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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