Immune checkpoint inhibitors, lymphocytes, and breast cancer. Megan L. Troxell, MD/PhD Stanford Pathology
|
|
|
- Anna Hodges
- 5 years ago
- Views:
Transcription
1 Immune checkpoint inhibitors, lymphocytes, and breast cancer Megan L. Troxell, MD/PhD Stanford Pathology
2 Objectives Recognize the potential prognostic & predictive importance of tumor infiltrating lymphocytes in breast cancer Describe the mechanism of action of CTLA-4 and PD-1/PD- L1 inhibitors Understand the advent of immune related Adverse Effects (irae s) with immune checkpoint inhibitors Recognize histopathologic features of IrAE s on tissue biopsy Understand the controversy surrounding biomarker analysis for immune checkpoint inhibitor therapy
3 Lymphocytes in breast Physiologic (involution) Diabetic mastopathy Duct ectasia Trauma/Procedure Autoimmune disease Infection Lymphoproliferative/Lymphoma Carcinoma
4 Diabetic mastopathy lymphocytic mastopathy or sclerosing lymphocytic lobulitis Presents as mass (esp. palpable) Dense lymphocytic infiltrates, circumscribed Mostly B-cells No germinal centers Surround atrophic lobules (or ducts, vessels) Dense fibrous stroma Keloid-like Rarely, epithelioid fibroblasts D Alfonso. JPTM 2015; 49:279-87
5 Lupus mastitis Lobular lymphocytic panniculitis Mixed B- T-cell infiltrate with germinal centers Vasculitis Hyaline fat necrosis In 2-3% of lupus patients Rx: immunosuppression Kinonen. Am J Surg Pathol 2010;34: Rosa, Mohammadi. Ann Diagn Pathol. 2013;17:230-3
6 Granulomatous mastitis Differential diagnosis: TB/infectious (fungal, cat scratch, bacterial) Bug stains (AFB/Fite, GMS and Gram) Idiopathic Dx of exclusion Autoimmune Sarcoid Rheumatoid nodules/ra GPA/vasculitis Rule out carcinoma Infarct SMOLD IgG4 related disease?? (Biopsy site/foreign body) Renshaw. AJCP :
7 AJCP. 2011; 136: Granulomatous & necrotizing mastitis Distinctive cystic spaces lined by polys Spaces larger than adipocyte Gram + organisms (corynebacterium) Bugs are IN THE SPACES Lipophilic, requires Tween to grow Rx with tetracycline, doxycycline (2+ weeks) Taylor. Pathology 2003:35: NZ study with culture data
8
9 CNGM
10 CNGM
11 Granulomatous mastitis Pattern Age (range) Child bearing Gram+ bugs? D Alfonso AJSP CNGM 34 (25-49) nd 5/12 Troxell AJCP CNGM 33 (19-47) 4.75 y ago 16/19 Troxell AJCP Other GM 47 (29-71) 14 y ago 0/16 CNGM histologic pattern lipophilic bacteria TB (T-cell lymphoma) Stromal idiopathic bilateral Post XRT for cancer
12 Core biopsy: granulomas
13 Same case: epithelioid histiocytes?
14 Same case: epithelioid histiocytes?
15 AJSP 2009;33: Lymphoplasmacytic infiltrate, mass-forming Stromal sclerosis and loss of breast lobules IgG4+ cells/hpf NO GRANULOMAS!! 3 of 4 with multiple masses, elevated IgG or IgG4 Controls Lymphocytic mastopathy 0-5 IgG4+/hpf (n=9) Granulomatous mastitis IgG4+/hpf (n=6)
16 IgG4-related sclerosing mastitis Cheuk. AJSP 2009;33:
17 IgG4 in granulomatous mastitis IgG4+ plasma cells not specific for IgG4-RSD in other organs Granulomas unusual in IgG4- RSD in other organs Granulomatous mastitis not IgG4-RSD (in my opinion) IgG4/hpf median range # >30/hpf CNGM /9 Other GM /5 Berg Evaluating breast lymphoplasmacytic infiltrates Hum Pathol :
18 Breast lymphoma Lymphoma % of breast malignancies Breast presentation in <3% of extranodal lymphomas Primary breast lymphoma criteria (Wiseman & Liao, Hugh): Lymphomatous infiltrate into breast tissue No antecedent diagnosis of lymphoma Breast as the clinical site of presentation Ipsilateral lymph node involvement allowed if simultaneous Secondary breast lymphoma : systemic lymphoma with concurrent or subsequent involvement of breast
19 Breast lymphoma subtypes Lymphoma % 1 BL Comments DLBCL 56-84% ABC type 60-70% Marginal Zone 9-28% age ~68 Follicular 10-19% Age ~62 Burkitt <6% Esp. bilateral, EBV younger women Implant associated ALCL SLL, LPL, T-cell, mantle, Hodgkin 1/500,000 with implants <1% each Cheah. Cancer Treatment Reviews. 2014;40: DLBCL PTLD Jeppesen. Breast J. 2011;17:
20 4 cases; Mod Pathol 2008; 21: Am J Surg Pathol 2012;36:
21 First reported 1997 Keech & Creech >90 cases reported Median 8 years with implants Effusion around implant +/-mass Phenotype: CD30+, EMA+, ALK- T-cell antigen expression (no B-cell) esp. CD43, CD4, cytotoxic granule CD3, CD5 weak or absent T-cell gene rearrangements Treatment surgical excision of implant and capsule chemo, XRT? Implant associated ALCL Miranda et al. J Clin Oncol 2013;32:
22 Implant ALCL Distribution: Effusion - sparse cells in fibrous capsule 93% remission Mass 72% remission R/o systemic or cutaneous Miranda et al. J Clin Oncol 2013;32: T1 T2 Clemens et al. J Clin Oncol 2016;34:160-68
23 Seroma cytology
24 Seroma CD30
25 Seroma ALCL CD5 ALK
26 Fibrous capsule
27 Lymphocytes & Carcinoma
28 DCIS: eos & lymphs
29 DCIS & lymphs
30 DCIS, lymphocytes & microinvasion
31 Calponin (p63, SMM similar) Her2
32 Kim et al. AJCP. 2016; 146: Feature mi Absent (177) Mi Present (27) Lymphoid aggregates around tumor (p=0.002) Absent 81.4% 3.7% Present 69.5% 96.3% Breast cancer subtype (p=0.001) ER+/HER2-59.9% 7.4% ER+/HER % 14.8% ER-/HER % 59.3% Triple neg 5.6% 18.5% Not shown: significant difference by DCIS necrosis, nuclear grade, germinal center in TLS
33 Calponin stain (p63, SMM similar) All DCIS?
34
35 Microinvasive CA (CAP/AJCC) Invasion measuring 1mm or less If multiple: Do not add sizes together Estimate # of foci, or too numerous to quantify IHC for myoepithelial cells IHC for ERPgRHer2 (?)
