Practical Applications in Immunohistochemistry: Evaluation of Diffuse Large B-Cell Lymphoma and Related Large B-Cell Lymphomas

2015 ◽  
Vol 139 (9) ◽  
pp. 1094-1107 ◽  
Author(s):  
Dennis P. O'Malley ◽  
Aaron Auerbach ◽  
Lawrence M. Weiss
Keyword(s):  
B Cell ◽  
Who Classification ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
World Health ◽  
Cell Of Origin ◽  
B Cell Lymphomas ◽  
Practical Applications ◽  
Large B Cell Lymphoma ◽  
Large B Cell

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 2014. Conclusions Features and diagnostic criteria of diffuse large B-cell lymphoma, aggressive variants of B-cell lymphomas, including Burkitt lymphoma and “double-hit” 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.

scholarly journals Grey Zone Lymphomas: Lymphomas with Intermediate Features

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Sylvia Hoeller ◽  
Christiane Copie-Bergman
Keyword(s):  
B Cell ◽  
Who Classification ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
World Health ◽  
Grey Zone ◽  
B Cell Lymphomas ◽  
Large B Cell Lymphoma ◽  
Large B Cell

The current classification of lymphoid neoplasms is based on clinical information, morphology, immunophenotype, and molecular genetic characteristics. Despite technical and scientific progress, some aggressive B-cell lymphomas with features overlapping between two different types of lymphomas remain difficult to classify. The updated 2008 World Health Organization (WHO) classification of Tumours of the Hematopoietic and Lymphoid Tissues has addressed this problem by creation of two new provisional categories of B-cell lymphomas, unclassifiable; one with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma and the second with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. We review here the diagnostic criteria of these two provisional entities and discuss new scientific findings in light of the 2008 WHO classification.

Intraocular Lymphoma: Diagnostic Approach and Immunophenotypic Findings in Vitrectomy Specimens

2009 ◽  
Vol 133 (8) ◽  
pp. 1233-1237 ◽  
Author(s):  
Kirtee Raparia ◽  
Chung-Che(Jeff) Chang ◽  
Patricia Chévez-Barrios
Keyword(s):  
Flow Cytometry ◽  
B Cell ◽  
Who Classification ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Intraocular Lymphoma ◽  
B Cell Lymphomas ◽  
Not Otherwise Specified ◽  
Large B Cell Lymphoma ◽  
Large B Cell

AbstractContext.—Diagnosis and classification of primary intraocular lymphoma can be challenging because of the sparse cellularity of the vitreous specimens.Objective.—To classify and clinically correlate intraocular lymphoma according to the World Health Organization (WHO) classification by using vitrectomy specimens.Design.—Clinical history, cytologic preparations, flow cytometry reports, and outcome of 16 patients diagnosed with intraocular lymphoma were reviewed.Results.—The study group included 10 women and 6 men. The mean age of the patients was 63 years (range, 19–79 years). Eleven patients had central nervous system involvement and 6 patients had systemic involvement. All cases were adequately diagnosed and classified according to the WHO classification by using combination of cytologic preparations and 4-color flow cytometry with a limited panel of antibodies to CD19, CD20, CD5, CD10, and κ and λ light chains. The cases included 9 primary diffuse large B-cell lymphomas of the CNS type; 2 diffuse large B-cell lymphomas, not otherwise specified; 1 extranodal, low-grade, marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT); 1 precursor B-lymphoblastic lymphoma; and 3 peripheral T-cell lymphomas, not otherwise specified. Of note, all 11 cases of diffuse large B-cell lymphoma were CD10−. All the patients received systemic chemotherapy and radiation therapy. Only 4 patients were free of disease at last follow-up (range, 18 months to 8 years), with severe visual loss.Conclusions.—Intraocular lymphoma cases can be adequately classified according to the WHO classification. Diffuse large B-cell lymphoma, CD10− and most likely of non–germinal center B-cell–like subgroup, is the most common subtype of non-Hodgkin lymphoma in this site, in contrast to ocular adnexal lymphoma for which MALT lymphoma is the most common subtype.

scholarly journals Tailoring front-line therapy in diffuse large B-cell lymphoma: who should we treat differently?

