cellular pathology user manual...mortuary manager david orrell 028 9615 5908 (option 1) mortuary...

Revision Number 18.0 Document Number TP-223

Author/Reviewer F Wood Authoriser G Clarke

Active Date 03/04/20 Page Number Page 1 of 43

Effective Date 03/04/20 Document Type Management Procedure

Cellular Pathology User Manual

Belfast Trust Laboratories Cellular Pathology


Contents

CONTACT US .............................................................................................. 2

COMMENTS OR COMPLAINTS ................................................ 2

KEY CONTACTS ....................................................................... 3

HOURS OF WORK .................................................................... 4

CELLULAR PATHOLOGY LABORATORY SERVICES ............................. 5

REQUEST FORM & SAMPLES ................................................. 6

CRITERIA FOR REJECTION OF SPECIMENS......................... 8

GUIDELINES FOR SPECIMEN COLLECTION ......................... 9

14-3-3 ANALYSIS .................................................................... 10

CONSENT ................................................................................ 10

HIGH RISK SAMPLES ............................................................. 10

TRANSPORT ........................................................................... 12

MINIMUM RE-TESTING INTERVALS ..................................... 13

RESULTS ................................................................................. 14

POST-MORTEM SERVICE ........................................................................ 15

ADULT POST-MORTEM SERVICE ......................................... 15

PAEDIATRIC POST-MORTEM SERVICE ............................... 17

Arranging a Paedriatric post-mortem ................................... 17

CATEGORY 3 CASES ............................................................. 19

RELEASE OF BODY AND REPORTS .................................... 19

SAMPLE REQUIREMENTS AND TURNAROUND TIMES (TATs) ............... 20

Appendix 1 - CSF 14-3-3 Analysis ......................................... 34

Appendix 2 - Molecular Pathology ........................................ 35

Appendix 3 - Instructions for Renal Biopsy Kits ................. 37

Appendix 4 - Referrals ........................................................... 39







CONTACT US

We welcome comments from users about the content of the user manual to enable us to improve the service or provide more appropriate information. This may be done by contacting the Quality Lead indicated below. In addition, specific groups of users are contacted annually by survey questionnaire (Multidisciplinary Teams, General Practitioners and laboratories that refer specimens to us) to establish the degree of user satisfaction pertaining to the usefulness and timeliness or otherwise of our reports and to solicit suggestions for improvement.

Switchboard 028 9024 0503

Cellular Pathology

Royal Victoria Hospital Institute of Pathology, Grosvenor Road, Belfast, BT12 6AB.

Molecular Pathology Laboratory Belfast City Hospital Health Sciences Building, Lisburn Road, Belfast, BT9 7AE.

Mortuary Royal Victoria Hospital, Grosvenor Road, Belfast, BT12 6AB

COMMENTS OR COMPLAINTS If you have a comment, compliment or complaint about our service, please let us know by contacting the quality officer who will try to help resolve the issue. The laboratory has documented policies on Data Protection, Protection of Personal Information and Complaints and Compliments available through the trust website http://www.belfasttrust.hscni.net/services/Laboratory-MortuaryServices.html

http://www.belfasttrust.hscni.net/services/Laboratory-MortuaryServices.html







KEY CONTACTS

Royal Victoria Hospital , Institute of Pathology, Grosvenor Road, Belfast, BT12 6AB

Clinical Director Dr Neil Anderson 028 9615 6054

Service Manager (acting) Ms Shauna McAuley

078 5054 2086

Discipline Specific Manager Mr Gerry Clarke 028 9504 5785 077 4769 8673

Quality Officer [email protected] [email protected] (acting)

Ms Leona Grant Ms Faye Wood

028 9615 0224 075 9080 6728 028 9615 0224

Operational Manager – Surgical Pathology Ms Hilary Diamond 077 8043 1497 028 9504 8100

General Histopathology

028 9615 0214 078 2453 9469

Neuropathology 028 961 50216

Neuropathology Consultants Dr Brian Herron Dr Estelle Healy

078 0186 6678 077 7925 5420

Diagnostic Cytology [email protected]

Rotational (interim) 028 9615 0217 078 2456 4169

Operational Manager – Cervical Cytology Ms Hilary Diamond 028 9504 8100 077 8043 1497

Operational Manager – Specialist Services Ms Hilary Diamond 077 8043 1497

Immunocytochemistry 028 9615 0226

Immunopathology 028 9615 0215 077 1780 5516

Electron Microscopy 028 9615 0224

Molecular Pathology [email protected] Dr Christine Quinn Dr Beatriz Cutillas-Moreno

028 950 42849 028 909 75799 028 909 72980

Post-Mortem Services

Adult Post-Mortem Consultant Dr Brian Herron 028 9615 5904

Paediatric Office (Post-Mortem Enquiries) 028 9615 5825 028 9615 5244

Mortuary Manager David Orrell 028 9615 5908 (option 1)

Mortuary Mortuary Mobile (On-call MTO)

028 9063 3679 079 7936 6041

Consultants 077 7563 5395

Admin and Clerical Operational Manager Ms Christine

McMillan 028 9165 5830

mailto:[email protected]:[email protected]:[email protected]:[email protected]:[email protected]







HOURS OF WORK

Specialty Hours of Service Out of Hours

(Monday-Friday) (Saturday, Sunday, Bank Holidays

and urgent specimens)

Surgical Pathology 7:30am – 5.30pm

General Histopathology The Consultant medical staff provide an out of hours rota (Band B* basis only). Consultant can be reached on 07775635395 (Lab Staff 07824539469) Neuropathology Dr. Brian Herron (07801866678) Dr. Estelle Healy (07779255420)

Diagnostic Cytopathology

8:45am – 5.00pm Contact Duty Consultant Cytopathologist via switchboard**

Specialist Services

Immunocytochemistry 8.30am – 5.30pm

Immunopathology 8.45am – 5.00pm

Electronmicroscopy 8:45am – 5.00pm

Molecular Pathology 9.00am – 5.00pm

Immunopathology (Renal Biopsies) only: Contact Duty Consultant Pathologist (Dr O’Rourke) via:

Switchboard* or

Immunopathology Laboratory (077 1780 5516)

Post-Mortem Service

Mortuary 9:00am – 5.00pm

Mortuary Saturday 9.00am – 12.30pm

Sunday & Bank Holidays by prior arrangement only.

Out of hours Adult and Paediatric post-mortems can be arranged by contacting the on-call MTO (07979 366041)

Laboratory 8.45 am – 5.00pm

Laboratory as required by Mortuary

* Band B basis means that the service provided is for telephone advice. No urgent intra-operative frozen section service is provided. **Switchboard 028 9024 0503







CELLULAR PATHOLOGY LABORATORY SERVICES (UKAS accredited Ref No. 8638 – Full list of accredited tests is available on the UKAS website) Schedule of Accreditation Cellular Pathology provides a diagnostic and reference service, not only to the BHSCT, but also to the whole of Northern Ireland. Cellular Pathology samples are usually submitted for the assessment of macroscopic, microscopic, molecular and ultrastructural abnormalities to aid diagnosis, treatment planning and management of disease states, including malignancy. The following range of diagnostic specialties is available:

breast pathology

bone & soft Cellular Pathology

cardiovascular pathology

cervical cytology

diagnostic cytopathology (including fine needle aspiration cytology)

dermatopathology

endocrine pathology

ENT pathology

gastrointestinal pathology

haematopathology

hepatopancreatobiliary pathology

lung pathology

ophthalmic pathology

oral & dental pathology

paediatric pathology

renal pathology

ultrastructural pathology

neuropathology

urological pathology These are underpinned by technical expertise in Immunocytochemistry, Immunofluorescence, Neuropathology, Molecular Pathology and Electron Microscopy. The majority of Cellular Pathology Laboratory services operate from the Royal Group Hospitals (RGH). Molecular Pathology operates from the Belfast City Hospital (BCH) We routinely process samples from:

Ards Hospital BCH Dental Practioners (Regional) Downe Hospital GP’S: North, South, East and West Legacy Trusts

Lagan Valley Hospital Mater Hospital Musgrave Park Hospital RGH Ulster Hospital

https://www.ukas.com/wp-content/uploads/schedule_uploads/00007/8638%20Medical%20Multiple.pdf







REQUEST FORM & SAMPLES REQUEST FORM DESCRIPTION

Cellular Pathology

Each sample must be accompanied by a fully completed Histopathology, Cytopathology, Immunopathology or Molecular Pathology (see appendix) request form signed by the submitting doctor. Advice on fixation and handling of different specimen types can be obtained from the duty consultant pathologist or by ringing the appropriate laboratory.

