Follicular Lymphoma: the WHO
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1 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
2 Disclosure of Relevant Financial Relationships The USCAP requires that anyone in a position to influence or control the content of all CME activities disclose any relevant relationship(s) which they or their spouse/partner have, or have had within the past 12 months with a commercial interest(s) [or the products or services of a commercial interest] that relate to the content of this educational activity and create a conflict of interest. Complete disclosure information is maintained in the USCAP office and has been reviewed by the CME Advisory Committee. Dr. Yuri Fedoriw declares he has no conflict(s) of interest to disclose.
3 Case Presentation 73 year old man with no significant oncologic history presents with left inguinal swelling. The mass has been slowly growing for 1 2 years. Recently becoming uncomfortable
4 Case Presentation Physical exam: Thin, healthy appearing man 6cm mass in left inguinal region CBC: No cytopenias No lymphocytosis
5 Touch Preparation Impression: monotonous population of predominantly small, mature appearing lymphocytes
6 Flow Cytometry
7 Flow Cytometry
8 Flow Cytometry and Cytogenetics Other immunophenotypic markers: CD19+ CD20+ CD10dim+ CD23variably+ kappa light chain restricted Karyotype: abnormal complex, including del 1(p36) notably absent for t(14;18) BCL2 not rearranged by FISH
9 Excisional Biopsy
10
11
12 CD21
13 BCL2 Ki67
14 Abnormalities of 1p36 in Lymphoma Loss of 1p36 is a FREQUENT secondary event in classic Follicular Lymphoma Frequent mutations of TNFRSF14 (? tumor suppressor) In classic FL, it s a poor prognostic indicator In pediatric FL it does NOT confer a poor prognosis In bulky lymph nodes in the inguinal region may define a uniquely well behaved subset! (in t(14;18) negative cases)
15 Highlights: 35 cases of predominantly diffuse FL Approximately 80% in the inguinal region The overwhelming majority lacked the t(14;18), but did have deletions of 1p36 Presenting as isolated, painless swelling
16 Follicular Lymphoma Lymphoma of mature, follicle center B cells Classically associated with t(14;18)(q32;q21) BCL2 translocation BCL2 overexpression (IHC) Anti apoptotic protein in a place of normally active apoptosis Grading: 1 3 based on the number of centroblasts per high power field CD10/BCL6 positive, CD5 negative, MUM1 negative
17 Translocation (14;18) IgH promoter (14) bcl2 (18) Bcl2 is antiapoptotic and overexpressed Bcl2 over-expression not unique to follicular lymphoma t(14;18) Translocation (2:18) rare Light chain-bcl2 Most FL have additional abnormalities EARLY event!
18 Follicular Hyperplasia Follicular Lymphoma
19 Follicular Hyperplasia Follicular Lymphoma BCL2 Ki67
20 Recapitulation of expected structure AND function Elderly man with CLL and Follicular Lymphoma: bone marrow clot section CD3
21 On the other hand. Not so follicular, follicular lymphoma
22 Is morphology dictated by site of involvement or tumor biology? Probably both.
23 not all Follicular Lymphomas are created equal
24 Other Follicular Lymphoma variants typically lacking t(14;18) Pediatric follicular lymphoma Head and neck Males >>> Females t(14;18) positive cases may be more similar to conventional FL Cutaneous follicle center cell Head and trunk t(14;18) positivity should raise concern for secondary involvement of the skin BCL2
25 Primary Intestinal Follicular Lymphoma CD20 CD21
26 Primary Intestinal Follicular Lymphoma BCL2 Ki67
27 Morphologic grade isn t necessarily a good correlate to clinical outcome
28 2001 version of Grading Grade 1 Grade 2 Grade 3 centroblasts t(14;18) BCL2 rearrangement Poor outcome
29 Evolution of Grading Grade 1 Grade 2 vs. vs. Grade 3 Grade 1 2 Grade 3 vs. Grade 1 2 3A vs. Grade 3B Grade 1 2 3A and other variants vs. Grade 3B
30 Survival curves by grade grade Ki67
31 Evolution of Grading Grade 1 Grade 2 vs. vs. Grade 3 Grade 1 2 Grade 3 vs. Grade 1 2 3A vs. Grade 3B Grade 1 2 3A and other variants vs. Grade 3B
32 Summary Table
33 Summary and Conclusions Follicular Lymphomas are a far more diverse group of neoplasms than originally appreciated Sites of disease are associated with distinct biologic variants with overlapping but unique molecular and immunophenotypic findings Accurate classification = precise therapy
34 Summary Table
35 Important Information Regarding CME/SAMs The Online CME/Evaluations/SAM claim process will only be available on the USCAP website until October 2, No claims can be processed after that date! After October 2, 2015 you will NOT be able to obtain any CME or SAMs credits for attending this meeting.
36 Thank You! Please go to the USCAP website to complete your Evaluation of the course and claim CME and/or SAMs Credits.
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