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 284-294 ◽  
Author(s):  
Andrew Davies
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Phase 1 ◽  
B Cell Lymphoma ◽  
Standard Of Care ◽  
World Health ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Health Organization ◽  
Large B Cell

AbstractAlthough there have been significant insights into the biology of diffuse large B-cell lymphoma (DLBCL) over recent years, progress in our therapeutic approach has been disappointing over the same timeframe. This is not for want of trying. In 2017, R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) remains the “gold standard,” despite all of our insights into cell-of-origin and other subgroups. We have traditionally used clinical risk factors to tailor our therapies and have tested intensification of chemotherapy with little success. We are now in an era of testing therapies according to the molecular phenotype of the individual’s tumor. Many phase 1/2 studies have looked at adding targeted agents to conventional R-CHOP with some promise. The phase 3 data are now starting to emerge. Are we ready yet to modify our standard of care and have we reached an era of precision medicine in DLBCL? The answer to this is “not yet.” The exception is perhaps patients with the newly defined World Health Organization category of high-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6, the so-called double- and triple-hit lymphomas. In these tumors there has been a move away from R-CHOP to more intensified regimens, however, has not been based upon rigorous prospective evaluation but review of retrospective datasets. This article will review the molecular subgroups of DLBCL, interventional strategies, and the outcomes of these interventions to date.

scholarly journals Cell-of-origin classification using the Hans and Lymph2Cx algorithms in primary cutaneous large B-cell lymphomas

2022 ◽  
Author(s):  
Anne M. R. Schrader ◽  
Ruben A. L. de Groen ◽  
Rein Willemze ◽  
Patty M. Jansen ◽  
Koen D. Quint ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Cell Of Origin ◽  
B Cell Lymphomas ◽  
Large B Cell Lymphoma ◽  
And Behavior ◽  
Large B Cell

Abstract Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) and primary cutaneous follicle center lymphoma with a diffuse population of large cells (PCFCL-LC) are both primary cutaneous B-cell lymphomas with large-cell morphology (CLBCL) but with different clinical characteristics and behavior. In systemic diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), gene-expression profiling (GEP) revealed two molecular subgroups based on their cell-of-origin (COO) with prognostic significance: the germinal center B-cell-like (GCB) subtype and the activated B-cell-like (ABC) subtype. This study investigated whether COO classification is a useful tool for classification of CLBCL. For this retrospective study, 51 patients with PCDLBCL-LT and 15 patients with PCFCL-LC were analyzed for their COO according to the immunohistochemistry-based Hans algorithm and the NanoString GEP-based Lymph2Cx algorithm. In PCFCL-LC, all cases (100%) classified as GCB by both Hans and Lymph2Cx. In contrast, COO classification in PCDLBCL-LT was heterogeneous. Using Hans, 75% of the PCDLBCL-LT patients classified as non-GCB and 25% as GCB, while Lymph2Cx classified only 18% as ABC, 43% as unclassified/intermediate, and 39% as GCB. These COO subgroups did not differ in the expression of BCL2 and IgM, mutations in MYD88 and/or CD79B, loss of CDKN2A, or survival. In conclusion, PCFCL-LC uniformly classified as GCB, while PCDLBCL-LT classified along the COO spectrum of DLBCL-NOS using the Hans and Lymph2Cx algorithms. In contrast to DLBCL-NOS, the clinical relevance of COO classification in CLBCL using these algorithms has limitations and cannot be used as an alternative for the current multiparameter approach in differentiation of PCDLBCL-LT and PCFCL-LC.

scholarly journals Primary Cutaneous Diffuse Large B-Cell Lymphoma – a Case Report