In order to ensure timely and appropriate testing on the correct patient it is essential that the request form and sample are labelled correctly. Essential criteria - required to correctly identify the patient, ensure the sample is handled correctly and to enable the result to go to the correct source. If all essential criteria are not present there will be a delay in sample turnaround time and the sample may not be processed. The laboratory strongly recommends that all criteria are completed to provide the best possible service for the patient. General Request are available from the Trust. In addition the following laboratories have their own forms. MPL: TP-435 Northern Ireland Molecular Pathology Request Form TP-666 NI-MPL Request Form cfDNA samples Diagnostic Cytology: TP-390 Diagnostic Cytopathology Request Form (CT/US FNA) TP-391 Diagnostic Cytopathology Request Form (EUS FNA) TP-392 Diagnostic Cytopathology Request Form (Head and Neck FNA)

http://belqpulse101/QPulseDocumentService_Labs/Documents.svc/documents/active/attachment?number=TP-435http://belqpulse101/QPulseDocumentService_Labs/Documents.svc/documents/active/attachment?number=TP-666http://belqpulse101/QPulseDocumentService_Labs/Documents.svc/documents/active/attachment?number=TP-390http://belqpulse101/QPulseDocumentService_Labs/Documents.svc/documents/active/attachment?number=TP-391http://belqpulse101/QPulseDocumentService_Labs/Documents.svc/documents/active/attachment?number=TP-392







Essential Criteria

REQUEST FORMS All request forms must contain: A

1. Health & Care Number* 2. Patients full name* (first name and surname) 3. Sex 4. Date of birth 5. Address

B. 6. Hospital/Practice and ward location 7. Consultant/GP 8. Requesting clinician details 9. Clinician’s contact number in the case of urgent or frozen section requests 10. Patient - Please tick appropriate box

C 11. Date 12. Specimen details 13. Clinical data

SAMPLE LABELLING All sample containers must contain:

1. H&C Number 2. Patients full name (first name and surname) 3. Date of birth 4. Specimen type (if more than one sample submitted – this excludes cervical

cytology)

Notes: A. *H&C number and Patient name are essential plus a minimum of 2 additional identifiers are required for correct identification of the patient. B. Information regarding the test requestor. This is required to ensure that the report is returned to the correct consultant and source. C Specimen information required to assist with diagnosis and assess specimen suitability. NB If the patient does not have a H&C number all other request form criteria must be present to safely identify the patient. This is only applicable in specific cases e.g. immigrants, private patients from Republic of Ireland (ROI), family planning patients.







KEY POINTS TO REMEMBER

All request forms and samples must be legible.

Hospital or GP practice printed labels are preferred for both request forms and samples.

Handwritten requests must be complete & legible.

Specimens may not be accepted for analysis in some laboratory disciplines where the essential criterion in the Minimum Data Set is not met on either the form or the specimen container.

Sample labeling / request form details must match. CRITERIA FOR REJECTION OF SPECIMENS Surgical Pathology, Diagnostic Cytopathology and Specialist Services

If a specimen is received without a fully completed request form, due to the unrepeatable nature of the samples, attempts will be made by laboratory staff to chase up the missing information. This will cause considerable delay in the examination process and is a waste of laboratory resources. This will be communicated to the requestor in the written report.

Cervical Cytology

Specimens may be rejected immediately if:

Form received with no specimen.

Discrepancy between the patient details on the form and the specimen.

No patient details on either the request form or the specimen.

Specimens which have leaked and are insufficient for testing.

Specimens deemed unsuitable for testing by BMS at the point of testing.

Specimens deemed inappropriate for testing by BMS at the point of testing.

Specimens accompanied by a request form with insufficient information to send out a report or to determine which test is required.

Vials which are out-of-date. Molecular Pathology

Specimens may be rejected immediately if:

Referral form received with no specimen or specimen received with no referral form

Molecular Pathology cannot accept SharePoint referrals.







Discrepancy between the patient details on the form and the specimen.

No patient details on either the request form or the specimen.

FFPE samples will be rejected for analysis upon receipt if the slides are broken and insufficient material remains for analysis.

Blood samples will be rejected for analysis upon receipt if the sample has leaked and insufficient material remains for analysis.

Specimens deemed unsuitable for testing by BMS/Genetic Technologist/Clinical scientist at the point of testing.

Specimens deemed inappropriate for testing by Clinical Scientist at the point of testing.

Specimens accompanied by a request form with insufficient information to send out a report or to determine which test is required.

Blood samples are rejected if they are not received in the correct Roche Cell-Free DNA Collection Tube or received in an out of date collection tube.

Molecular pathology cannot process known category 3 blood samples.

Incomplete documentation-Attempts will be made to complete documentation but, if necessary, the slides will be returned to the requesting laboratory.

GUIDELINES FOR SPECIMEN COLLECTION

Only laboratory approved, CE marked, in vitro devices IVDs, must be used as primary specimen containers, no substitutes or improvised containers.

Each sample should be placed in a separate sealed specimen bag.

Collect an adequate amount of specimen. Inadequate amounts of specimen may yield false-negative results.

All container tops must be firmly closed as leakage adversely affects not only that specimen but other specimens sharing the transit.

Specimens must be kept in a cool room awaiting dispatch, not in the sunlight or near a radiator.

Transit to the laboratory should be prompt and specimens must not be left in uncontrolled vehicles (hot/cold) for any prolonged period.

If processing is delayed please contact laboratory for sample storage guidance.

Samples which are of inadequate size, in incorrect containers, or badly delayed in transit may not be processed.

If a sample is unsuitable for testing a written report will be sent to the requestor giving the reason and, if appropriate, requesting another sample.







Samples must be packaged and sent so as to comply with the current regulations on the transport and postage of biological materials – see TRANSPORT below.

Ensure that all instruments and equipment are handled and disposed of in accordance to Trust Sharps policy and Waste Disposal policy

Sharps Injuries and Blood and Body Fluid Exposure (BBFEs) - Prevention and Management of V3.0.pdf Waste Trust Policy V1.0 14-3-3 ANALYSIS If a CSF sample is suspected of CJD and 14-3-3 Protein analysis is required contact the National CJD Surveillance Unit (Tel: 0131 537 1980) in Edinburgh, the Scientific staff there will have a discussion with the Clinical staff to determine if the sample is to go to Edinburgh via the Cellular Pathology Department. For further information and sample requirements please see appendix 1. CONSENT Products of conception specimens must have examination consent forms appropriately completed or they will be returned to source. HIGH RISK SAMPLES For suspected or known Category 3 pathogens, hazard warning Category 3 pathogen labels should be affixed both to the container and the accompanying request form. If there is any doubt as to whether a specimen is high risk, please contact the appropriate laboratory. Hazard Group 3 is defined as a biological agent that may cause severe human disease and presents a serious hazard to employees; it may present a risk of spreading to the community, but there is usually effective prophylaxis or treatment available. NB: Hazard warning Category 3 pathogen labels should be affixed to ALL samples taken from patients with pyrexia of unknown origin (PUO) following foreign travel. Examples of Category 3 Pathogens

Bacteria:

Bacillus anthracis (Anthrax)

Brucella species

Escherichia coli, vero-

Fungi:

Blastomyces dermatitidis

Coccidioides immitis

Histoplasma species

Viruses:

All viral hepatitis (except Hepatitis A)

