Diffuse large B-cell lymphoma (DLBCL) is one of the
|
|
- Laurence Scott
- 6 years ago
- Views:
Transcription
1 Practical Applications in Immunohistochemistry Evaluation of Diffuse Large B-Cell Lymphoma and Related Large B-Cell Lymphomas Dennis P. O Malley, MD; Aaron Auerbach, MD; Lawrence M. Weiss, MD Context. Diffuse large B-cell lymphoma is the most commonly diagnosed subtype of lymphoma worldwide. The current World Health Organization (WHO) classification includes several subtypes, based on a combination of clinical, immunohistochemical, and genetic differences. Immunohistochemical staining is essential in evaluating diffuse large B-cell lymphoma and many related large B- cell lymphomas and aggressive B-cell lymphomas. Objective. To address different immunohistochemical features used for identification, subclassification, prognosis and in some cases, therapy, of diffuse large B-cell lymphoma and related lymphomas. Data Sources. The information outlined in this review article is based on our experiences with routine cases, on the current WHO classification of hematopoietic and lymphoid tumors, and on a review of English-language articles published throughout Conclusions. Features and diagnostic criteria of diffuse large B-cell lymphoma, aggressive variants of B-cell lymphomas, including Burkitt lymphoma and doublehit lymphomas, are discussed. Identification of cell of origin (germinal center type versus activated B-cell type) is discussed at length. Finally, practical approaches for diagnosis are discussed. (Arch Pathol Lab Med. 2015;139: ; doi: /arpa CP) Diffuse large B-cell lymphoma (DLBCL) is one of the most common diagnoses in hematopathology, typically including approximately 30% to 40% of non-hodgkin lymphoma cases. In spite of being a common diagnosis, it represents a heterogeneous group of disorders that are related by the identification of a diffuse proliferation of B cells, which are typically large. However, from this simple starting point, distinguishing DLBCL from related disorders and proper determination of prognostic markers can add a degree of complexity to this diagnosis, which can be daunting to the practicing pathologist. In all cases, to confirm a diagnosis of DLBCL, one must confirm the B-cell lineage of the lymphoma cells. Therefore, a de facto standard for B-cell identification is expression of CD20. In untreated lymphomas, CD20 is expressed in the most mature B-cell neoplasms, with some notable exceptions Accepted for publication November 14, Published as an Early Online Release January 2, From Clarient Diagnostic Services, Aliso Viejo, California (Drs O Malley and Weiss); and Joint Pathology Center, Silver Spring, Maryland (Dr Auerbach). The authors have no relevant financial interest in the products or companies described in this article. This article is provided for educational purposes only and is not intended to suggest either a practice standard or the only acceptable pathway for diagnostic evaluation. The views presented reflect the authors opinions. The application of these opinions to a particular medical situation must be guided by the informed medical judgment of the responsible pathologist(s), based on the individual circumstances presented by the patient. The College of American Pathologists has no responsibility for the content or application of the views expressed herein. Reprints: Dennis P. O Malley, MD, Clarient Diagnostic Services, 31 Columbia, Aliso Viejo, CA ( domalley@clarientinc. com). discussed below. Since CD20 is a target for a successful and commonly used monoclonal antibody therapy (rituximab) for most B-cell lymphomas, the use of this antibody should be a first consideration. Rituximab-treated B-cell lymphomas may no longer express CD20 and they require additional immunostains, such as PAX5, CD79a, CD19, or CD22, to identify B cells. Confirming the presence of CD20 þ large B cells with an appropriate histologic pattern could be considered a minimal standard for the diagnosis of DLBCL. It is however incumbent on the practicing pathologist to recognize that several variants and subtypes of DLBCL, and related disorders, rely on a more extensive evaluation of clinical, histopathologic, immunohistochemical, and genetic features for their accurate identification (Table 1). The current classification of DLBCL and related disorders from the 2008 World Health Organization (WHO) classification is highlighted in Table 2. Further, some groups have established guidelines for lymphoma diagnosis and/or reporting, including the College of American Pathologists (CAP) (Table 3). 1 3 Currently, nationally recognized clinical guidelines for the treatment of patients with lymphoma emphasize the use of the 2008 WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues. 1,4 Based on this guidance, it is appropriate to provide subclassification and as specific a diagnosis as possible assuming that one has arrived at a diagnosis of diffuse large cell lymphoma. While this review emphasizes immunohistochemical studies, where relevant, other ancillary tests to identify subtypes of DLBCL and variants will also be discussed. DIAGNOSIS, PROGNOSIS, AND THERAPY As pathologists, our role in the care of patients is expanding rapidly. While in the past our focus was mainly 1094 Arch Pathol Lab Med Vol 139, September 2015 IHC in DLBCL O Malley et al
2 Marker Minimal Evaluation Table 1. Evaluation of Diffuse Large B-Cell Lymphoma by Immunohistochemistry a,b NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Adequate NCCN Guidelines Useful Basic Basic With Hans Basic With GC/NGC Thorough CD20 þ þ þ þ þ þ þ CD3 þ þ þ þ þ þ þ CD5... þ þ þ þ þ þ CD10... þ þ þ þ þ CD45... þ þ BCL2... þ þ þ þ þ þ BCL6... þ þ þ þ þ MUM1 c þ þ þ þ þ Ki þ þ þ þ þ þ MYC... þ þ þ þ þ þ Cyclin D þ þ j/k c... þ CD138 c... þ c c c c EBER-ISH þ þ ALK þ HHV þ GCET (þ) e þ þ FOXP (þ) e þ þ LMO (þ) e þ þ CD (þ) e þ PAX5 d d d d d CD79a d d d d d Abbreviations: ALK, anaplastic lymphoma kinase; EBER, Epstein-Barr virus encoded small RNAs; GC, germinal center; HHV8, human herpesvirus 8; ISH, in situ hybridization; NCCN, National Comprehensive Cancer Network; NGC, nongerminal center; þ, positive;, negative. a Minimal evaluation would be performed if there were limited sample or if resources were limited, and a minimal evaluation would suffice for therapeutic evaluation, such as in the case of a recurrence of a known lymphoma. The NCCN Guidelines specify adequate immunophenotype to establish diagnosis and GC versus NGC origin. Other markers are useful under certain circumstances to establish lymphoma subtype. Additional evaluations are based on the practice patterns of the authors and include a basic evaluation panel (without GC/non-GC), the basic panel with addition of markers for applying the Hans classifier, and the basic panel with markers for both Hans and Tally classifiers. The thorough panel addresses Epstein-Barr virus expression as well as cyclin D1 expression. b Adapted from Zelenetz et al 1 with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Hodgkin s Lymphoma V Copyright 2014 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK, NCCN, NCCN GUIDELINES, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. c CD138 and/or CD38 should be used in all cases with evidence of plasmacytic or plasmablastic differentiation. Light-chain staining may also be of benefit in these cases. d If there is an indication of previous anti-cd20 therapy (such as rituximab) or a lack of staining for CD20 in what would otherwise be a typical diffuse large B-cell lymphoma, then alternative B-cell markers, such as PAX5 or CD79a, should be used to confirm B-cell differentiation. e When available, may be useful per NCCN guidelines. on diagnosis, currently we are seeing an expansion of our role in establishing prognosis for patients, which may play an important role in directing therapy. Many prognostic factors may directly drive selection of the type of therapy (more or less aggressive) that is recommended (Table 4). The 2008 WHO classification includes at least 26 types of large B-cell lymphomas, guiding classification of clinicopathologic entities based on histologic features, immunohistochemical features, and genetics. 4 Evaluation of this large group of diagnoses often requires careful correlation of several clinical and pathologic findings. Immunohistochemistry is a keystone in identifying many of the different types of large B-cell lymphomas. In almost all cases, primary identification is made by a histologic pattern along with the presence of pan B-cell antigens. In the appropriate context, the combination of large cells in a diffuse pattern, with clear expression of CD20 may be adequate for identification of DLBCL, not otherwise specified (NOS). While this could be considered as a minimal standard of care, evaluation should take other morphologic, immunophenotypic, genetic, and clinical findings into account to completely classify DLBCL and related lymphomas. It is important to note that there are several specific subtypes of DLBCL that do not have distinctive histologic findings and as such can only be distinguished from DLBCL, NOS, by considering clinical, genetic, or immunophenotypic findings. Several markers may be expressed by specific subtypes of DLBCL but are not necessarily associated with specific morphologic features, including Epstein-Barr virus (EBV), CD5, anaplastic lymphoma kinase (ALK), CD30, and CD138. Prognosis in DLBCL has been a fertile area of research for several decades. A wide range of individual markers may be associated with prognosis in DLBCL and related lymphomas, supporting the idea that this is a complex and heterogeneous group of neoplasms, and each year additional markers are put forward for evaluation 5 18 (Table 5). While a plethora of unique aspects of DLBCL is prognostic, only those markers that have been vetted by extensive clinical study and can be routinely applied are the primary focus of this report. DIFFUSE LARGE B-CELL LYMPHOMA, NOS Most cases of DLBCL, NOS, express pan B-cell markers CD20, PAX5, and CD79a, although the plasmablastic types may lack CD20 and PAX5 in many cases. 19 Most cases also strongly express the B-cell transcription factors BOB1 and OCT2. Several markers are associated with general evaluation of large cell lymphomas and may be of prognostic value, Arch Pathol Lab Med Vol 139, September 2015 IHC in DLBCL O Malley et al 1095