2017 ◽  
Vol 9 (2) ◽  
pp. 57-62
Author(s):  
Milena Milovanović ◽  
Željko Mijušković ◽  
Lidija Kandolf Sekulović ◽  
Olga Radić-Tasić ◽  
Olivera Tarabar ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Surgical Excision ◽  
World Health ◽  
Necessary Condition ◽  
B Cell Lymphomas ◽  
European Organization ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract In 2005, the World Health Organization - European Organization for Research and Treatment of Cancer (WHOEORTC) classified cutaneous B-cell lymphomas into 4 categories: primary cutaneous marginal zone B-cell lymphoma (PCMZL), primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), and primary cutaneous diffuse large B-cell lymphoma, other (PCDLBCL-O). The absence of evident extra-cutaneous disease is a necessary condition for the diagnosis of primary cutaneous B-cell lymphomas, because they have a completely different clinical behavior and prognosis from their nodal counterparts. PCDLBCL-O basically represents a morphological variation, lacking the typical features of PCDLBCLLT, neither confirming the definition of PCFCCL, but on the clinical ground, its behavior seems at least to partially overlap the indolent course of PCFCCL. In fact, the present WHO lymphoma classification from 2008 overcame the previous WHO-EORTC classification, including at least a part of PCDLBCL-O within the spectrum of PCFCCL. However, owing to the rarity and heterogeneity of the PCDLBCL-O, the precise clinicopathological characteristics have not been well characterized and the optimal treatment for this group of lymphomas is yet to be defined. Nevertheless, dermatologists and pathologists should be aware of this entity in order to avoid unnecessary aggressive treatment. We present a case of a 46-year-old Caucasian male with one large round-shaped tumor and a few scattered nodules localized on the back. The histopathological features of the lesion corresponded to PCDLBCL-O. The patient follow-up showed that he was disease-free three months after surgical excision of the lesions and adjuvant local radiotherapy. No additional therapy was introduced, including chemotherapy with rituximab, cyclophosphamide, doxorubicin hydrochloride, oncovin, prednisolone (R-CHOP).

scholarly journals Aggressive B-Cell Lymphomas: A Review of New and Old Entities in the WHO Classification

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 506-514 ◽  
Author(s):  
Elaine S. Jaffe ◽  
Stefania Pittaluga
Keyword(s):  
B Cell ◽  
Who Classification ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
The Elderly ◽  
World Health ◽  
B Cell Lymphomas ◽  
Treatment Protocols ◽  
Double Hit ◽  
Large B Cell

Abstract Aggressive B-cell lymphomas are clinically and pathologically diverse and reflect multiple pathways of transformation. The 2008 World Health Organization (WHO) classification reflects this complexity with the addition of several new entities and variants. Whereas MYC translocations have long been associated with Burkitt lymphoma (BL), deregulation of MYC has been shown to occur in other aggressive B-cell lymphomas, most often as a secondary event. Lymphomas with translocations of both MYC and BCL2 are highly aggressive tumors, with a high failure rate with most treatment protocols. These “double-hit” lymphomas are now separately delineated in the WHO classification as B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and BL. A MYC translocation is also found uncommonly in DLBCL, but the clinical consequences of this in the absence of a double hit are not yet fully delineated. Most recently, MYC translocations have been identified as a common secondary event in plasma cell neoplasms, seen in approximately 50% of plasmablastic lymphoma. Another area that has received recent attention is the spectrum of EBV-driven B-cell proliferations in patients without iatrogenic or congenital immunosuppression; most of these occur in patients of advanced age and include the EBV-positive large B-cell lymphomas of the elderly.