HIV

Sudden Acute Respiratory

file:///C:/Users/david.mcclure/AppData/Local/Microsoft/Windows/Temporary%20Internet%20Files/Content.Outlook/082X356F/Sharps%20Injuries%20and%20Blood%20and%20Body%20Fluid%20Exposure%20(BBFEs)%20-%20Prevention%20and%20Management%20of%20V3.0.pdffile:///C:/Users/david.mcclure/AppData/Local/Microsoft/Windows/Temporary%20Internet%20Files/Content.Outlook/082X356F/Sharps%20Injuries%20and%20Blood%20and%20Body%20Fluid%20Exposure%20(BBFEs)%20-%20Prevention%20and%20Management%20of%20V3.0.pdfhttp://intranet.belfasttrust.local/policies/Documents/Waste%20Trust%20Policy.pdf







cytotoxigenic strains (e.g. 0157: H7 & others)

Mycobacterium tuberculosis

Mycobacteria other than tuberculosis (MOTT)

Salmonella typhi

Salmonella paratyphi

Shigella dysenteriae (Type 1)

Paracoccidioides brasiliensis

Penicillium marneffei

Syndrome (SARS)

Prion Proteins:

Transmissible spongiform encephalopathies (TSE) e.g. the agents of Creutzfeldt-Jacob disease (CJD): variant Creutzfeldt-Jacob disease (vCJD)

Fatal familial insomnia

Gerstman-Straussler-Scheinker syndrome

Kuru Hazard Group 4 is defined as a biological agent that will cause severe human disease and is a serious hazard to employees; it is likely to spread to the community, and there is usually no effective prophylaxis or treatment available. Please contact the Medical Microbiology team immediately if you suspect a group 4 pathogen, e.g. Lassa, Marburg, Ebola and Congo-Crimean. Under NO circumstances should any samples be taken from such patients without prior consultation.







TRANSPORT The Belfast Trust Laboratories transport procedures are detailed in ‘BTL Transport Policy’ (C-84). This document can be requested from the laboratory. There is a legal responsibility and a duty of care on anyone who dispatches clinical material (diagnostic specimens) to the Belfast Trust Laboratories. The legal responsibility is to ensure that if required, the specimens are packaged and labeled in compliance with the relevant road transport regulations (ADR/CDG). There is a further legal responsibility under COSHH regulations, since clinical materials may contain infectious agents, to ensure that the materials do not leak or injure anyone involved in the transportation or the wider public and environment. The duty of care (to the patient) is to ensure that the transport conditions do not damage the material being sent for testing or otherwise interfere with the validity of the test results, and to ensure the specimen reaches the laboratory in good condition within an appropriate time frame for good clinical management of the case. Specimens should be clearly labeled and dated. Place all specimens in leak proof containers in sealed plastic bags NB: Category 3 samples must be double bagged and clearly identified.

Samples from the Royal Group of Hospitals can be sent by hospital courier.

Samples from other hospitals / GPs may be sent by the relevant dispatch systems.

Postal samples must be sent in accordance with the guidelines issued by the Post Office in respect of postal transmission of pathological specimens.

Any referring Unit, Hospital, Clinic, GP Practice or Trust transporting specimens by road (which includes postal services) should take professional advice and guidance on the packaging and labeling of any materials they hand over for transportation. For exact sample containers and fixation requirements for specimen types please see Repertoire section below.







MINIMUM RE-TESTING INTERVALS Surgical Pathology It is not helpful to specify minimum retesting intervals for the majority of cellular pathology specimens which tend to be unique to a particular clinical episode. In general, biopsies are taken for specific clinical indications. A repeat biopsy may be necessary if: - An initial biopsy does not provide sufficient information for clinical

management. - When clinical features or disease progression do not fit with a previously

established diagnosis then review of previous biopsy material should be undertaken before considering a repeat biopsy.

- Where patients are undergoing regular clinical review, e.g. endoscopies for Barrett's, inflammatory bowel disease, repeated biopsies may be required to monitor response to treatment or to detect progressive disease at an early stage.

- Re-biopsy in chronic renal disease – an annual (for example) biopsy is recommended for monitoring and should not be repeated more frequently unless clinically indicated.

- Repeat liver biopsies are only done by protocol for disease progression monitoring e.g. post-transplant hep C, or if the initial sample is insufficient for diagnosis.

Diagnostic Cytopathology The investigation of symptoms or clinical abnormalities should be investigated as appropriate. When considering the appropriate tests to request, the negative predictive value should be considered. Some tests, such as urine or nipple discharge cytology, are recognised as having a low negative predictive value and thus cannot be used to exclude significant disease. Repeating such tests does not provide further reassurance or negate previous equivocal results. A repeat sample may be necessary if an initial specimen does not provide sufficient information for clinical management. Repeatedly sending samples when a definitive diagnosis (e.g. positive for specific tumour type) has been established is a waste of resources. Cytological surveillance of asymptomatic patients following malignant disease (e.g. urine specimens as follow up for urothelial carcinoma) should not be performed more frequently than annually. The development of symptoms should be investigated as appropriate.







This information is in compliance with the Royal College of Pathologists publication National minimum retesting intervals in pathology: A final report detailing consensus recommendations for minimum retesting intervals for use in pathology. Version 7 December 2015. Cervical Cytology A repeat cervical smear should not be taken less than three months after the previous test. The opinion offered by the pathologist(s) in the report may suggest repeat sampling if there be diagnostic uncertainty or a requirement for more tissue for other more specialised tests such as electron microscopy, immunofluorescence, and molecular testing or flow cytometry. If further information is required in this context, the pathologist(s) in question should be contacted directly. RESULTS Results from Cellular Pathology are conveyed in the form of a report, issued by the reporting Pathologist. The report will contain a diagnosis and details of the cellular features that determines this diagnosis. There is provision for the electronic reporting of results to the requesting clinician. This provision is only granted after a request has been made in writing to the Clinical Lead. In Histopathology and Diagnostic Cytology, decisions regarding telephone communication of results are at the discretion of the Pathologist. In general, unexpected significant malignant diagnoses from a General Practitioner will result in telephone communication with the requesting GP. For patients who are already under the care of the MDT, unexpected results are communicated through regular MDT communication channels. In Cervical Cytology, all suspected invasive squamous cell carcinomas, and all adenocarcinomas are communicated directly to the responsible GP as part of the urgent referral pathway.







POST-MORTEM SERVICE The BHSCT mortuary is licensed by the HTA (Human Tissue Authority) to undertake post- mortems and to store the deceased. ADULT POST-MORTEM SERVICE When there is a death in the hospital the Doctor may wish to issue a death certificate or request a post-mortem. Guidance on death certification and cremation certification is available from www.health-ni.gov.uk website in a document entitled “Guidance on death, stillbirth and cremation certification”. This has been circulated to hospital staff. https://www.health-ni.gov.uk/sites/default/files/publications/dhssps/guidance-death-stillbirth-and-cremation-certification-pt-b.pdf Transport All adult patients being referred to the Belfast Health & Social Care Trust Mortuary must be prepared in line with the BHSCT last offices procedures. The Belfast Health & Social Care Trust has a contracted Funeral Director to transfer patients from all areas of the Belfast Trust to the Belfast Trust Mortuary. To arrange for the transfer of a patient to the Mortuary, staff must contact the Trust switchboard (0) once the last offices has been completed. The name of the patient, location & staff name must be given to the contracted Funeral Director. The contracted Funeral Director will respond and transfer the patient to the Mortuary within the contracted response time. Consent Forms Consent forms are available on each ward if a consented post-mortem is requested. These are triplicate forms and all sections must be filled in. One copy of this form is given to the relatives. One copy is put in the hospital notes and a third copy is for the Pathologist. It is very useful if a Doctor, who knows the patient well, fills in a clinical summary form. This can guide the Pathologist as to the major issues involved in any case. The Doctor may wish to indicate specific questions that need answered by doing the post-mortem.

http://www.health-ni.gov.uk/https://www.health-ni.gov.uk/sites/default/files/publications/dhssps/guidance-death-stillbirth-and-cremation-certification-pt-b.pdfhttps://www.health-ni.gov.uk/sites/default/files/publications/dhssps/guidance-death-stillbirth-and-cremation-certification-pt-b.pdf







Body Transfer Form Body Transfer form 1A (Adult) must accompany each patient admitted to the mortuary. This form must be completed in full by ward staff and informs the Mortuary staff that a post-mortem is to be performed or if the death has been referred to the Coroner etc. Poorly completed body transfer forms may delay the management of the patient through the Mortuary. Documentation requirements:

Hospital notes.

