11/8/2018 DISCLOSURES. I have NO Conflicts of Interest to Disclose. UTILTY OF DETECTING PATTERNS

Transcription

1 Bharat N. Nathwani, M.D. City of Hope Medical Center Professor, Director of Pathology Consultation Services, 1500 East Duarte Road, Duarte, California, DISCLOSURES I have NO Conflicts of Interest to Disclose. bharat.nathwani@gmail.com UTILTY OF DETECTING PATTERNS The Fundamental Necessity for Accurately Detecting Patterns Since ALL diseases start focally, overall, the nodal architecture is PRESERVED. Thus, all nodal compartments have to be examined carefully to accurately detect abnormalities (Patterns of different types). All patterns have histologic spectrum, & multiple patterns coexist in 40% of cases. Diagnostic strategies & skills must be developed to search, locate, discover, unearth, & label Patterns accurately. These take time, energy, sustained effort. To accurately detect patterns, imprinting of images in mind will occur if seen >50 times critically. Every Pattern has a differential diagnosis of benign diseases & lymphomas. Immunostains are very useful to unmask patterns. Also, IHC are necessary to detect In Situ Neoplasia, Early Stages, & many other types of lymphoma. Caution: IHC lack specificity, sensitivity, & aberrant phenotypes are present. Also, lack of hematoxylin counterstain prevents visualization of nuclear details. HE slides & histology are still most important as a first diagnostic step. Formation of Patterns Patterns are formed in a preexisting lymph node that can be: unstimulated, stimulated without distortion of the architecture or that has mild or marked or effaced architecture, or combination. Architectural changes always occur within the nodal compartments. The nodal compartments are: pericapsular, capsule, sinuses, germinal centers, mantle zones, marginal zones, interfollicular & medullary. One or more of these nodal compartments display a spectrum of different types of histological changes that have to be distinguished from each other to make accurate diagnosis. The architectural changes detected are labelled as PATTERNS (21). Also, to distinguish patterns of different types requires knowledge about the methods required to distinguish them & practicing these methods, which is a slowly acquired diagnostic skill. METHODICAL APPROACH FOR IDENTIFYING SPHERICAL STRUCTURES 1.Morphology: A. Layers or compartments 1. Number: 1, 2, or 3 2. Arrangement: normal, inverse, intermingling of cells/layers 3. Expansion: follicle center, mantle cell, marginal zone &/or interfollicular B. Cytology in each layer: centrocytes, centroblasts, mantle cells, marginal zone cells, small lymphocytes, prolymphocytes, plasma cells, transformed cells, FDRCs 2.Immunohistochemical staining in each layer 3.Molecular biology: translocations & trisomies 1

2 Spherical Structures (Patterns) Non spherical Patterns One Layer Normal Inverse Two Layers Lighter color inside Darker color outside Darker color inside Lighter color outside Three Layers FCC Mantle Cell Marginal Zone 1.Follicular 2. Mantle zone 3. Marginal zone 4. Mantle cell nodules 5. Marginal zone nodules 6. Follicular colonization 7. Inverse follicular 8. Progressively transformed GC 9. L&H nodules 10. Proliferation centers 11. Paracortical nodular T zone hyperplasia 12. Fibrous nodular 13. Multiple (Specify) 13. Sinus 14. Interfollicular 15. Lennert 16. Mottling 17. Vascular 18. Necrosis 19. Diffuse 20. Starry Sky in Nonfollicular Areas 21. Multiple (Specify) Accurate identification & quantification of these patterns permits formation of a precise differential diagnosis Each Pattern has a list of Differential Diagnosis ONE EXAMPLE: Differential Diagnosis of Marginal zone/inverse Follicular Patterns* Benign B Lymphomas T Lymphomas Other Spleen Peyer s Patches Mesenteric Node SLL/CLL Mantle Cell FL with Inverse follicular pattern Perifollicular, Intrafollicular Angioimmunoblastic T- cell Lymphoma (AITL) 1. Mastocytosis 2. Carcinomas Peripheral Node Monocytoid B-cell Hyperplasia Marginal zone B- cell Hyperplasia FL with MZB differentiation FL with MZB & Plasmacytic differentiation Atypical Autoimmune Lymphoproliferativ e Syndrome (ALPS) 2

