Anjum Hassan

State of the art in myeloid sarcoma

Introduction:  Myeloid sarcomas are extramedullary lesions composed of myeloid lineage blasts that typically form tumorous masses and may precede, follow, or occur in the absence of systemic acute myeloid leukemia. They most commonly involve the skin and soft tissues, lymph nodes, and gastrointestinal tract and are particularly challenging to diagnose in patients without an antecedent history of acute myeloid leukemia.

Combined Core Needle Biopsy and Fine-Needle Aspiration With Ancillary Studies Correlate Highly With Traditional Techniques in the Diagnosis of Nodal-Based Lymphoma

Core needle biopsy (CNB) and fine-needle aspiration (FNA) are increasingly replacing excisional lymph node biopsy in the diagnosis of lymphomas. However, evaluation of CNB and FNA remains challenging owing to limited architectural information and the more detailed subclassification of lymphomas required by the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Our study is the largest study to assess diagnostic accuracy of CNB and FNA in conjunction with ancillary studies. We analyzed 263 cases and a diagnosis was established in 237, of which 193 were completely subclassified. In cases in which excisional biopsy was available as a reference for comparison, CNB and FNA had a sensitivity of 96.5%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 90%. CNB and FNA with ancillary studies represent a viable alternative in the diagnosis of lymphoma, as long as the number and size of cores for morphologic studies are not compromised.

Combination decitabine, arsenic trioxide, and ascorbic acid for the treatment of myelodysplastic syndrome and acute myeloid leukemia: a phase I study.

which various erythrocyte polymorphisms protect against severe malaria. A report from Kenya recently provided evidence for negative epistasis between SCT and alpha-thalassemia in protection against malaria [16]. How the protective mechanisms of these and other conditions including G6PD (A2) might interact to mutually interfere in malaria protection remains to be resolved. By the way, more recent study with a limited number of patients has shown that G6PD deficiency and SCT have no effect on the severity of anemia in children infected with both HIV-1 and P. falciparum [17] despite the high proportion of G6PD deficiency in coinfected children. Further study with large sample size is needed to confirm this observation. Understanding the interaction of malaria protective factors in various infectious diseases may be a valuable tool of medical interest. Our evaluation of data was previously collected in the villages of Kangaba and Kela, Mali [9]. Subjects in the case–control study included children 10 years or less of age who presented with clinical symptoms of malaria. Microscopic confirmations of parasitemia, assignments of the cases into uncomplicated or severe malaria, and hemoglobin typing and G6PD (A2) detection were as described [9]. Data evaluation and analysis were performed under consents and protocols approved by Institutional Review Boards of the National Institute of Allergy and Infectious Diseases, Bethesda, MD and of the University of Bamako, Mali.

CD163 Immunohistochemistry Is Superior to CD68 in Predicting Outcome in Classical Hodgkin Lymphoma

OBJECTIVES In recent years, research has increasingly focused on the microenvironment of classical Hodgkin lymphoma (CHL) as a predictor of treatment outcome. The focus of this study was to assess the interobserver reproducibility in interpreting macrophage-associated immunohistochemistry (IHC) for CD68 and CD163 in a retrospective cohort of 88 patients with CHL. METHODS Staining results were correlated with clinical outcome in all patients and those with a high international prognostic score (IPS). RESULTS The intraclass correlation (ICC) for the five hematopathologists interpreting the IHC was stronger for CD163 (0.70) than for CD68 (0.50). Using a cutoff of 25% mean macrophage reactivity and including all patients, a statistically significant difference in overall survival (OS) was seen only for CD163 (P = .0006) and not for CD68 (P = .414). Patients with a mean CD163 reactivity of 25% or more had a median OS of 71 months vs 101 months for patients with less than 25% reactivity. CD163 retained statistical significance in multivariate analysis. In patients with advanced-stage CHL with high IPS, OS was also significantly worse for those with a mean CD163 reactivity of 25% or higher. CONCLUSIONS Our study confirms previous reports of a prognostic role of tumor-infiltrating macrophages in CHL, but only for CD163. Although most of the literature supports an increasing role of macrophage IHC as a predictor of clinical outcome, successful clinical translation will require a standardized method and reporting system.

Neurobeachin (NBEA) is a target of recurrent interstitial deletions at 13q13 in patients with MGUS and multiple myeloma