3 Table World Health Organization Classification: Diffuse Large B-Cell Lymphoma (DLBCL) Variants, Subgroups, and Subtypes a DLBCL, not otherwise specified Common morphologic variants Centroblastic Immunoblastic Anaplastic Rare morphologic variants Molecular subgroups Germinal center B-cell like Activated B-cell like Immunohistochemical subgroups CD5 þ DLBCL Germinal center B-cell like Nongerminal center B-cell like Diffuse large B-cell subtypes T-cell/histiocyte rich large B-cell lymphoma Primary DLBCL of the CNS Primary cutaneous DLBCL, leg type EBV þ DLBCL of the elderly Other lymphomas of large B cells Primary mediastinal (thymic) large B-cell lymphoma Intravascular large B-cell lymphoma DLBCL associated with chronic inflammation Lymphomatoid granulomatosis ALK þ DLBCL Plasmablastic lymphoma Large B-cell lymphoma arising in HHV8-associated multicentric Castleman disease Primary effusion lymphoma Borderline cases B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma Abbreviations: ALK, anaplastic lymphoma kinase; CNS, central nervous system; EBV, Epstein-Barr virus; HHV8, human herpesvirus 8. a Reproduced with permission from the World Health Organization, from Table from Swerdlow et al. 4 therapeutic relevance, or are used in combination with other markers or studies for prognosis or subclassification. Ki-67 Some older studies 20 have shown that proliferation rate, as measured by Ki-67, is associated with prognosis in DLBCL. However, more recent studies have not shown these same associations. Nonetheless, Ki-67 is a valuable stain in the diagnostic approach to lymphomas and can provide considerable additional information besides prognosis. 21 Importantly, in cases with a near 100% proliferation rate, it may raise the diagnostic consideration of Burkitt lymphoma (BL) or other aggressive large B-cell lymphomas, but it is not useful alone in identifying double-hit lymphomas (DHLs). 22 BCL2 BCL2 expression in DLBCL is an adverse prognostic marker, particularly in cases of activated B-cell (ABC) type or with coexpression of MYC protein Its expression is not necessarily related to the presence or absence of the t(14;18) IgH/BCL2 genetic abnormality seen in follicular lymphomas and a subset of DLBCLs. The role of BCL2 in germinal center (GC) and ABC types differs and this may have an impact on therapeutic choices for these patients. MYC Protein Expression in Large B-Cell Lymphomas Because of its association with high proliferation, the MYC gene has been of considerable interest in DLBCL. In most cases, the presence of a MYC translocation, identified by classical cytogenetics, fluorescence in situ hybridization (FISH), or other molecular studies, has been of benefit in evaluating lymphomas. 26 The presence of MYC translocations is most often associated with a diagnosis of BL. However, DLBCLs may also have MYC translocations (8% 16%), as do a subset of DLBCLs with features intermediate between BL and DLBCL, DHLs (lymphomas with the combination of IGH/MYC translocations and either IGH/ BCL2 and/or BCL6 translocation) (Table 6), and rare B lymphoblastic lymphomas. 27 MYC amplifications have also been associated with poor prognosis. 28 MYC immunohistochemistry is associated with prognosis in DLBCL, especially in association with BCL2 protein expression (Figure 1, a through c). 29,30 High nuclear expression of MYC protein by immunohistochemistry (.40% 70%) in aggressive B-cell lymphomas may provide an appropriate triage step to indicate the need for additional genetic studies to evaluate for DHL or MYC translocations DLBCL and Cyclin D1 Expression Cyclin D1 expression can be seen in approximately 2% (30 of 1435) of DLBCLs. 34 However, in contrast to the staining seen in mantle cell lymphoma, it is only weakly positive and often seen in only a subset of lymphoma cells. It is not associated with differences in prognosis or pathologic features. Its primary use in the evaluation of DLBCL is to exclude the possibility of the blastoid or pleomorphic variants of mantle cell lymphoma, which may at times appear similar to DLBCL. 35 DLBCL and CD30 Expression CD30 expression can be seen in 10% to 21% (35 of 167) of cases of typical DLBCL, and the most recent studies suggest CD30 þ DLBCL may be associated with an overall better prognosis, with a unique gene expression profile. 36,37 It is seen with a high frequency in specific lymphoma types such as lymphomatoid granulomatosis, primary mediastinal large B-cell lymphoma (PMLBCL), plasmablastic lymphoma (PBL), and gray zone lymphomas. At present, its evaluation is especially relevant because brentuximab vedotin, an anti- CD30 monoclonal antibody, is currently in clinical trials and may be useful in the treatment of some cases of DLBCL. 36,38 COMMON AND RARE MORPHOLOGIC VARIANTS The common and rare morphologic variants in DLBCL do not require a specific evaluation distinct from DLBCL, NOS. Studies 39 have attempted to correlate immunoblastic morphology with prognosis in DLBCL. However, reproducibility of morphologic subtyping can be difficult in routine practice. CELL-OF-ORIGIN SUBGROUPS: MOLECULAR Gene expression microarray studies have led to the recognition that most DLBCLs may be separated into GC and ABC/nongerminal center (NGC) types, by RNA expression patterns Gene expression arrays are not currently applied in routine diagnosis, and as such, other immunohistochemical systems have been proposed to act as surrogate markers for gene expression arrays (see below) Arch Pathol Lab Med Vol 139, September 2015 IHC in DLBCL O Malley et al
4 Table 3. Summaries of Published Guidelines/Reporting Templates for Evaluation of Diffuse Large B-Cell Lymphoma a,b,c A. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Hodgkin Lymphoma 1. Adequate immunophenotyping to establish diagnosis and GC versus non-gc origin 2. IHC panel: CD20, CD3, CD5, CD10, CD45, BCL2, BCL6, Ki-67, MUM1, MYC or Cell surface marker analysis by flow cytometry: j/k, CD45, CD3, CD5, CD19, CD10, CD20 3. Useful under certain circumstances Additional immunohistochemical studies to establish lymphoma subtype IHC panel: cyclin D1, j/k, CD30, CD138, EBER-ISH, ALK, HHV8 Cytogenetics or FISH: t(14;18), t(3;v), t(8;14), t(8;v) B. Alberta Provincial Hematology Tumour Team Lymphoma 1. CD20 2. May include CD45/CD3/CD20/CD30/CD15/PAX5/MUM1 3. Routine use of immunohistochemical stains for the express purpose of subtyping ABC versus GC is not recommended 4. CD5 staining should be performed for all patients with DLBCL 5. EBER analysis should be performed for patients with immune suppression related lymphomas, or those who possibly have EBVrelated DLBCL of the elderly 6. Ki-67 (high proliferation rate by Ki %) 7. MYC rearrangement testing by FISH is required 8. If MYC is rearranged, the case should be followed up with BCL2 and BCL6 rearrangement testing by FISH d C. College of American Pathologists Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, Biomarker Reporting Template 1. Immunohistochemical staining BCL2, CD5, CD20, CD30, Ki-67, MYC 2. GC versus NGC e Hans (CD10, BCL-6, MUM1) Choi (GCET1, CD10, MUM1, BCL6, FOXP1) Tally (CD10, GCET1, MUM1, FOXP1, LMO2) Gene expression profiling 3. FISH MYC, BCL2, BCL6 Abbreviations: ABC, activated B cell; ALK, anaplastic lymphoma kinase; DLBCL, diffuse large B-cell lymphoma; EBER, Epstein-Barr virus encoded small RNAs; EBV, Epstein-Barr virus; FISH, fluorescence in situ hybridization; GC, germinal center; HHV8, human herpesvirus 8; IHC, immunohistochemistry; ISH, in situ hybridization; NCCN, National Comprehensive Cancer Network, Inc; NGC, nongerminal center. a Section A: Adapted with permission from Zelenetz et al, 1 the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non- Hodgkin s Lymphoma V Copyright 2014 National Comprehensive Cancer Network, Inc. All rights reserved. The NCCN Guidelines and illustrations herein may not be reproduced in any form for any purpose without the express written permission of the NCCN. To view the most recent and complete version of the NCCN Guidelines, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK, NCCN, NCCN GUIDELINES, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. b Section B: Copyright 2014 Alberta Health Service. 2 This material is protected by Canadian copyright law. Except as otherwise provided for under Canadian copyright law, this material may not be copied, published, or distributed without the prior written permission of the copyright owner. This material was originally published by Alberta Health Services and has been reprinted with permission. These materials are intended for general information only and are provided on an as is, where is basis. Although reasonable efforts were made to confirm the accuracy of the information, Alberta Health Services does not make any representation or warranty, express or implied, oral or written, statutory or otherwise, as to the accuracy, reliability, completeness, applicability or fitness for the particular purpose of such information, including without limitation implied warranties or warranties of noninfringement or merchantability. These materials are not a substitute for the advice of a qualified health professional. Alberta Health Services expressly disclaims all liability for the use of these materials, and for any claims, actions, demands or suits arising from such use. c Section C: Data derived from Duncavage et al. 3 d In patients younger than 70 years and in cases with high proliferation rate by Ki-67, with atypical (eg, Burkitt-like) morphology or with aggressive clinical behavior. e Germinal center type versus nongerminal center type. Specific classifier is not endorsed and Hans, Tally, and Choi classifiers are listed as possible options. CELL-OF-ORIGIN SUBGROUPS: IMMUNOHISTOCHEMISTRY Germinal Center Type Versus Nongerminal Center Type When considering DLBCL, NOS, determination of GC versus ABC type is of prognostic relevance. In general, GCtype DLBCL is associated with a better prognosis compared to ABC-type DLBCL. In the pre-rituximab era, the average 5-year survival associated with GC type was 60% versus 35% for ABC type; with the addition of rituximab to standard therapy, 5-year survival is 87% to 92% for GC type and 44% for ABC type. 42,45 Moreover, responses to newer therapeutic options may be significantly different for GC versus NGC types, making this classification even more important. 46 However, in the special types of DLBCL, those with a poor prognosis are typically of ABC type, and determination of GC versus ABC may not be relevant. Testing of GC versus ABC type of DLBCL is best accomplished by gene expression profiling. However, since this technique is not available for routine practice, other surrogate systems have been and continue to be tested. 44,45,47 51 While these immunohistochemical approaches are not without controversy, in general there is relatively good concordance with gene expression profiling results. 44,51 54 There are several schemes that allow for immunohistochemical classification of DLBCL, NOS (Figure 2, a through f). The first and most well known is the Hans classifier. 47 It is based on the application of 3 antibodies (CD10, BCL6, and MUM1). The overall concordance with gene expression array signatures is 80% (122 of 152). Other systems use combinations of other markers ([Choi et al 45 : GCET1, MUM1, CD10, BCL6, FOXP1], [Muris et al 48 : BCL2, CD10, MUM1], [Natkunam et al 49 : LMO2], [Nyman et al 50 : MUM1, Arch Pathol Lab Med Vol 139, September 2015 IHC in DLBCL O Malley et al 1097
