pancytopenia and predisposition to both hematologic malignancies and solid tumors. We report, a 14-year-old boy who presented with clinical features of aplastic anemia (AA). Subsequent bone marrow examination and multiparametric flowcytometric immunophenotyping revealed an evolving hypoplastic acute myeloid leukemia. Chromosomal breakage studies using clastogenic agent mitomycin C showed 88% stress induced chromosomal/chromatid breaks, gaps and rearrangements revealing an underlying FA. The case emphasizes upon the role of a systematic clinico-investigative approach in diagnosing such patients who by clinical criteria appear to have idiopathic AA and appear phenotypically normal. A timely and accurate diagnosis becomes vital in these cases to implement appropriate therapy.

SummaryIntroduction Tropical febrile illnesses such as malaria and dengue are challenging to differentiate clinically. Automated cellular indices from hematology analyzers may afford a preliminary rapid distinction. Methods Blood count and VCS parameters from 114 malaria patients, 105 dengue patients, and 105 febrile controls without dengue or malaria were analyzed. Statistical discriminant functions were generated, and their diagnostic performances were assessed by ROC curve analysis. Results Three statistical functions were generated: (i) malaria-vs.-controls factor incorporating platelet count and standard deviations of lymphocyte volume and conductivity that identified malaria with 90.4% sensitivity, 88.6% specificity; (ii) dengue-vs.-controls factor incorporating platelet count, lymphocyte percentage and standard deviation of lymphocyte conductivity that identified dengue with 81.0% sensitivity and 77.1% specificity; and (iii) febrile-controls-vs.-malaria/dengue factor incorporating mean corpuscular hemoglobin concentration, neutrophil percentage, mean lymphocyte and monocyte volumes, and standard deviation of monocyte volume that distinguished malaria and dengue from other febrile illnesses with 85.1% sensitivity and 91.4% specificity. Conclusions Leukocyte abnormalities quantitated by automated analyzers successfully identified malaria and dengue and distinguished them from other fevers. These economic discriminant functions can be rapidly calculated by analyzer software programs to generate electronic flags to trigger-specific testing. They could potentially transform diagnostic approaches to tropical febrile illnesses in cost-constrained settings.

Therapy-related myelodysplastic syndromes (t-MDS) occurring after the successful treatment of acute myeloid leukaemia (AML) are rare and may be difficult to distinguish from relapse of the primary leukaemia, especially if the second neoplasm overlaps morphologically with the initial one. We report a 78-year-old male who, 3 years after treatment for acute monocytic leukaemia, developed t-MDS (refractory anaemia with excess blasts-2) that was initially suspected to be a relapse. Cytogenetic analysis of the initial AML had revealed +8 and del(16). These abnormalities disappeared, along with monocytic markers on flow cytometry, 3 years later, and a new t(3;7) event was found instead. The cytogenetic findings, together with the clinical profile, the morphological data and the immunophenotypic shift, were crucial in correctly recognizing the t-MDS and excluding relapse. Repeat genetic and immunological analyses are often omitted at the time of morphologically evident relapse in AML, especially for economic reasons in resource-constrained settings. Our case shows that such investigations may be invaluable in avoiding a misdiagnosis and, indeed, may help reveal the true incidence of t-MDS/t-AML in treated AML patients.

This retrospective analysis of 254 children less than 15 years of age treated with MCP-841 protocol from June 1992 to June 2002 was undertaken to identify the pattern of relapse and determine management lacunae. Two hundred twenty-three (87.8%) children achieved a complete remission of whom 40 (17.9%) relapsed. The mean age of relapsed patients was 6.5 years. The male/female ratio was 9:1. There were 23 (57.5%) isolated bone marrow (BM), 7 (17.5%) isolated central nervous system (CNS), 2 (5%) isolated testicular, 5 (12.5%) BM+testes and 1 each of BM+CNS, CNS+testes, and isolated bone relapses. Twenty-seven children (67.5%) relapsed on-therapy whereas 13 (32.5%) relapsed posttherapy. All 9 CNS relapses occurred on-therapy whereas 5/8 (62.5%) of testicular relapses occurred posttherapy. Lymphadenopathy was the only significant predictor for relapse. High-risk features such as age less than 1 year and greater than 10 years (P=0.047) and white cell count greater than 50.0 x 10(9)/L (P=0.044) were significantly more frequent in patients with early on-therapy relapse than in patients with off-therapy relapse. The overall survival in the entire study cohort was 67+/-3.5%. Modest survival outcome, relapse while on chemotherapy and the higher incidence of CNS and testicular relapse indicate the need for reappraisal of our treatment protocol. There is a need of identifying risk factors and high-risk groups in our set of patients and risk-stratified intensification of chemotherapy in them.

Primary diagnosis of lymphomas from ascitic fluid is rare. We report a case in which a patient being worked up as a case of carcinoma head of pancreas turned out to be a lymphoma on routine ascitic fluid examination and was further sub-classified as a CD 10+ B-cell lymphoma on flow cytometric analysis.