36 Tumor-immune interactions Immune response can eliminate incipient tumors Advanced tumors have escaped host immunity Immune parameters may still influence survival Abundant CD8+ infiltration associated with survival Degree of lymphoid infiltrate associated with survival for triple-negative & Her2+ Hormone receptor+ tumors have least lymphoid infiltrate Immunologic parameters related to pcr in neoadjuvant setting Lymphocyte predominant breast cancer: more lymphocytes than tumor cells ; 50+% stromal TILS Immune cells shape microenvironment Immune modulation in cancer therapy Salgado et al. Annals of Oncology 2015;26:
37 Annals of Oncology 2015;26:
38 Nat Rev Clin Oncol. 2016;13: Immune microenvironment in breast cancer
39 TILS: invasive carcinoma Workgroup document with guidelines, tutorial for stromal TILs Stromal TILS Intratumoral Salgado. Annals of Oncology 2015;26:
40 CK7
41 Immune checkpoint inhibitors Takes the brakes off of the immune system, allowing enhanced attack on cancer cells Overcomes tumor immune evasion
42 Immune checkpoint: alphabet soup Agent Trade Target # Trials # breast ca Ipilimumab Yervoy CTLA Tremelimumab In trials CTLA Nivolumab Opdivo PD Pembrolizumab Keytruda PD Atezolizumab Tecentriq PD-L Durvalumab In trials PD-L Avelumab In trials PD-L Kerr & Hirsch Arch Pathol Lab Med. 2016;140: ; Kerr et al. J Thorac Oncol. 2015;10: Clinicaltrials.gov (Aug-Sept 2016)
43 Immune checkpoint inhibitors Takes the brakes off immune system, restoring attack on cancer cells Active CLTA-4 cytotoxic T- lymphocyteassociated protein 4 Ribas. NEJM. 2012; 366:2517-9; Baksh &Weber.Sem Oncol. 2015;42:363-77; Troxell Adv Anat Pathol. 2016;23:310-29
44 Immune checkpoint inhibitors Takes the brakes off immune system, restoring attack on cancer cells Inactive, no 2 nd signal CLTA-4 Ribas. NEJM. 2012; 366:2517-9; Baksh &Weber.Sem Oncol. 2015;42:363-77; Troxell Adv Anat Pathol. 2016;23:310-29
45 Immune checkpoint inhibitors Takes the brakes off immune system, restoring attack on cancer cells Active, 2 nd signal restored Ribas. NEJM. 2012; 366:2517-9; Baksh &Weber.Sem Oncol. 2015;42:363-77; Troxell Adv Anat Pathol. 2016;23:310-29
46 Immune checkpoint inhibitors Takes the brakes off immune system, restoring attack on cancer cells Active PD-1 Ribas. NEJM. 2012; 366:2517-9; Baksh &Weber.Sem Oncol. 2015;42:363-77; Troxell Adv Anat Pathol. 2016;23:310-29
47 Immune checkpoint inhibitors Takes the brakes off immune system, restoring attack on cancer cells Inactive, PD-1 inhibition PD-1 Ribas. NEJM. 2012; 366:2517-9; Baksh &Weber.Sem Oncol. 2015;42:363-77; Troxell Adv Anat Pathol. 2016;23:310-29
48 Immune checkpoint inhibitors Takes the brakes off immune system, restoring attack on cancer cells Active Ribas. NEJM. 2012; 366:2517-9; Baksh &Weber.Sem Oncol. 2015;42:363-77; Troxell Adv Anat Pathol. 2016;23:310-29
49 Breast cancer studies Drug N Inclusion (PD-L1 IHC) % of screen population + Response (% patients) Atezolizumab 21 5% lymphs 23% 19% TNBC Pembrolizumab 32 1% tumor 58% 18.5% TNBC Tremelimumab 26 0 (ER+) Savas et al. Nat Rev Clin Oncol. 2016;13:228-41
50 Problems with immune checkpoint inhibitors Immune related adverse effects (irae) Side effect: attack on normal tissues
51 Immune related adverse effects :irae s Voskens. PLoS ONE 2013; 8: e Troxell, Higgins, Kambham. Adv Anat Pathol. 2016;23:310-29
52 J Clin Oncol 2006; 24:
53 Oble et al. AJSP. 2008; 32: Stomach, SI, colon Lymphoplasmacytic expansion of LP Intraepithelial lymphocytes (T-cells) Epithelial apoptosis Cryptitis Villous blunting in SI autoimmune enteropathy like Marginean Archives 2016;140: GVHD-like pattern, or Focal acute colitis
54 Ipilimumab: Kidney 73 year old woman with melanoma Brisk AIN with eosinophils
55 Pembrolizumab: Kidney 66 year old man with urothelial CA Brisk AIN with eos, tubulitis, ATN
56 Arch Pathol Lab Med. 2016;140: ; Problems with immune checkpoint inhibitors Biomarker testing (&*^^%%$##!!!) Arch Pathol Lab Med. 2016;140:351 54
57 Drug & biomarker development New Drug Biomarker for drug (target) Clinical trial Companion diagnostics Approval with contingent biomarker
