Download document - Herts Valleys CCG

Mount Vernon
Cancer Network
OPERATIONAL POLICY FOR RESPIRATORY
PATHOLOGY
Contents
1
2
3
4
5
6
7
8
9
10
11
Introduction
Description of the Service
Specimen Types
Specimen Examination
Reporting Practice
Mutation Analysis
Staging
Multi-disciplinary team meetings
Audit
Referral for Review or Specialist Opinion
References
1
Introduction
This policy takes into account the relevant Royal College of Pathologists’
(RCPath) minimum dataset for Lung Pathology and the Tissue Pathway for
Pulmonary Pathology. It describes how this dataset and guidelines are to be
interpreted within the Mount Vernon Cancer Network (MVCN) and describes
recent changes in practice.
The MVCN comprises three main Hospital Trusts: West Hertfordshire Hospitals
NHS Trust (WHHT), East and North Hertfordshire NHS Trust (E&NH) and Luton
and Dunstable NHS Foundation Trust (L&D).
All lung cancer cases should be reviewed by the local Multi-disciplinary Team
(MDT). There should be a Network Lead pathologist but each Trust should have
a local lead pathologist for pulmonary cancer pathology. The Lead pathologist for
the Network should also attend the Tumour Site-Specific Group (TSSG)
meetings. All the leads should participate in a relevant EQA scheme and in local
audit, including correlation between biopsy and resection, where relevant. There
is currently no accepted national lung cancer EQA.
Specimens should be reported to an agreed timeframe to enable case discussion
at a planned lung cancer MDT meeting.
2
Description of the Service
Each Trust in the Network produces pulmonary biopsy and cytology specimens
but none undertake thoracic surgery, which is performed at Harefield Hospital
(for patients from L&D and WHHT) and Papworth (for patients from E&NH).
3
Specimen Types
Histopathology
Bronchial biopsies
Transbronchial biopsies
Transthoracic (often CT-guided) biopsies
Pleural biopsies
Lymph node biopsies
Cell blocks from Cytology samples
Cytology
Bronchial washings
Bronchial lavage
Bronchial brushings
Trans-bronchial needle aspirates (TBNA)
Endoscopic Bronchial Ultrasound (EBUS) aspirates
Endoscopic Ultrasound (EUS) aspirates
Lymph node FNAs
Pleural effusions
All the above may result in direct slides (and/or cytospins), liquid-based
preparations, cell blocks and flow cytometry (for possible lymphoid malignancies)
4
Specimen Examination
Each pathology service should have a defined protocol for all the above types of
specimen (some of which may be included under more generic headings), taking
into account the RCPath guidance. The protocols should be subject to regular
review by the relevant lead pathologist.
NB It is now recommended that residual Cytology specimens in positive
cases are processed to cell block to enable further testing including
immunohistochemistry and, particularly, mutational analysis. It is therefore
important to liaise with clinical colleagues to facilitate the delivery of liquidbased specimens wherever possible and to have a robust system in place
in the laboratory for cell block production.
5
Reporting Practice
There has been a recent major proposed change in the classification of lung
adenocarcinomas by the International Association for the Study of Lung Cancer
(IASLC) in association with the American Thoracic Society and the European
Respiratory Society. This was published in the Journal of Thoracic Oncology in
February 2011 and is available free of charge (see link below). This is partly
driven by advances in lung cancer therapies which require non-small cell
carcinomas (NSCLC) to be separated accurately into squamous carcinoma and
adenocarcinoma, wherever possible. This is elaborated in the most recent (April
2011) RCPath guidelines and dataset (link below in references) but the essential
points for biopsy and cytology specimens are as follows:
 The term “bronchiolo-alveolar carcinoma” should no longer be used, being
replaced by “adenocarcinoma with a lepidic growth pattern” for those
tumours growing along pre-existing alveolar walls
 If there is morphological evidence of squamous carcinoma or
adenocarcinoma, the case should be reported as such, describing a subtype if apparent
 If there is evidence based on immunohistochemical or mucin stains of
squamous carcinoma or adenocarcinoma, the case should be reported as
NSCLC, favour squamous carcinoma or NSCLC, favour adenocarcinoma
 The most useful stains in this regard are likely to be mucin stains and
TTF-1 (generally positive in adenocarcinomas, though 25% of
adenocarcinomas may be negative for TTF-1) and CK5 and p63
(generally positive in squamous carcinomas)
 If only two stains are possible, TTF-1 and p63 are the most likely to be
useful
 The percentage of cases reported as NSCLC NOS should be less than
20%
 For cytology specimens (in addition to the above comment about cell
blocks):
o The report should indicate if the diagnosis is definite or equivocal
o The report should be as precise as possible
o Papanicolaou staining should be used (apart from on-site rapid
assessment)
6
Mutation Analysis
The tyrosine kinase inhibitors (TKI) gefitinib (Iressa) and erlotinib (Tarceva) are
licensed for the treatment of locally advanced or metastatic NSCLC which
harbours “activating” Epidermal Growth Factor Receptor (EGFR) mutations,
usually L858R or del19.
