brave new world: pathology in 2020 dr. clive wells university college london ewgbsp

Brave New World:Pathology in 2020

Dr. Clive Wells

University College London

EWGBSP

Paul J van DiestHead, Department of PathologyUniversity Medical Center UtrechtThe Netherlands

Breast pathology 2020

With thanks to:-

No more sentinel nodes!

• sentinel node procedure is for staging

• in 2020 we can accurately stage based onprimary tumor features

No more axillary lymph nodes!

• wait-and-see policy for the axilla underultrasound 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 orinvasive cancer

follow up strategy, resection, non-inv. ablation


DCIS

• markers that predict presence of invasive cancer


• markers to guide image guided surgery

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Glut1 MUC1 TFR1 EGFR c-Met IGFR


Invasive cancer

• markers that predict presence of DCIS


• markers to guide image guided surgery

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Glut1 MUC1 TFR1 EGFR c-Met IGFR


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

ER+ PR+ HER2- ER- PR- HER2- translocation translocation

Luminal A Basal Secretory Adenoid Cystic

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


• all breast multidisciplinary meetings done digitally


• enough bandwidth, processor speed and screen resolution to go wireless on PDA/iPad


• image analysis guided immunoscoring


• we use image analysis applications to find • mitoses• SN metastases

SN metastases

mitoses


• no more histological grading

Breast pathology 2020: no more grading…

Markers of mitotic arrest

- Therapeutic targets in cell cycle


• 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


• 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)


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

brave new world: pathology in 2020 dr. clive wells university college london ewgbsp

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