58 Drug & biomarker: PD-L1 New Drug Biomarker for drug (target) Nivolumab 28-8 Dako Link Pembrolizumab 22C3 Dako Link Clinical trial Same drug mechanism, target & biomarker Approval with contingent biomarker SP142 Ventana Ultra Atezolizumab SP263 Ventana Ultra Durvalumab
59 Immune checkpoint: alphabet soup Agent Trade Drug Target Antibody (PD-L1) Platform Nivolumab Opdivo PD-1 Dako 28-8 Link 48 Envision FLEX Pembrolizumab Keytruda PD-1 Dako 22C3 Link 48 Envision FLEX Atezolizumab Tecentriq PD-L1 SP142 Ventana Ultra/Optiview Durvalumab PD-L1 SP263 Ventana Ultra/Optiview Defn + (tumor cells unless noted) 5% complementary diagnostic Strong= >50% Weak= 1-49% Tumor (1,5,50%) Immune (1, 5, 10%) Avelumab PD-L1 Dako? Kerr & Hirsch Arch Pathol Lab Med.2016;140:326 31; Kerr et al. J Thorac Oncol.2015;10: ; Ilie et al. Virchows Arch. 2016;468: %
60 Virchows Arch 2016;468:
61 Ilie et al. Virchows Arch 2016;468: CA & immune cells + CA neg; immune cells +
62 Ilie et al. Virchows Arch 2016;468:
63 PD-(L)1 assays: issues Pre-analytic Ischemic time Fixation type (cytology, FFPE) Triage of small tissue for dx, ALK, ROS, molecular, etc. Which, if any, assay for your lab? Tumor heterogeneity Spatial: small bx Temporal: primary vs. met,?retest VALIDATION/VERIFICATION Predictive marker Controls Normal tonsil, placenta Interpretation, reporting Training Must list assay details Score tumor vs. lymphs? Semi-quantitation (%) And overall pos/neg per kit Proficiency testing?digital analysis LDT regulation? Future: drug combinations Payment for unmatched drugtests? Malpractice?
64 Complexities in Personalized Medicine: Harmonizing Companion Diagnostics Across a Class of Targeted Therapies FDA-AACR-ASCO sponsored conference March, 2015 Blueprint project to evaluate comparability of PD-L1 assays (technical equivalence) The goal of this proposal is to agree and deliver, via cross industry collaboration, a package of information /data upon which analytic comparison of the various diagnostic assays may be conducted, potentially paving the way for post-market standardization and/or practice guideline development as appropriate. reduction to a single assay is considered to be neither feasible nor beneficial for the market
65 PD-(L)1 IHC, new reality or fad: Other biomarkers? PD-L2 inhibitors? Other checkpoints? IFN-gamma expression? Tumor infiltrating lymphocytes Morphologic or IHC Mutation burden: neoantigens (MMR-d colon, smoking-lung) Lung: EGFR or KRAS mutation Immune gene signatures (mrna) Change in peripheral lymphocyte counts during Rx Neoantigen specific circulating T-cells CTC s with high PD-L1?
66 Scholl et al. Arch Pathol Lab Med. 2016;140: Pathologists must take the lead in the rational incorporation of these biomarkers into clinical practice. It is imperative that concerned pathology societies gather their experts, consider feasible approaches to addressing these growing logistical and economic challenges, and begin to develop guidelines to inform pathology practice and, ultimately, influence trends in oncology.
67 Lymphocytes and the breast Inflammation in the breast may be associated with systemic or treatable conditions (CNGM) Consider occult carcinoma TILs in breast cancer: stay tuned Immune checkpoint inhibitors are here to stay irae s are becoming characterized, biopsied PD-L1 assays are a mess
68 Selected References Salgado et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group Annals of Oncology 26: , 2015 Clemens et al. Complete Surgical Excision Is Essential for the Management of Patients With Breast Implant-Associated Anaplastic Large-Cell Lymphoma. J Clin Oncol 2016;34: Postow et al. Immune Checkpoint Blockade in Cancer Therapy. J Clin Oncol. 33: , Borczuk & Allen. PD-L1 and Lung Cancer: The Era of Precision-ish Medicine?Arch Pathol Lab Med. doi: /arpa SA Kerr & Hirsch Programmed Death Ligand-1 Immunohistochemistry: Friend or Foe? Arch Pathol Lab Med. doi: /arpa SA See also on-slide citations
69 End
Inflammatory and Reactive Lesions of the Breast
Inflammatory and Reactive Lesions of the Breast Laura C. Collins, M.D. Vice Chair of Anatomic Pathology Professor of Pathology Beth Israel Deaconess Medical Center and Harvard Medical School Boston, MA
Predictive Biomarkers for Pembrolizumab. Eric H. Rubin, M.D.