Metody cytogenetyki molekularnej w różnicowaniu agresywnych B-NHL

2019 ◽  
Vol 50 (3) ◽  
pp. 109-115
Author(s):  
Beata Grygalewicz
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
World Health ◽  
High Grade ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
Health Organization ◽  
Large B Cell

StreszczenieB-komórkowe agresywne chłoniaki nieziarnicze (B-cell non-Hodgkin lymphoma – B-NHL) to heterogenna grupa nowotworów układu chłonnego, wywodząca się z obwodowych limfocytów B. Aberracje cytogenetyczne towarzyszące B-NHL to najczęściej translokacje onkogenów takich jak MYC, BCL2, BCL6 w okolice genowych loci dla łańcuchów ciężkich lub lekkich immunoglobulin. W niektórych przypadkach dochodzi do wystąpienia kilku wymienionych aberracji jednocześnie, tak jak w przypadkach przebiegających z równoczesną translokacją genów MYC i BCL2 (double hit), niekiedy także z obecnością rearanżacji BCL6 (triple hit). Takie chłoniaki cechuje szczególnie agresywny przebieg kliniczny. Obecnie molekularna diagnostyka cytogenetyczna przy użyciu techniki fluorescencyjnej hybrydyzacji in situ (FISH) oraz, w niektórych przypadkach, aCGH jest niezbędnym narzędziem rozpoznawania, klasyfikowania i oceny stopnia zaawansowania agresywnych, nieziarniczych chłoniaków B-komórkowych. Technika mikromacierzy CGH (aCGH) była kluczowym elementem wyróżnienia prowizorycznej grupy chłoniaków Burkitt-like z aberracją chromosomu 11q (Burkitt-like lymphoma with 11q aberration – BLL, 11q) w najnowszej klasyfikacji nowotworów układu chłonnego Światowej Organizacji Zdrowia (World Health Organization – WHO) z 2016 r. Omówione zostaną sposoby różnicowania na poziomie cytogenetycznym takich chłoniaków jak: chłoniak Burkitta (Burkitt lymphoma – BL), chłoniak rozlany z dużych komórek B (diffuse large B-cell lymphoma – DLBCL) oraz 2 nowych jednostek klasyfikacji WHO 2016, czyli chłoniaka z komórek B wysokiego stopnia złośliwości z obecnością translokacji MYC i BCL2 i/lub BCL6 (high-grade B-cell lymphoma HGBL, with MYC and BCL2 and/or BCL6 translocations) oraz chłoniaka BLL, 11q.

DIFFUSE LARGE B-CELL LYMPHOMA SURVIVAL PROGNOSTICATION, A COMPARATIVE ANALYSIS OF CELL OF ORIGIN VS. MYC/BCL2 EXPRESSION

2019 ◽  
Vol 37 ◽  
pp. 353-353
Author(s):  
M. Rodriguez ◽  
I. Fernandez-Miranda ◽  
R. Mondejar ◽  
J. Capote ◽  
S. Rodriguez-Pinilla ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Bcl2 Expression

scholarly journals How I treat double-hit lymphoma

Blood ◽  
2017 ◽  
Vol 130 (5) ◽  
pp. 590-596 ◽  
Author(s):  
Jonathan W. Friedberg
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Central Nervous System Involvement ◽  
B Cell Lymphoma ◽  
World Health ◽  
Large B Cell Lymphoma ◽  
Double Hit Lymphoma ◽  
Increased Risk ◽  
Double Hit ◽  
Large B Cell

Abstract The 2016 revision of the World Health Organization (WHO) classification for lymphoma has included a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6. These lymphomas, which occur in <10% of cases of diffuse large B-cell lymphoma, have been referred to as double-hit lymphomas (or triple-hit lymphomas if all 3 rearrangements are present). It is important to differentiate these lymphomas from the larger group of double-expressor lymphomas, which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, by using variable cutoff percentages to define positivity. Patients with double-hit lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of central nervous system involvement and progression. Double-hit lymphomas may arise as a consequence of the transformation of the underlying indolent lymphoma. There are no published prospective trials in double-hit lymphoma, however retrospective studies strongly suggest that aggressive induction regimens may confer a superior outcome. In this article, I review my approach to the evaluation and treatment of double-hit lymphoma, with an eye toward future clinical trials incorporating rational targeted agents into the therapeutic armamentarium.

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