5 Table 4. Large B-Cell Lymphoma Types and Association With Therapy and Prognosis Based on Suggested Therapies a Lymphoma Type Specialized Therapy b Difference in Prognosis b Centroblastic No No Immunoblastic No No Anaplastic No No GC type (GEP) Likely Yes ABC-like (GEP) Likely Yes CD5 þ DLBCL No Yes GC type (IHC) Likely Yes ABC type (IHC) Likely Yes TCHRLBCL No Yes Primary CNS DLBCL Yes Yes Primary cutaneous DLBCL Yes Yes EBV þ DLBCL of elderly No Yes Primary mediastinal large B-cell lymphoma Yes Yes IVLBCL No Yes DLBCL arising from chronic inflammation No Yes Lymphomatoid granulomatosis Yes Yes ALK þ DLBCL c No Yes Plasmablastic lymphoma Yes Yes LBCL associated with MCD Yes Yes Primary effusion lymphoma Yes Yes BCL, intermediate DLBCL/BL Likely Yes BCL, intermediate DLBCL/CHL Likely Yes Abbreviations: ABC, activated B cell; ALK, anaplastic lymphoma kinase; BCL, B-cell lymphoma; BL, Burkitt lymphoma; CHL, classical Hodgkin lymphoma; CNS, central nervous system; DLBCL, diffuse large B-cell lymphoma; EBV, Epstein-Barr virus; GC, germinal center; GEP, gene expression profiling; IHC, immunohistochemistry; IVLBCL, intravascular large B-cell lymphoma; LBCL, large B-cell lymphoma; MCD, multicentric Castleman disease; TCHRLBCL, T-cell/histiocyte rich large B-cell lymphoma. a Data derived from Zelenetz et al. 1 b Compared to typical de novo DLBCL. c Although not specific currently, anti-alk therapies (ie, crizotinib) may be used for patients with ALK þ DLBCL. FOXP1], and [Meyer et al 51 : CD10, GCET1, MUM1, FOXP1, LMO2]) to achieve a more accurate prediction of the gene expression profile results (Figure 3, a through n). There are differences suggested in the prognostic significance of BCL6 protein expression versus BCL6 translocation. If GC versus ABC type is relevant to prognosis, then expression of BCL6 generally supports GC type. However, genetic abnormalities of the BCL6 gene may be seen in ABC-type DLBCL. CD5 þ Diffuse Large B-Cell Lymphoma CD5 þ DLBCL has been described in the 2008 WHO classification and represents 5% to 10% of DLBCLs. 19,55,56 CD5 þ DLBCL is noted to have some differences from other typical DLBCL. In general, these cases are more often associated with a more aggressive clinical course, poor outcome, and are seen at a higher frequency in patients with human immunodeficiency virus (HIV)/AIDS. They express BCL2, with most expressing MUM1 and one-half expressing BCL6. 55 There are 4 recognized morphologic subtypes: common variant (centroblastic monomorphic) (76%; 91 of 120); giant cell rich variant, with intravascular involvement (11%; 13 of 120); polymorphic variant (12%; 14 of 120); and immunoblastic variant (1%; 2 of 120). 57 Approximately 25% (3 of 13) of the giant cell variant cases express CD The expression of CD5 raises the differential diagnosis of mantle Table 5. Selected Markers Associated With Prognosis in Diffuse Large B-Cell Lymphoma Marker Source, y Thymidine phosphorylase Nie et al, TNF-a Nakayama et al, CIP2A Lilja et al, Cyclin E Frei et al, MET Koh et al, RON Koh et al, PD1-L1 Chen et al, DcR3 Bedewy et al, IL9R Lv et al, IRF8 Tinguely et al, MYD88 Choi et al, MCL1 Wenzel et al, MLL2 Morin et al, PI3K Cui et al, AKT Cui et al, p105/p50 Montes-Moreno et al, p100/p52 Montes-Moreno et al, cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Conventional mantle cell lymphoma can be distinguished by morphology and in cases of blastoid mantle cell lymphoma, the uniform expression of cyclin D1 would distinguish this entity from DLBCL. The possibility of CD5 expression in a large cell transformation of CLL/SLL (ie, Richter syndrome) is dependent on an antecedent history of the low-grade disorder with subsequent transformation. DLBCL SUBTYPES T-Cell/Histiocyte Rich Large B-Cell Lymphoma T-cell/histiocyte rich large B-cell lymphoma (TCHRLBCL) has distinctive morphologic and clinicopathologic findings It is a rare large B-cell lymphoma. It is most commonly seen in middle-aged men, and is associated with an aggressive clinical course. By morphology, scattered large abnormal B cells (10% or less of the overall cellularity) are seen in a background rich in small lymphocytes (T cells) or histiocytes. Because of this distinctive appearance, the differential diagnosis of classical Hodgkin lymphoma (CHL) is frequently a consideration. The large B cells are positive for pan B-cell antigens including CD19, CD20, CD79a, PAX5, OCT2, and BOB1 with expression of CD CD30 expression is seen in a small subset of cases, but the large cells do not express CD15. They do not express CD5, CD43, or CD138. They are usually positive for BCL6 and BCL2, without expression of CD10. Epithelial membrane antigen (EMA) may show variable positivity in some cases. In contrast to many cases of CHL, staining for EBV is exceedingly rare in TCHRLBCL. If EBV is present, other diagnoses should be considered including CHL or EBV-positive DLBCL of the elderly. The background small lymphocytes are usually T cells that are positive for pan T-cell antigens, typically with more CD8 þ T cells compared to CD4 þ, in contrast to nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), which is typically rich in CD4 þ T cells. The histiocytes are positive for CD68 and CD163. Staining with follicular dendritic cell markers (eg, CD21, CD23) may be of benefit; follicular dendritic cell networks are absent in TCHRLBCL but are present in cases of NLPHL. Immunoglobulin (Ig) D is expressed in many of the small lymphocytes associated 1098 Arch Pathol Lab Med Vol 139, September 2015 IHC in DLBCL O Malley et al
6 Table 6. with NLPHL. Recently, gene expression arrays comparing the microdissected large cells of TCHRLBCL and NLPHL were performed and no consistent differences were identified between these two entities. While not specific, it does lend some credence to the suggestions that at least some cases of TCHRLBCL may arise from previous NLPHL. 61 Primary DLBCL of the Central Nervous System and Primary Cutaneous DLBCL, Leg Type Primary central nervous system lymphoma and diffuse large B-cell lymphoma, leg type are lymphomas of activated B cells (ABC type), and are negative for CD10. The leg type diffuse large B-cell lymphoma characteristically has very strong BCL2 expression, often stronger than the admixed T cells. In these cases, because of independent poor prognosis of the special type, complete evaluation of cell of origin is not necessary, provided CD10 expression is excluded in leg type. EBV-Associated DLBCL of the Elderly: DLBCL and Epstein-Barr Virus In the 2008 WHO classification the new entity, EBVassociated DLBCL of the elderly, was added. These lymphomas are always associated with EBV infection and by definition, are seen in patients 50 years or older These lymphomas are more common in Asian patients (8% 10%) and less common in Western populations (5% or less). The morphologic findings include monomorphous large transformed B cells with most having areas of geographic necrosis, although this is not a universal feature. 66 These lymphomas are associated with a poor prognosis compared to typical DLBCLs. They are identified most reliably by in situ staining for EBV (Epstein-Barr virus encoded small RNAs; EBER). 64 In the diagnosis of EBV-positive DLBCL, exclusion of impairment of the immune system secondary to immunosuppression, transplantation, autoimmune disease, medications, or previous lymphoma is necessary. The immunophenotype of EBV-associated DLBCL of the elderly is positive for the pan B-cell antigens CD79a, CD20, CD19, and PAX5. It is negative for CD15 and CD10. Epstein-Barr virus should show positivity in greater than 50% of cases and is usually present in virtually all of the lymphoma cells. 64 These lymphomas are usually of NGC B- cell type, lacking BCL6 and CD10, but expressing MUM1 and usually also CD30. The EBER marker consistently shows positivity, and EBV-latent membrane protein (EBV-LMP) also shows positivity in almost all cases. Several other large B-cell lymphomas are occasionally or always positive for EBV, including PBL, primary effusion lymphoma, DLBCL associated with chronic inflammation, Possible Genetic Abnormalities Seen in Double-Hit Lymphomas MYC-Associated Translocation Additional Translocation Additional Translocation Note IGH/MYC IGH/BCL2... Most common combination MYC/X IGH/BCL MYC/X BCL6/X IGH/MYC IGH/BCL2 BCL6/X Triple hit a MYC/X IGH/BCL2 BCL6/X Triple hit a MYC/X BCL3/X IGH/BCL2 BCL6... Controversial b Abbreviation: X, unidentified translocation partner (a subset of cases are j or k light-chain genes, others are nonimmunoglobulin genes). a Triple-hit lymphomas are considered to be equivalent to double-hit lymphomas and may be referred to as double-hit lymphomas. b It is unclear if combinations of translocations without involvement of MYC have comparable prognostic implications to those with MYC translocation, although technically these are still referred to as double-hit lymphomas. and lymphomatoid granulomatosis. Subsets of cases of BL are also positive for EBV. 67 Most cases of posttransplant lymphoproliferative disorders, including those of large cell, monomorphic type (eg, DLBCL) also show positivity. In all cases, consideration of these specific subtypes, clinical history, and overall pathologic findings are necessary to render an accurate diagnosis. Some types of large cell lymphomas that are associated with chronic EBV activity are positive for immunohistochemical staining for EBV-LMP; however, many types of EBV-positive lymphoproliferative disorders do not express EBV-LMP consistently. When possible, in situ stains for EBV (EBER) are recommended for evaluation of EBV expression in lymphoproliferative disorders. OTHER LYMPHOMAS OF LARGE B CELLS Primary Mediastinal Large B-Cell Lymphoma Primary mediastinal large B-cell lymphoma is associated with a fairly unique clinicopathologic presentation. 