Predictive Biomarkers for Pembrolizumab Eric H. Rubin, M.D. PD-1 and PD-L1/L2 Pathway PD-1 is an immune checkpoint receptor Binding of PD-1 by its ligands PD-L1 or PD-L2 leads to downregulation of T-cell
PD-L1 and Immunotherapy of GI cancers: What do you need to know
None. PD-L1 and Immunotherapy of GI cancers: What do you need to know Rondell P. Graham September 3, 2017 2017 MFMER slide-2 Disclosure No conflicts of interest to disclose 2017 MFMER slide-3 Objectives
Emerging Tissue and Serum Markers
Emerging Tissue and Serum Markers for Immune Checkpoint Inhibitors Kyong Hwa Park MD, PhD Medical Oncology Korea University College of Medicine Contents Immune checkpoint inhibitors in clinical practice
Vernieuwing en diagnostiek bij NSCLC: Immunotherapy: PD-L1 analyse: waar staan we
9e avondsymposium: "Nieuwe ontwikkelingen in de behandeling van NSCLC" 9 november 2016, UMCG Vernieuwing en diagnostiek bij NSCLC: Immunotherapy: PD-L1 analyse: waar staan we Wim Timens Professor and Chair
Role of the Pathologist in Guiding Immuno-oncological Therapies. Scott Rodig MD, PhD
Role of the Pathologist in Guiding Immuno-oncological Therapies Scott Rodig MD, PhD Department of Pathology, Brigham & Women s Hospital Center for Immuno-Oncology, Dana-Farber Cancer Institute Associate
Predictive markers for treatment with Immune checkpoint inhibitors - PD-L1 et al -
Predictive markers for treatment with Immune checkpoint inhibitors - PD-L1 et al - Lukas Bubendorf Pathology Improved overall survival as a result of combination therapy Predictive biomarkers for the treatment
El contexto molecular de la sobreexpresión de PD-L1 Esther Conde Gallego, MD, PhD
El contexto molecular de la sobreexpresión de PD-L1 Esther Conde Gallego, MD, PhD Laboratorio de Dianas Terapéuticas Hospital Universitario HM Sanchinarro Madrid, Spain Contents Background PD-L1 expression
Immunotherapy in NSCLC Pathologist role
Immunotherapy in NSCLC Pathologist role Pimpin Incharoen, M.D. Assistant Professor, Thoracic Pathology Department of Pathology, Ramathibodi Hospital Genetic alterations in NSCLC Khono et al, Trans Lung
International Society of Breast Pathology. Immune Targeting in Breast Cancer. USCAP 2017 Annual Meeting
International Society of Breast Pathology USCAP 2017 Annual Meeting Immune Targeting in Breast Cancer Ashley Cimino-Mathews, MD Assistant Professor of Pathology and Oncology The Johns Hopkins Hospital
Advances in Pathology and molecular biology of lung cancer. Lukas Bubendorf Pathologie
Advances in Pathology and molecular biology of lung cancer Lukas Bubendorf Pathologie Agenda The revolution of predictive markers Liquid biopsies PD-L1 Molecular subtypes (non-squamous NSCLC) Tsao AS et
Immunotherapie: algemene principes
Immunotherapie: algemene principes Prof. dr. Evelien Smits Tumorimmunologie, UAntwerpen 14 Oktober 2017, IKG evelien.smits@uza.be Concept of immune evasion Finn O. J. Ann Oncol. 2012 Sep; 23(Suppl 8):
Reflex Testing Guidelines for Immunotherapy in Non-Small Cell Lung Cancer
Reflex Testing Guidelines for Immunotherapy in Non-Small Cell Lung Cancer Jimmy Ruiz, MD Assistant Professor Thoracic Oncology Program Wake Forest Comprehensive Cancer Center Disclosures I have no actual
Biomarcatori per la immunoterapia: cosa e come cercare Paolo Graziano
Biomarcatori per la immunoterapia: cosa e come cercare Paolo Graziano Unit of Pathology Fondazione IRCCS Casa Sollievo della Sofferenza San Giovanni Rotondo, Foggia,Italy p.graziano@operapadrepio.it Disclosure
Cancer Immunotherapy Survey
CHAPTER 8: Cancer Immunotherapy Survey All (N=100) Please classify your organization. Academic lab or center Small biopharmaceutical company Top 20 Pharma Mid-size pharma Diagnostics company Other (please
Updates in Immunotherapy for Urothelial Carcinoma
Updates in Immunotherapy for Urothelial Carcinoma Andrew J Armstrong MD ScM FACP DUA 2018 Copyright 2006 SciMed. Talk Outline Immunotherapy progress in 2017: 5 new approved PD-1/PD-L1 inhibitory agents
Review of NEO Testing Platforms. Lawrence M. Weiss, MD Medical Director, Aliso Viejo
Review of NEO Testing Platforms Lawrence M. Weiss, MD Medical Director, Aliso Viejo Lawrence Weiss, M.D. Medical Director, Aliso Viejo Dr. Weiss currently serves as NeoGenomics Medical Director, Aliso
ORIEN NOVA TEAM SCIENCE AWARD
ORIEN NOVA TEAM SCIENCE AWARD CALL FOR LETTERS OF INTENT BACKGROUND: The Oncology Research Information Exchange Network (ORIEN) is a unique alliance to integrate data sharing and collaborative learning
Molecular Testing Updates. Karen Rasmussen, PhD, FACMG Clinical Molecular Genetics Spectrum Medical Group, Pathology Division Portland, Maine
Molecular Testing Updates Karen Rasmussen, PhD, FACMG Clinical Molecular Genetics Spectrum Medical Group, Pathology Division Portland, Maine Keeping Up with Predictive Molecular Testing in Oncology: Technical
IMMUNOTHERAPY FOR LUNG CANCER
IMMUNOTHERAPY FOR LUNG CANCER Patient and Caregiver Guide IMMUNOTHERAPY FOR LUNG CANCER Patient and Caregiver Guide TABLE OF CONTENTS Lung Cancer Basics... 2 Immunotherapy... 3 FDA Approved Immunotherapies...
PD-L1 Expression, Role, and Significance in Lung Pathology. Ross A Miller, MD FACP FASCP
PD-L1 Expression, Role, and Significance in Lung Pathology Ross A Miller, MD FACP FASCP Background information PD-1 and PD-L1 expression in tissues PD-L1 Ligand to PD-1 (PD-1 on T cells) Rarely expressed
Case year old Chinese female. Radiological echo-distortion in the right breast at o clock. Core biopsy of the o clock lesion.
