Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma

Written2016-06Antonino Carbone, Liron Pantanowitz, Sandro Sulfaro, Annunziata Gloghini
Department of Pathology Centro di Riferimento Oncologico Aviano (CRO), Istituto Nazionale Tumori, IRCCS, Aviano, Italy - acarbone@cro.it (AC); Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania - pantanowitzl@upmc.edu (LP); Department of Pathology, A.O. "S. Maria degli Angeli" Pordenone, Italy - sandro.sulfaro@aas5.sanita.fvg.it (SS); Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy; - annunziata.gloghini@istitutotumori.mi.it (AG)

Abstract The 2016 revised World Health Organization (WHO) classification includes several provisional borderline categories for lymphoma cases that do not clearly fit into one entity, such as B-cell lymphoma, unclassifiable (BCLU), with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL).
This CARD focuses on lymphomas that are intermediate between DLBCL of the primary mediastinal large B-cell lymphoma (PMLBCL) type and cHL

Keywords B-cell lymphoma unclassifiable; intermediate lymphomas; diffuse large B-cell lymphoma; primary mediastinal large B-cell lymphoma; classical Hodgkin lymphoma

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424
ICD-Morpho 9596/3 B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma
Atlas_Id 2131

Clinics and Pathology

Disease Most lymphomas are considered to represent distinct disease entities since they have characteristic immunophenotypic profiles and recurrent genetic abnormalities, and can accordingly be diagnosed using available techniques. However, the 2016 revised WHO classification has introduced new provisional borderline ("grey zone") categories for cases that do not clearly fit into one entity. This includes a category termed B-cell lymphoma, unclassifiable (BCLU), with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL). Another unclassifiable category was created for cases showing features intermediate between DLBCL and Burkitt lymphoma (BL) with the newer recognized categories now termed high grade B-cell lymphoma (HGBL) with and withoutMYC and BCL2 and/or BCL6translocations (the so-called double or triple hit lymphoma) . HGBL, NOS includes cases lacking MYC and BCL2 and/or BCL6 translocations that would formerly have been called BCLU with features intermediate between DLBCL and BL (Figure 1).This CARD focuses specifically on the category of B-cell lymphoma that is intermediate between DLBCL of the primary mediastinal large B-cell lymphoma (PMLBCL) type and cHL (Jaffe et al., 2008, Carbone et al., 2010; Swerdlow et al., 2016).
Epidemiology PMLBCL/cHL usually affects young people; females more than males.
Clinics Mediastinal presentation with limited stage disease. This B-cell lymphoma is usually aggressive with an intermediate prognosis between DLBCL and cHL.
 
Figure 1. Borderline categories for cases that do not clearly fit into one entity include a category termed B-cell lymphoma, unclassifiable (BCLU), with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (cHL). Another unclassifiable category was created for cases showing features intermediate between DLBCL and Burkitt lymphoma (BL) with the newer recognized categories now termed high grade B-cell lymphoma (HGBL) with and without MYC and BCL2 and/or BCL6 translocations.
Pathology Table 1: Morphologic features of the intermediate PMLBCL/cHL B-cell lymphoma overlap between those of PMLBCL and cHL (Gaulard et al., 2008; Stein et al., 2008; Carbone et al., 2010).
PMLBCL morphology
 - Tumour cells- Large cells with clear cytoplasm and multilobated nuclei
- Large cells with Hodgkin Reed-Sternberg (HRS)-like morphology
 -Tumor background- Contains eosinophils, plasma cells, T-cells. The inflammatory background is less abundant than that of cHL
- Fine compartmentalizing alveolar fibrosis
cHL morphology
     - Tumour cells- Typical Reed-Sternberg (RS) cells
- Mononuclaer Hodgkin cells
     - Tumor background- Contains admixed T-cells, B-cells, plasma cells, eosinophils, histiocytes, and fibroblasts
- Abundant sclerosis (especially in the nodular sclerosis subtype)
BCLU morphology with features intermediate between PMLBCL and cHL
     - Tumour cells

- Large cells resembling HRS cells, which comprise the majority of the infiltrate
- Large cells with clear cytoplasm
- Large cells resembling centroblasts