68 It is seen most frequently in young adults, with a slight female predominance and a rapidly growing mediastinal mass. The lymphoma cells are large, with round to slightly irregular nuclei, occasional pleomorphic multilobated nuclei, with moderate amounts of pale cytoplasm, imparting a clear cell appearance. This finding is not seen in all cases, and is only focal in some cases. In general, PMLBCL has an equivalent or slightly better prognosis than typical DLBCL. In most cases, the differential diagnosis is between PMLBCL, CHL, and other types of diffuse large B-cell lymphomas. Because of its distinct prognosis and a proposed origin from thymic B cells, it often has a distinctive immunophenotype. However, gene expression arrays in PMLBCL show considerable overlap with CHL, and overlapping diagnostic features can be seen. 69,70 In rare cases, collision tumors of PMLBCL and CHL, and synchronous and metachronous presentations of both, have been noted. The immunophenotype shares features with other typical large B-cell lymphomas. The lymphoma cells are positive for pan B-cell antigens including CD20, CD19, CD22, and PAX5. Distinctive features include expression of CD23 and MUM1 in most cases. Most cases are also positive for p CD30 expression is present in most cases, but is usually weak and heterogeneous, as compared to uniform and strong expression seen in CHL. CD15 is not typically identified and if present should raise the possibility of an overlap diagnosis (see below). Expression of BCL2 and BCL6 is variable and CD10 is typically negative. In comparing CHL and PMLBCL, Hoeller et al 72 suggest that Arch Pathol Lab Med Vol 139, September 2015 IHC in DLBCL O Malley et al 1099
7 expression of BOB1 favors PMLBCL and expression of cyclin E favors CHL. Although these immunohistochemical stains are not routinely evaluated, most cases of PMLBCL express MAL, CD54, CD95, and TRAF1. 72 Intravascular Large B-Cell Lymphoma Intravascular large B-cell lymphoma (IVLBCL) is an extremely rare lymphoma. 73,74 It occurs slightly more frequently in men (male to female ratio: 1.1:1) with a median age of presentation of 67 years. This lymphoma has an unusual range of clinical presentations dependent on tissue types involved, and the diagnosis is often unexpected. It can be seen in several tissue types, including skin, bone marrow, spleen, lung, brain, prostate, and many other sites. Hemophagocytosis is seen in a subset of cases and may be associated with significant cytopenias. As implied in the name, clusters and aggregates of large atypical lymphoid cells are seen in an intravascular distribution. Although classically associated with a poor prognosis, the advent of rituximab therapy has resulted in improved outcomes for many patients. 73 IVLBCLs express pan B-cell antigens, including CD19 (85%), CD20 (96%), CD79a (100%), and PAX5. They express CD5 in 38% and CD10 in 12% of cases. 73 Most cases are positive for MUM1 (95%), except those that are CD10 þ. BCL2 expression is seen in 91% of cases. IVLBCL likely has unique markers that account for its intravascular distribution (such as CXCR3), but surface proteins that are critical for endothelial transmigration or adhesion are absent (CD29, CD54); however, use of these markers are not required for lymphoma diagnosis. DLBCL Associated With Chronic Inflammation In patients with long-standing chronic inflammation, DLBCL may develop. The prototype of this type of lymphoma is pyothorax-associated lymphoma, although other clinical scenarios including cysts and pseudocysts, and association with joint replacement, have also been described These cases usually express pan B-cell antigens CD20, CD79a, and PAX5, although cases with plasmacytic or plasmablastic differentiation may lose expression of mature B-cell markers. In these cases expression of plasma cell associated markers, including MUM1 and CD138, may be seen. These cases will express EBV, and while EBER in situ staining may be more accurate, most cases will express EBV- LMP. They express BCL2 and lack CD10 and BCL6. 76 CD30 is expressed in a subset of cases. 77 Lymphomatoid Granulomatosis Lymphomatoid granulomatosis is a rare EBV-driven lymphoproliferative disorder involving extranodal sites in patients with inherited or acquired immunodeficiencies. 78,79 Pulmonary involvement is most common, followed by brain, kidney, liver, and skin. The morphologic features include a polymorphous lymphohistiocytic infiltrate associated with angioinvasive and angiodestructive lesions. Within this background are variable numbers of atypical Figure 1. High-grade B cell lymphoma (a) with expression of BCL2 (b) and a high percentage of MYC expression (c). Cases with BCL2 and high MYC expression are associated with an aggressive clinical course (hematoxylin-eosin, original magnification 3400 [a]; original magnification 3400 [b and c]) Arch Pathol Lab Med Vol 139, September 2015 IHC in DLBCL O Malley et al
8 Figure 2. Diagrams of classification systems (in general, markers are considered to show positivity if.30% of cells express the marker). a, Hans classifier. b, Visco-Young classifier. c, Choi classifier. d, Muris classifier (Note: group 1 is comparable to germinal center type and group 2 is comparable to nongerminal center/activated B-cell type). e, Nyman classifier. f, Tally classifier. Light gray shading: germinal center type or equivalent; medium gray shading: nongerminal center or equivalent. *Other type in Nyman classifier is poorly defined. Abbreviations: GC, germinal center; NGC, nongerminal center; þ, positive,, negative. EBV-positive B cells. These may appear Hodgkin-like, or as pleomorphic large lymphocytes. The large abnormal cells are positive for EBV (EBER, EBV- LMP) and CD20. They express CD30 in most cases but are negative for CD15, in contrast to CHL. ALK-Positive Large B-Cell Lymphoma Anaplastic lymphoma kinase positive large B-cell lymphoma (ALK-LBCL) is exceedingly rare, is more common in men (male to female ratio: 5:1) and presents in a wide age range (14 85 years). 80,81 It is composed of large cells with large round nuclei, with prominent nucleoli and often with large amounts of pale-staining cytoplasm. These cells express the ALK protein but lack T-cell antigen expression and T-cell receptor gene rearrangements seen in anaplastic large (T) cell lymphoma. 82 Staining with ALK is typically granular and cytoplasmic, although rare cases with cytoplasmic and nuclear staining can be seen, depending on the specific translocation present. These lymphomas will often express plasma cell associated markers, including CD138, CD38, IgA (88%; 29 of 33), and cytoplasmic restricted light chains. 81 They will often lack expression of pan B-cell antigens (CD19, CD20, and PAX5). 81,83 CD45 expression is seen in most cases (82%; 19 of 23) and EMA expression is seen in almost all cases. CD30 is rarely expressed (6%; 2 of 36) and in contrast to plasmablastic lymphoma, there is no association with human herpesvirus 8 (HHV8) or EBV (EBER). ALK-LBCL may be susceptible to the relatively recently developed anti-alk therapy, crizotinib. 38,84 Arch Pathol Lab Med Vol 139, September 2015 IHC in DLBCL O Malley et al 1101
9 Plasmablastic Lymphoma Plasmablastic lymphoma is an aggressive B-cell neoplasm, which has immunophenotypic features of plasma cells with large cell morphology, and varying degrees of associated, more typical mature plasma cells. 85,86 Most cases are associated with immunodeficiency, particularly HIV/ AIDS, although a subset of cases is seen in immunocompetent patients. Plasmablasts are large and round, with round nuclei, prominent nucleoli, and small or minimal amounts of cytoplasm. The immunophenotypic features of PBL include expression of CD138, CD38, and CD79a (50% 85%), but PBLs usually lack expression of CD45, CD20, and PAX5. They will also express monoclonal cytoplasmic light chain in approximately more than one-half of cases. The proliferation rate by Ki-67 is greater than 90%. They lack expression of CD56, which is seen more frequently in high-grade transformation of plasma cell myeloma. The EMA and CD30 markers often show positivity. Importantly, most cases are positive for EBV by in situ staining (EBER). Human herpesvirus 8 is not seen, in contrast to some plasma cell neoplasms associated with HIV/AIDS. 85 Expression of CD56, cyclin D1, or bone/bone marrow involvement would suggest plasmablastic plasma cell myeloma rather than PBL, while the presence of EBV positivity or a MYC translocation would favor PBL. 18 Large B-Cell Lymphoma Arising in HHV8-Associated Multicentric Castleman Disease An exceedingly rare lymphoma, this is a large B-cell lymphoma that arises in HHV8-associated multicentric Castleman disease Most cases occur in HIV/AIDS patients or in areas with endemic HHV8 infection, including Africa and the Mediterranean area. These lymphomas have a plasmablastic appearance and start as clusters and cell aggregates in a background of multicentric Castleman disease (so-called microlymphomas). The abnormal cells will have variable expression of CD20 and typically lack expression of CD79a and CD138. They show expression of HHV8-associated antigens (LANA-1) and viral interleukin 6. They also express cytoplasmic IgM and monotypic k light chain. In contrast to some other plasmablastic lymphomas seen in HIV/AIDS, there is no evidence of EBV infection. Primary Effusion Lymphoma Primary effusion lymphoma (PEL) is another exceedingly rare B-lineage lymphoma, most often seen in immunocompromised patients, such as those with HIV infection As its name implies, most cases are seen in fluid effusions of the pleural or peritoneal cavities and exhibit overlapping morphologic features of immunoblastic, anaplastic, or plasmablastic large cell lymphomas. Some rare cases of Figure 3. Immunohistochemical staining in diffuse large B-cell lymphomas: contrasting differences in immunophenotype and subsequent classification by Hans and Tally classifiers. Case 1: Left column (a, hematoxylin-eosin [H&E]; c, CD10; e, BCL6; g, MUM1; i, FOXP1; k, GCET1; m, LMO2); by Hans classifier, this case would be considered of germinal center (GC) type (CD10 þ, BCL6 þ, MUM1 ); by Tally classifier, this case would be of GC type (CD10 þ, GCET1 þ, MUM1, FOXP1 þ ;GC. NGC). Case 2: Right column (b, H&E; d, CD10; f, BCL6; h, MUM1; j, FOXP1; l, GCET1; n, LMO2); by Hans classifier, this case would be of non-gc (NGC) type (CD10, BCL6 þ, MUM1 þ ); by Tally classifier, this case would also be of NGC type (CD10, GCET1, MUM1 þ, FOXP1 þ ) (original magnification 3400) Arch Pathol Lab Med Vol 139, September 2015 IHC in DLBCL O Malley et al