Tumours which are reported as adenocarcinoma, NSCLC, favour
adenocarcinoma or NSCLC NOS should be tested for EGFR mutation. The
mutation and TKI response rate of tumours reported as squamous carcinomas or
NSCLC, favour squamous carcinoma is much lower than that in
adenocarcinomas and the testing of squamous tumours yields a very low rate of
positive results.
The molecular test can be performed on paraffin block (including Cytology cell
block) material as well as cytology slides or fluid preparations (depending on
testing lab protocols) and the process can detect 1% of mutated DNA in a
background of wild-type DNA.
Other mutations which may become clinically relevant in the future include KRAS
(generally in codons 12, 13 or 61), where a positive mutation reliably predicts
lack of response to TKI therapy, and detection of the EML4/ALK translocation, a
possible target for the drug crizotinib.
Currently, these tests are performed at UCL (for WHHT) and Source Bioscience
(for L&D and E&NH).
The protein kinase inhibitor Crizotinib (Xalkori) is licensed for the treatment of
NSCLC patients with tumours harbouring a translocation producing a fusion
protein ALK-EML4. Testing for this is currently (2013) funded by Pfizer. This is
either a FISH test or immunohistochemistry, followed by FISH. The same subset
of patients tested for EGFR mutations should be tested for this translocation.
7
Staging
Tumours will be staged according to the TNM classification of tumours (7 th
edition, UICC).
8
Multi-disciplinary team meetings
Each Trust will have a weekly MDT meeting in which biopsies and other local
specimens will be discussed. The local lead pathologist or a deputy will be
present at these meetings.
9
Audit
All pathologists reporting pulmonary cancer specimens should participate in a
relevant EQA scheme (though there is, as yet, no national Lung Cancer EQA
scheme and general EQA schemes will suffice for now) and in local audit
(including an assessment of consistency where more than one pathologist
participates in service provision). Audit may take the form of:






review of compliance with procedures for specimen examination and
reporting
completeness of datasets
systematic logging of diagnostic agreement/disagreement during review of
cases for MDTMs
correlation of tumour type between cytology and histology specimens and
between cytology/biopsy and resection specimens, where relevant
proportion of cases reported as NSCLC, NOS
correlation of tumour type with EGFR mutation
The results of the audit process should be discussed with all pathologists who
participate in service delivery.
10
Referral for Review or Second Opinion
The practice at WHHT, L&D and E&NH has been to refer to pathologists at the
Royal Brompton and Harefield NHS Trust for second or expert opinions.
11
References
1.
Revised TNM staging for Lung Cancer (TNM7):
http://www.atcs.jp/pdf/2009_15_1/4.pdf
2.
Proposed IASLC/ATS/ERS classification of lung cancer
http://journals.lww.com/jto/Fulltext/2011/02000/International_Association_f
or_the_Study_of_Lung.4.aspx
3.
Royal College of Pathologists, Dataset for Lung Cancer Histopathology
Reports, April 2011:
http://www.rcpath.org/resources/pdf/g048datasetlungapril11.pdf
4.
Royal College of Pathologists, Tissue Pathways for Pulmonary Pathology,
May 2008:
http://www.rcpath.org/resources/pdf/g063tissuepathwaypulmonaryfinal_m
ay08.pdf
20 January 2014