To resolve all indeterminate cases on HPLC screening with the help of family studies and to further confirm the results by genetic analysis.In our 11 years experience with HPLC at Sir Ganga Ram Hospital, we solved many cases with the help of family studies on parental blood samples in which patient could have possibly been homozygous vs compound heterozygous. Genetic analysis was done on index case as well as on parental samples with ARMS-PCR technique to confirm the results.In 100% of cases, we noted that the diagnosis obtained by family studies was commensurate with that obtained by DNA analysis.In centers, which do not have the facility for genetic analysis, family studies by HPLC can be equally useful.

This 22-year-old women presented to the ante-natal clinic of this hospital for prenatal screening for beta-thalassemia. Cation exchange high performance liquid chromatography (HPLC) using 'Beta Thalassemia Short Program' on Bio-Rad 'Variant' system revealed HbC value of 81.6%. The CBC showed microcytic hypochromic anemia. The HPLC and CBC suggested the possibility of compound heterozygote state for HbC/beta-thalassemia. The alkali and acid electrophoresis findings were consistent with the above diagnosis. The DNA analysis confirmed compound heterozygote state for HbC/beta(0)-thalassemia (Fr 8/9 mutation). The studies on the parents showed that mother was a compound heterozygote for HbD(Punjab) and HbC while father had beta-thalassemia trait. To the best of our knowledge, this is the first confirmed report of HbC from India. The paper discusses the hematological findings in this subject and her mother (a compound heterozygote for HbD(Punjab) and HbC).

A 74 years old male patient, presented with history of generalized weakness, fatigue, loss of appetite and breathlessness on exertion for past one and a half months. On examination, he was found to have significant pallor and generalized lymphadenopathy (cervical, axillary and inguinal). The skeletal survey showed punched out lytic lesions in skull and pelvic bones. The peripheral smear examination showed lymphocytosis with absolute lymphocyte count of 25,000/μL. The bone marrow aspirates revealed a hypercellular marrow with 74 % lymphocytes & 14 % plasma cells, suggestive of chronic lymphoplasmacytic disorder. The bone marrow biopsy had two morphologically distinct populations of lymphocytes & plasma cells. The immunohistochemical markers on bone marrow biopsy showed hat plasma cells were positive for CD138 with kappa light chain restriction. Flow cytometry showed B cell population with CD19/CD5 co expression, CD5/CD23 coexpression, were positive for CD22, CD20 and negative for FMC-7 and lambda light chain. In addition, plasma cells were also identified as CD45 negative cells and showed CD38/CD138 co-expression with variable CD19 and CD56 positivity. Serum protein electrophoresis revealed M band, serum immunofixation electrophoresis corresponded to IgA -Kappa. The final diagnosis of chronic lymphocytic leukemia with concomittant presence of plasma cell myeloma was concluded. This case imparts an important message to look for presence of coexisting entities in a single specimen and highlights the benefits of testing both plasma cell and B-cell compartments when the clinical features are not entirely consistent Flow cytometry together with protein electrophoresis can help to clinch difficult and rare dual diagnosis. These cases are rare and pose therapeutic challenge.

Summary Introduction Dual antiplatelet therapy with clopidogrel and aspirin is the current standard of care in the management of patients with coronary artery disease (CAD) and acute coronary syndrome (ACS). The variability in response to these antiplatelet agents may be due to the underlying genetic diversity. This study was designed to determine the resistance to aspirin and clopidogrel in Indian patients and to look for correlation, if any, with selected polymorphisms. Methods Platelet function testing by light transmission aggregometry was performed on 72 patients with CAD/ACS who were stable on dual antiplatelet therapy (clopidogrel 75 mg OD and aspirin 150 mg OD) along with 72 controls. Aspirin resistance was considered as mean platelet aggregation ≥70% with 10 μm ADP and ≥20% with 0.75 mm arachidonic acid. Clopidogrel resistance was defined as

Multiple genes have been shown to be independently hypermethylated in lymphoid malignancies. We report here on the extent of concurrent methylation of E-cadherin, Dap-kinase, O(6)MGMT, p73, p16, p15 and p14 in 129 pediatric ALL cases. While most of these genes demonstrated methylation in a proportion of cases, O(6)MGMT, p16 and p14 were infrequently methylated (11, 7 and 3%, respectively). Methylation of at least one gene was found in the vast majority (83%) of cases. To determine the extent and concordance of methylation we calculated a methylation index (MI=number of methylated genes/number of studied genes) for each sample. The average MI was 0.28, corresponding to 2/7 methylated genes. MI was correlated with standard prognostic factors, including immunophenotype, age, sex, WBC and presence of specific translocations (TEL-AML1, BCR-ABL, E2A-PBX1 or MLL-AF4). We determined that children >/=10 years old and children presenting with high WBC (>/=50 x 10(9)/l) both associated with a higher MI (P

Severe congenital neutropenia (SCN) is a rare disorder caused by heterogeneous genetic mutations. We describe here a rare association of SCN caused by a novel ELANE mutation and infantile hepatic hemangioendothelioma. In a 2-month-old infant, an abdominal ultrasound performed for omphalitis revealed a hepatic tumor, which was resected. Histopathology confirmed the diagnosis of hemangioendothelioma. Postoperatively, severe neutropenia was noted. Bone marrow examination showed myeloid maturation arrest, diagnostic of SCN. Mutation analysis for the neutrophil elastase gene identified a novel heterozygous de novo ELANE missense mutation in exon 2 (c.215T>A, p.Val72Glu). He was managed successfully with broad-spectrum antibiotics and high-dose granulocyte colony-stimulating factor.