10 solid tissue based PEL have been reported. Virtually all cases have evidence of HHV8 infection, and cases not associated with HIV/AIDS are typically seen in areas with endemic HHV8 infection. Coinfection with EBV (as identified by EBER staining) is seen in several cases (60%). Exceedingly rare cases of HHV8-negative PEL have been identified. 93 The immunophenotype includes expression of CD45 (88%; 38 of 43) but lack of expression of most pan B-cell markers (CD20: 67% [51 of 76]; CD19: 92% [45 of 49]; CD79a: 88% [21 of 24]; and CD22: 97% [32 of 33]). 90,91 Plasma cell associated markers including CD138 (77%; 17 of 22), CD38 (100%; 48 of 48), MUM1 (92%; 47 of 51), VS38c, and EMA show positivity. 90,91 CD30 often shows positivity (69% 81%; 62 of 76). Primary effusion lymphoma cells lack T-cell associated antigen expression, although exceedingly rare cases of PEL of T-cell lineage have been reported. 90,91 Almost all cases show evidence of clonal B-cell gene rearrangements by polymerase chain reaction. BURKITT LYMPHOMA Burkitt lymphoma is a distinctive, but relatively rare, aggressive B-cell lymphoma. 67 It can present in both extranodal and nodal sites. Patients are generally younger than 30 years, but BL may be seen in older patients as well. It has a distinctive morphology of intermediate-sized lymphocytes with round nuclei, mature chromatin, and small to moderate amounts of deeply staining cytoplasm. Mitotic figures and apoptotic bodies are frequently seen. Tingible body macrophages will often impart the classic starry-sky pattern at low magnification. The characteristic immunophenotype of BL shows pan Bcell antigen expression (CD20, PAX5, CD19, CD22, CD79a), with strong expression of CD10, and a very high proliferation rate by Ki-67 (approximately 100%). Burkitt lymphoma lacks expression of terminal deoxynucleotidyl transferase (to exclude B lymphoblastic leukemia/lymphoma). BCL2 usually shows negativity, but may show weak positivity in approximately 25% of cases. Admixed CD3 þ T cells are infrequent but CD68 þ /CD163 þ macrophages are consistently seen. The BL cells consistently express germinal center associated markers including BCL6, GCET1, and HGAL. Some cases will show expression of MUM1, and CD43 is expressed in about one-half of cases. Burkitt lymphoma lacks expression of cyclin D1, CD5, and CD23. Flow cytometry will often show strong expression of CD38, a reflection of the high proliferative cell fraction in BL. 67,94 A classic immunophenotype can accurately diagnose BL in approximately 94% of cases (CD20 þ, CD10 þ, Ki-67 expression of almost 100%, CD38 þ ; BCL2 ). 94 In situ staining for EBV (EBER) will be positive in some cases, more often in those associated with immunosuppression. In the current classification, the presence of a MYCassociated translocation (t(8;14) MYC/IGH) or variants is necessary to confirm all but the most classic cases. In some cases, BCL2 expression may be seen, and when present, particularly when strongly positive, other diagnoses, including MYC translocation positive DLBCL, B cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL, and DHL should be excluded. In MYC translocation positive lymphomas, a simple karyotype (IGH/MYC, with no or 1 other genetic abnormality) is supportive of a diagnosis of BL, while multiple genetic abnormalities support a diagnosis of either DHL or DLBCL. 26 BORDERLINE CASES B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma (BCLUWFIBDLBCLABL) and Double-Hit Lymphoma Within the category of aggressive B-cell lymphomas, a subset of cases with the morphologic appearance of DLBCL, or cases that fall in the BCLUWFIBDLBCLABL provisional category, will have evidence of a combination of genetic findings, leading to a diagnosis of DHL. This is estimated to occur in 11% of cases of DLBCL and B-cell lymphoma, unclassifiable. 27,95 99 Double-hit lymphoma is characterized by the presence of a translocation of MYC and another classic B-cell lymphoma driver translocation. The most commonly identified combination is the presence of an IGH/ MYC translocation and IGH/BCL2. Other possible combinations are shown in Table 6. The immunophenotype of DHL is not characteristic. CD10 is generally expressed (76% 100%), as well as BCL2 (63% 96%), which usually shows strong positivity. 95 BCL6 is expressed in 63% to 96% of cases. While Ki-67 expression is usually 90% or higher, several studies 22,95 have shown wide variation (15% 100%) caused by biologic factors, suggesting that Ki-67 alone is not adequate for triaging cases for DHL workups. B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma Occasional lymphomas have features that show considerable overlap in clinical, histologic, and/or immunophenotypic features between diagnoses of CHL and DLBCL. 100 In general, these occur in the mediastinum. These have been included in a provisional diagnosis in the 2008 WHO classification, B cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma (BCLUWFIBDLBCLACHL). As mentioned, there are considerable molecular similarities between PMLBCL and CHL, suggesting that lymphomas with overlapping features might exist. These are often referred to as gray zone lymphomas when distinction between DLBCL and CHL cannot be resolved with immunohistochemical staining. Table 7 highlights immunohistochemical findings which would help to resolve the differential diagnosis. In cases with equivocal results, a diagnosis of BCLUWFIBDLBCLACHL would be appropriate. When studied as a group, gray zone lymphomas are more aggressive than either PMLBCL or CHL. 68 PRACTICAL GUIDELINES FOR APPLICATION TO DIAGNOSIS With this myriad of entities and possibilities, some guidance to the practical application of this information is appropriate. Clinical scenarios are discussed below. Small/Limited Sample Small-gauge needle core biopsies of lymphoma are common practice and may present inherent diagnostic problems. However, in cases of a limited sample, with the minimal acceptable morphologic evidence of a large cell lymphoma (eg, diffuse sheets of large lymphocytes), a minimal evaluation for diagnostic confirmation would Arch Pathol Lab Med Vol 139, September 2015 IHC in DLBCL O Malley et al 1103
Aggressive B-cell Lymphomas
Neoplastic Hematopathology Update 2018 Aggressive B-cell Lymphomas Raju K. Pillai City of Hope National Medical Center I do not have any disclosures Disclosures Outline New entities and changes in WHO
More informationEQA SCHEME CIRCULATION 33 EDUCATIONAL SLIDES DR GRAEME SMITH MONKLANDS DGH
EQA SCHEME CIRCULATION 33 EDUCATIONAL SLIDES DR GRAEME SMITH MONKLANDS DGH CASE E1 M: 68 yrs Left destructive sinonasal lesion.?lymphoma?adenocarcinoma CD20 CD10 BCL6 MIB1 Answers Diffuse large B cell
More informationAggressive B-Cell Lymphomas
Aggressive B-cell Lymphomas Aggressive B-Cell Lymphomas Stephen Hamilton Dutoit Institute of Pathology Aarhus Kommunehospital B-lymphoblastic lymphoma Diffuse large cell lymphoma, NOS T-cell / histiocyte-rich;
More informationDefined lymphoma entities in the current WHO classification
Defined lymphoma entities in the current WHO classification Luca Mazzucchelli Istituto cantonale di patologia, Locarno Bellinzona, January 29-31, 2016 Evolution of lymphoma classification Rappaport Lukes
More informationAggressive B cell Lymphomas
Aggressive B cell Lymphomas I have nothing to disclose. Disclosures Raju K. Pillai City of Hope National Medical Center Outline WHO 2016 Classification Large B cell Lymphomas New entities and changes in
More informationDifferential diagnosis of hematolymphoid tumors composed of medium-sized cells. Brian Skinnider B.C. Cancer Agency, Vancouver General Hospital
Differential diagnosis of hematolymphoid tumors composed of medium-sized cells Brian Skinnider B.C. Cancer Agency, Vancouver General Hospital Lymphoma classification Lymphoma diagnosis starts with morphologic
More informationAggressive B cell Lymphomas
Aggressive B cell Lymphomas Raju K. Pillai City of Hope National Medical Center I have no disclosures Outline What is new in the WHO 2016 classification Insights from genomic studies Double Hit Lymphoma
More informationNEW ENTITIES IN AGGRESSIVE B CELL LYMPHOMA. Joon Seong Park, M.D. Dept. of Hematology-Oncology Ajou University School of Medicine
NEW ENTITIES IN AGGRESSIVE B CELL LYMPHOMA Joon Seong Park, M.D. Dept. of Hematology-Oncology Ajou University School of Medicine Historical background of Lymphoma classification Rappaport classification
More informationAggressive B-cell Lymphoma 2013
Aggressive B-cell Lymphoma 2013 Diffuse Large B-Cell Lymphoma Burkitt Lymphoblastic lymphoma Gray zone Intermediate DLBCL/HL Intermediate BL/DLBCL Diffuse Large B-cell lymphoma Common morphology: diffuse
More informationAggressive B-cell lymphomas and gene expression profiling towards individualized therapy?
