Transcript Pathology - Digital Pathology Association

Laboratory Medicine Program
Pathology
2020 Vision
Sylvia L. Asa, MD, PhD
What Is Pathology?
• Pathology, from the greek πάθος, pathos,
“feeling, suffering” and λογία, logia “study of”
• the study and diagnosis of disease through
examination of organs, tissues, bodily fluids,
and whole bodies
Laboratory Medicine Program
The Origins of Pathology
• The Autopsy
• Dates back to ancient Egypt and Greece
• The tool of the Physician-Scientist
– To identify the cause of death
– To explain signs and symptoms of disease
Laboratory Medicine Program
The First Clinical Applications
• Surgical Pathology by surgeons
• Laboratory hematology by hematologists
• Biochemistry in nephrology and
endocrinology
• Microbiology in infectious diseases
Laboratory Medicine Program
Pathology 2010
• Laboratory-based clinical testing
– Focus on QA/QC/GLP
• Microscope-based anatomical pathology
• Custodianship of patient samples on behalf
of patient
• Representative of patient in Quality of Care
events (M&M rounds)
• Minimal or no patient contact
Laboratory Medicine Program
The Pathology Diagnosis
• The pathological diagnosis is the gold standard
that indicates the presence or absence of disease,
the type of disease, and its classification
• Therapeutic decisions are based on the pathology
diagnosis
– a misdiagnosis can result in unnecessary, harmful and
aggressive therapy or inadequate treatment
Laboratory Medicine Program
Pathology is an Interpretive Discipline
BREAST
• Atypia on breast core needle biopsies: reproducibility and
significance.
• The impact of inter-observer variation in pathological
assessment of node-negative breast cancer on clinical risk
assessment and patient selection for adjuvant systemic
treatment.
• Inter-observer reproducibility of HER2 immunohistochemical
assessment and concordance with fluorescent in situ
hybridization (FISH): pathologist assessment compared to
quantitative image analysis
Laboratory Medicine Program
Pathology is an Interpretive Discipline
GENITOURINARY
• Interobserver variability between expert urologic pathologists
for extraprostatic extension and surgical margin status in
radical prostatectomy specimens
• Intraobserver and interobserver variability of fuhrman and
modified fuhrman grading systems for conventional renal cell
carcinoma
• Intra- and interobserver reproducibility of interpretation of
immunohistochemical stains of prostate cancer
Laboratory Medicine Program
What Does This Mean for Patients?
•
•
•
•
•
Is the diagnosis right?
Is the treatment right?
Is the prognosis right?
Was the trial right?
Are the data reliable?
Laboratory Medicine Program
Pathology 2000-2010
Laboratory Medicine Program
Challenges for 2020
• Volume
– aging population
– higher sensitivity for early disease
• Demand
– Sophisticated knowledgeable population
– Culture of “instant gratification”
• New technologies
–
–
–
–
genomics
proteomics
informatics
robotics
‘tissue soup’
instead of tissue
11 Medicine Program
Laboratory
The Challenge for 2020
• Faster
• Better
– Higher quality
– Personalized
• Cheaper
• Innovative
Laboratory Medicine Program
The New Paradigm: Faster
• Pathology must be faster
– “Same Day” diagnosis
– Automation
– 24/7 labs
Laboratory Medicine Program
The New Paradigm: Faster
• Speech-recognition integrated with LIS
means instant reporting without
the need for dictatyping
Laboratory Medicine Program
14
The New Paradigm: Better
• Synoptic Reporting
– Complete
• Standardized formats (CAP checklists)
– Adaptable and flexible
• No more verbose reports that no one reads!
– Database technology
•
•
•
•
Statistics collection
Administrative tracking
QA monitoring
Academic data mining
Laboratory Medicine Program
The New Paradigm: Better
What is “Correct”?