In a series of 185 patients (median age 7 years) of acute lymphoblastic leukaemia (ALL) from India, the overall incidence of ALL-1 gene rearrangement using the Southern blot technique was 11.4% (21/185). The incidence amongst the infants (ageor = 1 year, 70%) was significantly higher when compared to patients1 -or = 10 years (7.4%, P = 0.00001) as well as10 years old (9.3%, P = 0.0001). ALL-1 gene rearrangement was associated with significantly higher WBC count (P = 0.01) and CD10 negativity (P = 0.00000001). Complete remission (CR) and relapse rates in 98 patients evaluable for response to therapy on a uniform therapy protocol was independent of ALL-1 gene status.

In 120 cases of acute lymphoblastic leukemia (median age 8 years), IgH chain gene was rearranged in 99% B-Cell Precursor (BCP) ALLs and 13% T-ALLs. One or the other TCR locus was rearranged not only in all T-ALLs, but also in 87% of BCP-ALLs. TCR-beta rearrangement in BCP-ALL was associated with a higher mean age at presentation (8.7 vs. 6.2 years, P=0.008), lower mean platelet counts (61.2x10(9)/l vs. 103.7x10(9)/l, P=0.003) and a poorer DFS (% cummulative survival 0 vs. 88.9+/-10.5, P=0.004). TCR-gamma rearrangement in T-ALL was associated with a higher mean WBC count (186.3x10(9)/l vs. 63. 4x10(9)/l, P=0.002). Also, the pattern of rearrangement of these genes appeared to be different from the West; viz. TCR-beta rearrangement in a higher proportion of BCP-ALLs (58%, 95% confidence intervals 45-69%), invariable deletion of Cgamma1 and only monoallelic rearrangement for TCR-delta locus. This repertoire of gene rearrangement may have a bearing on the poor treatment outcome reported previously from our geographic region.

Only one case of primary non-secretory plasma cell leukemia with atypical morphology has been reported thus far. Here we report another such case of plasma cell leukemia diagnosed on fl ow cytometry, as morphological heterogeneity and lack of monoclonal immunoglobulins in both serum and urine, made it difficult to come to a conclusive diagnosis based purely on morphology.

Background Cation exchange-high performance liquid chromatography (CE-HPLC) is most commonly used to evaluate hemoglobin (Hb) variants, which elute in the Hb A2 window. This study aimed to assess prevalence of an uncommon Hb variant, Hb D-Iran, and compare its red cell parameters and peak characteristics with those of Hb E that commonly elutes in the Hb A2 window. Methods Generally, we assess abnormal Hb using CE-HPLC as the primary technique along with alkaline and acid electrophoresis. All cases with Hb A2 window >9%, as assessed by CE-HPLCs during 2009-2013, were selected. Results Twenty-nine cases with Hb D-Iran variant were identified-25 heterozygous, 2 homozygous, 1 compound heterozygous Hb D-Iran/β-thalassemia, and 1 Hb D-Iran/Hb D-Punjab. Overall prevalence of Hb D-Iran was 0.23%. Compared to patients with Hb E, those with Hb D-Iran had significantly higher Hb (12.1 vs. 11.3 g/dL, P=0.03), MCV (82.4 vs. 76.4 fL, P=0.0044), MCH (27.9 vs. 25.45 pg, P =0.0006), and MCHC (33.9 vs. 33.3 g/dL, P=0.0005). Amount of abnormal Hb (40.7 vs. 26.4%, P=0.0001) was significantly higher while retention time (3.56 vs. 3.70 min, P=0.0001) was significantly lower in Hb D-Iran than in Hb E. Conclusion Hb D-Iran peak can be easily missed if area and retention time of the Hb A2 window are not carefully analyzed. To distinguish between variants, careful analysis of peak area and retention time is sufficient in most cases and may be further confirmed by the second technique-alkaline electrophoresis.

Castleman's disease represents an atypical lymphoproliferative disorder which is non-clonal but can turn malignant in the form of lymphoma, Kaposi's sarcoma or plasma cell dyscrasia. It has been reported in association with diseases like polyneuropathy organomegaly endocrinopathy monoclonal gammopathy skin changes syndrome and myeloma and very rarely it can be associated with cutaneous vasculitis as in our case. It relatively runs an aggressive course and has a shorter survival. No standard of care therapy is yet established for multicentric Castleman's disease accompanying myeloma. We successfully treated one such patient with bortezomib-based therapy.