OBJECTIVE Chromosome 13 deletions (del[13]), detected by metaphase cytogenetics, predict poor outcomes in multiple myeloma (MM), but the gene(s) responsible have not been conclusively identified. We sought to identify tumor-suppressor genes on chromosome 13 using a novel array comparative genomic hybridization (aCGH) strategy. MATERIALS AND METHODS We identified DNA copy number losses on chromosome 13 using genomic DNA isolated from CD138-enriched bone marrow cells (tumor) from 20 patients with MM, monoclonal gammopathy of undetermined significance, or amyloidosis. We used matched skin biopsy (germline) genomic DNA to control for copy number polymorphisms and a novel aCGH array dedicated to chromosome 13 to map somatic DNA gains and losses at ultra-high resolution (>385,000 probes; median probe spacing 60 bp). We analyzed microarray expression data from an additional 262 patient samples both with and without del[13]. RESULTS Two distinct minimally deleted regions at 13q14 and 13q13 were defined that affected the RB1 and NBEA genes, respectively. RB1 is a canonical tumor suppressor previously implicated in MM. NBEA is implicated in membrane trafficking in neurons, protein kinase A binding, and has no known role in cancer. Noncoding RNAs on chromosome 13 were not affected by interstitial deletions. Both the RB1 and NBEA genes were deleted in 40% of cases (8 of 20; 5 patients with del[13] detected by traditional methods and 3 patients with interstitial deletions detected by aCGH). Forty-one additional MM patient samples were used for complete exonic sequencing of RB1, but no somatic mutations were found. Along with RB1, NBEA gene expression was significantly reduced in cases with del[13]. CONCLUSIONS The NBEA gene at 13q13, and its expression are frequently disrupted in MM. Additional studies are warranted to evaluate the role of NBEA as a novel candidate tumor-suppressor gene.

Flow Cytometric Evaluation of Posttransplant B-Cell Lymphoproliferative Disorders

CONTEXT Posttransplant B-cell lymphoproliferative disorders (PTLDs) constitute a heterogeneous group that includes hyperplastic and unique polymorphic lesions at one end of the spectrum and monomorphic lymphoid proliferations indistinguishable morphologically from conventional B-cell non-Hodgkin lymphomas (NHLs) at the other end. Almost all the PTLDs are of B-cell origin, with only rare examples of T-cell phenotype described. Despite a plethora of information available on the morphologic spectrum, pathogenetic role of Epstein-Barr virus, and various treatment options, a detailed flow cytometric immunophenotypic evaluation of PTLDs is largely lacking. OBJECTIVE To evaluate the immunophenotypic profiles of various PTLDs using multiparameter flow cytometric analysis to compare and contrast with conventional de novo B-cell lymphoproliferative disorders and to identify any immunophenotypic patterns useful in diagnosis. DESIGN We retrospectively analyzed data on the immunophenotype of 25 cases of pediatric and adult PTLD (12 cases of monomorphic PTLD [m-PTLD] and 13 cases of polymorphic PTLD [p-PTLD]) using multiparameter flow cytometry in addition to routine morphologic and immunohistochemical evaluation. The flow cytometric immunophenotypic data were also compared and contrasted with 334 cases of various de novo B-cell NHLs during the same period as a control group. RESULTS We observed a much higher incidence of lack of surface immunoglobulin light chains and CD20 expression in B-cell PTLDs using multiparameter flow cytometry in comparison with de novo B-cell NHL as a group (with the exception of small lymphocytic lymphoma). Four (16%) of 25 cases of PTLD (3 m-PTLD and 1 p-PTLD) showed almost complete lack (CD20%/CD19% ratio < 1:9) of CD20 expression in contrast to only 8 ( approximately 2%) of 334 cases of de novo B-cell NHL (P =.007). Several other cases of both m-PTLD and p-PTLD also showed partial and dim expression of CD20. Nine (36%) of 25 cases, including 5 cases of m-PTLD and 4 of p-PTLD, showed either an almost complete lack (light chains%/CD19% ratio < 1:9) or significant loss (>50% loss) of surface immunoglobulin light chains in contrast to less than 5% incidence of light-chain negativity in conventional de novo B-cell NHL. Immunoglobulin light-chain clonality was observed in 9 cases (5 m-PTLD and 4 p-PTLD). Seven cases (5 p-PTLD and 2 m-PTLD) had polyclonal expression of immunoglobulin kappa and lambda light chains. The m-PTLD showed expression patterns of CD5, CD10, and CD23 similar to their de novo counterparts. CONCLUSIONS Both polymorphic and monomorphic PTLDs show a higher incidence of lack of CD20 and surface immunoglobulin light-chain expression. The lack of CD20 expression in these lesions may have therapeutic implications, since anti-CD20 antibody has increasingly become an important modality in the treatment of B-cell lymphoproliferative disorders, including posttransplant disorders.

Bone marrow biopsy in patients with hepatitis C virus infection: spectrum of findings and diagnostic utility.