• Objective classification by
– mRNA expression
– DNA sequencing
– Response to therapy
Laboratory Medicine Program
Technologic Advances: “omics”
DNA
RNA
HT-Sequencing
Metabolomics
Protein
Mass Spectrometry
Microarray
Expression
Profiling
Laboratory Medicine Program
The New Paradigm: Better
Subspecialty Pathology
– All cases reported by a pathologist with
expertise in the specific subspecialty required
– Benefits:
• Better quality and faster patient care
• Fiscal responsibility: 1 pathologist per case
• Pathologist satisfaction – enhanced academic
excellence
– Challenges:
• Requirement for appropriate staffing
in all areas and redundancy
18 Medicine Program
Laboratory
Digital Pathology
• Whole slide imaging
• A disruptive enabling technology
Laboratory Medicine Program
19
Digital Pathology Enables
• Remote access
• Multiple viewers
• Immediate access to the right pathologist
at the right time
Laboratory Medicine Program
20
Requirements for Full Adoption
• Workflow integration
– From the lab to the pathologist
• LIS integration
– Barcodes
– Slide tracking and retrieval
Laboratory Medicine Program
Informatics: The LIS
• LIS as part of the e-chart
• LIS e-orders and processes
• Specimen tracking and
management
• Integration of lab data from all
disciplines into a consolidated
report
22 Medicine Program
Laboratory
Computer-Assisted Diagnostics
• Automated analysis of:
–
–
–
–
Measurement
Mitoses
Ki67 LI
Other IHC
• intensity
• distribution
– Her2 FISH
– Hematology
• QA of technical quality
– Section thickness
– Stain quality
? Need for Westgard rules in AP?
• Cellavision
– More?
Laboratory Medicine Program
Digital Pathology Enables
• Novel approaches to address issues of
inter- and intra-observer variability
GENIE© (GENetic Imagery Exploration)
is a GP software system that builds
automatic feature extraction algorithms
for image analysis, utilizing spectral and
spatial signatures of the images
“GENIE© can recognize benign and
malignant areas in H&E stained slides
and it does not have intra- or interobserver variation in the analysis”
Laboratory Medicine Program
24
The New Paradigm: Personalized
• Patient-Centred Care
• Individualized diagnostics
• Targeted therapies
All based on “omics”
Will “omics” replace pathology?
25 Medicine Program
Laboratory
Targeted Therapies
• Hormone receptors in breast cancer
• Herceptin
DP does it better……
26 Medicine Program
Laboratory
EGF-R Rx in Lung and Colon Cancer
Laboratory Medicine Program
And When It Doesn’t Work?
• K-ras mutations in Colon Cancer
Laboratory Medicine Program
The Future of Pathology?
$15.00
$15.00each
each
$1000.00
$1000.00each
each
Laboratory Medicine Program
Epigenetic Control:
Can it Override the Genotype?
Laboratory Medicine Program
N Engl J Med. 2007 Feb 15;356(7):731-3
BRAF Mutation
• Most common event in
thyroid cancer
• Diagnostic marker of PTC
• Genotype-phenotype correlations
– BRAFV600E in classical variant PTC (40-50%)
– BRAFK601E in FVPTC (rare)
– VK600-1E deletion (BRAFVK600-1E) in solid
variant (single case)
• Prognostic significance controversial
Laboratory Medicine Program
BRAF Mutation & Outcome
• BRAF mutant carriers show increased risk of tissue
invasion compared to WT cases
• However, when classified morphologically, classic
papillary thyroid carcinomas (PTCs) showed much higher
risk estimates for invasive outcomes compared with
follicular variant PTCs, independent of BRAF mutational
status
• The combined risk of BRAFV600E mutant allele and
morphology showed higher risk values for the classic wild
type cases, indicating that morphologic classification as
classic PTC is a stronger predictor of aggressive behavior
than BRAF mutation
Cheng et al, 2010 submitted
Laboratory Medicine Program
What Is Anatomical Pathology?