Aggressive B-cell lymphomas and gene expression profiling towards individualized therapy? Andreas Rosenwald Institute of Pathology, University of Würzburg, Germany Barcelona, June 18, 2010 NEW WHO CLASSIFICATION
More informationPearls and pitfalls in interpretation of lymphoid lesions in needle biopsies
Pearls and pitfalls in interpretation of lymphoid lesions in needle biopsies Megan S. Lim MD PhD University of Pennsylvania October 8, 2018 Objectives To understand how the trend toward less invasive lymph
More informationHepatic Lymphoma Diagnosis An Algorithmic Approach
Hepatic Lymphoma Diagnosis An Algorithmic Approach Ryan M. Gill, M.D., Ph.D. University of California, San Francisco PLEASE TURN OFF YOUR CELL PHONES Disclosure of Relevant Financial Relationships USCAP
More informationAggressive B-cell Lymphomas Updated WHO classification Elias Campo
Aggressive B-cell Lymphomas Updated WHO classification Elias Campo Hospital Clinic, University of Barcelona Diffuse Large B-cell Lymphoma A Heterogeneous Category Subtypes with differing: Histology and
More informationPathology of aggressive lymphomas
Institute of Pathology Pathology of aggressive lymphomas Leticia Quintanilla-Martinez Changes in the new 2016 WHO Aggressive B-cell lymphoid neoplasms Major changes that impact how cases should be evaludated
More informationImmunopathology of Lymphoma
Immunopathology of Lymphoma Noraidah Masir MBBCh, M.Med (Pathology), D.Phil. Department of Pathology Faculty of Medicine Universiti Kebangsaan Malaysia Lymphoma classification has been challenging to pathologists.
More informationPathology of aggressive lymphomas
Institute of Pathology Pathology of aggressive lymphomas Leticia Quintanilla-Martinez Changes in the new 2016 WHO Aggressive B-cell lymphoid neoplasms Major changes that impact how cases should be evaludated
More informationUpdate on the Classification of Aggressive B-cell Lymphomas and Hodgkin Lymphoma
Update on the Classification of Aggressive B-cell Lymphomas and Hodgkin Lymphoma Nancy Lee Harris, M. D. Massachusetts General Hospital Harvard Medical School Aggressive B-cell Lymphomas WHO 4 th Edition
More informationNon-Hodgkin s Lymphomas Version
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines ) Non-Hodgkin s Lymphomas Version 2.2015 NCCN.org Continue Use of Immunophenotyping/ Genetic Testing in Differential Diagnosis of Mature B-Cell
More information3/23/2017. Disclosure of Relevant Financial Relationships. Pitfalls in Immunohistochemistry in Hematopathology: CD20 and CD3 Can Let Me Down?!
Pitfalls in Immunohistochemistry in Hematopathology: CD20 and CD3 Can Let Me Down?! Judith A. Ferry Massachusetts General Hospital Disclosure of Relevant Financial Relationships USCAP requires that all
More informationMany of the hematolymphoid disorders are derived
REVIEW ARTICLE Practical Immunohistochemistry in Hematopathology: A Review of Useful Antibodies for Diagnosis Ji Lu, MD and Karen L. Chang, MD Abstract: This review article offers some useful panels of
More informationHigh grade B-cell lymphomas (HGBL): Altered terminology in the 2016 WHO Classification (Update of the 4 th Edition) and practical issues Xiao-Qiu Li,
High grade B-cell lymphomas (HGBL): Altered terminology in the 2016 WHO Classification (Update of the 4 th Edition) and practical issues Xiao-Qiu Li, M.D., Ph.D. Fudan University Shanghai Cancer Center
More informationMost reviews on diffuse large B-cell lymphoma
Diffuse Large B-Cell Lymphoma More Than a Diffuse Collection of Large B Cells An Entity in Search of a Meaningful Classification Sandeep Gurbaxani, MBBS, PhD; John Anastasi, MD; Elizabeth Hyjek, MD, PhD
More informationGray Zones and Double Hits Distinguishing True Burkitt Lymphoma from Other High-Grade B-NHLs Burkitt Lymphoma Burkitt-Like Lymphoma DLBCL Patrick Tres
Gray Zones and Double Hits Distinguishing True Burkitt Lymphoma from Other High-Grade B-NHLs Burkitt Lymphoma Burkitt-Like Lymphoma DLBCL Patrick Treseler, MD, PhD University of California San Francisco
More information7 Omar Abu Reesh. Dr. Ahmad Mansour Dr. Ahmad Mansour
7 Omar Abu Reesh Dr. Ahmad Mansour Dr. Ahmad Mansour -Leukemia: neoplastic leukocytes circulating in the peripheral bloodstream. -Lymphoma: a neoplastic process in the lymph nodes, spleen or other lymphatic
More informationThe next lymphoma classification Luca Mazzucchelli Istituto cantonale di patologia, Locarno
Evolution of classification The next classification Luca Mazzucchelli Istituto cantonale di patologia, Locarno The Lymphoma Forum of Excellence, Bellinzona, January 2011 Rappaport Lukes and Collins (immunophenotype)
More informationHIGH GRADE B-CELL LYMPHOMA DAVID NOLTE, MD (PGY-2) HUSSAM AL-KATEB, PHD, FACMG DEBORAH FUCHS, MD
HIGH GRADE B-CELL LYMPHOMA DAVID NOLTE, MD (PGY-2) HUSSAM AL-KATEB, PHD, FACMG DEBORAH FUCHS, MD OUTLINE High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements Patient presentation 2008/2016
More informationLymphoma Update: Lymphoma Update: What s Likely to be New in the New WHO. Patrick Treseler, MD, PhD University of California San Francisco
Lymphoma Update: What s Likely to be New in the New WHO Blood 127:2375; 2016 Patrick Treseler, MD, PhD University of California San Francisco Lymphoma Update: What IS New in the New WHO! Patrick Treseler,
More informationCase Report A case of EBV positive diffuse large B-cell lymphoma of the adolescent
Int J Clin Exp Med 2014;7(1):307-311 www.ijcem.com /ISSN:1940-5901/IJCEM1311029 Case Report A case of EBV positive diffuse large B-cell lymphoma of the adolescent Qilin Ao 2, Ying Wang 1, Sanpeng Xu 2,
More informationDiagnostic Molecular Pathology of Lymphoid Neoplasms
Diagnostic Molecular Pathology of Lymphoid Neoplasms (Part II) Rational use of molecular testing in lymphomas Beirut, Lebanon Friday December 2, 2011: Hematopathology Session Adam Bagg University of Pennsylvania
More informationMimics of Lymphoma in Routine Biopsies. Mixed follicular and paracortical hyperplasia. Types of Lymphoid Hyperplasia
Mimics of Lymphoma in Routine Biopsies Patrick Treseler, MD, PhD Professor of Pathology University of California San Francisco Types of Lymphoid Hyperplasia Follicular hyperplasia (B-cells) Paracortical
More informationMimics of Lymphoma in Routine Biopsies. I have nothing to disclose regarding the information to be reported in this talk.
Mimics of Lymphoma in Routine Biopsies Patrick Treseler, MD, PhD Professor of Pathology University of California San Francisco I have nothing to disclose regarding the information to be reported in this
More informationFrom Morphology to Molecular Pathology: A Practical Approach for Cytopathologists Part 1-Cytomorphology. Songlin Zhang, MD, PhD LSUHSC-Shreveport
From Morphology to Molecular Pathology: A Practical Approach for Cytopathologists Part 1-Cytomorphology Songlin Zhang, MD, PhD LSUHSC-Shreveport I have no Conflict of Interest. FNA on Lymphoproliferative
More informationFOLLICULARITY in LYMPHOMA
FOLLICULARITY in LYMPHOMA Reactive Follicular Hyperplasia Follicular Hyperplasia irregular follicles Follicular Hyperplasia dark and light zones Light Zone Dark Zone Follicular hyperplasia MIB1 Follicular
More informationContents. vii. Preface... Acknowledgments... v xiii
Contents Preface... Acknowledgments... v xiii SECTION I 1. Introduction... 3 Knowledge-Based Diagnosis... 4 Systematic Examination of the Lymph Node... 7 Cell Type Identification... 9 Cell Size and Cellularity...
More information10/31/2017. Immunodeficiencies. Outline. Discuss EBV. Non-destructive Polymorphic Monomorphic Therapies Challenges
I have no financial disclosures Joo Y. Song, MD Assistant Professor of Clinical Pathology City of Hope National Medical Center Immunodeficiencies Outline Transplant Congenital Autoimmunity T-cell/immune
More information11/2/2017. Immunodeficiencies. Joo Y. Song, MD Assistant Professor of Clinical Pathology. I have no financial disclosures.
