WHO UPDATE ON LYMPHOMAS. Dr Priya Mary Jacob Asst Professor, Pathology.
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1 WHO UPDATE ON LYMPHOMAS Dr Priya Mary Jacob Asst Professor, Pathology
2 3 rd 4 th 4 th revised
3 The Change The Significance of the Change- Diagnostic, Prognostic The Rationale behind the change.
4 CHRONIC LYMPHOCYTIC LEUKAEMIA 2008 Monoclonal B cell lymphocyotosis monoclonal B cells with phenotype of CLL / atypical CLL or non CLL (CD5) B cells in peripheral blood upto a count of 5000, in the absence of other lymphomatous features. >5000 makes it CLL Not known if it is a precursor of CLL.
5 Whats Changed In 2017? Criteria for MBL remains the same. Acknowledged as precursor of CLL low count (<500) with extramedullarydisease high count (>500 & <5000) Tissue based MBL LN size < 1.5cm, no Proliferation centres.
6 In CLL, Proliferation centres- large, confluent, high MIB are an independent adverse prognostic factor. Typical PC x400 PC rich Giemsa, Giemsa, x 40 Ciccone et al, Leukaemia,2012
7 FOLLICULAR LYMPHOMA Bit by the renaming bug. Victoria Terminus Chattrapati Shivaji Terminus Chattrapati Shivaji Maharaj Terminus
8 Criteria same, with a new name. ISFL is now ISFN ( In situ Follicular Neoplasia )
9
10 Criteria same, with a new name. Paediatric FL is now Paediatric type FL Localized, early stage IHC- Bcl2 usually negative, can be rarely +, Bcl2 rearrangements must not be present. Exclude cases with diffuse areas. No Rx other than excision - Criteria strictly followed to avoid missing out FL grade 3.
11
12 A new provisional entity in paediatric age group Large B cell lymphoma with IRF4 rearrangement
13 Follicular, follicular & diffuse, pure diffuse. Children & young adults. Low stage - cervical nodes,waldeyer ring. IHC- Strong IRF4/MUM1 expression is seen usually with BCL6, Bcl2 + in 50% cases. FISH- most cases have IRF4 & Bcl6 rearrangements, but uniformly lack Bcl2 rearrangements. More aggressive, but responds well to Rx.
14 IRF4 / MUM1 Bcl6
15 Duodenal-type Follicular Lymphoma FL constitutes only 1% to 3% of primary GI lymphomas. When FL involves the GI tract, the duodenum is most often affected (89%) Always low grade (grade 1 2) Wait & watch policy.
16 CD 23 CD 21 Takata K et al, Modern Pathology, 2009 Follicular dendritic cells are arranged at the periphery of the neoplastic follicle. hollowing out pattern
17 Predominantly Diffuse FL with 1p36 deletion Accounts for some cases of diffuse FL Lacks Bcl2 rearrangement Presents as a localized mass, often inguinal. Low grade
18 MANTLE CELL LYMPHOMA Criteria same, with a new name. ISMCL is now ISMCN (In situ Mantle cell Neoplasia)
19 2 different pathways SOX11 + SOX11 Cyclin D1 / t(11;14)(q13;q32) translocation are the pathognomonic hallmarks of mantle cell lymphoma (MCL). Negative CCND1/t(11,14) were there but still had a gene expression profile suggesting a diagnosis of MCL. SOX11 was found to be 100 % positive in MCL with negative CCND1/t(11,14)
20
21 Impact Of NGS Studies
22 2008. no specific cytogenetic abnormality for HCL, HCL-v, LPL Mutations in BRAF V600E for Hairy Cell leukemia Mutations in MAP2K1 which encodes MEK1 for Hairy Cell Leukemia-variant. Mutations in MYD88 L265P for Lymphoplasmacytic Lymphoma Mutations affecting different genes.- CLL & MCL.
23
24 DIFFUSE LARGE B CELL LYMPHOMA 2008 Cell of origin classification IHC markers : CD 10, Bcl-6, MUM1 ( >30% positivity)
25 2008 B- Cell lymphoma, unclassifiable, with features intermediate between Diffuse large B cell lymphoma and Burkitt Lymphoma BCLUDLBCLBL
26 FAQ By The Medical Oncology Resident
27 Q. Unclassifiable? Does it mean you can t classify it? A. No. That s the name of the diagnosis. It s the category it fits in as per the 2008 WHO. Q. So is it going to behave like a DLBCL or Burkitt? A. Neither. Its going to behave like a BCLUDLBCLBL.