• Integrative
morphology based
interpretation
Gross Morphology
Chemistry on a glass slide
Immunoassay on a glass slide
Laboratory Medicine Program
Garbage In – Garbage Out
• We have the technical capacity
to produce low quality data
from low quality analytes
with unprecedented efficiency
• We arrive at the wrong answer
with unprecedented speed
Laboratory Medicine Program
The New Paradigm: Innovative
• Pathology / Laboratory Medicine
– critical players in ensuring the highest quality
of translational research:
• The right specimen, the right test, the right
interpretation
• Biobanking in Translational Research
– Value is in the technical and diagnostic
excellence of the specimens
The “Biobank” is the current phraseology for
the “Department of Pathology”
Laboratory Medicine Program
The Expanding Role of Lab Medicine
• To provide the right diagnosis
• To provide the right material
• To provide the right leads
• To provide the right experiments
• To evaluate the consequences of
genetic manipulation
36 Medicine Program
Laboratory
Where Are We Heading?
• Predictive genetics/epigenetics will define
individual risk and prognosis
• Targeted prevention
• Monitoring for onset with multimodal
biomarkers
• Targeted therapies based on host genetics
and epigenetics
• Signatures of stage-specific progression
• Mechanisms of escape
Laboratory Medicine Program
The Uncontestable Trends
• Clinicians want increasingly detailed,
reliable and relevant information from
specimen analyses that can be translated
into optimal treatments
• Pathology must re-educate and re-invent
itself if it is to maintain the central role it
plays as the ultimate arbiter of treatment
“As is your pathology, so goes your clinical care”
Sir William Osler
38 Medicine Program
Laboratory
The New Paradigm
• Pathology labs must be faster and better
– QA is the sine qua non
• Pathology reports must be comprehensive
– Incorporation of molecular, biochemical and other
data is critical to the consultative value of the report
• Pathology data must be synoptic and
database-oriented
• Pathology must be innovative
39 Medicine Program
Laboratory
The Virtual Autopsy
Laboratory Medicine Program
After “The Anatomy Lecture of Dr. Nicolaes Tulp” – Rembrandt, 1632
(Courtesy of Dr. Carlos Cordón, New York,Laboratory
USA) Medicine Program
2020 Vision
• Large automated core laboratories
• Electronic support for specimen tracking
and handling, QMS
• Highly subspecialized teams providing a
matrix of subject and technical expertise
–
–
–
–
Biochemistry
- Microbiology
Hematology, Transfusion & Hematopathology
Subspecialty Anatomical Pathology
Molecular/Genetics
“Blurring the lines between AP and CP”
Laboratory Medicine Program
42
Laboratory Management
in the Electronic Era
• Specimen tracking
• Workload tracking
and personnel
• Supplies and
equipment
• QA processes
“………sophisticated refrigerators and
Radio Frequency Identification (RFID) technology
will be able to monitor the products household members use,
create shopping lists, and even communicate with
other networked devices to arrange deliveries”
43 Medicine Program
Laboratory
Critical Elements
• Specimen ID
• Specimen tracking
What
next?
• Patient ID
44 Medicine Program
Laboratory
The 2020 Paradigm
• Comprehensive pathology reports
– Incorporation and integration of radiologic,
biochemical, morphologic , molecular, cytogenetic
and epigenetic data
Biochemistry
Radiology
Gross
Pathology
Biomarkers
Histopathology
Molecular
Pathology
•The Pathologist’s Cockpit
Laboratory Medicine Program
2020 Pathology
Digital radiology
Digital genetics
History, Physical,
Family History
Digital EMR
Pathology:
the center
of
Clinical
Gross
Pathology Pathology
Biomarkers
& CAD
Personalized
Medicine
QA
Digital cardiology
Laboratory Medicine Program
Endoscopy
2020 Pathologist
Laboratory Medicine Program
The Philosophical Response
In a time of drastic change
it is the learners who inherit
the future. The learned
usually find themselves
equipped to live in a world
that no longer exists.
Eric Hoffer
Laboratory Medicine Program
48
The Future of Pathology
The best way to predict the future
is to invent it
Alan Kay
Laboratory Medicine Program
49