The differential diagnosis between primary mediastinal B-cell … · Conclusion •Primary...
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The differential diagnosis between primary mediastinal B-cell lymphoma and diffuse large B-cell lymphoma
Daphne de Jong, MD PhD Amsterdam UMC, VU University Medical Center Amsterdam The Netherlands [email protected]
ECP, Bilbao September 2018
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Large B-cell Lymphoma
GCB-DLBCL ABC-DLBCL
HGBCL-NOS HGBCL-DTH
cHL
IP-DLBCL PMBCL
Savage et al. Blood 2003;102;3871-3879, Rosenwald et al. JExMed 2003;198; 851-862, Green et al. Blood 2010;116:3268-3277, Chapuy et al. Blood 2016;127:869-881
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The relevance of lymphoma classification
Definition of (clinico-pathological entities – basis of the WHO classification • based on morphological spectrum, immunofenotypical spectrum, genetic characteristrics, clinical characteristics • class provides information for treatment choices (intensification, radiotherapy)
Dissection of specific oncogenesis
• may provide a basis for specific or targeted treatment
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Case 2 – TVU16-5646
14 year old female patient Presented with bilateral cervical, supraclavicular, anterior mediastinal, hilar and subcarinal and upper abdominal lymphadenopathy Superior vena cava syndrome Some right-sided pleural effusion No hepato-splenomagalie No other organ localizations
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CD20
CD10
MUM1
BCL6
MIB1
CD79a, PAX5, BCL2 positive EBER, CD15 negative
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CD30
CD23
Second line IHC may include: MAL, HLA-II, PDL1/PDL2 and other markers that are rarely routinely available
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Molecular features of PMBCL
Green et al Blood 2010, 116;2455-3277, Chapuy et al. Blood 2016;127:869-881
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Pasqualucci et al Semin Hematol. 2015 Apr; 52(2): 67–76
Molecular features of PMBCL
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Reflection of the different genetic landscape of PMBCL and DLBCL
Dunleavy, Wilson, Blood 2015 125:33-39, Savage et al. Blood 2003;102;3871-3879, Rosenwald et al. JExMed 2003;198; 851-862, Green et al. Blood
2010;116:3268-3277, Steidl et al. Nature 2010;471:377-381, Shi et al AmJSurgPathol 2014;38:1715-1723, Twa et al Blood 2014;123:2062-2065
Overall genetic differences result in characteristic gene expression patterns
Specific structural alterations result in characteristic protein expression patterns
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Methods for the analysis of specific molecular features of PMBCL
Gene-expression profile expression-array, RNAseq, RT-MLPA Mutation spectrum WGS/WES, targeted NGS, (multiplex) PCR-techniques Copy number alterations SNP-NGS, shallow sequencing (off-target), FISH Structural alterations SeqCap-NGS, FISH
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Molecular features in case 2- TVU16-5646
PDL2 - 366C.9E5
PDL1- 22C3
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Molecular features in case 2- TVU16-5646
Various gains and losses are noted including large segments, but also focal aberrations: Losses on chromosome 1, 3, 4q, 7p,10p12 14q31-32, 19p13 and 20q13.13-13.2. Gaines on chromosome 5p, 9p24.3-p23 and 20
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Molecular features in case 2- TVU16-5646
A combined assay gives information on copy numbers amplification 9p24 Structural alterations translocation PDL2 Mutation spectrum Additional (structural) alterations
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Molecular information, especially isolated PDL2 amplification, adds an additional level to morphology, immunophenotype and clinical information
Case 2 favor Primary Mediastinal B-cell Lymphoma
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Conclusion
• Primary Mediastinal B-cell lymphoma is a distinctly separate disease from Diffuse Large B-cell lymphoma
• Morphological and immunohistochemical markers are characteristic, but not specific
• The copy number landscape and translocation spectrum of PMBCL is characteristic and bears similarities to CHL, but less so to DLBCL
• Additional diagnostic arguments may be needed in equivocal situations • Custom made and commercial FISH assays for 9p24 are helpful as a
diagnostic tool in daily practice • NGS techniques require a specialized lab, but if available may be an
attractive alternative
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Acknowledgements VU University Medical Center, Amsterdam The Netherlands Marit Roemer Tjitske Los-de Vries Matias Mendeville Daniella Berry Nathalie Hijmering Bauke Ylstra