3 Differential Diagnosis Marginal zone / Inverse Follicular Pattern UTILTY OF DETECTING PATTERNS Benign Spleen Peyer s Patches Mesenteric Node Peripheral Node Monocytoid B-cell Hyperplasia Marginal zone B- cell Hyperplasia B Lymphomas SLL/CLL Mantle Cell FL with Inverse follicular pattern FL with MZB differentiation FL with MZB & Plasmacytic differentiation T Lymphomas PTCL, Perifollicular Angioimmunoblastic T- cell Lymphoma (AITL) Other 1. Mastocytosis 2. Carcinomas Atypical Autoimmune Lymphoproliferativ e Syndrome (ALPS) Patterns that will be Shown Today Since the typical patterns present in tissues is well known, I will show slides from cases that have multiple patterns (13 Cases & 107 slides. This is done as an educational exercise. EXAMPLE: INVERSE FOLLICULAR PATTERN Malignant follicles showing centrocytes in the center surrounded by centroblasts at the periphery 3

4 CD20 CD2 0 CD23 bcl-6 CD23 bcl-6 CD23 CD23 CD10 bcl THREE LAYER SPHERICAL STRUCTURES: MARGINAL ZONE PATTERN FCC Mantle Cell Marginal Zone Diagnosis with Most Important Diagnostic Information Diagnosis: Marginal zone lymphoma with IgM kappa plasmacytic differentiation in the interfollicular areas & the germinal centers. Important features: Marginal zone & inverse follicular patterns. Marginal zone clear cells in interfollicular areas & within follicles. The plasmacytoid cells in interfollicular areas & within follicles. 4

5

6 31 Lambda Kappa Kappa Kappa 6

7 11/8/2018 Kappa Kappa EXAMPLE: SPHERICAL STRUCTURES WITH INTERMINGLING OF CELLS / LAYERS Paracortical nodular T-zone hyperplasia Kappa Lambda 7

8 11/8/2018 CD20 CD3 S100 Follicular Colonization By Marginal Zone B-cells and with Plasmacytic Differentiaton in Interfollicular areas S CD20 BCL-2 Kappa Kappa EXAMPLE: SPHERICAL STRUCTURES WITH INTERMINGLING OF CELLS / LAYERS Progressively transformed germinal centers (PTGC) without Hodgkin cells 8

9 EXAMPLE: SPHERICAL STRUCTURES WITH INTERMINGLING OF CELLS / LAYERS Progressively transformed germinal centers (PTGC) with Hodgkin cells EXAMPLE: SPHERICAL STRUCTURES WITH INTERMINGLING OF CELLS / LAYERS L&H nodules in Hodgkin lymphoma, lymphocyte predominance with an additional moth-eaten pattern produced by malignant cells 9

10 Spherical Patterns 1. Follicular 2. Mantle zone 3. Marginal zone 4. Mantle cell nodules 5. Marginal zone nodules 6. Follicular colonization 7. Inverse follicular 8. Progressively t f d GC Non-spherical Patterns 13. Sinus 14. Interfollicular 15. Lennert s 16. Mottling 17. Vascular 18. Necrosis 19. Diffuse 20. Starry-Sky in Nonfollicular Areas 21. Multiple (Specify) Accurate identification and quantification of these patterns permits formation of a precise differential diagnosis Pattern A: Classical B-cell Rich Nodular L&H NODULAR PATTERN Moth-eaten (pale) areas produced by: Transformed T- cells Popcorn cells Epithelioid cells Follicular dendritic cells Non- moth- eaten (dark) areas produced by: Small benign lymphocytesmantle cells (IgD+) T-cells (CD3+) 10

11 11/8/2018 CD20 CD20 CD3 CD3 CD21 IgD CD57 CD57 11

12 11/8/2018 CD4 CD4 CD8 CD8 CD4 CD4 CD8 CD8 Follicular Lymphoma with Marginal Zone B-cell Differrentiation and with Follicular Colonization

