Search

Supplementary Figures 1-5 from Utilization of Pathway Signatures to Reveal Distinct Types of B Lymphoma in the Eμ-myc Model and Human Diffuse Large B-Cell Lymphoma

Supplementary Tables 6-9 from Utilization of Pathway Signatures to Reveal Distinct Types of B Lymphoma in the Eμ-myc Model and Human Diffuse Large B-Cell Lymphoma

Supplementary Tables 1-5 from Utilization of Pathway Signatures to Reveal Distinct Types of B Lymphoma in the Eμ-myc Model and Human Diffuse Large B-Cell Lymphoma

The authors declare that there are no disclosures or conflicts of interest regarding the publication of this manuscript. We did not receive any financial support and have no financial interests which could create a potential conflict of interest or the appearance of a conflict of interest with regard to the work.

Objectives Lineage switch occurs in rare leukemias, and the mechanism is unclear. We report two cases of B-lymphoblastic leukemia (B-ALL) relapsed as acute myeloid leukemia (AML). Methods Retrospective review of clinical and laboratory data. Results Complex cytogenetic abnormalities were detected in B-ALL for both cases with subclone heterogeneity. Postchemotherapy marrow biopsies showed trilineage hematopoiesis without detectable B-ALL. Cytogenetics in both showed stemline abnormalities. The cases were considered "occult" myelodysplastic syndrome (MDS) preceding B-ALL. The patients relapsed 6.5 and 9 months following induction, respectively. Case 1 relapsed as AML-M5 initially, was treated as such, and then relapsed again as B-ALL. Case 2 relapsed as AML-M6. Cytogenetics demonstrated persistent abnormalities. Both patients died soon after relapse. Conclusions Lineage switch between B-ALL and AML could be intermediated by occult MDS. A pluripotent progenitor likely undergoes neoplastic transformation, resulting in a genomically unstable clone. This leads to a repertoire of heterogeneous subclones that may be selected by chemotherapy. Lineage switch heralds a dismal clinical outcome.

As therapeutic options for various lymphomas have rapidly expanded in the last decade, accurate classification and prognostic stratification of common and uncommon lymphoma types are of utmost importance. The most recent WHO classification continues to emphasize morphology, immunophenotype, molecular genetic abnormalities, and clinical behavior as the necessary pillars for correct diagnosis. Surgical excisional biopsy (SEB) is both historically and currently the gold standard technique for morphological examination, but it requires more time and preparation, often with more extensive anesthesia with higher potential for medical complications. Because of this, elderly and/or frail patients may not be able to tolerate the stress of the procedure, particularly when abdominal, retroperitoneal, and thoracic masses are to be examined. Indeed, excisional biopsy may not be technically feasible in certain locations (e.g., retroperitoneal midline). Patients may want to avoid the discomfort and inconvenience associated with excisional biopsy and may prefer an alternative, even when it is not medically necessary. In response to these issues, over the last 25 years, there has been increasing utilization of fine needle aspiration (FNA) cytology and core needle biopsy (CNB) techniques for diagnostic screening of enlarged lymph nodes or other mass lesions suspected to harbor lymphomas, metastatic neoplasms, and reactive lymphadenopathies. We provide guidelines for appropriate handling of the limited specimens obtained by these “small biopsies” and suggest how to optimize the use of ancillary technics such as flow cytometry, immunohistochemistry (IHC), and molecular analysis, firstly, to differentiate reactive lesions from lymphomas and, secondly, to provide accurate classification and prognostic information. The ability to render a definite diagnosis according to the WHO classification on these “small biopsies” varies for different lymphoma types, and we discuss the limitations of these specimens for common lymphomas. In the second half of the chapter, the correct handling of small biopsies performed in previously diagnosed and treated patients is discussed. We emphasize the evaluation of these repeat biopsies for disease recurrence, disease progression, emergence of secondary pathological processes due to prior treatment, and presence of therapeutic targets for the second- and third-line treatments. The clinically crucial distinctions among lymphomas with overlapping features are mentioned, and guidance for issuing descriptive reports and for requesting additional material is provided.