Consent form with the clinical summary.

Fully completed body transfer form. All of the above must accompany the body to the mortuary. The clinical notes should be available to the Pathologist; these will be returned to the ward within 24 hours of autopsy. Coroners Cases A death may be reported to the Coroner in the following situations:

A doctor did not treat the person during their last illness.

A doctor did not see or treat the person in the 28 days before they died.

The cause of death was sudden, violent or unnatural, such as an accident or suicide.

The cause of death was murder.

The cause of death was industrial disease of the lungs, such as asbestosis.

The death occurred in other circumstances that may require investigation.

A death in hospital should be reported to the Coroner if:

There was a question of negligence or misadventure about the treatment of the person who died. They died before a provisional diagnosis was made and the doctor was not willing to certify the cause.

The patient died as the result of the administration of anaesthetic. Consent is not required for Coroners Cases. Information on Coroner’s post-mortems may be obtained from the Coroner’s Service for Northern Ireland at www.coronersni.gov.uk/questions

http://www.coronersni.gov.uk/questions







All adult patients directed by the Coroner for Post Mortem will be transferred from the Belfast Trust Mortuary to the Northern Ireland Regional forensic Mortuary were the examination will take place. Ward staff must not make arrangements for the eventual release of a body without first contacting the mortuary staff to ensure that families are not given unnecessary expectations of return of a body. Further information may be obtained from the mortuary or the Bereavement Support Office available during opening hours through the RGH Switchboard. PAEDIATRIC POST-MORTEM SERVICE All children, infants and babies over 12 week’s gestation by size, i.e. crown-rump length 6 cm, must be transferred to the Belfast Trust Mortuary for post-mortem. All paediatric post-mortems are carried out by Alder Hey Children’s NHS Foundation Trust which is based in Eaton Road, Liverpool, L12 2AP. The Belfast Trust Mortuary will make the necessary arrangements for the baby or child to be transferred to Alder Hey for the Post Mortem to take place. All clinical units referring a child, infant or baby to the Belfast Trust Mortuary for Post Mortem in Alder Hey must consult the ‘Guidance for the Admission of Perinatal / Paediatric to the BTM for consented Post Mortem’ (TP-1612). TP-1612 Guidance for the admission of perinatal/paediatric cases to BTM for consented hospital post mortem Paediatric cases are hospital consented post-mortem examinations. Arranging a Paediatric post-mortem Contact the Mortuary: Monday - Friday: 9.00 am - 5.00pm: 02890 633679 Saturday: 9.00am – 12.30pm 02890 633679

Out of hours: 07979 366041

NB Ward staff should not give a time for post-mortem examination/funeral to the family until they have spoken to the Mortuary. Transport It is the responsibility of the referring unit to arrange transport to Belfast Trust Mortuary with their Trust Funeral Director.

http://belqpulse101/QPulseDocumentService_Labs/Documents.svc/documents/active/attachment?number=TP-1612http://belqpulse101/QPulseDocumentService_Labs/Documents.svc/documents/active/attachment?number=TP-1612







The baby must be transferred during Belfast Trust Mortuary the working hours (Mon to Fri 9.00am – 5.00pm, Sat 9.00am-12.30pm). If this is not possible the body should be transferred early the next working day. If from UHD, LVH or MIH, bodies can be admitted outside these hours as the funeral director is that of BHSCT. All bodies must be transferred in a suitable casket, coffin or corrugated plastic box. Larger infants may be wrapped in a sheet or blanket. If no suitable casket is available advice should be sought from Paediatric Pathology before transfer. The body along with the outside and inside of the casket must both be clearly labelled with the name and DOB of the baby. Any personal items accompanying the remains may be placed in the casket or forwarded along with it. Any personal items must be recorded on the Body Transfer form 1B. A body transfer form 1B MUST be fully completed in every case to ensure full traceability. There are three copies: white, blue and green. The white and blue copies must accompany the body. The green copy is retained by the ward. Further instructions are on the inside cover of the book of body transfer forms held in the ward. Documentation Requirements Documents to be sent with the body to the mortuary are: Consented case –

1. A fully completed, appropriately signed DHSSPS consent for Post Mortem form (baby or child), white copy only.

2. A Coroners Authorisation Proforma completed by the referring consultant/consent taker as appropriate to the case (Coroners Authorisation Proforma A or Proforma B).

3. A Belfast HSC Trust Regional request for post-mortem examination of a baby form.

4. A body transfer form (1B). 5. A copy of the MCCD or Stillborn certificate as appropriate. 6. A copy of the obstetric or clinical notes as appropriate (were required).

Coroner’s case – SUDI proforma/clinical history and hospital notes and fully completed body transfer form (1B). Parental consent is not required for a Coroner’s post-mortem.







Hospital cremation – if the baby is to be cremated by the Paediatric Pathology Service the appropriate forms should be included with post-mortem documentation. Place all paperwork in a sealed envelope labelled with the name and DOB of the baby and give to the funeral director at the time of transfer. NB: Do not place in the container with the body.

SUDI (Sudden unexpected Deaths in Infancy) All sudden unexpected deaths in infancy (SUDI) and in childhood must be reported to the coroner and investigated thoroughly. Priority must be given to the preservation of forensic evidence at all times. For further information/advice please contact the Mortuary at the numbers above. CATEGORY 3 CASES Category 3 cases (communicable diseases) pose a risk to staff handling the remains, including mortuary staff, pathologists and designated funeral directors.

Place the into a body bag and clearly label as such by using a hazard group 3 label on the wrappings around the body.

Complete the Body transfer form, ensuring that the infection risk section is clearly completed.

Place any patient notes or summaries into a sealed envelope or bag to ensure patient confidentiality.

Ensure the designated funeral director who is transferring the remains to the Belfast Trust Mortuary is made aware of the Category 3 status of the remains, but for patient confidentiality reasons, the nature of the infection need not be disclosed.

Senior Mortuary MTO staff will contact the referring ward or the infection control team to discuss the management of the patient if required. RELEASE OF BODY AND REPORTS Upon completion of the post-mortem the Mortuary will release the body to the designated family Funeral Director. Coroners authorization for the release of a body will be required for all coroners cases. When the post-mortem has been completed the Belfast Trust Mortuary will contact the Mortuary or contracted funeral director of the referring hospital to arrange the return of the body to the referring hospital.







Patients not requiring a post-mortem will be released from the Belfast Trust Mortuary to the designated family funeral director upon completion of the Medical Certificate Cause of Death (MCCD), or the issue of a Proforma letter from the Coroner’s office. The report will be forwarded electronically by password protected email. Autopsy reports aim to be completed within 12 weeks, although complex cases or those with peripheral laboratory involvement may take considerably longer. TISSUE DONATION SERVICE The Belfast Trust Mortuary assists the NHS Blood & Transplant Service (NHSBT) under a service level agreement, with the National Eye Donation Service. All patients referred to, or pending referral to the NHSBT for eye donation, must be forwarded to the Mortuary with a Body Transfer Form (1A) with the organ retrieval section completed appropriately. Consent for donation will be forwarded to the Mortuary by the National Referral Centre when the next of kin consents to the donation. In cases of solid organ donation, local Specialist Nurse Organ Donation (SNOD) may take consent from the next of kin for Eye Donation. In these cases the consent must be forwarded to the Mortuary along with the appropriate Ante-Mortem blood samples for the Mortuary to facilitate the eye donation. If practical Mortuary MTO staff will facilitate eye retrievals in theatres in cases of solid organ donation. This can be discussed by contacting the Mortuary on 028 9615 5908 (opt 1).

