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The South East Genomic Laboratory Hub provides genetic and genomic testing for 19 acute NHS Trusts and 9 non-acute NHS Trusts in the South London, Kent, Surrey and Sussex region. Within the solid tumours service, we process DNA and RNA from patients with a range of cancer types and analyse them using next generation sequencing (NGS) assays.

Once the variants within a patient’s sample are identified, Clinical Scientists review them and consider what impact they would have on the function on the protein encoded by that gene. Through a process called somatic variant interpretation, the variant will be classified according to its clinical significance in relation to providing diagnostic, prognostic, or therapeutic information.

Some examples of the utility of this service include identification of:

resistance variants in EGFR within the tumours of patients with non-small cell lung cancer, providing the clinician with information to support a change to the patient’s treatment.
gene rearrangements involving TMPRSS2 can support a diagnosis of prostate cancer.
certain variants in POLE within the tumours of patients with endometrial cancer can classify their tumour into a subgroup which is associated with an excellent prognosis

Delegates will learn and understand:

What spatial profiling is about
Multi-omic techniques on tissues
How combining spatial profiling and multi-omic approaches leads to a better understanding of the pathophysiology of disease.

Specialist Portfolios – updated, flexible and achievable

Emergency presentation of adenocarcinoma in a young female.



This case study was carried out as part of the Advanced Specialist Diploma in Histological Dissection of Lower GI Pathology. The patient was a 34-year-old female who presented at A&E with sudden onset of abdominal pain and constipation. A CT scan showed multiple colonic polyps and a likely descending colon tumour. The differential diagnosis of the tumour was of an inflammatory process, in view of her young age and negative family history of colorectal cancer. Endoscopic biopsies confirmed the diagnosis of a well to moderately differentiated mucinous adenocarcinoma. A stent was placed to relieve obstructive symptoms and a genetic questionnaire was completed. The patient subsequently underwent a subtotal colectomy in view of the large number of polyps. Histology of the resection specimen showed a circumferential mucinous adenocarcinoma multiple lymph node metastases and lymphovascular invasion, TNM 8 pT3 N2b R0 V0 L1 Pn0.

Routine Mismatch Repair (MMR) immunohistochemistry detected a loss of MSH2 and MSH6, indicating possible Lynch syndrome. Further molecular testing including Microsatellite Instability (MSI) showed that Lynch syndrome was not present, and no genetic explanation could be found as to why the patient developed bowel cancer at a young age. Detection of a KRAS mutation in the tumour cells suggests that treatment with anti-EGFR therapies such as Cetuximab may not be effective in this patient. After discussion of the histology at MDT, the patient was referred to oncology for adjuvant chemotherapy which consisted of 6 months Oxaliplatin and 5-Fluorouracil. The patient completed the course in 2019 and was referred to the surgical team for follow up with CT scans, endoscopy and CEA monitoring.

In summary, this case demonstrates the essential role of appropriate sampling and molecular testing of colonic cancer resection specimens in guiding decisions about the patient’s subsequent treatment.

Delegates attending this session will learn about and gain knowledge on the introduction and application of the new EQA scheme to cover digital pathology in Cellular Pathology.

Mark Lundy was convicted of killing his wife and daughter in 2002 and again in 2015 after a retrial ordered by the Privy Council. His conviction continues to divide public opinion in New Zealand. A key piece of evidence was the presence of small smears on a shirt which prosecution experts identified as central nervous system tissue relying on immunohistochemistry.

The successful challenge to his original conviction was part motivated by arguments challenging the reliability of the latter in forensic practice. This has again come under scrutiny following a 2016 report by the US President’s Council of Advisors on Science and Technology. The PCAST concluded that there were two important deficiencies in ensuring scientific validity of so-called ‘feature-comparison methods’. These are procedures by which an examiner seeks to determine whether an evidentiary sample is or is not associated with a source sample based on similar features. Proponents of Lundy’s innocence argue that the application of immunohistochemistry must be regarded as a subjective feature-comparison method.

There was a need for (1) clarity about the scientific standards for the validity and reliability of forensic methods and (2) the need to evaluate specific forensic methods to determine whether they have been scientifically established to be valid and reliable. The report emphasized 2 key elements that are required to meet the scientific criteria of foundation validity; (1) a reproducible and consistent procedure and (2) empirical measurements from multiple independent studies of a method’s false positive rate and sensitivity.

It is this author’s position that the manner in which the immunohistochemistry was applied in the Lundy case to identify central nervous system tissue was sufficiently robust in terms of rigor and reproducibility and that to insist otherwise would be tantamount to believing in biological alchemy.

Histopathology has numerous stages in the production of a digital image and its subsequent use. Each of the stages can introduce variations that are compounded resulting in a net variation in image quality for nominally the same tissue. Humans are tolerant of variation so this variation in quality has minimal impact on outcomes, which are additionally validated by EQA services.

But AI is in some cases being negatively impacted by variation and highlights the need for quality metrics and subsequently standards for each stage, where possible. But currently there are few independent QC tools for digital histopathology. This presentation will present the results of our work in NPIC were we have developed QC tools for staining, digitisation and display in digital histopathology.

Diagnostic services are a fundamental aspect of modern healthcare delivery. Clinical pathways can only function properly with sufficient capacity to turnaround diagnostic tests, procedures, and reports in a timely manner. Large backlogs of diagnostic procedures hold NHS Wales back from making improvements in referral to treatment times, impair screening pathway effectiveness, result in poor patient experience, and have the potential to result in harms and poorer outcomes. COVID-19 has not gone away, and alongside the effects of global changes in behaviours and other factors, it will continue to present new and emerging challenges that must be addressed to drive improvement and deliver safe, sustainable services for the people of Wales.

The NHS Wales Diagnostics Recovery and Transformation strategy is aimed at leading and co-ordinating supportive actions to aid recovery of diagnostic services post-pandemic and ensure that our interventions implemented in the immediate term align with foreseeable future demand, and shift towards optimised delivery models as the foundation on long-term sustainable transformation. Importantly, the strategy will seek to improve outcomes for patients and reduce pressure on secondary care enabling earlier, faster detection of disease. It sets out the immediate priorities and objectives for diagnostics in NHS Wales, and how it intends to deliver against the extraordinarily challenging needs of now, but with one eye on future need and the challenges that are yet to come.

This presentation will support the introduction of the Digital Pathology EQA explaining the assessment criteria and how the technical issues may be overcome in a routine laboratory.

Electron microscopy is essential for the diagnosis of a range of medical renal disorders, and its use is detecting immune deposits and basement membranes changes in native kideny biopsies will be familiar to many biomedical scientists and pathologists. EM is also used in the assessment of renal transplant biopsies.

In cases of recurrent disease the features are similar to those seen in native kidneys, but there are also specific features only seen in the transplant setting. This talk will focus on the utility of EM in renal transplant biopsies, demonstrating examples from relevant cases.