28 2008 B- Cell lymphoma, unclassifiable, with features intermediate between Diffuse large B cell lymphoma and Burkitt Lymphoma BCLUDLBCLBL
29 2017 Prognostic impact of the cell of origin status is impacted by MYC / Bcl2 status. MYC & Bcl2 by IHC for protein expression (MYC >40%, Bcl2>50%) MYC, Bcl2 and Bcl6 by FISH for translocations
30 High Grade B-cell Lymphoma With And Without MYC And Bcl2 Or Bcl6 Translocations. Double expressor IHC MYC and Bcl2 + FISH MYC and Bcl2 translocations ( - ) Double or Triple Hit IHC MYC and Bcl2 +/- FISH MYC and Bcl2 and Bcl6 translocations +
31 So Do We Need To Do FISH For All Cases Of DLBCL? All DLBCL Limit them to cases with a GCB phenotype / high grade morphology / >40% MYC+ cells.
32 Orange arrow - single hit Red arrow - double or triple hit * Except for cases that fulfill criteria for FL and LBL *
33 Do true BL without MYC translocations exist? Burkitt like lymphoma with 11q aberration. Lower levels of MYC expression on IHC Cytological pleomorphism whether true BL without MYC translocations really exist. Occasionally a follicular pattern Chromosomal 11q aberration.
34 EBV + DLBCL of elderly Recognizes the fact that it can occur in younger patients. Better survival than previously thought EBV+ DLBCL, NOS.
35 A New Provisional entity EBV+ mucocutaneous ulcer. Self limited growth Good response to conservative management Advanced age or with iatrogenic immunosuppression
36 EBV+ Mucocutaneous Ulcer. Isolated, well-circumscribed ulcers involving oropharyngeal mucosa, skin, GI tract Polymorphous infiltrate with T cell/histiocyte-rich background, immunoblasts and Hodgkin-like cells Prominent rim of small T-cells at base of ulcer CD30+ EBER+ CD20+/- CD15+/- CD10- BCL6- MUM1+ CD45+ Localized defect in immune surveillance? Dojcinov et al, AJSP 2010
37
38
39 Angioimmunoblastic T Cell Lymphoma, Follicular Tcell lymphoma, PTCL With TFH Phenotype now under the same umbrella
40 Nodal T- cell lymphomas with T-follicular helper (TFH) phenotype Lot of similarities in genetic changes. Neoplastic cells should express atleast 2 or 3 TFH related antigens CD279/PD-1 CD10 Bcl6 CXCL13 ICOS SAP CCR5
41 Lymphomatoid Papulosis A, B, C New subsets in 2017 D, E and Lp with 6p25 rearrangement. New indolent provisional entities Indolent T cell Lymphoproliferative disorder of the GIT Primary cutaneous acral CD8+ T cell lymphoma.
42 Breaking News :ALK ALCL is now a definite entity.
43 In 2008, criteria for separating CD30+ PTCL from ALK- ALCL were imperfect and ambiguous. GEP has facilitated this distinction, with ALK- ALCL having a superior prognosis over PTCL, NOS. Application of quantitative RT-PCR in validated a 3-gene model (TNFRSF8, BATF3, and TMOD1) able to successfully separate ALK ALCL from peripheral T-cell lymphoma not otherwise specified, with overall accuracy near 97%. Agnelli et al, Blood 2012
44 Breast Implant Associated ALCL
45
46 This is very, very, rare. In the scientific literature from January 1, 1997 through May 21, 2010, the FDA identified 34 definite cases. Number of breast imlplants during this time period in the USA? 4 million.
47 EATL Type II Is now Called MEITL Monomorphic epitheliotropic intestinal TCL (MEITL) Systemic EBV +T cell lymphoproliferative disorder of childhood Systemic EBV +T cell lymphoma of childhood Hydroa vacciniforme like lymphoma Hydroa vacciniforme like lymphoproliferative disorder
48
49 NLPHL, THRLBCL-like THRLBCL-like transformation of NLPHL. Erdheim Chester disease distinguished from other members of juvenile xanthogranuloma family.
50 Diagnostic approach to Lymphomas Good morphology, Clear clinical picture, IHC, FISH, followed by NGS is the way to go. Walking towards a closer integration between morphology and genetics.
51 References The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood May 19;127(20): Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD 1, Jaffe ES 1. Follicular Lymphomas in children and young adults: A comparison of the pediatric variant with usual follicular lymphoma Am J Surg Pathol Mar; 37(3): Qingyan Liu, Itziar Salaverria,Stefania Pittaluga, Armin G. Jegalian, Liqiang Xi, Reiner Siebert, Mark Raffeld, Stephen M. Hewitt, Elaine S. Jaffe. Identification of a 3-gene model as a powerful diagnostic tool for the recognition of ALK-negative anaplastic largecell lymphoma. Blood. 2012;120(6): Agnelli L, Mereu E, Pellegrino E, et al; European T-Cell Lymphoma Study Group.
52 Thank you
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