Events on 28 September 2023

This presentation will examine a specific case study submitted as part of the 'Advanced Specialist Diploma in Breast Pathology'. The case in question was a mastectomy sample for the treatment of diffuse multifocal invasive ductal carcinoma.

Within the presentation I intend to highlight the importance of pre-analysis and emphasise its correlation with macroscopic examination and block sampling. I will also highlight the importance of post analysis and the understanding of how the role of the Advanced Practitioner can directly impact patient treatment.

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 will learn:

What Gestational trophoblastic disease is, including the different types and how they arise
How to handle a sample at the dissection bench including comparison with normal products of conception
How to distinguish between the different types of disease and mimics
What a diagnosis of gestational trophoblastic disease means for the patient
What the malignant entities of Gestational Trophoblastic Disease include

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.

The UK has the 4th highest prevalence rate of alcohol consumption in pregnancy in the world. Fetal Alcohol Spectrum Disorder (FASD) is the most common non-genetic learning disability in the UK with a prevalence rate of at least 5%, more than autism and ADHD combined. A high-profile public health campaign combined with effective antenatal and pre-conception care is urgently required.

Accurate and early identification of women at risk from alcohol consumption during pregnancy allows education and support to be targeted at those most in need. Self-report has limited sensitivity but is commonplace due to its acceptability and affordability. Biomarkers have the potential to provide an objective and reliable antenatal alcohol screening solution.

To explore the utility of blood biomarkers, we conducted a systematic review comparing the diagnostic accuracy of blood analysis and maternal self-report in detecting at antenatal alcohol exposure. We discovered that none of the biomarkers identified had both high sensitivity and specificity when compared to self-report. There was some evidence that a combination of biomarkers, or combining biomarkers with self-report, increases accuracy. Blood biomarkers examined were of limited use in screening for low and moderate alcohol consumption in pregnancy when compared to self-report. However, certain biomarkers, such as carbohydrate deficient transferrin (CDT) and phosphatidylethanol (PEth) may complement self-report and help improve the accuracy of diagnosis.

We applied these findings to practice with two studies comparing the prevalence of alcohol consumption in the first trimester of pregnancy using self-report and blood biomarker analysis. The booking bloods were from women under the care of Northumbria Healthcare NHS Foundation Trust (NHCT) and North Tees and Hartlepool NHS Foundation Trust (NTHFT).

Six-hundred routine blood samples were anonymously analysed from each location for the presence of Carbohydrate Deficient Transferrin (CDT), a validated marker of chronic alcohol exposure (normalising 2–3 weeks from abstinence) and Gamma-glutamyltransferase (GGT), a liver enzyme elevated for up to 8 weeks after alcohol exposure. At NHCT, CDT analysis revealed a prevalence rate of 1.4% and GGT a prevalence rate of 3.5% in the first trimester of pregnancy. Although those with elevated CDT generally had high levels of GGT, only one person was positive for CDT and GGT. The NTHFT data revealed a CDT prevalence rate of 1.7% (95% CI: 0.7–2.9) and GGT prevalence rate of 4.2% (95% CI: 2.6–5.9). No overlapping cases were identified, or a significant correlation was demonstrated between CDT or GGT. Although CDT and GGT analysis are not sensitive to low levels of alcohol, prevalence rates were similar in both areas, suggesting similar patterns of sustained alcohol use in pregnancy across the region.

We also took a full year's sample of data from the antenatal visits of women at NHCT, which documented the women's self-reported alcohol consumption. The percentage of women who reported alcohol intake in the first trimester was 0.8%, approximately half the rate of those identified by CDT. This compared to 74.1% of women who reported consuming alcohol before pregnancy, indicating the limited value of self-report in clinical practice.

Androgens are the naturally occurring or synthetic hormones which can increase lean body mass and decrease fat mass and are the most effective and widely abused ergogenic drugs in sport. The detection methodologies for the exogenous steroids is mostly based on the gas/liquid chromatography and mass spectrometry, while detection of the exogenous administration of endogenous steroids requires more complex methodologies including the longitudinal monitoring of individual urinary steroid concentrations/ratios and isotope ratio mass spectrometry. Although, urine has always been the first choice of sample matrix to detect androgens in sports. However, blood matrix is also now paving its way towards a complementary matrix for detection of androgens in sports. Dried blood spots (DBS) analysis is the latest tool in sports drug testing. DBS testing has advantages in the collection, shipment, and storage compared to traditional urine and blood-based procedures.

The World Anti-Doping Agency (WADA) has recently introduced DBS testing as an implementation for routine doping analysis during the recent Olympic and Paralympic Games in Tokyo and Beijing. DBS samples can be obtained with relatively little training and require minimal invasion at the collection site. A variety of devices based on micro-lancet and micro-needle approaches have been applied in the DBS collection.

Most androgens in DBS are stable at room temperature, so there are no specific requirements during transport. Also, considering the small size and weight of DBS, the DBS-based technique is more cost-effective compared to urine or blood samples. However, as a microscale sample, DBS require more sensitive and accurate analytical methods. The Drug Control Centre, King’s College London (a WADA accredited lab), we are currently investigating the use of DBS testing in our systematic regular analysis as a new methodology.

This presentation will discuss the current situation, perspectives, and challenges of implementing DBS testing for detecting androgens in sports.

Androgens are the naturally occurring or synthetic hormones which can increase lean body mass and decrease fat mass and are the most effective and widely abused ergogenic drugs in sport. The detection methodologies for the exogenous steroids is mostly based on the gas/liquid chromatography and mass spectrometry, while detection of the exogenous administration of endogenous steroids requires more complex methodologies including the longitudinal monitoring of individual urinary steroid concentrations/ratios and isotope ratio mass spectrometry. Although, urine has always been the first choice of sample matrix to detect androgens in sports. However, blood matrix is also now paving its way towards a complementary matrix for detection of androgens in sports. Dried blood spots (DBS) analysis is the latest tool in sports drug testing. DBS testing has advantages in the collection, shipment, and storage compared to traditional urine and blood-based procedures.

The World Anti-Doping Agency (WADA) has recently introduced DBS testing as an implementation for routine doping analysis during the recent Olympic and Paralympic Games in Tokyo and Beijing. DBS samples can be obtained with relatively little training and require minimal invasion at the collection site. A variety of devices based on micro-lancet and micro-needle approaches have been applied in the DBS collection.

Most androgens in DBS are stable at room temperature, so there are no specific requirements during transport. Also, considering the small size and weight of DBS, the DBS-based technique is more cost-effective compared to urine or blood samples. However, as a microscale sample, DBS require more sensitive and accurate analytical methods. The Drug Control Centre, King’s College London (a WADA accredited lab), we are currently investigating the use of DBS testing in our systematic regular analysis as a new methodology.

This presentation will discuss the current situation, perspectives, and challenges of implementing DBS testing for detecting androgens in sports.

Heroin markers

Dimorphine-assisted treatment programme

The public health side of drug misuse