SAMPLE REQUIREMENTS AND TURNAROUND TIMES (TATs)

Cellular Pathology aim to achieve TATs within Young Person and Adult Screening Team** Guidelines Turnaround times are currently under review as the RCPATH guidelines are unattainable due to workload increases and Consultant staff shortages. Updated figures will be published once agreed. The figures published below are for financial year 2017/18.







Surgical Pathology Specialty /

Sub-Specialty Specimen

Type Specimen Requirement TAT

General Histopathology

Surgical Biopsies

Immediately place specimen in 10% formalin.

All specimens must be delivered to the laboratory in adequately sized leak proof containers in accordance with UN3373:

o Supplied to BHSCT sites by Belfast Trust Laboratories o Sources outside the BHSCT can purchase suitable containers

through SARSTEDT website (https://www.sarstedt.com/en/home/)

63% reported within 7 days. 74% reported within 10 days.

General Histopathology Frozen

Sections (including brain frozen sections)

Tissue must be fresh and delivered to the laboratory immediately.

The tissue must reach the laboratory between 8:45am - 4.00pm.

For out of hours see table on page 4.

- Transport arrangements are the responsibility of the requestor. PRE-BOOKING:

Frozen sections must be pre-booked if required during planned surgery.

1 hour onsite 2 hours offsite (verbal report). A written report will follow, TAT as stated above for surgical biopsies.

Paediatric Pathology

NB: Frozen section analysis is unsuitable for primary diagnostic purposes in many aspects of e.g. breast disease or lymphoreticular malignancies or where hazard of infection is suspected. Also, frozen sections give poorer histological definition than specimens routinely fixed in formalin. Advice on the appropriateness of frozen section diagnosis may be obtained by contacting the Duty Consultant.

Mohs

Frozen Sections (skin)

Contact No: 02890650407 Level 5 Dermatology Outpatients Department, RGH. Clinic every Tuesday from 08:30 a.m

Same day diagnosis.

https://www.sarstedt.com/en/home/







Specialty / Sub-Specialty

Specimen Type

Specimen Requirement TAT

Neuro- Pathology

Muscle Biopsy

Request Liquid nitrogen and EM fixative from laboratory and ensure that staff will be available to receive specimen.

85% within 14 days.

Inflammatory myopathy cases - provisional report available in 3 working days.

Three separate specimens are required from each muscle biopsy: 1. Histology and Enzyme Histochemistry:

Specimen size should be approximately 0.3 x 0.3 x 0.3 cm.

Place the specimen on a piece of lollipop stick or tongue depressor and wrap in a piece of saline “dampened” gauze.

Place the gauze and specimen in a dry sterilin jar and immediately place on ice. 2. Electron Microscopy:

The specimen can be smaller than that for histology.

Place the specimen on a piece of lollipop stick or tongue depressor and immerse in the EM fixative provided. 3. Specialist Investigation

Specimen size should be similar to that of the piece taken for Histology.

Wrap the specimen in the Parafilm supplied and drop into the liquid nitrogen. If a skin biopsy is also required inform the Neuropathology Laboratory who will supply an extra EM fixative and transport medium for cell culture. Muscle biopsies & skin in EM fixative: Send immediately to the Neuropathology Laboratory. Specimen for cell culture: Send to the Department of Medical Genetics (with the appropriate request form).







Specialty / Sub-specialty

Specimen Type


Neuro- Pathology

Peripheral Nerve Biopsy

2 x 1 cm pieces nerve tissue, stretched on stiff card on saline dampened gauze (normal tension to avoid contraction).

Send to laboratory immediately.

90% within 14 days. (In cases of vasculitis a provisional report can be provided in 4 working days).


Paediatric Tumour Biopsies

Tumour biopsies (needle biopsies, incisional biopsies or tumour resections) should be sent immediately to the laboratory fresh and unfixed.

Contact laboratory prior to sending the specimen.

Needle biopsies, may be placed onto paper.

The tissue must be kept moist with a small amount of sterile saline.

In order to obtain the most information possible, as much tissue as possible should be obtained and submitted.

Under review NB: Excludes bone


Products of Conception

Requires completed ‘Consent to Histopathological Examination and Disposal of First Trimester Pregnancy Loss’ form in addition to a completed General Histopathology request form.

If no consent form is received, the specimen will be returned to the referring unit until one is completed.

Any residual tissues left after processing for histopathological examination are communally cremated at Roselawn Crematorium, or returned to the mother if requested.

Under review


Placentas

At present, the service is limited to examination of placentas from babies who are born dead, or who die following delivery.

Other placentas can be examined at the request of a consultant obstetrician or neonatologist.

A completed ‘Request for Histopathological Examination of Placenta’ form should be submitted with the placenta.

Under review







Cervical Cytology Specialty /



Cervical Cytology

Cervical Samples

Do not use expired vials.

Ensure the entire plastic seal is removed from the lid of the vial and discarded before taking the smear.

The cervix should be visualized.

Immediately rinse the collected material vigorously into the vial.

Seal the vial and send to the lab. Clinical advice on cervical smear taking can be obtained by phoning: Dr D McGibben - Lead Cytopathologist on 028 9504 6141 or Dr Avril Cullen - Consultant Pathologist on 028 9504 4789

If unsure of how to provide specimens for cytological investigation please contact the appropriate laboratory for advice. Supplies Requests – Cervical Cytology Requests for ThinPrep LBC vials, brushes and request forms should be directed to Screenlink:

Phone/voicemail: 00353 1 4605270 Fax: 00353 1 4605248 E-mail: [email protected]

80% within 28 days.

mailto:[email protected]







Diagnostic Cytopathology Specialty /




Peritoneal/ Pleural/ Pericardial Fluid

Please send no more than one litre of peritoneal/ pleural fluid.

Submit Fresh fluid in a sterile wide-mouthed container.

Do not use fixative.

Do not send in a plastic drain bag or a rigid Perspex drain box.

92% within 7 days


Urine

Submit a freshly voided sample in a sterile wide mouthed container.

Do not use fixative.

Prior to collection of the urine sample the patient should be well hydrated for 1.5 to 2 hours.

During the period of hydration the urine should be discarded. The next voided urine sample should be collected and submitted for cytological examination.

Early morning samples are of little value as these show marked cellular degeneration.

State on the request form if the patient has been catheterised, had any form of instrumentation, has stones in the urinary tract or is receiving chemotherapy.

97% within 7 days


Bronchial Washings and Brushings

Bronchial washings should be submitted fresh. No fixative should be used. The bronchial brush should be placed in the fixative provided by Cytopathology and shaken vigorously.

98% within 7

days


Sputum Three deep-cough early morning samples should be submitted.

83% within 10

days

87% within 10

days








Specimen Type


Diagnostic Cytopathology (Ext 50217 or 07824564169)

Fine Needle Aspirates

Clearly label slides

Radiologists performing image-guided FNAs of deep sites may arrange for a BMS to be present by emailing DL-Lab-ROSE-FNA or phoning the laboratory.

Notification of the approximate time should be given as soon as it is known and contact the laboratory again approximately 15 minutes before assistance is required.

Arrangements can be made for a pathologist to carry out fine needle aspiration of superficial sites by phoning the laboratory.

If appropriate, saline solution can be used to rinse the needle to allow collection of residual cells from the needle hub. These should be forwarded to the laboratory in an appropriately labelled sterile specimen container (eg White top sterilin pot) along with any labelled slides and completed request form.

95% within 7 days


ERCP Brushings

Fixative is provided by Cytopathology.

Place brush in pot and shake vigorously.

84% within 7 days

Diagnostic Cytopathology Neuro- Pathology (for CSF 14-3-3 analysis see Appendix 1)

Cerebro- spinal Fluid (CSF), Cyst Fluid or Aspirate for Cytological Examination

1 ml or more of fresh unfixed fluid, preferably not bloodstained.