13 73 74 CD20 CD20 Bcl- 2 CD10 ONE LAYER SPHERICAL STRUCTURES I. FOLLICULAR PATTERN: A. Malignant follicular center cell proliferation B. Benign follicular center cell proliferation II. PSEUDOFOLLICULAR PATTERN (PROLIFERATION CENTERS): A. SLL/CLL 75 FOLLICULAR COLONIZATION May result in one, two or three-layer spherical structures, & these structures may co-exist Either benign or malignant cells of different types may colonize follicles The follicles colonized may be either benign or malignant SPHERICAL STRUCTURES WITH INTERMINGLING OF CELLS / LAYERS Paracortical T-zone hyperplasia Dermatopathic lymphadenitis Non-specific Progressive transformation of germinal centers (PTGC) Without Hodgkin cells With Hodgkin cells L&H nodules 13

14 11/8/2018 OTHER (NON-SPHERICAL) PATTERNS Lysozyme Sinus Pattern Interfollicular Pattern Lennert s Pattern Mottling Pattern Vascular Pattern Necrosis Pattern Diffuse Pattern Starry-Sky Pattern in Diffuse Areas Multiple (Specify) Lysozyme MPO MPO OTHER (NON-SPHERICAL) PATTERNS Sinus Pattern Interfollicular Pattern Lennert s Pattern Mottling Pattern Vascular Pattern Necrosis Pattern Diffuse Pattern Starry-Sky Pattern in Diffuse Areas Mixed Pattern Miscellaneous 83 14

15 11/8/2018 Mast Cell Disease Producing Inverse Follicular Patterns CD117 Tryptase Metastatic Carcinoma 90 15

16 11/8/ SLL with Hodgkin Transformation 16

17 11/8/2018 CD15 CD15 CD20 CD3 CD3 CD3 CD30 EXAMPLE OF MULTIFOCAL HODGKIN LYMPHOMA CD

18 11/8/ EXAMPLE OF MULTIFOCAL HODGKIN LYMPHOMA 18

19 11/8/ Focal Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL) Example 1 19

20 IgD CD 20 20

21 CD 20 CD20 CD 3 CD3 CD3 Spherical Patterns 1. Follicular 2. Mantle zone 3. Marginal zone 4. Mantle cell nodules 5. Marginal zone nodules 6. Follicular colonization 7. Inverse follicular 8. Progressively t f d GC Non-spherical Patterns 13. Sinus 14. Interfollicular 15. Lennert s 16. Mottling 17. Vascular 18. Necrosis 19. Diffuse 20. Starry-Sky in Nonfollicular Areas 21. Multiple (Specify) Accurate identification and quantification of these patterns permits formation of a precise differential diagnosis 21

22 Lessons Learned from Experience (1 of 3) We don t know what we don t know We see (recognize) what we know All recognition is done by the mind, none by the eyes. Thus, if the mind does not know, we cannot recognize what is present and therein lies the dangers of making wrong diagnosis The more we know, the more we see (recognize) (due to acquired experience) Process of Imprinting of Images in the Mind (2 of 3) 1. In order to recognize an image instantly, we must see it critically & repeatedly (> 100 times) for it to be permanently imprinted in the mind, & instantly recalled, when seen again 2. Each histologic feature and its spectrum gets imprinted in the mind as a separate image 3. Those images that form the criteria of diseases are tightly linked & get imprinted as hierarchical clusters forming patterns 4. For imprinting to occur systematically, and for accurate instantaneous recall, slides (cases) have to be studied critically, at different magnifications (1x, 2x,4x, 10x, 40x 60x objective lenses), using a methodical approach 5. Using a methodical approach consistently & continuously reinforces precise systematic imprinting and hence, instant accurate recall Lessons Learned From Experience (3 of 3) What we see is also greatly influenced by our: 1. Concepts about pathogenesis of lymphoid diseases 2. Histologic, immunophenotypic & other criteria that we use in our daily practice to make diagnosis 3. The approach & the methods we use in our diagnostic practice to detect pathologic areas, the problem solving strategies we use to resolve a differential diagnosis, & the knowledge & experience required to integrate all information available 4. Making histologic diagnosis & interpreting immunohistochemical stains and integrating these with clinical & other information is an ART and NOT a SCIENCE Thank You