Case 3 64 year old Chinese female. Radiological echo-distortion in the right breast at 10-12 o clock. Core biopsy of the 11-12 o clock lesion. Division of Pathology Courtesty of Dr Lester Leong ill-defined,
SIGNIFICANT OTHERS. Miscellaneous Benign Breast Conditions
SIGNIFICANT OTHERS Miscellaneous Benign Breast Conditions Epworth HealthCare 1 FAT NECROSIS TRAUMATIC Cell rupture Seat-Belt injury Blunt trauma Iatrogenic injury Surgery, Flaps, Radiotherapy Pathology
Breast cancer: Molecular STAGING classification and testing. Korourian A : AP,CP ; MD,PHD(Molecular medicine)
Breast cancer: Molecular STAGING classification and testing Korourian A : AP,CP ; MD,PHD(Molecular medicine) Breast Cancer Theory: Halsted Operative breast cancer is a local-regional disease The positive
04/09/2018. Salivary Gland Pathology in the Molecular Era Old Friends, Old Foes, & New Acquaintances
Salivary Gland Pathology in the Molecular Era Old Friends, Old Foes, & New Acquaintances Jennifer L. Hunt, MD, MEd Aubrey J. Hough Jr, MD, Endowed Professor of Pathology Chair of Pathology and Laboratory
2018 KSMO Immune Oncology Forum. Immune checkpoint inhibitors in hematologic. malignancies: evidences and perspectives 서울아산병원종양내과 홍정용
2018 KSMO Immune Oncology Forum Immune checkpoint inhibitors in hematologic malignancies: evidences and perspectives 서울아산병원종양내과 홍정용 2018-07-18 Contents Introduction Immune checkpoint inhibtors in lymphomas
News from ASCO. Niven Mehra, Medical Oncologist. Radboud UMC Institute of Cancer Research and The Royal Marsden Hospital
News from ASCO Niven Mehra, Medical Oncologist Radboud UMC Institute of Cancer Research and The Royal Marsden Hospital Disclosures Speaker fees: Merck, Bayer Advisory boards: Janssen-Cilag Research and
From Morphology to Molecular Pathology: A Practical Approach for Cytopathologists Part 1-Cytomorphology. Songlin Zhang, MD, PhD LSUHSC-Shreveport
From Morphology to Molecular Pathology: A Practical Approach for Cytopathologists Part 1-Cytomorphology Songlin Zhang, MD, PhD LSUHSC-Shreveport I have no Conflict of Interest. FNA on Lymphoproliferative
Agilent companion diagnostics for cancer immunotherapy
Agilent companion diagnostics for cancer immunotherapy Annika Eklund, PhD Global Product Manager Companion Diagnostics Agilent Technologies Aalborg 1 Agilent Trusted Answers. Together OUR FOCUS life sciences,
Immune Checkpoint Inhibitors: The New Breakout Stars in Cancer Treatment
Immune Checkpoint Inhibitors: The New Breakout Stars in Cancer Treatment 1 Introductions Peter Langecker, MD, PhD Executive Medical Director, Global Oncology Clinipace Worldwide Mark Shapiro Vice President
Benign Mimics of Malignancy in Breast Pathology
Arthur Purdy Stout Society of Surgical Pathologists Companion Meeting Benign Mimics of Malignancy in Breast Pathology Stuart J. Schnitt, M.D. Beth Israel Deaconess Medical Center and Harvard Medical School,
Immunotherapy in breast cancer. Carmen Criscitiello, MD, PhD European Institute of Oncology Milan, Italy
Immunotherapy in breast cancer Carmen Criscitiello, MD, PhD European Institute of Oncology Milan, Italy Outline Rational for immune-based therapy in breast cancer Immunogenic chemotherapy Targeting immune
PAAF vs Core Biopsy en Lesiones Mamarias Case #1
5/19/2014 PAAF vs Core Biopsy en Lesiones Mamarias Case #1 Fine Needle Aspiration Cytology of Breast: Correlation with Needle Core Biopsy 64-year-old woman Mass in breast Syed Hoda, MD CD31 Post-Radiation
Contents. vii. Preface... Acknowledgments... v xiii
Contents Preface... Acknowledgments... v xiii SECTION I 1. Introduction... 3 Knowledge-Based Diagnosis... 4 Systematic Examination of the Lymph Node... 7 Cell Type Identification... 9 Cell Size and Cellularity...
Methotrexate-associated Lymphoproliferative Disorders
Methotrexate-associated Lymphoproliferative Disorders Definition A lymphoid proliferation or lymphoma in a patient immunosuppressed with methotrexate, typically for treatment of autoimmune disease (rheumatoid
Carcinoma Urotelial: La Célula Inflamatoria Clave en la Inmunoterapia Fernando López-Ríos
Carcinoma Urotelial: La Célula Inflamatoria Clave en la Inmunoterapia Fernando López-Ríos Laboratorio de Dianas Terapéuticas Hospital Universitario HM Sanchinarro Madrid, Spain Contents Background Immunotherapy
Triple Negative Breast Cancer
Triple Negative Breast Cancer Prof. Dr. Pornchai O-charoenrat Division of Head-Neck & Breast Surgery Department of Surgery Faculty of Medicine Siriraj Hospital Breast Cancer Classification Traditional
Question 1 A. ER-, PR-, HER+ B. ER+, PR+, HER2- C. ER-, PR+, HER2- D. ER-, PR-, HER2- E. ER-, PR+, HER2+
Triple Negative Breast Cancer Laura C. Collins, M.D. Department of Pathology Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA Question 1 The tumor depicted on the next slide
The Role of Immuno-Oncology Biomarkers in Lung Cancer
The Role of Immuno-Oncology Biomarkers in Lung Cancer Vamsidhar Velcheti, MD, FACP Staff Physician, Associate Director Center for Immuno-Oncology Research Taussig Cancer Institute Cleveland Clinic November
Immuno-Oncology Clinical Trials Update: Therapeutic Anti-Cancer Vaccines Issue 7 April 2017
Delivering a Competitive Intelligence Advantage Immuno-Oncology Clinical Trials Update: Therapeutic Anti-Cancer Vaccines Issue 7 April 2017 Immuno-Oncology CLINICAL TRIALS UPDATE The goal of this MONTHLY
Immunotherapy for Breast Cancer Clinical Development
Immunotherapy for Breast Cancer Clinical Development Laurence Buisseret, MD, PhD Breast Cancer Translational Research Laboratory Institut Jules Bordet Université Libre de Bruxelles (ULB) ESMO preceptorship
Tumor Immunity and Immunotherapy. Andrew Lichtman M.D., Ph.D. Brigham and Women s Hospital Harvard Medical School
Tumor Immunity and Immunotherapy Andrew Lichtman M.D., Ph.D. Brigham and Women s Hospital Harvard Medical School Lecture Outline Evidence for tumor immunity Types of tumor antigens Generation of anti-tumor
O DESAFIO DA INOVAÇÃO EM ONCOLOGIA EM PORTUGAL The Challenges of innovative oncology care in Portugal. Gabriela Sousa Oncologia Médica IPO Coimbra
O DESAFIO DA INOVAÇÃO EM ONCOLOGIA EM PORTUGAL The Challenges of innovative oncology care in Portugal Gabriela Sousa Oncologia Médica IPO Coimbra Incidência aumenta 3% ao ano Envelhecimento populacional
Contemporary Classification of Breast Cancer
Contemporary Classification of Breast Cancer Laura C. Collins, M.D. Vice Chair of Anatomic Pathology Professor of Pathology Beth Israel Deaconess Medical Center and Harvard Medical School Boston, MA Outline
Papillary Lesions of the Breast A Practical Approach to Diagnosis. (Arch Pathol Lab Med. 2016;140: ; doi: /arpa.