If clinically indicated, label both the biohazard bag and the request form with a category 3 (green) sticker.

62% within 48 Hours


CUSA Fluids

Send to lab immediately.

Store refrigerated at 4°C if a delay in transport is anticipated.

CUSA washings to be sent from all neurosurgery cases.

94% within 7 days.







1 ml or more of fresh unfixed sample.

If clinically indicated, label both the biohazard bag and the request form with a category 3 (green) sticker.

Specialist Services Specialty /



Immuno- Pathology

If Immunofluorescence is required for diagnosis, the tissue sample and/ or blood sample must be unfixed.

Immuno- Pathology

Dermatology Specimens

Dermatology specimens requiring Immunofluorescence consist of a skin biopsy/ mucosal biopsy/ conjunctival biopsy/ blister fluid/ and a clotted blood sample.

Request transport medium from the laboratory.

Once the biopsy has been performed please arrange return transport to the laboratory.

91% reported within 7 days. 94% reported within 10 days.

Immuno- Pathology

Blood for Erythropoetii Protoporphyria

Use Anti-coagulant sample container (purple top).

Keep sample in darkness.

Send to the laboratory immediately.

Notify laboratory that sample is in transit.

24 hours.







Immuno- Pathology

Renal Specimens

Phone the laboratory to arrange delivery of the special fixatives kit.

Once the biopsy has been performed please arrange transport to the Immunopathology Laboratory and phone to advise that the specimens are in transit.

If a kit is unavailable, the tissue specimen may be placed in saline & transported as quickly as possible to the laboratory (please phone the Immunopathology Laboratory to advise that a specimen is in transit).

Kit instructions are available in appendix 3.

83% reported within 7 days. 92% reported within 10 days. (If EM is required see below).








Specimen Type


Electron- Microscopy

All specimens

Blood

Renal Specimens

Request EM fixative from the EM laboratory.

Blood needs to have anticoagulant added. Cover the sample and transport to the laboratory as quickly as possible (please phone the EM Laboratory to arrange this).

Renal specimens (see above for Immunopathology).

90% within 14 days.

Molecular Pathology (BCH) (see appendix 2) Continued on next page…

FFPE material for the following tests

For all tests requested please provide a copy of the Pathology report OR original request form. Sharepoint referrals CANNOT be accepted. Lung Adenocarcinoma

H&E stained section plus the following

EGFR-5x 5-µm unstained sections on uncoated slides OR Tumour block.

ALK IHC expression analysis-2x4 µm unstained sections on TOMO-branded slides.

PD-L1 IHC expression analysis-2x 3 µm sections on TOMO-branded slides

Lung Squamous cell carcinoma

H&E stained section plus the following

PD-L1 IHC expression analysis-2x 3 µm sections on TOMO-branded slides

Please note: If sections are from a cell block a TTF-1 IHC slide is required.

90% within 7 days. 90% within 7 days.








Specimen Type


Continued from previous page…

Current algorithms deal with EGFR, ALK and PDL-1 requests at the same time to save on material (see below).

Lung Cancer only: Our current diagnostic algorithm encompasses EGFR, ALK and PD-L1 requests for lung adenocarcinoma, and PD-L1 for squamous cell carcinomas. Where sample material is limited, we recommend that the FFPE block is carefully trimmed to expose the surface of the material on the microtome and the sectioning protocol as shown in the table is followed: The H&E can provide “levels” and can be sent to us along with the blank sections for EGFR, ALK & PDL-1 testing. Further information is available upon request

Section Number Purpose

1 H&E

2-4 IHC

5 H&E

6-10 EGFR

11 H&E

12-15 ALK/PD-L1

16 H&E

90% within 7 days.







Molecular Pathology (BCH) (see appendix 2)

Blood sample cfDNA EGFR Mutation Analysis

We will send to centres dedicated cell free DNA collection tubes (Roche) specifically designed for analysis of EGFR mutation analysis of cfDNA, upon request to the laboratory, Tel. 028 95042849.

A completed cfDNA Request Form (available upon request from the laboratory) TP-666 NI-MPL Request Form cfDNA samples

8.5 mL peripheral blood in 1 x Cell-free DNA (cfDNA) collection tube sent at room temperature (18-24ºC) (important: please fill the tube fully as failure to do so may compromise the suitability of the specimen)

Collection tubes should be stored upright

Collection tube must not be past the expiry date.

Do not freeze or refrigerate the sample

Please telephone the duty Scientist to advise of samples departure. The latest time samples can be received in Molecular Pathology is 4.30pm.

Samples in transit ≥7 days will be rejected at sample receipt.

90% within 7 days.

http://belqpulse101/QPulseDocumentService_Labs/Documents.svc/documents/active/attachment?number=TP-666







FFPE material for the following test:-

Gastric Her2 IHC

H&E plus 2 x 3 µm unstained sections on TOMO-branded slides. (Ordered initially from NI MPL).

Breast Her2 FISH

2x 3-µm unstained sections on 90ºedge TOMO slides OR Tumour block. And Her2 IHC-stained slide.

90% within 7 days 90% within 7 days.

FFPE material for the following test:-

Microsatellite Instability analysis (MSI) (Colorectal carcinoma only)

5 x 5um unstained sections on uncoated slides plus H&E stained section

Advanced Colorectal Carcinoma KRAS/NRAS/BRAF Mutation Analysis

5x 5-µm unstained sections on uncoated slides plus H&E stained section OR Tumour block.

Melanoma (BRAF/NRAS Mutation Analysis)

5x 5-µm unstained sections on uncoated slides plus H&E stained section OR Tumour block.

BRCA Mutation Analysis (Currently a send away test)

5 x 5-µm unstained sections on uncoated slides. Plus H&E stained section (NB these are referred to Manchester Genomics Lab)

90% within 14 days 85% within 14 days. 90% within 7 days. 28 days

Cytology specimens

Protocols as above from cytoblocks OR cytospins fixed in Polyethylene Glycol (PEG) or formalin. Please indicate the means of preparation when making the request.

As above

depending







These items should be placed inside an envelope: Marked Urgent Pathological Specimen and addressed to: Northern Ireland Molecular Pathology Laboratory, 1ST Floor Health Sciences Building, 97 Lisburn Road, Belfast, BT9 7AE. Measurement of uncertainty for the above tests can be requested via email [email protected]

on test

required.








Appendix 1 - CSF 14-3-3 Analysis

Before sending a sample to Cellular Pathology for 14-3-3 analysis the patient's clinician should make direct contact with the National CJD Surveillance Unit (Tel: 0131 537 1980) in Edinburgh where they can discuss the patient's clinical picture with one of the unit’s specialist staff. They will give guidance as to whether the sample should be directed to Cellular Pathology for onward dispatch to Edinburgh or sent directly. If the Cellular Pathology laboratory receives the specimen, contact will be made with the National CJD Surveillance Unit to arrange for onward transportation. When requesting CSF samples for 14-3-3 analysis the CJD Surveillance Unit has produced its own specially formatted request form which was circulated to the Neurology and Neurosurgical Wards, this must be completed and forwarded to Neuropathology along with the sample. If a copy of this form isn't available on the ward the clinician may request an emailed copy to be sent to them by either the CJD Unit or the Cellular Pathology laboratory (02896150216). CSF samples requiring 14-3-3 analysis must be sent to the Cellular Pathology laboratory as soon as possible. For this to happen in a timely fashion the laboratory should be contacted Monday to Friday 8.45am to 5.00pm (02896150216) for arrangements to be made for the dedicated laboratory courier to collect the sample. Ideally 0.5-1.0ml of CSF fluid should be submitted for testing. Samples for 14-3-3 analysis must not be blood stained as this will render the sample unsuitable for diagnosis. If cytological examination is also required a separate sample should be submitted. The sample/s must be placed in a leak proof sample container and be clearly labelled with the patient's details and a Category 3 sticker, and placed in a "Danger Risk of Infection" bag which also contains a pouch where the appropriately completed and Cat 3 labelled Pathology request form and CJD Surveillance Unit request form can be placed to accompany the sample and where it will be protected from sample leaks. Copies of 14-3-3 prion testing results will be forwarded directly to both the Consultant and the laboratory.







