Transcript Brave New World Pathology in 2020

Brave New World:
Pathology in 2020
Dr. Clive Wells
University College London
EWGBSP
Breast pathology 2020
With thanks to:-
Paul J van Diest
Head, Department of Pathology
University Medical Center Utrecht
The Netherlands
No more sentinel
nodes!
• sentinel node procedure is for staging
• in 2020 we can accurately stage based on
primary tumor features
No more axillary
lymph nodes!
• wait-and-see policy for the axilla under
ultrasound follow up
or
• radiotherapy of the axilla
 lymph node dissection only in case of recurrence
No more resections!
• non-invasive ablation therapy for smaller tumors
• radio frequency ablation
• highly focused ultrasound
• laser induced thermal therapy
• neoadjuvant chemotherapy for bigger tumors
• adjuvant radiotherapy
 only (bigger) biopsies remain
Extensive typing on
biopsies!
Intermediate/high risk benign lesions
• reliable markers that predict presence of DCIS or
invasive cancer
 resection, non-invasive ablation
• reliable markers that predict progression to DCIS or
invasive cancer
 follow up strategy, resection, non-inv. ablation
Extensive typing on
biopsies!
DCIS
• markers that predict presence of invasive cancer
 resection, non-invasive ablation
• markers to guide
image guided surgery
100
90
80
70
60
50
40
30
20
10
0
Glut1
MUC1
TFR1
EGFR
c-Met
IGFR
Extensive typing on
biopsies!
Invasive cancer
• markers that predict presence of DCIS
 resection, non-invasive ablation
• markers to guide image
guided surgery
100
90
80
70
60
50
40
30
20
10
0
Glut1
MUC1
TFR1
EGFR
c-Met
IGFR
Extensive typing on
biopsies!
Invasive cancer
• prognostic markers
 type of adjuvant therapy
• predictive markers
 type of neoadjuvant therapy
 response monitoring by PET
…. but not histological
typing….
… except for quality control!
• typing will be overshadowed by biomarker typing
• classical typing will merely serve as quality control
Luminal A
ER+ PR+ HER2-
Basal
ER- PR- HER2-
Secretory
Adenoid
Cystic
translocation
translocation
Test to detect early breast lesions
in nipple fluid
Nipple aspiration
• intranasal oxytocin
• vacuum
• nipple fluid > 90%
• 10 gene QM-MSP
(APC, BRCA1, BRCA2, CyclinD2, ERα,
E-Cad, HIN1, p16, RARβ, RASSF1A, TWIST)
Test to detect breast
cancer in blood
DCIS and invasive cancer?
• methylation
• same genes as in nipple fluid
• microRNAs
• circulating tumor cells
• mutations?
Ductoscopy
• ductoscopy guided surgery
• fluorescent markers
• ductoscopic excisions
• ductoscopic biopsies
• fluorescent markers
(LIFE)
Tissue processing 2020
• uniform protocols to avoid interlaboratory variation
• during the day
• fully automated (including embedding)
• no more toxic chemicals
• formaldehyde
• xylene
Immunohistochemistry
2020
• fully automated
• uniform protocols
• within 2 hours
Molecular pathology
2020
• based on “whole” genome sequencing
• set of 200 genes that matter
• costs 2000 US $
• replaces
• single gene mutation
• amplification tests
• translocation tests
Whole genome
sequencing 2020
• primary tumours and metastases
• in search of treatable mutations with drugs
• implies that molecular makeup is more important
than morphologic typing and origin
• requires large pipeline of new targeted drugs
• requires a huge setup of early clinical trials
Digital pathology 2020
• all labs have a scanner and decent storage
• digital consultation, remote revision, digital slide panels
Digital pathology 2020
• all breast multidisciplinary meetings done digitally
Digital pathology 2020
• enough bandwidth, processor speed and screen
resolution to go wireless on PDA/iPad
Digital pathology 2020
• image analysis guided immunoscoring
Digital pathology 2020
• we use image analysis applications to find
• mitoses
• SN metastases
mitoses
SN metastases
Breast pathology
2020
• no more histological grading
Breast pathology 2020: no
more grading…
Markers of mitotic arrest
- Therapeutic targets in
cell cycle
Breast pathology
2020
• uniform and sensible nomenclature
 no more “atypical” for lesions without atypia
• good classification of apocrine lesions
• precursor of high grade DCIS identified
• more reproducible classification based on
immunohistochemical and molecular markers
Breast pathology
2020
• web based image archive for matching rare cases
• all labs have superspecialists in breast pathology
• needed or just for consultation?
• probably required
• molecular breast pathology in all pathology labs
in developed countries (ISH, PCR)
Breast pathology
2020
What about microarrays?
• no more microarrays for prognosis
Mammaprint
Oncotype Dx
• no microarrays for molecular typing
2000 euro
3000 $
What is stopping us?
• Money for research to explore new areas
• Bureaucracy to be overcome before use of tissue
(especially UK)
• Creating innovation only valued once a commercial
market is visible
• Salary scale for academics discourages the best people
• Multicentre research needed but difficult to organise