Papillary Lesions of the Breast A Practical Approach to Diagnosis (Arch Pathol Lab Med. 2016;140:1052 1059; doi: 10.5858/arpa.2016-0219-RA) Papillary lesions of the breast Span the spectrum of benign,
Combination Immunotherapy Approaches Chemotherapy, Radiation Therapy, and Dual Checkpoint Therapy
Combination Immunotherapy Approaches Chemotherapy, Radiation Therapy, and Dual Checkpoint Therapy Dr. David B. Page Providence Portland Medical Center Earle A. Chiles Research Institute Funding & Disclosures
Companion & Complementary Diagnostics: Clinical and Regulatory Perspectives
Companion & Complementary Diagnostics: Clinical and Regulatory Perspectives Workshop on Companion Diagnostics January 31, 2017 Jan Trøst Jørgensen, M.Sc.Pharm., Ph.D. Dx-Rx Institute Fredensborg, Denmark
Overview of Biomarker Development for Immune PD-1/L1 Checkpoint Blockade
Overview of Biomarker Development for Immune PD-1/L1 Checkpoint Blockade David L. Rimm MD-PhD Professor Departments of Pathology and Medicine (Oncology) Director, Yale Pathology Tissue Services Disclosures
Highlights from AACR 2015: The Emerging Potential of Immunotherapeutic Approaches in Non-Small Cell Lung Cancer
Transcript Details This is a transcript of a continuing medical education (CME) activity accessible on the ReachMD network. Additional media formats for the activity and full activity details (including
Merck Oncology Overview. The Development of MSI-H Cancer Therapy. Development of Anti-Cancer Drugs Forum Tokyo, Japan, 18, February 2017
Merck Oncology Overview The Development of MSI-H Cancer Therapy Development of Anti-Cancer Drugs Forum Tokyo, Japan, 18, February 217 Andrew Joe, MD Executive Director, Late Stage Oncology Merck & Co.,
Checkpoint Regulators Cancer Immunotherapy takes centre stage. Dr Oliver Klein Department of Medical Oncology 02 May 2015
Checkpoint Regulators Cancer Immunotherapy takes centre stage Dr Oliver Klein Department of Medical Oncology 02 May 2015 Adjuvant chemotherapy improves outcome in early breast cancer FDA approval of Imatinib
Evolution of Pathology
1 Traditional pathology Molecular pathology 2 Evolution of Pathology Gross Pathology Cellular Pathology Morphologic Pathology Molecular/Predictive Pathology Antonio Benivieni (1443-1502): First autopsy
NSCLC. Harmonization study 1. Lung cancer and other malignancies -PD-L1 assay, QuIP EQA
Lung cancer and other malignancies -PD-L1 assay, QuIP EQA Korinna Jöhrens Institute for pathology Carl Gustav Cars Universitätsklinikum Dresden, Germany Medical consultant QuIP 11.05.2018 NSCLC Harmonization
Oncologist-induced Disease of the GI tract: New Developments
Oncologist-induced Disease of the GI tract: New Developments Jeffrey D Goldsmith, MD Children s Hospital Boston, Beth Israel Deaconess Medical Center, Harvard Medical School Boston, MA Everyone s on drugs
Immunotherapy in Colorectal cancer
Immunotherapy in Colorectal cancer Ahmed Zakari, MD Associate Professor University of Central Florida, College of Medicine Medical Director, Gastro Intestinal Cancer Program Florida Hospital Cancer Institute
Hepatic Lymphoma Diagnosis An Algorithmic Approach
Hepatic Lymphoma Diagnosis An Algorithmic Approach Ryan M. Gill, M.D., Ph.D. University of California, San Francisco PLEASE TURN OFF YOUR CELL PHONES Disclosure of Relevant Financial Relationships USCAP
DETERMINATION OF A LYMPHOID PROCESS
Chapter 2 Applications of Touch Preparation Cytology to Intraoperative Consultations: Lymph Nodes and Extranodal Tissues for Evaluation of Hematolymphoid Disorders INTRODUCTION As discussed in Chap. 1,
Immunopathology of Lymphoma
Immunopathology of Lymphoma Noraidah Masir MBBCh, M.Med (Pathology), D.Phil. Department of Pathology Faculty of Medicine Universiti Kebangsaan Malaysia Lymphoma classification has been challenging to pathologists.