Patients with hepatitis C virus (HCV) infection develop a number of hematologic disorders, with benign and malignant B‐cell proliferations being the most common. HCV‐infected patients are also prone to developing peripheral cytopenias, the etiologies of which are multifactorial and include hypersplenism and/or antiviral medications. Some of these patients may undergo bone marrow biopsy but no study has systematically recorded the bone marrow findings in this patient group. Here, we report on the range of bone marrow findings in 47 adult HCV‐infected patients. These patients, who lacked concurrent human immunodefiency virus (HIV) infection, most commonly presented for a bone marrow biopsy due to abnormal peripheral cell counts. The bone marrow biopsies displayed a range of findings. Dyserythropoiesis, present in 19% of the cases, was the most common finding. Patients with pancytopenia(n = 6), as defined by current World Health Organization standards, were the most likely to have bone marrow abnormalities; two pancytopenic patients had acute myeloid leukemia, and one patient had a primary myelodysplastic syndrome. There was no correlation in bone marrow findings and antiviral medications, MELD score, cirrhosis or splenomegaly, suggesting that the degree of bone marrow dysfunction is independent of stage of HCV. The results of this study suggest that bone marrow biopsy in HCV‐infected patients, even those with features of hypersplenism and/or documented antiviral therapy, can be a valid test for hematologic evaluation, especially for patients with severe pancytopenia and/or sudden alterations in peripheral cell counts. Am. J. Hematol. 85:106–110, 2010.

Use of classic and novel immunohistochemical markers in the diagnosis of cutaneous myeloid sarcoma

Cutaneous myeloid sarcoma is often challenging to diagnose based solely upon histopathological features. Although immunohistochemistry can aid in its diagnosis, specific markers have not been clearly identified. We evaluated the utility of immunohistochemical markers in 57 cutaneous myeloid sarcoma cases. In addition to classical markers (CD117, CD163, CD34, myeloperoxidase and lysozyme), we used CD33 and CD14, recently described markers in paraffin‐embedded tissue samples, and Kruppel‐like factor 4 (KLF‐4), a novel monocytic marker. Our results show that lysozyme was expressed in 91%, CD33 in 60%, myeloperoxidase in 54%, CD34 in 39% and CD117 in 36% of cases. An antibody panel that included lysozyme, CD117 and CD33 identified all cases. The monocytic markers CD14, KLF‐4 and CD163 were expressed in 60, 58 and 40% of all cases, respectively. CD14 and KLF‐4 expression was significantly more common in cases with monocytic differentiation. CD14 is the single most sensitive and specific marker for monocytic differentiation (79 and 80%). Although KLF‐4 in isolation is relatively insensitive (50 and 87%), it enhances sensitivity in detecting monocytic cutaneous myeloid sarcoma when combined with CD14. Our results indicate that in addition to classical immunohistochemical markers, targeted use of newer antibodies, including CD33, CD14 and KLF‐4 is useful in the diagnosis of cutaneous myeloid sarcoma and in the detection of monocytic differentiation.

Molecular pathology of myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs; formerly chronic myeloproliferative disorders) are a class of myeloid hematologic malignancies that represent a stem cell-derived expansion of 1 or more hematopoietic cell lineages. The current 2008 World Health Organization system recognizes 8 types of MPN: chronic myelogenous leukemia, chronic neutrophilic leukemia, polycythemia vera, primary myelofibrosis, essential thrombocythemia, chronic eosinophilic leukemia, mastocytosis, and myeloproliferative neoplasm, unclassifiable. This review summarizes the salient characteristics of the MPNs, with emphasis on recent developments in the molecular pathophysiology and therapeutic monitoring of these disorders.

Cystic lymphoid hyperplasia of the parotid gland in HIV-positive and HIV-negative patients: quantitative immunopathology.

BACKGROUND Benign lymphoepithelial lesions of the parotid include a spectrum of disorders ranging from lymphoepithelial sialadenitis (LESA) of Sjögren syndrome to lymphoepithelial cysts (LEC) and both human immunodeficiency virus (HIV)-related and -unrelated cystic lymphoid hyperplasia (CLH). They share a common microscopic appearance characterized by epimyoepithelial islands and/or epithelial lined cysts in a lymphoid stroma. However, they differ greatly regarding their etiology, clinical presentation, and management. OBJECTIVE The purpose of this study was to establish specific immunophenotypic profiles for these diverse disease entities. STUDY DESIGN Four cases of HIV+ CLH, 5 cases of HIV- CLH, 3 cases of LESA of Sjögren syndrome, and 3 cases of sporadic LEC were quantitatively analyzed for distribution of lymphoreticular cell subpopulations, using antibodies against CD20, CD45RO, CD4, CD8, CD57, and CD68. RESULTS The cystic lesions in both the HIV+ and HIV- cases were microscopically analogous. However, a marked decrease in the interfollicular CD4:CD8 ratio was observed in all HIV+ CLH cases, which was statistically significant when compared with the HIV- cases (P = .02) and cases of LESA of Sjögren syndrome (P = .03). No significant differences regarding the distribution of CD20+ B lymphocytes in epithelial cyst lining or the interfollicular or follicular distribution of CD20+, CD45RO+, CD57+, and CD68+ cells were present among the different groups. CONCLUSION Analysis of the interfollicular CD4:CD8 ratio may offer a simple immunophenotypic approach in the distinction of HIV+ from other lymphoepithelial lesions of the parotid gland, when HIV status is unknown and p24 immunohistochemistry is not readily available.