A bone marrow biopsy sometimes demonstrates two hematolymphoid neoplasms. In a majority of these cases, a second neoplasm is discovered unexpectedly when examining the marrow for a known or suspected hematolymphoid neoplasm. There are several possible combinations of neoplastic components, but in practice, many cases show a myeloid neoplasm along with a nonmyeloid neoplasm such as plasma cell neoplasm (PCN), chronic lymphocytic leukemia (CLL), other small mature B-cell leukemia/lymphoma, T-cell large granular lymphocytic leukemia (T-LGL), or other T-cell lymphomas. The myeloid neoplasm, usually myelodysplastic syndrome, may occur as a consequence of therapy given for the lymphoid neoplasm, and such cases are covered in Chapter 25. In addition, two different nonmyeloid neoplasms can be seen together, including PCN with CLL, PCN with lymphoplasmacytic lymphoma, CLL with T-LGL, CLL with B-lymphoblastic leukemia, etc. Diagnosis of these concomitant hematolymphoid neoplasms is challenging in that one neoplastic component can potentially mask the other in the bone marrow examination. Here, we highlight the diagnostic approach to correctly identify more than one neoplastic components by using ancillary test on the marrow as well as other laboratory studies, discuss potential etiologies of the concurrency, and emphasize the clinical significance of the phenomenon for treatment and prognosis. Bone marrow involvement by solid tumors, with or without concurrent hematolymphoid neoplasm, is discussed in Chapter 28.

Key concepts in immunology intersect the practice of hematopathology because the biology and classification of lymphoid neoplasms are best understood on this basis and accurate diagnosis of most hematolymphoid neoplasms very often relies on immune-based techniques. This chapter summarizes the fundamental divisions of the immune system at the cellular and functional level and relates these divisions to the immune responses in health and disease. The normal development of B-cells and T-cells is mapped to the anatomical and histological distribution of these cells at various stages of maturation and through immune responses. The pros and cons of the two principal techniques of determining the immunophenotype of normal and abnormal cells—multiparameter flow cytometry and immunohistochemistry—are compared. The immunophenotype of normal lymphoid cell subsets, developing myeloid cells, and major types of lymphomas and acute leukemias are presented. Finally, the rapidly expanding repertoire of antibody based therapies for hematolymphoid maligngncies is highlighted with this background of key immunologic concepts.

Bone marrow examinations are done for a variety of benign and malignant conditions and are often triggered by abnormalities in the complete blood count and peripheral blood smear. In this chapter, a diagnostic approach to evaluating bone marrows in both adults and children will be reviewed. Optimal use of different aspects of the examination will be discussed as well as the use of ancillary testing. Finally, the organization of bone marrow reports and determination of when one can render a definitive versus a descriptive diagnosis will be reviewed.

Myeloid neoplasms occasionally occur in patients with sickle cell disease, and the underlying connection between the two diseases is unclear. Herein, we retrospectively analyzed four cases of sickle cell disease patients who developed myeloid neoplasm. Age at time of diagnosis ranged from 27 to 59 years with a median of 35.5 years. Two patients were treated with hydroxyurea and the other two with supportive care alone, with one out of the four patients receiving additional treatment with hematopoietic stem cell transplant. Three patients presented with leukocytosis, and the remaining patient presented with pancytopenia. Two patients were diagnosed with myelodysplastic syndrome/myeloproliferative neoplasm, one with myelodysplastic syndrome, and the other with acute myeloid leukemia. All four cases demonstrated certain degrees of myelodysplasia and complex cytogenetic abnormalities with - 7/7q- and/or - 5/5q- or with 11q23 (KMT2A) rearrangement. This cytogenetic profile resembles that seen in therapy-related myeloid neoplasm, suggesting that myeloid neoplasm in the setting of sickle cell disease may represent a subcategory of the disease distinct from de novo myeloid neoplasm in general. Extensive literature review further demonstrates this similarity in cytogenetic profile, as well as in other associated pathologic features. Potential etiology includes therapy for sickle cell disease, disease-related immunomodulation, or disease-related chronic inflammation. We hypothesize that constant hematopoietic hyperplasia, stimulated by a hemolysis-induced cytokine storm, may increase the chance of somatic mutations/cytogenetic aberrations, resulting in transformation of myeloid precursors. This group of myeloid neoplasms seems to herald a dismal clinical outcome, with median survival