Evening specialty conference: Liver
Evening specialty conference: Liver Joseph Misdraji, M.D. Disclosure of Relevant Financial Relationships Disclosure of Relevant Financial Relationships USCAP requires that all planners (Education Committee)
Product Introduction
Product Introduction Product Codes: HCL026, HCL027 and HCL028 Contents Introduction to HER2 2 HER2 immunohistochemistry 3 Cell lines as controls 5 HER2 Analyte Control DR IHC 7 HER2 Analyte Control DR
The PD-1 pathway of T cell exhaustion
The PD-1 pathway of T cell exhaustion SAMO 18.3.2016 Overview T cell exhaustion Biology of PD-1 Mechanism Ligands expressed on tumor cell and on non-tumor cells other receptor pairs Biomarkers for apd-1/pd-l1
Patient Selection: The Search for Immunotherapy Biomarkers
Patient Selection: The Search for Immunotherapy Biomarkers Mark A. Socinski, MD Executive Medical Director Florida Hospital Cancer Institute Orlando, Florida Patient Selection Clinical smoking status Histologic
Getting the Whole Picture for Immuno-Oncology Therapies
Joseph Krueger, Chief Scientific Officer, Flagship Biosciences, Inc. Getting the Whole Picture for Immuno-Oncology Therapies Key concepts: Immuno-oncology (IO) therapies have changed the way we think about
immunotherapy a guide for the patient
immunotherapy FOR LUNG CANCER a guide for the patient TABLE OF CONTENTS lung cancer basics... 2 immunotherapy... 5 Checkpoint Inhibitors... 6-9 Monoclonal Antibodies... 9 Vaccines... 10 Adoptive T-Cell
PD-L1 Analyte Control DR
Quality in Control PD-L1 Analyte Control DR PD-L1_PI_v2 Product Codes: HCL019, HCL020 and HCL021 Contents PD-L1 Analyte Control DR 2 What is PD-L1? 3 The Role of PD-L1 in Cancer 3 PD-L1 Assessment 4 PD-L1
Defined lymphoma entities in the current WHO classification
Defined lymphoma entities in the current WHO classification Luca Mazzucchelli Istituto cantonale di patologia, Locarno Bellinzona, January 29-31, 2016 Evolution of lymphoma classification Rappaport Lukes
Disclosures 5/27/2012. Outline of Talk. Outline of Talk. When Is LCIS Clinically Significant? Classic LCIS. Classic LCIS
When Is LCIS Clinically Significant? Disclosures I have nothing to disclose Yunn-Yi Chen, MD, PhD Professor Outline of Talk Outline of Talk Classic LCIS Classic LCIS Definition of lobular differentiation
Applications of IHC. Determination of the primary site in metastatic tumors of unknown origin
Applications of IHC Determination of the primary site in metastatic tumors of unknown origin Classification of tumors that appear 'undifferentiated' by standard light microscopy Precise classification
Novel RCC Targets from Immuno-Oncology and Antibody-Drug Conjugates
Novel RCC Targets from Immuno-Oncology and Antibody-Drug Conjugates Christopher Turner, MD Vice President, Clinical Science 04 November 2016 Uveal Melanoma Celldex Pipeline CANDIDATE INDICATION Preclinical
Post Neoadjuvant therapy: issues in interpretation
Post Neoadjuvant therapy: issues in interpretation Disclosure: Overview D Prognostic features in assessment of post treatment specimens: Tumor size Cellularity Grade Receptors LN Neoadjuvant chemotherapy:
Interpretation of Breast Pathology in the Era of Minimally Invasive Procedures
Shahla Masood, M.D. Professor and Chair Department of Pathology and Laboratory Medicine University of Florida College of Medicine Jacksonville Medical Director, UF Health Breast Center Chief of Pathology
Renal Cell Carcinoma: Systemic Therapy Progress and Promise
Renal Cell Carcinoma: Systemic Therapy Progress and Promise Michael B. Atkins, M.D. Deputy Director, Lombardi Comprehensive Cancer Ctr Georgetown University Medical Center Everolimus Rini, Campbell, Escudier.
MICROSCOPY PREDICTIVE PROFILING
Immunomodulatory therapy in NSCLC: a year into clinical practice Professor J R Gosney Consultant Thoracic Pathologist Royal Liverpool University Hospital Disclosure JRG is a paid advisor to and speaker
HODGKIN LYMPHOMA DR. ALEJANDRA ZARATE OSORNO HOSPITAL ESPAÑOL DE MEXICO
HODGKIN LYMPHOMA DR. ALEJANDRA ZARATE OSORNO HOSPITAL ESPAÑOL DE MEXICO HODGKIN LYMPHOMA CLASSIFICATION Lukes & Butler Rye WHO-2016 Linphocytic and/or histiocytic Nodular & diffuse Nodular Sclerosis Lymphocyte
Diseases of the breast (1 of 2)
Diseases of the breast (1 of 2) Introduction A histology introduction Normal ducts and lobules of the breast are lined by two layers of cells a layer of luminal cells overlying a second layer of myoepithelial
Immunotherapies for Advanced NSCLC: Current State of the Field. H. Jack West Swedish Cancer Institute Seattle, Washington
Immunotherapies for Advanced NSCLC: Current State of the Field H. Jack West Swedish Cancer Institute Seattle, Washington Nivolumab in Squamous NSCLC Chemo-pretreated (1 st line) Adv squamous NSCLC N =
Interpreting Therapeutic Response on Immune Cell Number and Spatial Distribution within the Tumor Microenvironment. Lorcan Sherry, CSO OracleBio
Interpreting Therapeutic Response on Immune Cell Number and Spatial Distribution within the Tumor Microenvironment Lorcan Sherry, CSO OracleBio Company Overview OracleBio is a specialised CRO providing
Surgical Pathology Issues of Practical Importance
Surgical Pathology Issues of Practical Importance Anne Moore, MD Medical Oncology Syed Hoda, MD Surgical Pathology The pathologist is central to the team approach needed to manage the patient with breast
Cancer Immunotherapy Patient Forum. for the Treatment of Melanoma, Leukemia, Lymphoma, Lung and Genitourinary Cancers - November 7, 2015
Cancer Immunotherapy Patient Forum for the Treatment of Melanoma, Leukemia, Lymphoma, Lung and Genitourinary Cancers - November 7, 2015 Biomarkers and Patient Selection Julie R. Brahmer, M.D. Director
Mariano Provencio Servicio de Oncología Médica Hospital Universitario Puerta de Hierro. Immune checkpoint inhibition in DLBCL
Mariano Provencio Servicio de Oncología Médica Hospital Universitario Puerta de Hierro Immune checkpoint inhibition in DLBCL Immunotherapy: The Cure is Inside Us Our immune system prevents or limit infections
Assessment Run C1 2017
Assessment Run C1 2017 PD-L1 The first assessment in this new NordiQC Companion module C1 focused on the accuracy of the PD-L1 IHC assays performed by the participating laboratories to identify patients
Case Scenario 1: Thyroid
Case Scenario 1: Thyroid History and Physical Patient is an otherwise healthy 80 year old female with the complaint of a neck mass first noticed two weeks ago. The mass has increased in size and is palpable.