I have no financial disclosures Joo Y. Song, MD Assistant Professor of Clinical Pathology City of Hope National Medical Center Immunodeficiencies Transplant Autoimmunity Drugs T-cell dysfunction (Age,
More informationNon-Hodgkin lymphomas (NHLs) Hodgkin lymphoma )HL)
Non-Hodgkin lymphomas (NHLs) Hodgkin lymphoma )HL) Lymphoid Neoplasms: 1- non-hodgkin lymphomas (NHLs) 2- Hodgkin lymphoma 3- plasma cell neoplasms Non-Hodgkin lymphomas (NHLs) Acute Lymphoblastic Leukemia/Lymphoma
More informationIX. Is it only about MYC? How to approach the diagnosis of diffuse large B-cell lymphomas
Hematological Oncology Hematol Oncol 2015; 33: 50 55 Published online in Wiley Online Library (wileyonlinelibrary.com).2217 Supplement Article IX. Is it only about MYC? How to approach the diagnosis of
More informationCommentary on the WHO Classification of Tumors of Lymphoid Tissues (2008): Aggressive B-cell Lymphomas
Commentary on the WHO Classification of Tumors of Lymphoid Tissues (2008): Aggressive B-cell Lymphomas The Harvard community has made this article openly available. Please share how this access benefits
More informationLymphoma/CLL 101: Know your Subtype. Dr. David Macdonald Hematologist, The Ottawa Hospital
Lymphoma/CLL 101: Know your Subtype Dr. David Macdonald Hematologist, The Ottawa Hospital Function of the Lymph System Lymph Node Lymphocytes B-cells develop in the bone marrow and influence the immune
More information5003 Immunohistochemistry in hematopathology, what's in, what's out, what's useful
www.ascp.org/ascp2014 5003 Immunohistochemistry in hematopathology, what's in, what's out, what's useful Kathryn Rizzo, DO, PhD VIRGINIA COMMONWEALTH UNIVERSITY Department of Pathology School of Medicine
More informationPhenoPath. Diagnoses you can count on B CELL NON-HODGKIN LYMPHOMA
PhenoPath Diagnoses you can count on B CELL NON-HODGKIN LYMPHOMA C urrent diagnosis of B cell non-hodgkin lymphoma (B-NHL) is based on the 2008 WHO Classification of Tumours of Haematopoietic and Lymphoid
More informationBurkitt lymphoma. Sporadic Endemic in Africa associated with EBV Translocations involving MYC gene on chromosome 8
Heme 8 Burkitt lymphoma Sporadic Endemic in Africa associated with EBV Translocations involving MYC gene on chromosome 8 Most common is t(8;14) Believed to be the fastest growing tumor in humans!!!! Morphology
More informationWHO 4th ED Classification of Mature B-cell Neoplasms
WHO 4th ED Classification of Mature B-cell Neoplasms Chronic lymphocytic leukemia /Small lymphocytic lymphoma B-cell prolymphocytic leukaemia Splenic marginal zone lymphoma Hairy cell leukemia Splenic
More informationImmunohistochemical classification of haematolymphoid tumours. Stephen Hamilton-Dutoit Institute of Pathology Aarhus University Hospital
Immunohistochemical classification of haematolymphoid tumours Stephen Hamilton-Dutoit Institute of Pathology Aarhus University Hospital Malignant lymphoproliferative diseases What are they? Haematolymphoid
More informationSmall B-cell (Histologically Low Grade) Lymphoma
Frequency of Lymphoid Neoplasms Small B-cell (Histologically Low Grade) Lymphoma Stephen Hamilton-Dutoit Institute of Pathology Aarhus University Hospital B-cell neoplasms 88% Diffuse large B-cell lymphoma
More informationIncidence. Bimodal age incidence 15-40, >55 years Childhood form (0-14) more common in developing countries M:F=1.5:1; in all subtypes except NS
Hodgkin Lymphoma Hodgkin Lymphoma 30% of all lymphomas Absolute incidence unchanged Arise in lymph node, cervical region Neoplastic tissues usually contain a small number of tumor cells Incidence Bimodal
More informationAnaplastic Large Cell Lymphoma (of T cell lineage)
Anaplastic Large Cell Lymphoma (of T cell lineage) Definition T-cell lymphoma comprised of large cells with abundant cytoplasm and pleomorphic, often horseshoe-shaped nuclei CD30+ Most express cytotoxic
More informationCase year old male with abdominal lymphadenopathy Treated with 8 cycles of R-CHOP One year later B-symptoms and progressive disease
Codirectors Tsieh Sun, M.D., FASCP Francisco Vega, M.D., Ph.D. Department of Hematopathology UT MD Anderson Cancer Center Houston Texas There is no conflict of interest involved in the content and presentation
More informationA Practical Guide To Diagnose B-Cell Lymphomas on FNAs. Nancy P. Caraway, M.D.
A Practical Guide To Diagnose B-Cell Lymphomas on FNAs Nancy P. Caraway, M.D. Major Factors Impacting Dx Lymphomas on Small Bxs Classification systems Immunophenotyping by multiprobe flow cytometry and
More informationLYMPHOMAS an overview of some subtypes of NHLs
One of the confusing aspects of the lymphoid neoplasms concerns the use of the descriptive terms "leukemia" and "lymphoma." LYMPHOMAS an overview of some subtypes of NHLs Leukemia is used for lymphoid
More informationDETERMINATION OF A LYMPHOID PROCESS
Chapter 2 Applications of Touch Preparation Cytology to Intraoperative Consultations: Lymph Nodes and Extranodal Tissues for Evaluation of Hematolymphoid Disorders INTRODUCTION As discussed in Chap. 1,
More informationHODGKIN LYMPHOMA DR. ALEJANDRA ZARATE OSORNO HOSPITAL ESPAÑOL DE MEXICO
HODGKIN LYMPHOMA DR. ALEJANDRA ZARATE OSORNO HOSPITAL ESPAÑOL DE MEXICO HODGKIN LYMPHOMA CLASSIFICATION Lukes & Butler Rye WHO-2016 Linphocytic and/or histiocytic Nodular & diffuse Nodular Sclerosis Lymphocyte
More informationVENTANA hematopathology solutions. Deliver diagnostic confidence
VENTANA hematopathology solutions Deliver diagnostic confidence 2 Hematopathology diagnostic solutions Contents VENTANA hematopathology assays 3 Detecting and subtyping hematological cancers 4 The importance
More informationCase 3. Ann T. Moriarty,MD
Case 3 Ann T. Moriarty,MD Case 3 59 year old male with asymptomatic cervical lymphadenopathy. These images are from a fine needle biopsy of a left cervical lymph node. Image 1 Papanicolaou Stained smear,100x.
More informationLow-grade B-cell lymphoma
Low-grade B-cell lymphoma Patho-Basic 11. September 2018 Stephan Dirnhofer Pathology Outline Definition LPL, MBL/CLL/SLL, MCL FL Subtypes & variants Diagnosis including Grading Transformation Summary Be
More informationLearn more about diffuse large B-cell lymphoma (DLBCL), the most common aggressive form of B-cell non-hodgkin s lymphoma 1
Learn more about diffuse large B-cell lymphoma (DLBCL), the most common aggressive form of B-cell non-hodgkin s lymphoma 1 Expression of B-cell surface antigens drives several non-hodgkin s lymphomas (NHLs)
More informationLarge cell immunoblastic Diffuse histiocytic (DHL) Lymphoblastic lymphoma Diffuse lymphoblastic Small non cleaved cell Burkitt s Non- Burkitt s
Non Hodgkin s Lymphoma Introduction 6th most common cause of cancer death in United States. Increasing in incidence and mortality. Since 1970, the incidence of has almost doubled. Overview The types of
More information1/14/2018. Objectives
2018 Pathology CME Cutaneous Hematopathology Maui, HI Jan 18 th 26 th Updates in Cutaneous B-cell Lymphomas Alejandro A. Gru, M.D. Assistant Professor of Pathology & Dermatology Dermatopathology Division
More informationVENTANA hematopathology solutions Comprehensive aids for detecting and subtyping
VENTANA hematopathology solutions Comprehensive aids for detecting and subtyping 1 12/4/2015 9:47:24 AM 2 Hematopathology diagnostic solutions Contents VENTANA hematopathology assays 3 Detecting and subtyping
More informationPulmonary biopsy specimens demonstrate
A PRACTICAL APPROACH TO THE EVALUATION OF LYMPHOID AND PLASMA CELL INFILTRATES IN THE LUNG Fiona E. Craig, MD KEYWORDS Lymphoma Pulmonary Immunophenotyping Genotyping ABSTRACT Pulmonary biopsy specimens
More informationMethods used to diagnose lymphomas
Institut für Pathologie Institut für Pathologie Methods used to diagnose lymphomas Prof. Dr.Med. Leticia Quintanilla-Fend Molecular techniques NGS histology Cytology AS-PCR Sanger seq. MYC Immunohistochemistry
More informationClinical Policy: Bendamustine (Bendeka, Treanda) Reference Number: PA.CP.PHAR.307
Clinical Policy: (Bendeka, Treanda) Reference Number: PA.CP.PHAR.307 Effective Date: 01/18 Last Review Date: 11/17 Coding Implications Revision Log Description The intent of the criteria is to ensure that
More informationCommon Problem Areas. WHO Classification. Defines separate diseases (entities) with their CLINICAL AGGRESSIVENESS LOW GRADE / HIGH GRADE
WHO Classification Defines separate diseases (entities) with their CLINICAL AGGRESSIVENESS REVIEW OF MOST COMMON LYMPHOMA ENTITIES Dr Stefan Dojcinov LOW GRADE / HIGH GRADE (June 2014) The Non-Hodgkin
More information3/24/2017 DENDRITIC CELL NEOPLASMS: HISTOLOGY, IMMUNOHISTOCHEMISTRY, AND MOLECULAR GENETICS. Disclosure of Relevant Financial Relationships
DENDRITIC CELL NEOPLASMS: HISTOLOGY, IMMUNOHISTOCHEMISTRY, AND MOLECULAR GENETICS Jason L. Hornick, M.D., Ph.D. Director of Surgical Pathology and Immunohistochemistry Brigham and Women s Hospital Professor
More information2012 by American Society of Hematology
2012 by American Society of Hematology Common Types of HIV-Associated Lymphomas DLBCL includes primary CNS lymphoma (PCNSL) Burkitt Lymphoma HIV-positive patients have a 60-200 fold increased incidence
More informationDiffuse large B-cell lymphomas. G. Verhoef, MD, PhD University Hospital Leuven BHS, March 9, 2013
Diffuse large B-cell lymphomas G. Verhoef, MD, PhD University Hospital Leuven BHS, March 9, 2013 Case A 72-year-old previously healthy man presented with acute abdominal pain and a 15 kg weight loss. Positron
More informationClassification of Hematologic Malignancies. Patricia Aoun MD MPH
Classification of Hematologic Malignancies Patricia Aoun MD MPH Objectives Know the basic principles of the current classification system for hematopoietic and lymphoid malignancies Understand the differences
More informationRecent advances in the genetics & biology of lymphoma
Recent advances in the genetics & biology of lymphoma Chris Bacon Northern Institute for Cancer Research Newcastle University & Newcastle Upon Tyne Hospitals NHS Foundation Trust Lymphoma Rate per 100,000
More informationDoes the proliferation fraction help identify mature B cell lymphomas with double- and triple-hit translocations?
