PhenoPath. Diagnoses you can count on B CELL NON-HODGKIN LYMPHOMA

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1 PhenoPath Diagnoses you can count on B CELL NON-HODGKIN LYMPHOMA

2 C urrent diagnosis of B cell non-hodgkin lymphoma (B-NHL) is based on the 2008 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues reference (1), which incorporates clinical, histologic, immunophenotypic, cytogenetic and other molecular information to arrive at specific diagnoses. The type of therapy used for B-NHL is critically dependent on the specific B-NHL subtype. It is essential that all pathologists who diagnose B-NHL have an intimate understanding of the 2008 WHO diagnostic criteria. Recent advances in genomics (2, 3) have led to the discovery of many mutations associated with different types of B-NHL. It is likely that future classification systems will incorporate this new mutational information into disease-defining criteria. Refs: 1. Swerdlow SH, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC Press, Lyon, Blombery PA, et al. Leuk Lymphoma. May 9, 2013 [Epub ahead of print] 3. Shaffer AL, et al. Annu Rev Immuno. 30: , 2012 Trisomy 12 in CLL/SLL Reproducible clonal peak Clonal IgH rearrangement in extranodal marginal zone B cell lymphoma bcl-2 clone 124 bcl-2 clone C2 CD10 bcl-6 MUM1 DLBCL subtyping Burkitt lymphoma bcl-6 Unusual follicular lymphoma showing bcl-2 positivity with only 1 of 2 antibodies

3 Diagnosing & Subtyping B Cell NHL PhenoPath recommends the judicious use of flow cytometry, IHC, FISH, cytogenetics and/or PCR to diagnosis these entities per WHO 2008 recommendations PhenoPath recommends the use of assays optimized for small tissue samples NOTE: PhenoPath s consultation service is optimized for handling small specimens WHO Lymphoma Diagnoses bcl-2 CD5 CD10/bcl-6 CD23 CD43 Cyclin D1 t(14;18)(q32;q21) IGH/BCL2 ENTITY IMMUNOHISTOCHEMISTRY CYTO Chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL/SLL) Low-grade B-NHL Lymphoplasmacytic lymphoma Hairy cell leukemia Splenic marginal zone B cell lymphoma (SMZL) Extranodal (EMZL/MALToma) & nodal marginal zone B cell lymphoma Follicular lymphoma (FL), Grade 1-2 Intermediate/high-grade B-NHL Follicular lymphoma (FL), Grade 3B* Mantle cell lymphoma DLBCL Double-hit lymphoma Burkitt lymphoma In almost all cases, the entities above express the pan-b cell markers CD20, CD79a, and PAX-5. In terms of potential therapeutic targets other than CD20, most B-NHLs express CD22 and CD52 at some level, and the latter two antigens are easily assayed by flow cytometry. * Grade 3B FL is felt to be a distinct biological entity compared to Grades 1 to 3A; there is some controversy about the clinical behavior of grade 3A FL; therefore, it is omitted from this chart.

4 Our philosophy is to follow a testing strategy based on constant and rigorous review of the most current clinical trials and scientific literature. We only order clinically relevant tests necessary to render a definitive diagnosis. PhenoPath s approach is both cost effective and supports optimal clinical care. BCL6 rearrangement MYC rearrangement t(11;14)(q13;q32) CCND1/IGH t(11;18)(q21;q21) API2/MALT1 t(14;18)(q32;q21) IGH/MALT1 del(7q32) trisomy(12) del(13q14) del(11q23) del(17p13) MYD88 L265P mutation BRAF V600E GENETIC / FISH (TARGETED FISH STUDIES ARE RECOMMENDED Ω Ω Ω Ω PCR Ω One or more usually positive 7q32 deletions reported in roughly 40% of SMZL CD43 is coexpressed in roughly 50% of cases Frequency of MALT1 rearrangement varies with anatomic location of EMZL/MALToma Almost always positive Usually positive Usually negative Almost always negative

5 Why use PhenoPath Laboratories? Differentiated by quality, clinical accuracy and physician access Physician run and owned with full oversight over laboratory operations and quality control Highly trained and knowledgeable technologists participate in daily slide review with pathologists Pathologist review and sign out of every case One-on-one phone consultations with referring physicians Your resource for reference pathology testing Leaders in ancillary techniques applied to surgical pathology Widely published in clinical and diagnostic journals Extensive experience in the application of new technologies for diagnostic needs Pertinent directed testing in specific organ system diseases Focused on providing relevant directed testing supported by the most current literature for optimal clinical care Cost effective clinically relevant approach Integration of current literature with clinical diagnosis Innovative, cutting-edge services Advanced assays and methods (10-color flow, real time PCR, up-to-date comprehensive IHC library) Data integration with pathology and hospital information systems Full-service anatomic pathology capabilities Consults, IHC, flow, molecular, FISH, cytogenetics, IF Quality and quantity of antibody library second to none Test menu covering the breadth of diagnostic anatomic pathology.... Diagnoses you can count on

6 PhenoPath Diagnoses you can count on 551 N 34th St., Suite 100 Seattle, WA, p: f: Cover images: Bottom: Peripheral blood involved by CLL/SLL Top: Double-hit aggressive B cell lymphoma