Breast implant-associated anaplastic large cell lymphoma. (BIA-ALCL): a collaborative effort for diagnosis and treatment
Case Report Page 1 of 5 Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL): a collaborative effort for diagnosis and treatment Kerry E. Fine, Matthew Wi, Della C. Bennett Department of
Invasive Papillary Breast Carcinoma
410 This is an Open Access article licensed under the terms of the Creative Commons Attribution- NonCommercial-NoDerivs 3.0 License (www.karger.com/oa-license), applicable to the online version of the
Role of the pathologist in the diagnosis and mutational analysis of lung cancer Professor J R Gosney
Role of the pathologist in the diagnosis and mutational analysis of lung cancer Professor J R Gosney Consultant Thoracic Pathologist Royal Liverpool University Hospital Disclosure JRG is a paid advisor
Benign, Reactive and Inflammatory Lesions of the Breast
Benign, Reactive and Inflammatory Lesions of the Breast Marilin Rosa, MD Associate Member Section Head of Breast Pathology Department of Anatomic Pathology Program Director, Breast Pathology Fellowship
ACCME/Disclosures. Diagnosing Mesothelioma in Limited Tissue Samples. Papanicolaou Society of Cytopathology Companion Meeting March 12 th, 2016
Diagnosing Mesothelioma in Limited Tissue Samples Papanicolaou Society of Cytopathology Companion Meeting March 12 th, 2016 Sanja Dacic, MD, PhD University of Pittsburgh ACCME/Disclosures GENERAL RULES
Papillary Lesions of the breast
Papillary Lesions of the breast Emad Rakha Professor of Breast Pathology The University of Nottingham Papillary lesions of the breast are a heterogeneous group of disease, which are characterised by neoplastic
TOTALS 30. Preliminary analysis of NNDEQA 004 (May 2013 TSL workshops) 1) 70 year old female with focal irregularity in the right breast.
-- Preliminary analysis of NNDEQA 00 (May 0 TSL workshops) ) 70 year old female with focal irregularity in the right breast. Fat necrosis (with organising thrombus/foreign body granuloma/surgical site
Problems in staging breast carcinoma
Problems in staging breast carcinoma Primary systemic therapy (PST) of breast carcinoma pathologists tasks Dr. Janina Kulka, 2nd Department of Pathology, Semmelweis University Budapest Austro-Hungarian
ACCME/Disclosures ALK FUSION-POSITIVE MESENCHYMAL TUMORS. Tumor types with ALK rearrangements. Anaplastic Lymphoma Kinase. Jason L.
Companion Meeting of the International Society of Bone and Soft Tissue Pathology The Evolving Concept of Mesenchymal Tumors ALK FUSION-POSITIVE MESENCHYMAL TUMORS Jason L. Hornick, MD, PhD March 13, 2016
Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment with Targeted Tyrosine Kinase Inhibitors
Q: How is the strength of recommendation determined in the new molecular testing guideline? A: The strength of recommendation is determined by the strength of the available data (evidence). Strong Recommendation:
3/24/2017 DENDRITIC CELL NEOPLASMS: HISTOLOGY, IMMUNOHISTOCHEMISTRY, AND MOLECULAR GENETICS. Disclosure of Relevant Financial Relationships
DENDRITIC CELL NEOPLASMS: HISTOLOGY, IMMUNOHISTOCHEMISTRY, AND MOLECULAR GENETICS Jason L. Hornick, M.D., Ph.D. Director of Surgical Pathology and Immunohistochemistry Brigham and Women s Hospital Professor
Is Prostate Cancer Amenable to Immunotherapy Approaches? New Frontiers in Urologic Oncology, September 12, 2015
Is Prostate Cancer Amenable to Immunotherapy Approaches? New Frontiers in Urologic Oncology, September 12, 2015 J. J. Mulé Associate Center Director, Translational Research U.S. Senator Connie Mack & Family
ESMO PRECEPTORSHIP IN IMMUNO-ONCOLOGY
ESMO PRECEPTORSHIP IN IMMUNO-ONCOLOGY LUGANO, MAY 4-5, 2018 Clinical development in ovarian cancer C. Sessa, CH CONTENT Rationale for immunotherapy in ovarian cancer Clinical data with single agent immune
ULTIMATE GBG 95 UC-0140/1606 BIG UnLock The IMmune cells ATtraction in ER+ breast cancer
ULTIMATE GBG 95 UC-0140/1606 BIG 16-01 UnLock The IMmune cells ATtraction in ER+ breast cancer A PHASE II TRIAL TESTING DURVALUMAB COMBINED WITH ENDOCRINE THERAPY IN PATIENTS WITH ER+/HER2- BREAST CANCER
Gábor CSERNI. 1. Bács-Kiskun County Teaching Hospital, Kecskemét 2. University of Szeged, Szeged
Lymphocytes infiltrant la tumeur (TIL) sur micro-biopsies et pièces opératoires Quel impact clinique? Quels moyens de mise en évidence? Comment restituer les résultats? TILs - Clinical impact / Evaluation
10/15/2012. Biologic Subtypes of TNBC. Topics. Topics. Histopathology Molecular pathology Clinical relevance
Biologic Subtypes of TNBC Andrea L. Richardson M.D. Ph.D. Brigham and Women s Hospital Dana-Farber Cancer Institute Harvard Medical School Boston, MA Topics Histopathology Molecular pathology Clinical
Lymphoma: What You Need to Know. Richard van der Jagt MD, FRCPC
Lymphoma: What You Need to Know Richard van der Jagt MD, FRCPC Overview Concepts, classification, biology Epidemiology Clinical presentation Diagnosis Staging Three important types of lymphoma Conceptualizing
LYMPHATIC DRAINAGE AXILLARY (MOSTLY) INTERNAL MAMMARY SUPRACLAVICULAR
BREAST LYMPHATIC DRAINAGE AXILLARY (MOSTLY) INTERNAL MAMMARY SUPRACLAVICULAR HISTOLOGY LOBE: (10 in whole breast) LOBULE: (many per lobe) ACINUS/I, aka ALVEOLUS/I: (many per lobule) DUCT(S): INTRA- or