Histopathology 2012, 61, 1214 1218. DOI: 10.1111/j.1365-2559.2012.04351.x SHORT REPORT Does the proliferation fraction help identify mature B cell lymphomas with double- and triple-hit translocations?
More informationCorrigenda. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (revised 4th edition): corrections made in second print run
Corrigenda WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (revised 4th edition): corrections made in second print run In addition to corrections of minor typographical errors, corrections
More informationBone Marrow. Procedures Blood Film Aspirate, Cell Block Trephine Biopsy, Touch Imprint
Bone Marrow Protocol applies to acute leukemias, myelodysplastic syndromes, myeloproliferative disorders, chronic lymphoproliferative disorders, malignant lymphomas, plasma cell dyscrasias, histiocytic
More informationLymph node cytopathology : A practical approach to lymphoproliferative disorders
Lymph node cytopathology : A practical approach to lymphoproliferative disorders Koray Ceyhan, M.D Department of Pathology Faculty of Medicine Ankara University Ankara, Turkey Diagnostic use of FNA in
More informationThomas Hodgkin and Hodgkin lymphoma
J Hematopathol (2014) 7:123 138 DOI 10.1007/s12308-014-0214-3 REVIEW ARTICLE Thomas Hodgkin and Hodgkin lymphoma Judith A. Ferry Received: 26 June 2014 /Accepted: 31 July 2014 /Published online: 12 August
More information2010 Hematopoietic and Lymphoid ICD-O Codes - Alphabetical List THIS TABLE REPLACES ALL ICD-O-3 Codes
Acute basophilic leukemia 9870/3 Acute biphenotypic leukemia [OBS] 9805/3 Acute erythroid leukemia 9840/3 Acute megakaryoblastic leukemia 9910/3 Acute monoblastic and monocytic leukemia 9891/3 Acute myeloid
More information2012 Hematopoietic and Lymphoid ICD-O Codes - Numerical List THIS TABLE REPLACES ALL ICD-O-3 Codes
Malignant lymphoma, NOS 9590/3 Non-Hodgkin lymphoma, NOS 9591/3 B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma 9596/3 Primary
More informationApproach to Core Biopsy Specimens
BDIAP 108th Symposium on Haematopathology Joint Meeting of the BDIAP and BLPG at-bristol, Anchor Road, Harbourside, Bristol BS1 5DB 15th - 17th May 2014 Approach to Core Biopsy Specimens Dr Stefan Dojcinov
More informationWHO Classification. B-cell chronic lymphocytic leukemia/small T-cell granular lymphocytic leukemia
Blood Malignancies-II Prof. Dr. Herman Hariman, a Ph.D, SpPK (KH). Prof. Dr. Adikoesoema Aman, SpPK (KH) Dept. of Clinical Pathology, School of Medicine, University of North Sumatra WHO classification
More information3/2/2010. Case 1. Clinical History. Infectious Disease Pathology Specialty Conference Case 1
Case 1. Clinical History Infectious Disease Pathology Specialty Conference Case 1 A 6 year-old girl with a large left neck mass. Past medical history: Biliary cirrhosis secondary to extra hepatic biliary
More informationWHO UPDATE ON LYMPHOMAS. Dr Priya Mary Jacob Asst Professor, Pathology.
WHO UPDATE ON LYMPHOMAS Dr Priya Mary Jacob Asst Professor, Pathology 3 rd 4 th 4 th revised 2001 2008 2017 The Change The Significance of the Change- Diagnostic, Prognostic The Rationale behind the change.
More informationClassification! Immunohistochemical classification of haematolymphoid tumours. Malignant lymphoproliferative diseases
Immunohistochemical classification of haematolymphoid tumours Haematolymphoid Neoplasias: Leukaemia vs Lymphoma C L O N A L M A L I G N A N C I E S Stephen Hamilton-Dutoit Institute of Pathology Aarhus
More informationMethotrexate-associated Lymphoproliferative Disorders
Methotrexate-associated Lymphoproliferative Disorders Definition A lymphoid proliferation or lymphoma in a patient immunosuppressed with methotrexate, typically for treatment of autoimmune disease (rheumatoid
More informationT cell lymphoma diagnostics and differential diagnosis to Hodgkin lymphoma
T cell lymphoma diagnostics and differential diagnosis to Hodgkin lymphoma Sylvia Hartmann Dr. Senckenberg Institute of Pathology Goethe University Frankfurt Overview Borderline ALCL classical HL Borderline
More informationPathology of the indolent B-cell lymphomas Elias Campo
Pathology of the indolent B-cell lymphomas Elias Campo Hospital Clinic, University of Barcelona Small B-cell lymphomas Antigen selection NAIVE -B LYMPHOCYTE MEMORY B-CELL MCL FL LPL MZL CLL Small cell
More informationInfectious Disease Pathology Specialty Conference Case 1
Infectious Disease Pathology Specialty Conference Case 1 Miguel Reyes Múgica, M.D. Department of Pathology Children s Hospital of Pittsburgh University of Pittsburgh Medical Center USCAP Annual Meeting.
More informationPrimary Cutaneous CD30-Positive T-cell Lymphoproliferative Disorders
Primary Cutaneous CD30-Positive T-cell Lymphoproliferative Disorders Definition A spectrum of related conditions originating from transformed or activated CD30-positive T-lymphocytes May coexist in individual
More informationDOUBLE-HIT AND TRIPLE-HIT LYMPHOMAS: NEW PERSPECTIVES FOR THEIR CLASSIFICATION
DOUBLE-HIT AND TRIPLE-HIT LYMPHOMAS: NEW PERSPECTIVES FOR THEIR CLASSIFICATION *Cristiano Claudino Oliveira, Maria Aparecida Custódio Domingues Department of Pathology, Botucatu School of Medicine, São
More informationCombinations of morphology codes of haematological malignancies (HM) referring to the same tumour or to a potential transformation
Major subgroups according to the World Health Organisation (WHO) Classification Myeloproliferative neoplasms (MPN) Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or
More information3/27/2017. Pulmonary Pathology Specialty Conference. Disclosure of Relevant Financial Relationships. Clinical History:
Pulmonary Pathology Specialty Conference Saul Suster, M.D. Medical College of Wisconsin Disclosure of Relevant Financial Relationships USCAP requires that all planners (Education Committee) in a position
More information88-year-old Female with Lymphadenopathy. Faizi Ali, MD
88-year-old Female with Lymphadenopathy Faizi Ali, MD Clinical History A 88-year-old caucasian female presented to our hospital with the complaints of nausea, vomiting,diarrhea, shortness of breath and
More informationClinicopathologic features of 112 cases with mantle cell lymphoma
Cancer Biol Med 2015;12:46-52. doi: 10.7497/j.issn.2095-3941.2015.0007 ORIGINAL ARTICLE Clinicopathologic features of 112 cases with mantle cell lymphoma Dong-Mei Zhou, Gang Chen, Xiong-Wei Zheng, Wei-Feng
More informationFollicular Lymphoma: the WHO
Follicular Lymphoma: the WHO and the WHERE? Yuri Fedoriw, MD Associate Professor of Pathology and Laboratory Medicine Director of Hematopathology University of North Carolina Chapel Hill, NC Disclosure
More informationLINFOMA B (INCLASIFICABLE) CON RASGOS INTERMEDIOS ENTRE LINFOMA DE BURKITT Y LINFOMA B DIFUSO DE CÉLULAS GRANDES.
Congreso Nacional SEAP 2013. LINFOMA B (INCLASIFICABLE) CON RASGOS INTERMEDIOS ENTRE LINFOMA DE BURKITT Y LINFOMA B DIFUSO DE CÉLULAS GRANDES. Santiago Montes Moreno Servicio de Anatomía Patológica, HUMV
More informationExploring the Borderlands between Diffuse Large B-cell Lymphoma and Classical Hodgkin s Lymphoma
Exploring the Borderlands between Diffuse Large B-cell Lymphoma and Classical Hodgkin s Lymphoma Elaine S. Jaffe National Cancer Institute Bethesda, MD, USA On the Pathological Changes In Hodgkin s Disease
More informationDiffuse Large B-Cell Lymphoma (DLBCL)
Diffuse Large B-Cell Lymphoma (DLBCL) DLBCL/MCL Dr. Anthea Peters, MD, FRCPC University of Alberta/Cross Cancer Institute Disclosures Honoraria from Janssen, Abbvie, Roche, Lundbeck, Seattle Genetics Objectives
More informationDepartment of Pathology, University of California San Diego Health Sciences, 3855 Health Sciences Drive, San Diego, CA 92093, USA.
Int J Clin Exp Pathol 2011;4(2):190-196 www.ijcep.com /IJCEP1012012 Case Report Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma presenting as an isolated nasopharyngeal mass: a case report
More informationConflict of Interest Disclosure Form NAME :James O. Armitage, M.D AFFILIATION: University of Nebraska Medical Center
What Is Personalized Medicine For Patients With Lymphoma? Conflict of Interest Disclosure Form NAME :James O. Armitage, M.D AFFILIATION: University of Nebraska Medical Center DISCLOSURE I have no potential
More informationCase Report PAX5-Negative Classical Hodgkin Lymphoma: A Case Report of a Rare Entity and Review of the Literature
Hindawi Case Reports in Hematology Volume 2017, Article ID 7531729, 4 pages https://doi.org/10.1155/2017/7531729 Case Report PAX5-Negative Classical Hodgkin Lymphoma: A Case Report of a Rare Entity and
More information