Appendix 2 - Molecular Pathology Descriptions of Tests KRAS/NRAS/BRAF-Advanced Colorectal Carcinoma Clinical Rationale Several studies have shown the high prognostic value of KRAS and NRAS mutation response to anti-EGFR (Cetuximab) treatment in metastatic colorectal cancer. Patients with wild-type KRAS and NRAS (Mutation NOT detected) are more likely to have disease control on cetuximab therapy. Patients with KRAS or NRAS mutations may not benefit from this treatment. BRAF mutations are associated with a poorer prognosis in advanced colorectal cancer, and there is no clear evidence suggesting significant benefit from anti-EGFR monoclonal therapies in isolation. Known “hotspot” mutations on KRAS, NRAS, BRAF genes are identified by COBAS QPCR. See MSI section regarding BRAF mutations in sporadic cancer. EGFR Clinical Rationale Several studies have shown the high prognostic value of certain EGFR mutations’ response to Gefitinib and Erlotinib treatment in adenocarcinoma of the lung. Patients with mutations in the EGFR gene, specifically exons 18, 19 or 21 are more likely to have disease control on Gefitinib or Erlotinib therapy. Patients with no detectable EGFR mutation may not benefit from such treatments. Patients with mutations in the EGFR gene exon 20 however, may not benefit from such treatments. In addition, patients who harbour the T790M mutation have been shown to confer resistance to first and second generation anti-EGFR Tki treatment, therefore these patients may benefit from 3rd generation TKI therapy. Known “hotspot” mutations on the EGFR gene are identified by COBAS QPCR. EGFR Cell free DNA (cfDNA) NIMPL have validated the cobas EGFR mutation test v.2 to detect EGFR mutations -including the EGFR p.T790M mutation- in plasma isolated from peripheral blood samples. This allows the testing for EGFR mutations in patients whose previous tissue sample failed analysis or no tissue sample is available for analysis. NIMPL use the cobas ® cfDNA EGFR mutation test capable of detecting >95% of mutations described in the regions analysed with a limit of detection of 1%. ALK Clinical Rationale ALK Clinical Rationale Several studies have shown the high prognostic value of translocations involving the ALK gene in adenocarcinoma of the lung. Patients with ALK translocations show







overexpression of ALK protein using IHC methods. Patients showing ALK overexpression are more likely to respond to ALK inhibitor therapy. Patients showing no ALK overexpression by IHC may not benefit from such treatments. Translocations involving ALK are identified by Immunohistochemistry only (Ventana). PD-L1 Clinical Rationale Pembrolizumab has been given EMA approval for the treatment of squamous and non-squamous non-small lung carcinomas. Patients with an identified PDL1 expression may be treated with Pembrolizumab in second line treatment based on PDL1 expression equal to or greater than 1% in 2nd line treatment or where PDL1 expression is equal to or greater than 50% in 1st line treatment (EMA favourable opinion, awaiting approval). We have validated the Ventana SP263 antibody for the detection of PDL1 in suitable formalin fixed paraffin embedded (FFPE) material and can provide a reflex test upon a diagnosis of NSCLC, squamous or adenocarcinoma. BRAF/NRAS Clinical Rationale Several studies have shown the high prognostic value of BRAF mutation response to Vemurafenib treatment in malignant melanoma. Patients with BRAF mutation are more likely to have disease control on Vemurafenib therapy. NRAS mutations have been described in up to 25% cutaneous melanomas. Clinical trials have shown some activity of MEK inhibitors in NRAS mutant melanomas. Mutations on the BRAF and NRAS genes are identified by COBAS QPCR (Roche). Her2 FISH Clinical Rationale HER2 is a member of the human epidermal growth factor receptor (HER/EGFR/ERBB) family. Amplification or over-expression of this oncogene has been shown to play an important role in the development and progression of certain aggressive types of breast cancer. The protein is targeted by the monoclonal antibody trastuzumab (Herceptin) therapy. In breast cancer, patient samples with a HER2 score of 2+ by immunohistochemistry are referred for HER2 gene amplification analysis by Fluorescence In Situ Hybridisation (FISH). HER2 gene amplification status is determined using the algorithm set by the Updated UK HER2 guidelines.

MSI testing in Colorectal Carcinoma Clinical Rationale Microsatellite unstable tumours are found in approximately 15% of all colorectal

cancers and although deficient DNA MMR systems indicate that a person may have

Lynch syndrome, they can also be seen in sporadic colorectal cancers. Sporadic

colorectal cancers can also show BRAF V600 mutations. Using MSI and reflex

https://en.wikipedia.org/wiki/Epidermal_growth_factor_receptorhttps://en.wikipedia.org/wiki/Epidermal_growth_factor_receptorhttps://en.wikipedia.org/wiki/Gene_duplicationhttps://en.wikipedia.org/wiki/Oncogenehttps://en.wikipedia.org/wiki/Breast_cancer







BRAF mutation testing can identify sporadic colorectal tumours that are MSI

unstable with BRAF mutations, in people who are not at risk for Lynch syndrome,

and therefore prevent unnecessary further genetic testing. Conversely, for patients

who are found to have MSI unstable, BRAF wildtype tumour a referral to genetics for

germline lynch syndrome testing will be recommended on the patient report.

If you need further clarification, please do not hesitate to contact: NI MPL Tel. 028 95042849 Email: [email protected]

Appendix 3 - Instructions for Renal Biopsy Kits

Kit contents 10% Formalin for Light Microscopy. PBS for Immunofluorescence. 3% Gluteraldehyde for Electron Microscopy. Dental wax. Request Form. Procedure Ideally there should be 3 cores; 1 each for light microscopy (LM), Immunofluorescence (IMF) and electron microscopy (EM). The fixatives for each are labelled as such. Usually the cores are collected and fixed at the same time to allow best division of material in the laboratory.

1. Place the core on dental wax to keep the core flat. 2. Drop the wax + core into PBS. 3. 2nd core is dropped into Glut. 4. 3rd core is dropped into 10% Formalin.

It is essential that there is NO cross contamination of fixatives. If there is only one core and both IMF and LM are required it is best to drop the core into PBS as this can be stained for IMF and then reprocessed for LM. Please note that reprocessing a single core for light microscopy after it has been frozen for immunofluorescence results in significant freeze-thaw artefact which can make interpretation of the light microscopic findings difficult. If electron microscopy is also then required on this tissue, the same applies with regards to freeze-thaw artefact and there may be insufficient tissue remaining for this examination. Single cores should therefore be avoided if possible.








Laboratory phone number: 02896150215 Laboratory mobile number: 07717805516







Appendix 4 - Referrals For Referrals please liaise with the Consultant Histopathologist, Cytopathologist or Neuropathologist as appropriate. The UKAS accreditation status of referral laboratories is regularly checked. Human Papilloma Virus (HPV) Testing in Cervical Cytology The aetiological role of Human Papilloma Virus (HPV) in the development of cervical cancer is well established. The NHSCSP has therefore introduced additional High Risk (HR) HPV testing on selected cervical cytology samples which has the benefit of fast tracking women at risk for treatment and also reduces unnecessary repeat tests. Samples for HPV testing are dispatched to Altnagelvin Area Hospital. HPV Triage The HPV Triage test is performed on routine cervical samples showing a low grade cytological abnormality. This includes borderline changes and mild dyskaryosis. A negative (not detected) HPV test allows a woman to return to normal recall whereas a positive (detected) HPV test initiates a referral to colposcopy. HPV Test of Cure The HPV Test of Cure (ToC) is performed on samples taken following large loop excision of the transformation zone (LLETZ) treatment for an abnormality, as per request from colposcopy clinician. Uncertainty of Measurement In cervical cytology the examination of the sample is used to indicate the presence or absence of disease. Where biological variation in samples occurs, this can lead to difficulties in interpreting results. Where there is genuine doubt as to whether cells changes are abnormal an equivocal report “borderline changes‟ is issued. This report will initiate either an HPV test on the original sample to aid patient management or a repeat test. Within the NHSCSP the sensitivity and specificity of the test is well understood and documented. All laboratories and screening individuals are monitored and expected to achieve sensitivities in excess of 90% for all abnormalities and more than 95 % for high grade abnormalities.