Background Flow cytometric immunophenotyping (FCI) is recognized as a rapid, sensitive, and accurate method for diagnosis of B-cell lymphomas. We observed that FCI failed to identify the clonal B-cell population in several cases of large B-cell lymphoma (DLBCL) when tissue samples were prepared by a commercially available mechanical tissue disaggregation method. We tested a manual tissue disaggregation method and compared it with the mechanical method. Methods FCI findings from 51 cases of DLBCL processed with the mechanical tissue disaggregation method, 27 cases processed using the manual method, and 15 cases processed using a combination of both methods were compared. The histological and immunohistochemical findings in each case were reviewed. Results FCI detected a clonal B-cell population in 88.9% of cases processed by the manual tissue disaggregation method, 66.7% of cases processed by a combination of the manual and mechanical disaggregation methods, and in 62.7% of cases processed solely by the mechanical tissue disaggregation method (P

Background Major heterogeneity between laboratories in flow cytometry (FC) minimal residual disease (MRD) testing in multiple myeloma (MM) must be overcome. Cytometry societies such as the International Clinical Cytometry Society and the European Society for Clinical Cell Analysis recognize a strong need to establish minimally acceptable requirements and recommendations to perform such complex testing. Methods A group of 11 flow cytometrists currently performing FC testing in MM using different instrumentation, panel designs (≥ 6-color) and analysis software compared the procedures between their respective laboratories and reviewed the literature to propose a consensus guideline on flow-MRD analysis and reporting in MM. Results/Conclusion Consensus guidelines support i) the use of minimum of five initial gating parameters (CD38, CD138, CD45, forward, and sideward light scatter) within the same aliquot for accurate identification of the total plasma cell compartment; ii) the analysis of potentially aberrant phenotypic markers and to report the antigen expression pattern on neoplastic plasma cells as being reduced, normal or increased, when compared to a normal reference plasma cell immunophenotype (obtained using the same instrument and parameters); and iii) the percentage of total bone marrow plasma cells plus the percentages of both normal and neoplastic plasma cells within the total bone marrow plasma cell compartment, and over total bone marrow cells. Consensus guidelines on minimal current and future MRD analyses should target a lower limit of detection of 0.001%, and ideally a limit of quantification of 0.001%, which requires at least 3 × 106 and 5 × 106 bone marrow cells to be measured, respectively. © 2015 International Clinical Cytometry Society

Objectives To compare the features of the blast phase of chronic myelogenous leukemia (CML) in patients treated with tyrosine kinase inhibitors (TKIs) with those in the pre-TKI era. Methods Sixty-seven patients with blast phase CML were identified in the Duke Pathology database from 1991 to 2011. The morphology and immunophenotype of blasts were evaluated, along with cytogenetic studies and associated findings in the peripheral blood and bone marrow. Results In the TKI era, the blasts were more frequently of a type other than the usual myeloid or lymphoid types when compared with the pre-TKI era. Blast phase in TKI-treated patients was associated with a higher peripheral WBC count and a lower blast percentage in the bone marrow. Of the 23 patients with cytogenetic studies during blast phase, additional cytogenetic changes more frequently occurred in patients with an unusual blast type, and some patients showed these changes months before the onset of blast phase. Conclusions Blast phase CML in TKI- and non-TKI-treated patients differs in the morphology and immunophenotype of blasts, cytogenetic findings, and associated findings in the peripheral blood and bone marrow.

We present a case report of an 80-year-old woman with volume overload thought initially to be secondary to heart failure, but determined to be amiodarone-induced acute and chronic liver injury leading to submassive necrosis and bridging fibrosis consistent with early cirrhosis. Her histopathology was uniquely absent of steatosis and phospholipidosis, which are commonly seen in AIC.

Plasmacytosis is a common finding in lymph node biopsies and can be seen in diverse circumstances ranging from reactive lymphadenopathy to malignant lymphoma. Familiarity with various histopathologic features of the different entities and awareness of their typical clinical and ancillary study findings are essential for an accurate diagnosis. In this review, we present common and representative nonneoplastic entities and lymphomas that have plasmacytic differentiation or associated plasmacytosis. We focus on the histological classification with an emphasis on the diagnostic approach and areas of diagnostic challenge.