     - Tumor background- Sparse inflammatory infiltrate with eosinophils, plasma cells, histiocytes, and T-cells
- Sclerosis (variable and focal)
- Necrosis (frequent)
     - Variation in morphology, with some tumor areas resembling DLBCL and other regions more closely resembling cHL
 
Figure 2. B-cell lymphoma, unclassifiable (BCLU) with features intermediate between DLBCL and cHL This lymphoma has a diffuse growth pattern and is composed of many large atypical cells with distinct nucleoli and a scant inflammatory background. H&E stain, magnification x60.
Other features IMMUNOPHENOTYPE
Table 2:Transitional features between PMLBCL and cHL (Gaulard et al., 2008; Stein et al., 2008; Carbone et al., 2010).
PMLBCL
     - CD30+ (80% of the cases, weak and heterogeneous)
- CD15- (occasionally present)
- B-cell antigens+ (CD20, CD19, CD22, CD79a)
- BCL6+, BCL2+, CD23+, CD10+ (less common)
- IRF4/MUM1+
cHL
     - CD30+ strong (100% of the cases)
- CD15+
- CD45-
- CD20-
- CD40 (consistently positive)
- BCL6-
- IRF4/MUM1 (consistently positive)
- B-cell transcription factors-
BCLU with features intermediate between PMLBCL and cHL
     - CD30+ (variable amount)
- CD15+ (variable amount)
- CD45+
- B-cell antigens+
- B-cell transcription factors+

Genetics

Specific genetic changes characteristic of BCLU with features intermediate between PMLBCL and cHL have not been definitively shown. Like DLBCL (NOS) and PMLBCL, these lymphomas may demonstrate deregulation of B-cell signaling or transcriptional regulation and apoptosis (e.g. BCL6 gene rearrangement, activation of NFKB pathway, constitutive activation of STAT6) (Carbone et al., 2010; Swerdlow et al., 2016; Carbone and Gloghini 2016).
However, unlike cHL Epstein-Barr virus sequences have been found in fewer (20% or less) cases.
<
DLBCL, NOS
     - BCL6 gene rearrangement, activation of NFKB pathway, constitutive activation of STAT6
PMLBCL
     - Activation of the NFkB pathway, altered JAK/STAT signaling, activation of PI3K/AKT pathway
- Immunoglobulin (Ig) heavy chain gene rearrangement with high somatic hypermutation (SHM) and class switch recombination (CSR)
- No Ig expression
cHL
     - EBV (a subset of cHL), activation of the NFkB pathway
- Altered JAK/STAT signaling, activation of PI3K/AKT pathway
- IGH Re non functional. No Ig expression
BCLU with features intermediate between PMLBCL and cHL
     - Overlap with cHL and PMLBCL

Bibliography

Classical Hodgkin lymphoma
Carbone A, Gloghini A.
Atlas Genet Cytogenet Oncol Haematol. in press
 
Primary mediastinal (thymic) large B-cell lymphoma.
Gaulard P, Harris NL, Pileri SA, Kutok JL, Stein H, Kovrigina AM, Delsol G, Jaffe ES, Moller P..
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele H, Vardiman JW (eds.) World Health Organization Classification of Tumours, Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues, Lyon: IARC Press, 2008: 250-251
 
B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma.
Jaffe ES, Stein H, Swerdlow SH, Campo E, Pileri SA, Harris NL.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele H, Vardiman JW (eds.) World Health Organization Classification of Tumours, Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues, Lyon: IARC Press, 2008: 267-268
 
Classical Hodgkin lymphoma, introduction.
Stein H, Delsol G, Pileri SA,Weiss LM, Poppema S, Jaffe ES.
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele H, Vardiman JW (eds.) World Health Organization Classification of Tumours, Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues, Lyon: IARC Press, 2008: 326-329
 
The 2016 revision of the World Health Organization (WHO) classification of lymphoid neoplasms.
Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, Jaffe ES.
Blood 2016;127(20):2375-2390 (Review).
PMID 26980727
 

Citation

This paper should be referenced as such :
Carbone A, Pantanowitz L, Sulfaro S, Gloghini A
B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Anomalies/IntermediateDLBCL-cHDID2131.html


External links

arrayMapMorph ( 9596/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
 
Disease databaseB-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon Sep 18 17:18:43 CEST 2017


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.