Referral Laboratories Samples

Institution Samples Referred

Address

Alder Hey Hospital

Placenta Paediatric Post Mortems

Alder Hey Hospital Children’s NHS Foundation, Mortuary Dept. Eaton Rd, Liverpool, L12 2AP

Altnagelvin Area Hospital

HPV, regional reporting

Department of Cellular Pathology, Altnagelvin Area Hospital,, Glenshane Road,, Londonderry, BT47 6SB

Antrim Area Hospital

Regional reporting

Department of Cellular & Molecular Pathology, Antrim Area Hospital, 45 Bush Rd, Antrim, BT41 2RL

Belfast City Hospital

Flow Cytometry

Department of Haematology, ‘C Floor’, Tower Block, Belfast City Hospital, Lisburn Road Belfast, BT9 7AB

PCR Department of Medical Genetics,‘A Floor’, Tower Block, Belfast City Hospital, Lisburn Road, Belfast, BT9 7AB

Bristol Royal Infirmary

Oral Pathology

Department of Histology, Level 9, Bristol Royal Infirmary, Marlborough street, Bristol, BS2 8HW

Cardiff University

Oral Pathology

School of Dentistry, Heath Park, Cardiff University, CF14 4XY

Charing Cross Molar Pregnancy

Trophoblastic Tumour Screening and Treatment Centre, Department of Medical Oncology, Charing Cross Hospital, Fulham Palace Road London, W6 8RF

Craigavon Area Hospital

Regional Reporting

68 Lurgan Rd, Portadown, Craigavon BT63 5QQ

Genomic Diagnostics

Molecular Tests

Genomic Diagnostics Laboratory, Genetic Medicine (6TH Floor), St Marys Hospital, Oxford Road, Manchester, M13 9WL

Genomic Diagnostics

Molecular Tests

Genomic diagnostics laboratory, Manchester centre for genomic medicine, St Mary's Hospital, Oxford rd, Manchester M13 9WL

Genomic Health Oncotype DX

Genomic Health, Inc. 301 Penobscot Drive Redwood City, CA 94063-4700

HMDS Lymphomas additional

Haematological Malignancy Diagnostic Service St. James' Institute of Oncology, Level 3 Bexley








Address

testing ISH and ICC.

Wing Beckett Street, Leeds, LS9 7TF

HSL (Analytics) Molecular Tests

HSL, Advanced Diagnostics 1st Floor, Rockefeller Building 21 University Street London, WC1E 6JJ

HSL (Analytics) Tau/Amyloid Analysis

HSL, Institute of Neurology, Queen Square, London, WC1N 3BG

Kings College Hospital

Liver studies Institute of Liver Studies, Kings College Hospital, Denmark Hill, London, SE5 9RS

Muscle Immunoanalysis Unit

Rare Muscle Diseases

Muscle Immunoanalysis Unit, Lower Ground Floor, Dental Hospital, Richardson Road, Newcastle upon Tyne, NE2 4AZ

Queen Elizabeth Hospital, Birmingham

Oral Pathology Molecular Kit Testing

Department of Pathology, Queen Elizabeth Hospital Mindelsohn Way, Edgbaston, Birmingham, B15 2WB

Queen Elizabeth Glasgow

Eye Specimens

Department of Pathology, Queen Elizabeth University Hospital Govan Road, Glasgow, G51 4TF

Robert Aitken Institute

Sarcoma, Soft Tissue and , Bone Specimens

Department of Musculoskeletal Pathology, Robert Aitken Institute, The Medical School, Vincent Drive, Edgbaston Birmingham, B15 2TT

Royal Marsden BRCA1/2 Head of Clinical Genomics, The centre for Molecular Pathology, The royal Marsden NHS Foundation Trust, Cotswold Rd, Sutton, Surrey SM2 5NG

Royal Victoria Infirmary

Paediatric Tumours

Cellular Pathology, L3 New Victoria Wing Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP

Source Bioscience

POCS Source Bioscience, Medical Solutions Nottingham Business Park, Nottingham, NG8 6PX

St Georges Cardiac Prof Mary Sheppard, St Georges University of London, Cranmer Terrace, London SW17 0RE

University Hospital Wales

Urology All Wales Genetics Lab, Institute of Medical Genetics, University Hospital of Wales, Heath Park, Cardiff, CF14 4XW







National Referral labs


Address

National Amyloidosis Centre

Amyloid National Amyloidosis Centre, UCL Division of Medicine Royal Free Hospital, Rowland Hill Street, London, NW3 2PF

NCG Pseudomyxoma Peritonei Centre

Pseudomyxoma Peritonei cancers

NCG Pseudomyxoma Peritonei Centre, Basingstoke & N. Hampshire NHS Foundation Trust, Aldermaston Road, Basingstoke, Hampshire, RG24 9NA

Newcastle University

Muscle Newcastle Mitochondrial NCG Diagnostic Laboratory Department. of Neurology, 4th Floor Cookson Building The Medical School, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH

Second Opinion

Institution Address

Addenbrooke's Hospital

Histopathology Department, Box 235, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ

Birmingham Children’s Hospital

Department of Pathology, Diana Princess of Wales Children’s Hospital, Steelhouse Lane, Birmingham,B4 6NH.

Cancer Prevention Centre

Jewish General Hospital, Department of Cancer Prevention, 3755 Cote-Sainte- Catherine Road, Room E-740, Montreal, Quebec, Canada

Christie NHS Foundation Trust

Department of Pathology, Christie NHS Foundation Trust Wilmslow Road, Manchester, M20 4BX

Great Ormond Street Hospital for Children NHS Trust

Department of Pathology, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London, WC1N 3JH

HSL (Analytics) HSL, Haematology, UCL Cancer Institute, Paul O Gorman Building, 72 Huntley St, London, WC1E 6DD

John Radcliffe Hospital

Nuffield Division of Clinical Laboratory Sciences Radcliffe Department of Medicine Level 4, Academic Block, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU







Institution Address

Department of Cellular Pathology, John Radcliffe Hospital Level 1, Headley Way, Headington, Oxford, OX3 9DU

Kings College Neurosciences Academic Building, Kings College Hospital Denmark Hill, London, SE5 9RS

Manchester Royal Infirmary

Department of Pathology, Manchester Royal Infirmary Oxford Road, Manchester, M13 9WL

Royal Brompton & Harefield NHS Foundation Trust

Department of Pathology, Royal Brompton & Harefield NHS Foundation Trust, Sydney Street, London, SW3 6NP

Royal Marsden Hospital Department of Pathology, Royal Marsden Hospital Fulham Road, London, SW3 6JJ

Royal Liverpool University Hospital

Royal Liverpool University Hospital, Prescot Street Liverpool, Merseyside, L7 8XP

Royal Manchester Children's Hospital

Department of Paediatric Pathology 4th Floor, Royal Manchester Children's Hospital Oxford Road, Manchester, M13 9WL

Royal National Orthopaedic Hospital

Department of Pathology, Royal National Orthopaedic Hospital Brockley Hill, Stanmore, Middlesex, HA7 4LP

St Judes Tennessee St. Jude Children's Research Hospital 262 Danny Thomas Pl, Memphis, Tennessee, TN 38105, USA

Salford Royal Hospitals NHS Foundation Trust

Department of Cellular Pathology Neurosciences Centre Salford Royal Hospitals NHS Foundation Trust Stott Lane, Salford, M6 8HD

University Hospital Southampton

Cellular Pathology, University Hospital Southampton NHS Foundation Trust, Tremona Rd, Southampton, Hampshire, SO16 6YD

University Hospital Wales

Department of Cellular Pathology University Hospital of Wales, Heath Park, Cardiff, CF14 4XW